307 results on '"TAO WANG"'
Search Results
2. The influence of physical activity on internet addiction among Chinese college students: the mediating role of self-esteem and the moderating role of gender
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Zhihao, Du, Tao, Wang, Yingjie, Sun, and Feng, Zhai
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- 2024
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3. mbDenoise: microbiome data denoising using zero-inflated probabilistic principal components analysis
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Zeng, Yanyan, Li, Jing, Wei, Chaochun, Zhao, Hongyu, and Tao, Wang
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- 2022
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4. Correction to: Metabolic analysis of early nonalcoholic fatty liver disease in humans using liquid chromatography–mass spectrometry
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Cheng Hu, Tao Wang, Xiaoyu Zhuang, Qiaoli Sun, Xiaochun Wang, Hui Lin, Mingli Feng, Jiaqi Zhang, Qin Cao, and Yuanye Jiang
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Adult ,Adolescent ,Correction ,Reproducibility of Results ,General Medicine ,Middle Aged ,General Biochemistry, Genetics and Molecular Biology ,Mass Spectrometry ,Young Adult ,Non-alcoholic Fatty Liver Disease ,Medicine ,Humans ,Metabolomics ,Biomarkers ,Chromatography, Liquid - Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disease that affects 20-30% of individuals worldwide. Liver puncture remains the gold standard for the diagnosis of liver diseases despite limitations regarding invasive nature and sample variability. It is of great clinical significance to find noninvasive biomarkers to detect and predict NAFLD.The aims of this study were to identify potential serum markers in individuals with early-stage NAFLD and to advance the mechanistic understanding of this disease using a high-throughput mass spectrometry-based untargeted metabolomics approach.One hundred and twelve patients with early-stage NAFLD aged 18-55 were recruited according to the guidelines. The control group included 112 healthy participants. The demographic, anthropometric, clinical and laboratory data of all participants were systematically collected. Serum samples were obtained after an overnight fast. The comprehensive serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. The resultant data was processed by Compound Discover and SIMCA-P software to validate the potential biomarkers. Significantly altered metabolites were evaluated by variable importance in projection value (VIP 1) and ANOVA (p 0.01). Pathway analysis was performed using MetaboAnalyst 4.0.The liver function test of early NAFLD patients showed no statistical differences to control group (p 0.05). However, obvious differences in blood lipids were observed between subjects with NAFLD and controls (p 0.001). In total, 55 metabolites showed significant changes in experimental group were identified. The area under curve (AUC) values deduced by receiver operating curve (ROC) analysis indicated that these newly identified biomarkers have high predictability and reliability. Of these, 15 metabolites with AUC greater than 0.9 were of great diagnostic value in early NAFLD patients.In this study, a total of 15 serum metabolites were found to strongly associate with early NAFLD. These biomarkers may have great clinical significance in the early diagnosis of NAFLD, as well as to follow response to therapeutic interventions.
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- 2022
5. Current efforts towards safe and effective live attenuated vaccines against African swine fever: challenges and prospects
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Tao Wang, Rui Luo, Yuan Sun, and Hua-Ji Qiu
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Differentiation of infected from vaccinated animals ,Efficacy ,Swine ,Sus scrofa ,Public Health, Environmental and Occupational Health ,Viral Vaccines ,General Medicine ,Infectious and parasitic diseases ,RC109-216 ,Vaccines, Attenuated ,African Swine Fever Virus ,Infectious Diseases ,Live attenuated vaccine ,Biosecurity ,Commentary ,Animals ,Public aspects of medicine ,RA1-1270 ,African swine fever ,Safety - Abstract
Background African swine fever (ASF) is a fatal hemorrhagic disease in domestic pigs and wild boar caused by African swine fever virus (ASFV). Since ASF has been introduced into Europe and Asia, the major pig-raising areas, posing a huge threat to the pork industry worldwide. Currently, prevention and control of ASF are basically dependent on strict biosecurity measures and stamping-out policy once ASF occurs. Main text The major risks of ASF spread are insufficient biosecurity measures and human behaviors. Therefore, a safe and effective vaccine seems to be a reasonable demand for the prevention and control of ASF. Due to the efficacy advantage over other types of vaccines, live attenuated vaccines (LAVs), especially virulence-associated genes deleted vaccines, are likely to be put into emergency and conditional use in restricted areas if ASF is out of control in a country with a huge pig population and pork consumption, like China. However, the safety, efficacy, and genetic stability of current candidate ASF LAVs require comprehensive clinical evaluations prior to country-wide field application. Several critical issues need to be addressed to commercialize an ideal ASF LAV, including a stable cell line for manufacturing vaccines, differentiation of infected from vaccinated animals (DIVA), and cross-protection from different genotypes. Conclusion A safe and effective DIVA vaccine and an accompanying diagnostic assay will facilitate the prevention, control, and eradication of ASF, which is quite challenging in the near future. Graphical Abstract
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- 2021
6. Visceral adiposity index is associated with arterial stiffness in hypertensive adults with normal-weight: the china H-type hypertension registry study
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Yun Yu, Tianyu Cao, Ziheng Tan, Junpei Li, Wei Zhou, Huihui Bao, Linfei Luo, Jian Zhu, Xiaoshu Cheng, Linjuan Zhu, Lishun Liu, Tao Wang, and Xiao Huang
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medicine.medical_specialty ,RC620-627 ,Endocrinology, Diabetes and Metabolism ,Registry study ,Population ,Medicine (miscellaneous) ,Clinical nutrition ,Internal medicine ,medicine ,TX341-641 ,Normal weight ,Nutritional diseases. Deficiency diseases ,education ,Body mass index ,education.field_of_study ,Nutrition and Dietetics ,Brachial-ankle pulse wave velocity ,Nutrition. Foods and food supply ,business.industry ,Research ,Confounding ,Mean age ,medicine.disease ,Visceral adiposity index ,Hypertension ,Cardiology ,Arterial stiffness ,business - Abstract
Background Limited information is available on arterial stiffness risk among hypertensive patients with metabolically abnormal but normal weight. Visceral adiposity index (VAI) is a novel indicator for visceral fat mass and metabolism, however, whether can be used to assessed arterial stiffness in a normal-weight population remains unclear. The goal of this study was to examine the independent association of VAI with arterial stiffness in normal-weight hypertensive patients. Methods 3258 participants recruited from the China H-type Hypertension Registry Study. VAI value was calculated using sex-specific equations. High arterial stiffness was defined as baPWV ≥ 18 m/s. Multivariable regression analysis was used to identify the association of VAI with baPWV and high arterial stiffness. Results Of participants, 50.5% (1644) were males, the mean age was 65.5 (SD, 9.1) years. Mean VAI and baPWV were 2.0 (SD, 2.3) and 18.2 (SD, 3.9) m/s, respectively. For each unit increase of lg VAI in multivariable regression analysis, there was a 1.05 m/s increase in baPWV (95% CI 0.67, 1.43) and a 2.13-fold increase in the risk of high arterial stiffness (95% CI 1.59, 2.86). In all models, the VAI was consistently and significantly associated with baPWV after adjustment for different confounders. High VAI levels were stably associated with baPWV in all subgroups. Conclusions We found positive association of VAI with baPWV and high arterial stiffness in normal-weight adults with hypertension. The establishment of this association could help the arterial stiffness risk stratification in normal-weight hypertensive populations, who are frequently overlooked in preventing cardiovascular disease.
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- 2021
7. Mendelian randomization to evaluate the effect of plasma vitamin C levels on the risk of Alzheimer’s disease
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Tao Wang, Haihua Zhang, Guiyou Liu, Yang Hu, Yan Zhang, Longcai Wang, Shan Gao, Zhifa Han, and Haijie Liu
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Oncology ,medicine.medical_specialty ,Genome-wide association study ,Vitamin C ,business.industry ,Genetic heterogeneity ,Endocrinology, Diabetes and Metabolism ,Research ,Disease ,Clinical nutrition ,Human genetics ,Internal medicine ,Mendelian randomization ,Genetics ,Medicine ,Effects of sleep deprivation on cognitive performance ,business ,Inverse-variance weighted ,Alzheimer’s disease - Abstract
Objective Until now, observational studies have explored the impact of vitamin C intake on Alzheimer’s disease (AD) risk, however, reported ambiguous findings. To develop effective therapies or prevention, the causal link between vitamin C levels and AD should be established. Methods Here, we selected 11 plasma vitamin C genetic variants from a large-scale plasma vitamin C GWAS dataset (N = 52,018) as the potential instrumental variables. We extracted their corresponding summary statistics from large-scale IGAP clinically diagnosed AD GWAS dataset (N = 63,926) and UK Biobank AD proxy phenotype GWAS dataset (N = 314,278), as well as two UK Biobank subgroups including the maternal AD group (27,696 cases of maternal AD and 260,980 controls) and paternal AD group (14,338 cases of paternal AD and 245,941 controls). We then performed a Mendelian randomization (MR) study to evaluate the causal association between plasma vitamin C levels and the risk of AD and AD proxy phenotype. Meanwhile, we further verified these findings using a large-scale cognitive performance GWAS dataset (N = 257,841). Results In IGAP, we found no significant causal association between plasma vitamin C levels and the risk of AD. In UK Biobank, we found that per 1 SD increase in plasma vitamin C levels (about 20.2 μmol/l) was significantly associated with the reduced risk of AD proxy phenotype (OR = 0.93, 95% CI 0.88–0.98, P = 7.00E−03). A subgroup MR analysis in UK Biobank indicated that per 1 SD increase in plasma vitamin C levels could significantly reduce the risk of AD proxy phenotype in the maternal AD group (OR = 0.89, 95% CI 0.84–0.94, P = 7.29E−05), but not in the paternal AD group (OR = 1.02, 95% CI 0.92–1.12, P = 7.59E−01). The leave-one-out permutation further showed that the SLC23A1 rs33972313 variant largely changed the precision of the overall MR estimates in all these four GWAS datasets. Meanwhile, we did not observe any significant causal effect of plasma vitamin C levels on the cognitive performance. Conclusion We demonstrated that there may be no causal association between plasma vitamin C levels and the risk of AD in people of European descent. The insistent findings in clinically diagnosed AD and AD proxy phenotype may be caused by the phenotypic heterogeneity.
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- 2021
8. EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma
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Xiaoming Zhou, Run Tong, Zhe Zhang, Tao Wang, Gang Hou, Chao-Nan Liang, and Mingming Deng
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Cancer Research ,medicine.medical_treatment ,Biology ,Genetics ,medicine ,Ephrin ,Lung cancer ,RC254-282 ,QH573-671 ,Erythropoietin-producing hepatocellular (Eph) receptor ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunotherapy ,Biomarker ,Immunotherapy response ,medicine.disease ,Prognosis ,EFNA3 ,Immune checkpoint ,Oncology ,Cancer research ,Immunohistochemistry ,Biomarker (medicine) ,Adenocarcinoma ,Cytology ,Primary Research - Abstract
Background Ephrin receptors (Eph) and their ligands, called ephrins, function in various disease processes. However, the expression level and prognostic value of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear. Methods The Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. Kaplan–Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Immunohistochemistry was used to analyze the expression level and clinical value of ephrin-A3 protein in clinical LUAD tissue. Weighted coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3. CCK-8 assays and colony-forming experiments were used to investigate whether EFNA3 can regulate cell proliferation ability in LUAD. Analysis of lactate, ATP, and glucose uptake levels was used to explore the effect of EFNA3 on glycolysis ability. In addition, we investigated the relationship between EFNA3 and tumor infiltrating immune cells (TIICs). Finally, the potential immunotherapy response prediction value of EFNA3 was also explored. Results In this study, we found that EFNA3 expression was significantly correlated with both overall survival (OS) and progression-free survival (PFS) in LUAD patients based on a comprehensive analysis of the Eph/Ephrin family. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated an independent prognostic risk factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. In vitro experiments confirmed the role of EFNA3 in promoting LUAD cells and showed that it could regulate glycolytic capacity. Moreover, EFNA3 was negatively associated with immunity, stromal infiltration, and several TIICs. Finally, EFNA3 was found to be positively related to multiple immunotherapy biomarkers. Conclusions In conclusion, increased EFNA3 in LUAD patients predicted worse clinical prognosis, promoted LUAD cell proliferation and glycolysis ability, and was related to immunotherapy response.
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- 2021
9. Clinical characteristics and outcomes of critically ill patients with acute COVID-19 with Epstein-Barr virus reactivation
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Yujing Chai, Hui Lv, Luyu Yang, Xiaolei Teng, Xiaoyan Zhang, Yun Xie, Jiaxiang Zhang, Hui Dong, Tao Wang, Song Cao, Ruilan Wang, Jun Liu, and Yun Qin
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ARDS ,medicine.medical_specialty ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Critical Illness ,Infectious and parasitic diseases ,RC109-216 ,Procalcitonin ,law.invention ,law ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Epstein-Barr virus ,Humans ,Epstein–Barr virus infection ,Outcome ,Retrospective Studies ,business.industry ,SARS-CoV-2 ,Mortality rate ,Incidence (epidemiology) ,COVID-19 ,Retrospective cohort study ,medicine.disease ,Intensive care unit ,Infectious Diseases ,Respiratory failure ,Virus Activation ,business ,Research Article - Abstract
Background Our goal is to further elucidate the clinical condition and prognosis of patients with severe acute COVID-19 with EBV reactivation. Method This is a retrospective single-center study of COVID-19 patients admitted to the intensive care unit of Wuhan No. 3 Hospital (January 31 to March 27, 2020). According to whether Epstein-Barr virus reactivation was detected, the patients were divided into an EBV group and a Non-EBV group. Baseline data were collected including epidemiological, larithmics, clinical and imaging characteristics, and laboratory examination data. Results Of the 128 patients with COVID-19, 17 (13.3%) were infected with Epstein-Barr virus reactivation. In the symptoms,the rate of tachypnoea in the EBV group was apparently higher than that in the Non-EBV group. In lab tests, the lymphocyte and albumin of EBV group decreased more significantly than Non-EBV group, and the D-dimer and serum calcium of EBV group was higher than Non-EBV group. Regarding the infection index, CRP of EBV group was apparently above the Non-EBV group, and no significant difference was found in procalcitonin of the two groups. The incidence of respiratory failure, ARDS, and hypoproteinaemia of EBV group had more incidence than Non-EBV group. The 28-day and 14-day mortality rates of EBV group was significantly higher than that of Non-EBV group. Conclusions In the COVID-19 patients, patients with EBV reactivation had higher 28-day and 14-day mortality rates and received more immuno-supportive treatment than patients of Non-EBV group.
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- 2021
10. Autotaxin levels in serum and bronchoalveolar lavage fluid are associated with inflammatory and fibrotic biomarkers and the clinical outcome in patients with acute respiratory distress syndrome
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Jun Hu, Yongfang Zhou, Mengxin Cheng, Zijian Zeng, Xiaoou Li, Hao Wang, Ke Wang, Tao Wang, Fuqiang Wen, Yue Liao, and Lijuan Gao
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medicine.medical_specialty ,ARDS ,Serum albumin ,Critical Care and Intensive Care Medicine ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Internal medicine ,medicine ,Mortality ,030304 developmental biology ,0303 health sciences ,medicine.diagnostic_test ,biology ,Acute respiratory distress syndrome ,business.industry ,RC86-88.9 ,Research ,Albumin ,Area under the curve ,Interleukin ,Medical emergencies. Critical care. Intensive care. First aid ,Biomarker ,respiratory system ,medicine.disease ,Prognosis ,respiratory tract diseases ,Bronchoalveolar lavage ,Autotaxin ,030228 respiratory system ,biology.protein ,SOFA score ,business - Abstract
Background Autotaxin (ATX) is a secreted glycoprotein that is widely present in extracellular biological fluids and has been implicated in many inflammatory and fibrotic diseases. However, the clinical impact of the release of ATX in patients with acute respiratory distress syndrome (ARDS) remains unclear. Methods Serum and bronchoalveolar lavage fluid (BALF) levels of ATX, interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-7, fibronectin, oncostatin M (OSM), and SPARC (secreted protein acidic and rich in cysteine) were collected from 52 patients with ARDS within 24 h of diagnosis. All cytokines were measured by Magnetic Luminex Assay. BALF albumin (BA) and serum albumin (SA) were measured by enzyme-linked immunosorbent assay. Results Serum ATX, MMP-7, and BALF IL-8 levels were significantly higher in patients who did not survive than in those who survived up to 28 days after diagnosis of ARDS (P < 0.05). BALF and serum ATX levels were correlated with IL-6, IL-8, and MMP-7 levels in BALF and serum, respectively. In addition, BALF ATX was positively correlated with BALF TNF-α, fibronectin, OSM, and SPARC as well as the BA/SA ratio, while serum ATX was correlated with severity of illness based on the SOFA score and PaO2/FIO2 ratio. Furthermore, serum ATX was better able to predict 28-day ARDS-related mortality (area under the curve 0.744, P < 0.01) than the SOFA score, APACHE II score, or PaO2/FIO2 ratio. Serum ATX independently predicted mortality in a univariate Cox regression model (P < 0.0001). Conclusion The serum ATX level is a potential prognostic biomarker in patients with ARDS. BALF ATX is associated with pulmonary biomarkers of inflammation and fibrosis, suggesting a role of ATX in the pathogenesis of ARDS.
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- 2021
11. Analysis of selection signatures on the Z chromosome of bidirectional selection broiler lines for the assessment of abdominal fat content
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Kun Ding, Tao Wang, Peng Wang, Jing Guo, Meng Zhou, Yuanyuan Guo, and Zhipeng Wang
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0301 basic medicine ,Male ,Candidate gene ,Population genetics ,Population ,Abdominal Fat ,SNP ,Health Informatics ,Biology ,Quantitative trait locus ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,Animals ,education ,Selection (genetic algorithm) ,Z chromosome ,education.field_of_study ,Sex Chromosomes ,Research ,Haplotype ,Selection signature ,SNP genotyping ,030104 developmental biology ,Haplotypes ,030220 oncology & carcinogenesis ,Female ,Gene expression ,Chickens - Abstract
Background The discovery of selection signatures has enabled the identification of genomics regions under selective pressure, enhancing knowledge of evolutionary genotype-phenotypes. Sex chromosomes play an important role in species formation and evolution. Therefore, the exploration of selection signatures on sex chromosomes has important biological significance. Results In this study, we used the Cross Population Extend Haplotype Homozygosity Test (XPEHH), F-statistics (FST) and EigenGWAS to assess selection signatures on the Z chromosome in 474 broiler chickens via Illumina chicken 60 K SNP chips. SNP genotype data were downloaded from publicly available resources. We identified 17 selection regions, amongst which 1, 11 and 12 were identified by XPEHH, FST, and EigenGWAS, respectively. Each end of the Z chromosome appeared to undergo the highest levels of selection pressure. A total of 215 candidate genes were located in 17 selection regions, some of which mediated lipogenesis, fatty acid production, fat metabolism, and fat decomposition, including FGF10, ELOVL7, and IL6ST. Using abdominal adipose tissue expression data of the chickens, 187 candidate genes were expressed with 15 differentially expressed genes (DEGs) in fat vs. lean lines identified. Amongst the DEGs, VCAN was related to fat metabolism. GO pathway enrichment analysis and QTL annotations were performed to fully characterize the selection mechanism(s) of chicken abdominal fat content. Conclusions We have found some selection regions and candidate genes involving in fat metabolism on the Z chromosome. These findings enhance our understanding of sex chromosome selection signatures.
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- 2021
12. A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia
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Xianliang Xin, Huidong Tang, Meiyu Geng, Dongsheng Fan, Yi Li, Qinyong Ye, Shuai Liu, Lu Shen, Wenwei Ren, Zhenxin Zhang, Dan Gao, Jian Ding, You Yin, Junjian Zhang, Raoli He, Dantao Peng, Qiumei Wang, Xueyan Chen, Lanlan Chen, Yong Yan, Xu Zhang, Yingchun Zhang, Zhen Hong, Yu Ding, Wei Chen, Jinsong Xiao, Marc Cantillon, Yan Wang, Bin Jiao, Xiaowei Liu, Hui Zhang, Benyan Luo, Ying Peng, Hua Hu, Lijun Jiang, Jincai He, Teng Feng, Yongtao Zhou, Chun-Feng Liu, Yuying Zhou, Jianjun Jia, Yihui Guan, Qiu Huang, Yong Ji, Tingyi Feng, Shuhua Li, Yifeng Du, Nan Zhang, Yuncheng Wu, Jeffrey L. Cummings, Lin Cong, Xiaoping Pan, Wenyuan Wu, Xi Cheng, Minghua Xia, Hongjian Chen, Weihong Kuang, Qiumin Qu, Guoping Peng, Shuzhen Wang, Luning Wang, Shifu Xiao, Wenhui Lu, Kewei Chen, Peixian Mao, Lei Wang, Zhongxin Zhao, Qihao Guo, Xiaoping Wang, Shengdi Chen, Zhonglin Liu, Qianhua Zhao, Qun Xu, Piu Chan, Tao Wang, Ping Gao, Jing Zhang, Yansheng Li, Yan Cheng, Ruixue Cui, Jun Xu, Weixian Chen, Yingjun Ouyang, Wei Zhang, and Tenghong Lian
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medicine.medical_specialty ,China ,Neurology ,Efficacy ,Cognitive Neuroscience ,Phases of clinical research ,Oligosaccharides ,Placebo ,lcsh:RC346-429 ,lcsh:RC321-571 ,Double-Blind Method ,Alzheimer Disease ,Internal medicine ,Activities of Daily Living ,medicine ,Humans ,Adverse effect ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,lcsh:Neurology. Diseases of the nervous system ,business.industry ,Incidence (epidemiology) ,Research ,Sodium ,Sodium oligomannate ,Confidence interval ,Clinical trial ,Treatment Outcome ,Tolerability ,Pharmaceutical Preparations ,Neurology (clinical) ,Cholinesterase Inhibitors ,Safety ,business ,Alzheimer’s disease ,Mannose - Abstract
Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014
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- 2021
13. Cis-acting lnc-eRNA SEELA directly binds histone H4 to promote histone recognition and leukemia progression
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Yue-Qin Chen, Qi Pan, Qian-Qian Yang, Wei Huang, Lin-Yu Sun, Wen-Tao Wang, Yu-Meng Sun, Tian-Qi Chen, Cai Han, Ke Fang, Xue-Qun Luo, and Zhan-Cheng Zeng
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BRD4 ,Transcription, Genetic ,lcsh:QH426-470 ,Lnc-eRNA ,Cell Cycle Proteins ,Biology ,Epigenesis, Genetic ,Histone recognition ,Histone H4 ,Histones ,Transcription (biology) ,Humans ,Epigenetics ,MLL leukemia ,Enhancer ,lcsh:QH301-705.5 ,Cell Proliferation ,SEELA ,Sphingolipids ,Leukemia ,Oncogene ,Research ,Cell Cycle ,Sphingolipid metabolism ,Membrane Proteins ,Cell biology ,Chromatin ,lcsh:Genetics ,Histone ,Enhancer Elements, Genetic ,HEK293 Cells ,Gene Expression Regulation ,lcsh:Biology (General) ,biology.protein ,Enhancer activity ,RNA, Long Noncoding ,Transcription Factors - Abstract
Background Long noncoding enhancer RNAs (lnc-eRNAs) are a subset of stable eRNAs identified from annotated lncRNAs. They might act as enhancer activity-related therapeutic targets in cancer. However, the underlying mechanism of epigenetic activation and their function in cancer initiation and progression remain largely unknown. Results We identify a set of lncRNAs as lnc-eRNAs according to the epigenetic signatures of enhancers. We show that these lnc-eRNAs are broadly activated in MLL-rearranged leukemia (MLL leukemia), an aggressive leukemia caused by a chromosomal translocation, through a mechanism by which the HOXA cluster initiates enhancer activity, and the epigenetic reader BRD4 cooperates with the coregulator MLL fusion oncoprotein to induce transcriptional activation. To demonstrate the functional roles of lnc-eRNAs, two newly identified lnc-eRNAs transcribed from the SEELA eRNA cluster (SEELA), SEELA1 and SEELA2, are chosen for further studies. The results show that SEELA mediated cis-activated transcription of the nearby oncogene Serine incorporate 2 (SERINC2) by directly binding to the K31 amino acid (aa) of histone H4. Chromatin-bound SEELA strengthens the interaction between chromatin and histone modifiers to promote histone recognition and oncogene transcription. Further studies show that the SEELA-SERINC2 axis regulated aspects of cancer metabolism, such as sphingolipid synthesis, to affect leukemia progression. Conclusions This study shows that lnc-eRNAs are epigenetically activated by cancer-initiating oncoproteins and uncovers a cis-activating mechanism of oncogene transcription control based on lnc-eRNA-mediated epigenetic regulation of enhancer activity, providing insights into the critical roles of lnc-eRNAs in cancer initiation and progression.
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- 2020
14. Explore potential disease related metabolites based on latent factor model.
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Yongtian Wang, Liran Juan, Jiajie Peng, Tao Wang, Tianyi Zang, and Yadong Wang
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METABOLITES ,MATRIX decomposition ,DECOMPOSITION method ,METABOLIC models ,LATENT infection ,FRUIT rots - Abstract
Background: In biological systems, metabolomics can not only contribute to the discovery of metabolic signatures for disease diagnosis, but is very helpful to illustrate the underlying molecular disease-causing mechanism. Therefore, identification of disease-related metabolites is of great significance for comprehensively understanding the pathogenesis of diseases and improving clinical medicine. Results: In the paper, we propose a disease and literature driven metabolism prediction model (DLMPM) to identify the potential associations between metabolites and diseases based on latent factor model. We build the disease glossary with disease terms from different databases and an association matrix based on the mapping between diseases and metabolites. The similarity of diseases and metabolites is used to complete the association matrix. Finally, we predict potential associations between metabolites and diseases based on the matrix decomposition method. In total, 1,406 direct associations between diseases and metabolites are found. There are 119,206 unknown associations between diseases and metabolites predicted with a coverage rate of 80.88%. Subsequently, we extract training sets and testing sets based on data increment from the database of disease-related metabolites and assess the performance of DLMPM on 19 diseases. As a result, DLMPM is proven to be successful in predicting potential metabolic signatures for human diseases with an average AUC value of 82.33%. Conclusion: In this paper, a computational model is proposed for exploring metabolite-disease pairs and has good performance in predicting potential metabolites related to diseases through adequate validation. The results show that DLMPM has a better performance in prioritizing candidate diseases-related metabolites compared with the previous methods and would be helpful for researchers to reveal more information about human diseases. [ABSTRACT FROM AUTHOR]
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- 2022
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15. Regulation effects of total flavonoids in Morus alba L. on hepatic cholesterol disorders in orotic acid induced NAFLD rats
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Sijian Wang, Haiyang Yu, Jingqi Xu, Tao Wang, Mengyang Liu, Yucheng Hu, Yi Zhang, and Qian Chen
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Male ,Orotic acid ,China ,Down-Regulation ,Pharmacology ,Cholesterol 7 alpha-hydroxylase ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,In vivo ,Non-alcoholic Fatty Liver Disease ,NAFLD ,medicine ,Cholesterol metabolism ,Animals ,Humans ,heterocyclic compounds ,Mulberry leaves flavonoids ,Liver injury ,Flavonoids ,Orotic Acid ,Chemistry ,Cholesterol ,Plant Extracts ,Lipid metabolism ,lcsh:Other systems of medicine ,Hep G2 Cells ,lcsh:RZ201-999 ,medicine.disease ,In vitro ,Rats ,Plant Leaves ,Disease Models, Animal ,Complementary and alternative medicine ,lipids (amino acids, peptides, and proteins) ,Quercetin ,Morus ,medicine.drug ,Research Article - Abstract
Background Mulberry leaves are the dried leaves of Morus alba L., flavonoids from mulberry leaves (MLF) has showed regulatory effect on abnormal lipid metabolism, but the regulatory mechanism of MLF on cholesterol metabolism is still missing. This study was designed to investigate the effect of MLF and its active metabolite quercetin on regulating cholesterol disorders. Methods The mechanism of MLF on alleviating liver injury and regulating cholesterol was examined in dyslipidemic SD rats. The regulatory mechanism of quercetin for cholesterol disorders have also been detected through lipid laden HepG2 cell model. Results Our results showed that MLF significantly inhibited lipid accumulation and alleviate hepatic injury in NAFLD rat model. The hepatic expression level of SREBP2, HMGCR and miR-33a were significantly down-regulated, while CYP7A1 was induced by MLF treatment. In vitro, Quercetin significantly decreased lipid accumulation in HepG2 cells. Mechanistically, quercetin could inhibit the mRNA and protein expression level of SREBP2 and HMGCR with or without LDL treatment. In addition, quercetin could also reduce the LXRβ while induced SR-BI mRNA expression. Conclusion Our findings indicate that MLF and quercetin could reduce the excessive cholesterol accumulation in vivo and in vitro. These cholesterol-regulating phenomenon might attribute to its effect on down-regulating the expression of lipid-related markers such as SREBP2 and HMGCR, which may exert a protective role in the NAFLD treatment.
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- 2020
16. HnRNP A1 - mediated alternative splicing of CCDC50 contributes to cancer progression of clear cell renal cell carcinoma via ZNF395
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Guoliang Sun, Hui Zhou, Ke Chen, Jin Zeng, Yangjun Zhang, Libin Yan, Weimin Yao, Junhui Hu, Tao Wang, Jinchun Xing, Kefeng Xiao, Lily Wu, Zhangqun Ye, and Hua Xu
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Heterogeneous Nuclear Ribonucleoprotein A1 ,RNA Splicing ,Apoptosis ,lcsh:RC254-282 ,ZNF395 ,Mice ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Animals ,Humans ,HnRNP A1 ,Carcinoma, Renal Cell ,Cell Proliferation ,Research ,ccRCC ,Intracellular Signaling Peptides and Proteins ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Xenograft Model Antitumor Assays ,Kidney Neoplasms ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Alternative Splicing ,CCDC50 ,Transcription Factors - Abstract
Background Aberrant alternative splicing events play critical roles in carcinogenesis and progression of many cancers, while sparse studies regarding to alternative splicing are available for clear cell renal cell carcinoma (ccRCC). We identified that alternative splicing of coiled-coil domain containing 50 (CCDC50) was dysregulated in ccRCC, whereas the clinical significance of this splicing event and its splicing regulation mechanisms were still elusive. Methods Bioinformatic algorithm was utilized to identify significant exon skipping events in ccRCC via exon sequencing data from The Cancer Genome Atlas. Semi-quantitative real-time polymerase chain reaction and western blot were used to validate the aberrant expression of different transcripts in renal cancer tissues, cell lines and corresponding noncancerous controls. Short hairpin RNA targeting CCDC50 and overexpressing plasmids for each transcript were introduced into ccRCC cell lines, followed by a series of in vitro and in vivo functional experiments. Moreover, a panel of splicing factors were identified and their roles on splicing regulation of CCDC50 precursor mRNA (pre-mRNA) were studied. Furthermore, RNAseq data were analyzed to elucidate downstream molecules of CCDC50. Two-way analysis of variance and unpaired Student t test were used in statistical analysis. Results Pre-mRNA of CCDC50 generated two transcripts, full-length transcript (CCDC50-FL) and truncated transcript (CCDC50-S) with exon 6 skipped. CCDC50-S was overexpressed in ccRCC tissues and cell lines compared to noncancerous counterparts, but CCDC50-FL was only detected in noncancerous tissues and normal renal epithelial cells. Higher percent spliced-in index was associated with better survival in ccRCC patients. In vitro and in vivo functional experiments indicated that CCDC50-S transcript promoted the proliferation, migration, invasion and tumorigenesis of ccRCC, while CCDC50-FL exerted opposite tumor suppressive functions. Besides, we identified that heterogeneous nuclear ribonucleoprotein A1 (HnRNP A1) could promote the skipping of exon 6, which resulted in higher portion of CCDC50-S and oncogenic transformation. Moreover, zinc finger protein 395 (ZNF395) was identified as a downstream protein of CCDC50-S, and the interaction initiated oncogenic pathways which were involved in ccRCC progression. Conclusions Aberrant alternative splicing of CCDC50 is regulated by HnRNP A1 in ccRCC. This splicing event contributes to cancer progression through the downstream pathway involving ZNF395.
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- 2020
17. Early awake prone position combined with high-flow nasal oxygen therapy in severe COVID-19: a case series
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Tao Wang, Xuemei Qin, Weihua Lu, Yanli Jie, Lei Zha, and Qiancheng Xu
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Adult ,Male ,2019-20 coronavirus outbreak ,Time Factors ,Letter ,Coronavirus disease 2019 (COVID-19) ,medicine.medical_treatment ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Treatment outcome ,Pneumonia, Viral ,Prone positioning ,Critical Care and Intensive Care Medicine ,Severity of Illness Index ,Betacoronavirus ,Oxygen therapy ,medicine ,Research Letter ,Prone Position ,Humans ,Wakefulness ,Pandemics ,Aged ,business.industry ,SARS-CoV-2 ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,Oxygen Inhalation Therapy ,COVID-19 ,lcsh:RC86-88.9 ,Middle Aged ,Oxygen ,Prone position ,Treatment Outcome ,Anesthesia ,High-flow nasal cannula ,Female ,business ,High flow ,Coronavirus Infections - Published
- 2020
18. Quantitative evaluation of carotid atherosclerotic vulnerable plaques using in vivo T1 mapping cardiovascular magnetic resonaonce: validation by histology
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Huimin Xu, Huijun Chen, Dongye Li, Yongjun Han, Xihai Zhao, Tao Wang, Hualu Han, Yajie Wang, Shuo Chen, Huiyu Qiao, Haikun Qi, and Jingli Cao
- Subjects
Male ,medicine.medical_specialty ,lcsh:Diseases of the circulatory (Cardiovascular) system ,Intraclass correlation ,medicine.medical_treatment ,Carotid endarterectomy ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Intraplaque hemorrhage ,Severity of Illness Index ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Carotid Stenosis ,Prospective Studies ,Stage (cooking) ,Angiology ,Aged ,Endarterectomy, Carotid ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Rupture, Spontaneous ,business.industry ,Research ,Reproducibility of Results ,Magnetic resonance imaging ,Histology ,T1 mapping ,Middle Aged ,Atherosclerosis ,Vulnerable plaque ,Magnetic Resonance Imaging ,Plaque, Atherosclerotic ,Carotid Arteries ,lcsh:RC666-701 ,Female ,Cardiology and Cardiovascular Medicine ,business ,Nuclear medicine ,Kappa ,Carotid artery - Abstract
Background It has been proved that multi-contrast cardiovascular magnetic resonance (CMR) vessel wall imaging could be used to characterize carotid vulnerable plaque components according to the signal intensity on different contrast images. The signal intensity of plaque components is mainly dependent on the values of T1 and T2 relaxation. T1 mapping recently showed a potential in identifying plaque components but it is not well validated by histology. This study aimed to validate the usefulness of in vivo T1 mapping in assessing carotid vulnerable plaque components by histology. Methods Thirty-four subjects (mean age, 64.0 ± 8.9 years; 26 males) with carotid plaques referred to carotid endarterectomy were prospectively enrolled and underwent 3 T CMR imaging from May 2017 to October 2017. The T1 values of intraplaque hemorrhage (IPH), necrotic core (NC) and loose matrix (LM) which were identified on multi-contrast vessel wall images or histology were measured on in-vivo T1 mapping. The IPHs were divided into two types based on the proportion of the area of fresh hemorrhage on histology. The T1 values of different plaque components were compared using Mann-Whitney U test and the agreement between T1 mapping and histology in identifying and quantifying IPH was analyzed with Cohen’s Kappa and intraclass correlation coefficient (ICC). Results Of 34 subjects, 19 had histological specimens matched with CMR imaging. The mean T1 values of IPH (651 ± 253 ms), NC (1161 ± 182 ms) and LM (1447 ± 310 ms) identified by histology were significantly different. The T1 values of Type 1 IPH were significantly shorter than that of Type 2 IPH (456 ± 193 ms vs. 775 ± 205 ms, p p p = 0.028) and segmentation (ICC = 0.816, 95% CI 0.679–0.894) of IPHs between T1 mapping and histology. Conclusions The T1 values of carotid plaque components, particularly for intraplaque hemorrhage, are differentiable, and the stage of intraplaque hemorrhage can be classified according to T1 values, suggesting the potential capability of assessment of vulnerable plaque components by T1 mapping.
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- 2020
19. Retraction Note: Mir-655 up-regulation suppresses cell invasion by targeting pituitary tumor-transforming gene-1 in esophageal squamous cell carcinoma
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Ziming Dong, Tao Wang, Ping Li, Yuanyuan Wang, Min Li, Wenqiao Zang, Xudong Chen, Guoqiang Zhao, Yuwen Du, and Yunyun Ma
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Male ,Esophageal Neoplasms ,Cell ,lcsh:Medicine ,Down-Regulation ,Enzyme-Linked Immunosorbent Assay ,Biology ,Real-Time Polymerase Chain Reaction ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,Downregulation and upregulation ,Western blot ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Neoplasm Invasiveness ,Neoplasm Metastasis ,Lymph node ,medicine.diagnostic_test ,lcsh:R ,General Medicine ,Transfection ,Middle Aged ,medicine.disease ,digestive system diseases ,Up-Regulation ,Securin ,MicroRNAs ,medicine.anatomical_structure ,Retraction Note ,Cell culture ,Cancer research ,Carcinoma, Squamous Cell ,Female - Abstract
MicroRNAs (miRNAs) can act as either oncogenes or tumor suppressor genes under different conditions and thus can play a significant role in cancer development. We investigated miR-655 expression in a cohort of esophageal squamous cell carcinoma (ESCC) to assess the impact of this miRNA on ESCC cell invasion and metastasis. A qRT-PCR assay was used to quantify miR-655 expression levels in 34 paired ESCC samples and adjacent non-tumor tissues. Wound healing and transwell assays were used to evaluate the effects of miR-655 expression on the invasiveness of ESCC cells. Luciferase reporter and western blot assays were used to determine whether the mRNA encoding pituitary tumor-transforming gene-1 (PTTG1) is a major target of miR-655. The expression level of miR-655 in ESCC tissues was found to be lower than in adjacent non-tumor tissues (P
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- 2020
20. High anti-Ascaris seroprevalence in fattening pigs in Sichuan, China, calls for improved management strategies
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Robin B. Gasser, Youle Zheng, Peter Geldhof, Tao Wang, Yue Xie, Johnny Vlaminck, and Guangxu Ma
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Veterinary medicine ,China ,PROVINCE ,Farms ,Swine ,Short Report ,Antibodies, Helminth ,Seroprevalence ,Biology ,Feed conversion ratio ,Serology ,lcsh:Infectious and parasitic diseases ,REGION ,FARMS ,Seroepidemiologic Studies ,Ascariasis ,medicine ,Helminths ,Animals ,Food Industry ,lcsh:RC109-216 ,Serologic Tests ,Veterinary Sciences ,Ascaris suum ,INTESTINAL PARASITES ,Swine Diseases ,Pig ,Serodiagnosis ,Ascaris ,Disease Management ,PERFORMANCE ,medicine.disease ,biology.organism_classification ,PREVALENCE ,Infectious Diseases ,Liver ,INFECTIONS ,Parasitic disease ,RISK-FACTORS ,Pork Meat ,Parasitology ,As-Hb-based ELISA ,SUUM - Abstract
Background Ascariasis, caused by Ascaris suum, is an important soil-transmitted parasitic disease of pigs worldwide. It leads to significant economic losses in the pork industry, as a consequence of low feed conversion efficiency in pigs and liver condemnation at slaughter. Despite ascariasis still being widespread on pig farms in many developing and the industrialised countries, there are surprisingly limited data on porcine ascariasis in China, where nearly half of the world’s total pork is produced. Methods In the present study, using the recently developed A. suum-haemoglobin (As-Hb) antigen-based serological test, we screened 512 individual serum samples from fattening pigs from 13 farms across seven distinct locations of Sichuan Province in China for anti-Ascaris antibody. Results The prevalence of anti-Ascaris antibody ranged from 0% to 100% on the distinct farms, with the mean (overall) seroprevalence being > 60%. There was no significant difference in seroprevalence between the intensive and extensive farms. Conclusions To our knowledge, this is the first study to measure anti-Ascaris seroprevalence in China. The results of this ‘snapshot’ investigation indicate that Ascaris infection in commercial pig farms in Sichuan Province is seriously underestimated, encouraging future, large-scale serological studies to assess the distribution and extent of Ascaris exposure and infection in various regions of China and the world.
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- 2020
21. Author Correction: Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity
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Christopher C. Sollecito, Michael C. Wu, Kari E. North, Zheng Wang, Marc D. Gellman, Daniel McDonald, Neil Schneiderman, Carmen R. Isasi, Bharat Thyagarajan, Martha L. Daviglus, Tao Wang, Jee-Young Moon, Robert C. Kaplan, Qibin Qi, Yoshiki Vázquez-Baeza, Justin P. Shaffer, Jessica Williams-Nguyen, Gregory A. Talavera, Robert D. Burk, Rob Knight, Mykhaylo Usyk, and Daniela Sotres-Alvarez
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Adult ,Male ,lcsh:QH426-470 ,Bioinformatics ,Section (typography) ,Biology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Information and Computing Sciences ,medicine ,Humans ,Obesity ,Author Correction ,lcsh:QH301-705.5 ,Composition (language) ,030304 developmental biology ,Nutrition ,Aged ,0303 health sciences ,Hispanic or Latino ,Biological Sciences ,Emigration and Immigration ,Middle Aged ,medicine.disease ,Gut microbiome ,Diet ,Gastrointestinal Microbiome ,lcsh:Genetics ,Latin America ,lcsh:Biology (General) ,Community health ,Female ,Paragraph ,Relocation ,030217 neurology & neurosurgery ,Sentence ,Environmental Sciences ,Acculturation ,Demography - Abstract
Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment.Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA.Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.
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- 2020
22. circRNA circAF4 functions as an oncogene to regulate MLL-AF4 fusion protein expression and inhibit MLL leukemia progression
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Ke Fang, Xue-Qun Luo, Tian-Qi Chen, Zhen-Hua Chen, Cai Han, Yu-Meng Sun, Lin-Yu Sun, Zhan-Cheng Zeng, Qian-Qian Yang, Qi Pan, Wei Huang, Yue-Qin Chen, and Wen-Tao Wang
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Oncogene Proteins, Fusion ,Chromosomal translocation ,Apoptosis ,Mice, SCID ,Biology ,lcsh:RC254-282 ,Cell Line ,Fusion gene ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Circular RNA ,Bone Marrow ,hemic and lymphatic diseases ,MLL-AF4 fusion protein ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Leukemia progression ,Molecular Biology ,Gene ,Cell Proliferation ,Gene knockdown ,Leukemia ,lcsh:RC633-647.5 ,Research ,RNA ,Hematology ,lcsh:Diseases of the blood and blood-forming organs ,Neoplasms, Experimental ,RNA, Circular ,Cell cycle ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cell biology ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Myeloid-Lymphoid Leukemia Protein - Abstract
Background Circular RNAs (circRNAs) represent a type of endogenous noncoding RNAs that are generated by back-splicing events and favor repetitive sequences. Recent studies have reported that cancer-associated chromosomal translocations could juxtapose distant complementary repetitive intronic sequences, resulting in the aberrant formation of circRNAs. However, among the reported fusion genes, only a small number of circRNAs were found to originate from fusion regions during gene translocation. We question if circRNAs could also originate from fusion partners during gene translocation. Methods Firstly, we designed divergent primers for qRT-PCR to identify a circRNA circAF4 in AF4 gene and investigated the expression pattern in different types of leukemia samples. Secondly, we designed two small interfering RNAs specially targeting the back-spliced junction point of circAF4 for functional studies. CCK8 cell proliferation and cell cycle assay were performed, and a NOD-SCID mouse model was used to investigate the contribution of circAF4 in leukemogenesis. Finally, luciferase reporter assay, AGO2 RNA immunoprecipitation (RIP), and RNA Fluorescent in Situ Hybridization (FISH) were performed to confirm the relationship of miR-128-3p, circAF4, and MLL-AF4 expression. Results We discovered a circRNA, named circAF4, originating from the AF4 gene, a partner of the MLL fusion gene in MLL-AF4 leukemia. We showed that circAF4 plays an oncogenic role in MLL-AF4 leukemia and promotes leukemogenesis in vitro and in vivo. More importantly, knockdown of circAF4 increases the leukemic cell apoptosis rate in MLL-AF4 leukemia cells, while no effect was observed in leukemia cells that do not carry the MLL-AF4 translocation. Mechanically, circAF4 can act as a miR-128-3p sponge, thereby releasing its inhibition on MLL-AF4 expression. We finally analyzed most of the MLL fusion genes loci and found that a number of circRNAs could originate from these partners, suggesting the potential roles of fusion gene partner-originating circRNAs (named as FP-circRNAs) in leukemia with chromosomal translocations. Conclusion Our findings demonstrate that the abnormal elevated expression of circAF4 regulates the cell growth via the circAF4/miR-128-3p/MLL-AF4 axis, which could contribute to leukemogenesis, suggesting that circAF4 may be a novel therapeutic target of MLL-AF4 leukemia.
- Published
- 2019
23. A giant Brunner’s gland hamartoma being treated as a pedunculated polyp: a case report
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Lizhi Yi, Ke Liu, Zhengyu Cheng, Jianjun Yang, Huarong Qiu, and Tao Wang
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Hamartoma ,Hot snare polypectomy ,Case Report ,Brunner Glands ,Pedunculated polyp ,Asymptomatic ,Severe anemia ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,lcsh:RC799-869 ,Duodenal Diseases ,Brunner’s gland hamartoma ,medicine.diagnostic_test ,business.industry ,Dissection ,Gastroenterology ,Intestinal Polyps ,Endoscopy ,General Medicine ,Hepatology ,Middle Aged ,medicine.disease ,Polypectomy ,Surgery ,Tumor Burden ,medicine.anatomical_structure ,Treatment Outcome ,030220 oncology & carcinogenesis ,Brunner's glands ,lcsh:Diseases of the digestive system. Gastroenterology ,030211 gastroenterology & hepatology ,Female ,medicine.symptom ,business - Abstract
Background With the development and application of endoscopic technology, most pedunculated polyps can be absolutely resected with a complete specimen by hot snare polypectomy (HSP). Brunner’s gland hamartoma (BGH) is a rare benign small bowel tumor. The majority of BGH measuring about 2 cm in diameter, rarely larger than 5 cm. Most patients are asymptomatic, some may present with gastrointestinal hemorrhage or intestinal obstruction. Symptomatic larger lesions leading to bleeding or obstruction should be excised either endoscopically or surgically. Whether it is safe and effective that removing a BGH measuring about 7 cm by HSP is not known. Case presentation Here, we reported a rare case of a proximal duodenum pedunculated mass measuring about 7 cm which was responsible for the patient’s severe anemia. we treated it as a pedunculated polyp. After being pretreated the stalk with an endoloop which was placed around the base of the mass to prevent post-polypectomy bleeding (PPB), the pedunculated BGH was removed by HSP completely. The stalk of the mass was negative. We achieved a curative resection. Conclusion It is a safe and effective for our patient to treat the pedunculated BGH measuring about 7 cm as a pedunculated polyp and remove it by HSP. And future prospective studies in larger cohorts are needed to confirm it.
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- 2019
24. Metabolic tumor burden on postsurgical PET/CT predicts survival of patients with gastric cancer
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Danni Li, Jian Yang, Xiao Li, Chao Cheng, Gaofeng Sun, and Tao Wang
- Subjects
lcsh:Medical physics. Medical radiology. Nuclear medicine ,Adult ,Male ,medicine.medical_specialty ,lcsh:R895-920 ,Tumor burden ,Standardized uptake value ,Metabolic tumor burden ,Gastroenterology ,lcsh:RC254-282 ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,2-[18F] Fluoro-2-deoxy-D-glucose (18F-FDG) ,Positron emission tomography/computed tomography (PET/CT) ,Fluorodeoxyglucose F18 ,Stomach Neoplasms ,Internal medicine ,Positron Emission Tomography Computed Tomography ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,PET-CT ,Radiological and Ultrasound Technology ,Receiver operating characteristic ,medicine.diagnostic_test ,business.industry ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Tumor Burden ,Exact test ,Oncology ,Positron emission tomography ,030220 oncology & carcinogenesis ,Female ,Radiopharmaceuticals ,business ,Gastric cancer ,Research Article - Abstract
Background The prognostic value of postoperative 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) to patients with gastric cancer remains unclear. This study aims to investigate the prognostic value of whole body (WB) metabolic tumor burden (MTBWB) on postsurgical 18F-FDG PET/CT to patients with gastric cancer. Methods A total of 376 patients with surgeries-confirmed gastric cancer were enrolled. Clinicopathologic information, overall survival (OS) and MTBWB parameters on postsurgical PET/CT, in terms of WB maximum standardized uptake value (SUVWBmax), WB metabolic tumor volume (MTVWB), and WB total lesion glycolysis (TLGWB) were collected. In-between differences of patient clinicopathologic characteristics, OS and MTBWB measurements were compared using chi-square test, Fisher’s exact test, Student’s t test or the Kaplan-Meier survival analysis. The optimal cutoffs of MTBWB measurements were calculated through the receiver operating characteristic (ROC) curve analysis. Univariable and multivariable Cox proportional hazard regression were performed to test the predictive value of the clinicopathologic factors and MTBWB measurements to patient survival. Results The PET-positive patients had significantly decreased OS based on either Kaplan-Meier survival analysis (P 8.6, MTVWB > 91.5 cm3, and TLGWB > 477.6 cm3 were significantly different (P = 0.001, P
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- 2019
25. Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects against Aβ toxicity via attenuating Aβ-induced endoplasmic reticulum stress
- Author
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Runjie Wang, Yujun Shen, Shengchun Xu, Yuxian Shen, Tao Wang, Ze-min Di, Jing Li, Shengyun Fang, Lijie Feng, Rui Sun, Yufeng He, and Yuyang Ma
- Subjects
0301 basic medicine ,Apoptosis ,lcsh:RC346-429 ,Amyloid beta-Protein Precursor ,Mice ,Neuroblastoma ,0302 clinical medicine ,Neurotrophic factors ,RNA, Small Interfering ,Cells, Cultured ,MANF ,Cerebral Cortex ,Neurons ,Chemistry ,β-amyloid ,General Neuroscience ,Brain ,Endoplasmic Reticulum Stress ,Cell biology ,Up-Regulation ,medicine.anatomical_structure ,Neurology ,ER stress ,Alzheimer’s disease ,Astrocyte ,Programmed cell death ,Immunology ,Mice, Transgenic ,Neuroprotection ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,medicine ,Presenilin-1 ,Animals ,Humans ,Nerve Growth Factors ,lcsh:Neurology. Diseases of the nervous system ,Amyloid beta-Peptides ,ATF6 ,Endoplasmic reticulum ,Research ,Neurotoxicity ,medicine.disease ,Embryo, Mammalian ,Peptide Fragments ,Mice, Inbred C57BL ,030104 developmental biology ,Phosphopyruvate Hydratase ,Unfolded protein response ,030217 neurology & neurosurgery - Abstract
Background Extracellular accumulation of amyloid β-peptide (Aβ) is one of pathological hallmarks of Alzheimer’s disease (AD) and contributes to the neuronal loss. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) stress-inducible neurotrophic factor. Many groups, including ours, have proved that MANF rescues neuronal loss in several neurological disorders, such as Parkinson’s disease and cerebral ischemia. However, whether MANF exerts its protective effect against Aβ neurotoxicity in AD remains unknown. Methods In the present study, the characteristic expressions of MANF in Aβ1–42-treated neuronal cells as well as in the brains of APP/PS1 transgenic mice were analyzed by immunofluorescence staining, qPCR, and Western blot. The effects of MANF overexpression, MANF knockdown, or recombination human MANF protein (rhMANF) on neuron viability, apoptosis, and the expression of ER stress-related proteins following Aβ1–42 exposure were also investigated. Results The results showed the increased expressions of MANF, as well as ER stress markers immunoglobulin-binding protein (BiP) and C/EBP homologous protein (CHOP), in the brains of the APP/PS1 transgenic mice and Aβ1–42-treated neuronal cells. MANF overexpression or rhMANF treatment partially protected against Aβ1–42-induced neuronal cell death, associated with marked decrease of cleaved caspase-3, whereas MANF knockdown with siRNA aggravated Aβ1–42 cytotoxicity including caspase-3 activation. Further study demonstrated that the expressions of BiP, ATF6, phosphorylated-IRE1, XBP1s, phosphorylated-eIF2α, ATF4, and CHOP were significantly downregulated by MANF overexpression or rhMANF treatment in neuronal cells following Aβ1–42 exposure, whereas knockdown of MANF has the opposite effect. Conclusions These findings demonstrate that MANF may exert neuroprotective effects against Aβ-induced neurotoxicity through attenuating ER stress, suggesting that an applicability of MANF as a therapeutic candidate for AD. Electronic supplementary material The online version of this article (10.1186/s12974-019-1429-0) contains supplementary material, which is available to authorized users.
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- 2019
26. A case report of community-acquired Pseudomonas aeruginosa pneumonia complicated with MODS in a previously healthy patient and related literature review
- Author
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Yijun Hou, Ruilan Wang, and Tao Wang
- Subjects
Adult ,Male ,medicine.medical_specialty ,Poor prognosis ,Antibiotic regimen ,Multiple Organ Failure ,Case Report ,medicine.disease_cause ,MODS ,lcsh:Infectious and parasitic diseases ,Medical microbiology ,Central Nervous System Bacterial Infections ,Internal medicine ,Medicine ,Humans ,lcsh:RC109-216 ,Pseudomonas Infections ,Pathogen ,business.industry ,Pseudomonas aeruginosa ,Septic shock ,Healthcare-Associated Pneumonia ,medicine.disease ,CAP ,Shock, Septic ,Anti-Bacterial Agents ,Community-Acquired Infections ,Pneumonia ,Infectious Diseases ,business ,Multiple organ dysfunction syndrome - Abstract
Background Pseudomonas aeruginosa is an unusual pathogen in community-acquired pneumonia, especially in previously healthy adults, but often indicates poor prognosis. Case presentation We report a previously healthy patient who developed severe community-acquired pneumonia (CAP) caused by P. aeruginosa. He deteriorated to septic shock and multiple organ dysfunction syndrome (MODS) quickly, complicated by secondary hematogenous central nervous system (CNS) infection. After 1 month of organ support and antipseudomonal therapy, he had significant symptomatic improvement and was discharged from hospital. During treatment, the pathogen developed resistance to carbapenems quickly and the antibiotic regimen was adjusted accordingly. Conclusions According to our case and related literature review, we conclude that more attention should be paid to community-acquired Pseudomonas aeruginosa pneumonia, because of its rapid progression and poor prognosis.
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- 2019
27. FADS1-FADS2 genetic polymorphisms are associated with fatty acid metabolism through changes in DNA methylation and gene expression
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Aihua Zhao, Li Jin, Wei Jia, Feng Jiang, Weiping Jia, Cheng Hu, Tao Wang, Hong Zhang, Bo Xu, Rong Zhang, and Zhen He
- Subjects
0301 basic medicine ,Adult ,Fatty Acid Desaturases ,Male ,China ,lcsh:QH426-470 ,FADS1 ,FADS2 ,Quantitative Trait Loci ,lcsh:Medicine ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Delta-5 Fatty Acid Desaturase ,Genetics ,Humans ,Fatty acids ,Molecular Biology ,Genetics (clinical) ,Regulation of gene expression ,DNA methylation ,Research ,Fatty acid desaturase ,lcsh:R ,Methylation ,Middle Aged ,Lipid Metabolism ,lcsh:Genetics ,030104 developmental biology ,CpG site ,Gene Expression Regulation ,Expression quantitative trait loci ,biology.protein ,Fatty Acids, Unsaturated ,Genetic markers ,CpG Islands ,Female ,Gene expression ,Developmental Biology ,Genome-Wide Association Study - Abstract
Background Genome-wide association studies (GWASs) have shown that genetic variants are important determinants of free fatty acid levels. The mechanisms underlying the associations between genetic variants and free fatty acid levels are incompletely understood. Here, we aimed to identify genetic markers that could influence diverse fatty acid levels in a Chinese population and uncover the molecular mechanisms in terms of DNA methylation and gene expression. Results We identified strong associations between single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) region and multiple polyunsaturated fatty acids. Expression quantitative trait locus (eQTL) analysis of rs174570 on FADS1 and FADS2 mRNA levels proved that minor allele of rs174570 was associated with decreased FADS1 and FADS2 expression levels (P
- Published
- 2018
28. Molecular investigation of Cryptosporidium in farmed chickens in Hubei Province, China, identifies ‘zoonotic’ subtypes of C. meleagridis
- Author
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Robin B. Gasser, Min Hu, Cong Liao, Yingying Fan, Tao Wang, and Anson V. Koehler
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0301 basic medicine ,Veterinary medicine ,Entomology ,animal diseases ,Cryptosporidiosis ,Polymerase Chain Reaction ,law.invention ,Zoonosis ,Feces ,0302 clinical medicine ,law ,Zoonoses ,Genotype ,Prevalence ,Child ,Polymerase chain reaction ,Phylogenetic analyses ,Phylogeny ,biology ,Age Factors ,Cryptosporidium ,Infectious Diseases ,PCR-based sequencing ,Sequence Analysis ,Human ,China ,030231 tropical medicine ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Bird ,parasitic diseases ,medicine ,Animals ,Humans ,lcsh:RC109-216 ,Poultry Diseases ,Research ,Ribosomal RNA ,DNA, Protozoan ,medicine.disease ,biology.organism_classification ,030104 developmental biology ,Parasitology ,RNA, Ribosomal ,Chickens - Abstract
Background Cryptosporidium is a key genus of parasitic protists that infect humans and other vertebrates (mammals and birds). Birds are typically infected with C. avium, C. baileyi, C. galli and/or C. meleagridis, the latter of which is recognised as being zoonotic. Stimulated by the previous finding of C. meleagridis subtypes IIIbA21G1R1, IIIbA22G1R1 and IIIbA26G1R1 in diarrhoeic children in Wuhan city and environs in Hubei Province, China, we performed a molecular epidemiological survey to explore whether these or similar subtypes might occur in farmed chickens in this province. Methods PCR-coupled sequencing analyses of regions in the small subunit (SSU) of the nuclear ribosomal RNA and 60 kDa glycoprotein (gp60) genes were utilised to characterise Cryptosporidium in faecal samples from chickens (n = 471) from 14 farms from six distinct regions in Hubei Province. Results Cryptosporidium baileyi (33/471; 7.0%) and C. meleagridis (15/471; 3.2%) were identified in chickens on eight farms in five of the six distinct geographical regions. No significant age-associated difference in the prevalence of C. baileyi was evident, whereas the prevalence of C. meleagridis was significantly higher in younger (≤ 4 months) than in older chickens (> 4 months). For C. meleagridis, two subtype families, IIIb and IIIe, were defined; some of the subtypes (i.e. IIIbA26G1R1b and IIIbA22G1R1c) characterised here matched those identified previously in diarrhoeic children in Wuhan. Conclusions This is the first molecular study reporting the genetic identity and prevalence of C. baileyi and C. meleagridis in chickens in Hubei. The findings suggest that C. meleagridis subtypes IIIbA26G1R1b and IIIbA22G1R1c are cross-transmissible between chickens and humans, raising awareness about the significance of birds as potential reservoirs of zoonotic variants of Cryptosporidium. Future studies might focus on investigating the prevalence of ‘zoonotic’ subtypes of Cryptosporidium meleagridis in various species of wild and domesticated birds, and on comparing them with those found in humans in China and other countries. Electronic supplementary material The online version of this article (10.1186/s13071-018-3056-5) contains supplementary material, which is available to authorized users.
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- 2018
29. Unmet care needs of advanced cancer patients and their informal caregivers: a systematic review
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Alex Molassiotis, Tao Wang, Betty Pui Man Chung, and Jing-Yu Tan
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medicine.medical_specialty ,Palliative care ,lcsh:Special situations and conditions ,MEDLINE ,Context (language use) ,Information needs ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Neoplasms ,Surveys and Questionnaires ,Prevalence ,Medicine ,Humans ,030212 general & internal medicine ,Descriptive statistics ,business.industry ,lcsh:RC952-1245 ,Multimethodology ,General Medicine ,Caregivers ,030220 oncology & carcinogenesis ,Family medicine ,Needs assessment ,Patient Care ,business ,Needs Assessment ,Research Article - Abstract
Background This systematic review aimed to identify the unmet care needs and their associated variables in patients with advanced cancer and informal caregivers, alongside summarizing the tools used for needs assessment. Methods Ten electronic databases were searched systematically from inception of each database to December 2016 to determine eligible studies. Studies that considered the unmet care needs of either adult patients with advanced cancer or informal caregivers, regardless of the study design, were included. The Mixed Methods Appraisal Tool was utilized for quality appraisal of the included studies. Content analysis was used to identify unmet needs, and descriptive analysis was adopted to synthesize other outcomes. Results Fifty studies were included, and their methodological quality was generally robust. The prevalence of unmet needs varied across studies. Twelve unmet need domains were identified in patients with advanced cancer, and seven among informal caregivers. The three most commonly reported domains for patients were psychological, physical, and healthcare service and information. The most prominent unmet items of these domains were emotional support (10.1–84.4%), fatigue (18–76.3%), and “being informed about benefits and side-effects of treatment” (4–66.7%). The most commonly identified unmet needs for informal caregivers were information needs, including illness and treatment information (26–100%) and care-related information (21–100%). Unmet needs of patients with advanced cancer were associated with their physical symptoms, anxiety, and quality of life. The most commonly used instruments for needs assessment among patients with advanced cancer were the Supportive Care Needs Survey (N = 8) and Problems and Needs in Palliative Care questionnaire (N = 5). The majority of the included studies investigated unmet needs from the perspectives of either patients or caregivers with a cross-sectional study design using single time-point assessments. Moreover, significant heterogeneity, including differences in study contexts, assessment methods, instruments for measurement, need classifications, and reporting methods, were identified across studies. Conclusion Both advanced cancer patients and informal caregivers reported a wide range of context-bound unmet needs. Examining their unmet needs on the basis of viewing patients and their informal caregivers as a whole unit will be highly optimal. Unmet care needs should be comprehensively evaluated from the perspectives of all stakeholders and interpreted by using rigorously designed mixed methods research and longitudinal studies within a given context.
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- 2018
30. New operational taxonomic units of Enterocytozoon in three marsupial species
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Robin B. Gasser, Anson V. Koehler, Yan Zhang, Tao Wang, and Shane R. Haydon
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0301 basic medicine ,Enterocytozoon bieneusi ,Genotype ,030106 microbiology ,Genotypes ,Zoology ,Operational taxonomic units ,Wallabia bicolor ,Polymerase Chain Reaction ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Feces ,Wombat ,fluids and secretions ,biology.animal ,parasitic diseases ,DNA, Ribosomal Spacer ,Microsporidiosis ,Prevalence ,Eastern grey kangaroo ,Animals ,lcsh:RC109-216 ,Internal transcribed spacer ,DNA, Fungal ,Phylogeny ,Marsupial ,Macropodidae ,biology ,Research ,Swamp wallaby ,Common wombat ,fungi ,Australia ,Genetic Variation ,Macropus giganteus ,Sequence Analysis, DNA ,Enterocytozoon ,biology.organism_classification ,030104 developmental biology ,Infectious Diseases ,Parasitology - Abstract
Background Enterocytozoon bieneusi is a microsporidian, commonly found in animals, including humans, in various countries. However, there is scant information about this microorganism in Australasia. In the present study, we conducted the first molecular epidemiological investigation of E. bieneusi in three species of marsupials (Macropus giganteus, Vombatus ursinus and Wallabia bicolor) living in the catchment regions which supply the city of Melbourne with drinking water. Methods Genomic DNAs were extracted from 1365 individual faecal deposits from these marsupials, including common wombat (n = 315), eastern grey kangaroo (n = 647) and swamp wallaby (n = 403) from 11 catchment areas, and then individually tested using a nested PCR-based sequencing approach employing the internal transcribed spacer (ITS) and small subunit (SSU) of nuclear ribosomal DNA as genetic markers. Results Enterocytozoon bieneusi was detected in 19 of the 1365 faecal samples (1.39%) from wombat (n = 1), kangaroos (n = 13) and wallabies (n = 5). The analysis of ITS sequence data revealed a known (designated NCF2) and four new (MWC_m1 to MWC_m4) genotypes of E. bieneusi. Phylogenetic analysis of ITS sequence data sets showed that MWC_m1 (from wombat) clustered with NCF2, whereas genotypes MWC_m2 (kangaroo and wallaby), MWC_m3 (wallaby) and MWC_m4 (kangaroo) formed a new, divergent clade. Phylogenetic analysis of SSU sequence data revealed that genotypes MWC_m3 and MWC_m4 formed a clade that was distinct from E. bieneusi. The genetic distinctiveness of these two genotypes suggests that they represent a new species of Enterocytozoon. Conclusions Further investigations of Enterocytozoon spp. from macropods and other animals will assist in clarifying the taxonomy and epidemiology of these species in Australia and elsewhere, and in assessing the public health risk of enterocytozoonosis. Electronic supplementary material The online version of this article (10.1186/s13071-018-2954-x) contains supplementary material, which is available to authorized users.
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- 2018
31. Knockdown delta-5-desaturase in breast cancer cells that overexpress COX-2 results in inhibition of growth, migration and invasion via a dihomo-γ-linolenic acid peroxidation dependent mechanism
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Xiaoyu Yang, Steven Y. Qian, Yi Xu, Liu Yang, Tao Wang, Keith Miskimins, and Yu-Ying He
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0301 basic medicine ,Fatty Acid Desaturases ,Cancer Research ,Cell ,D5D knockdown MDA-MB 231 and 4 T1 cells ,Gene Expression ,Apoptosis ,Breast Neoplasms ,lcsh:RC254-282 ,delta-5-desaturase ,Metastasis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,8,11,14-Eicosatrienoic Acid ,Delta-5 Fatty Acid Desaturase ,Cell Movement ,Pancreatic cancer ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,Cell Proliferation ,Dihomo-γ-linolenic acid ,Chemistry ,Cancer ,COX-catalyzed DGLA peroxidation ,Transfection ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,3. Good health ,breast cancer growth, migration and invasion ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Cyclooxygenase 2 ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Cancer research ,Arachidonic acid ,Female ,RNA Interference ,Fluorouracil ,Lipid Peroxidation ,Caprylates ,Research Article - Abstract
Background Cyclooxygenase-2 (COX-2), the inducible COX form, is a bi-functional membrane-bound enzyme that typically metabolizes arachidonic acid (downstream ω-6 fatty acid) to form 2-series of prostaglandins known to be involved in cancer development. Overexpression of COX-2 has been found in a majority of breast carcinomas, and has also been associated with increased severity and the development of the metastasis. Our lab recently demonstrated that COX-2 can also metabolize dihomo-γ-linolenic acid (DGLA, a precursor of ω-6 arachidonic acid) to produce an anti-cancer byproduct, 8-hydroxyoctanoic acid (8-HOA) that can inhibit growth and migration of colon and pancreatic cancer cells. We thus tested whether our strategy of knocking down delta-5-desaturase (D5D, the key enzyme that converts DGLA to arachidonic acid) in breast cancer cells overexpressing COX-2 can also be used to promote 8-HOA formation, thereby suppressing cancer growth, migration, and invasion. Methods SiRNA and shRNA transfection were used to knock down D5D expression in MDA-MB 231 and 4 T1 cells (human and mouse breast cancer cell lines expressing high COX-2, respectively). Colony formation assay, FITC Annexin V/PI double staining, wound healing and transwell assay were used to assess the effect of our strategy on inhibition of cancer growth, migration, and invasion. GC/MS was used to measure endogenous 8-HOA, and western blotting was performed to evaluate the altered key protein expressions upon the treatments. Results We demonstrated that D5D knockdown licenses DGLA to inhibit growth of breast cancer cells via promoting formation of 8-HOA that can inhibit histone deacetylase and activate cell apoptotic proteins, such as procaspase 9 and PARP. Our strategy can also significantly inhibit cancer migration and invasion, associated with altered expression of MMP-2/− 9, E-cadherin, vimentin and snail. In addition, D5D knockdown and DGLA supplementation greatly enhanced the efficacy of 5-fluorouracil on breast cancer growth and migration. Conclusions Consistent to our previous studies on colon and pancreatic cancer, here we demonstrate again that the high level of COX-2 in breast cancer cells can be capitalized on inhibiting cancer growth and migration. The outcome of this translational research could guide us to develop new anti-cancer strategy and/or to improve current chemotherapy for breast cancer treatment. Electronic supplementary material The online version of this article (10.1186/s12885-018-4250-8) contains supplementary material, which is available to authorized users.
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- 2018
32. Retraction Note: Astragalus saponins affect proliferation, invasion and apoptosis of gastric cancer BGC-823 cells
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Xiaoyan Xuan, Yuling Zheng, Tao Wang, Guoqiang Zhao, Ping Gao, Min Li, and Wenqiao Zang
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Pathology ,medicine.medical_specialty ,Histology ,medicine.medical_treatment ,Mice, Nude ,Apoptosis ,In Vitro Techniques ,Pathology and Forensic Medicine ,Flow cytometry ,Metastasis ,Mice ,In vivo ,Cell Movement ,Stomach Neoplasms ,Cell Line, Tumor ,lcsh:Pathology ,medicine ,Animals ,Humans ,Medicine, Chinese Traditional ,Cell Proliferation ,Mice, Inbred BALB C ,medicine.diagnostic_test ,biology ,business.industry ,Plant Extracts ,Cell Cycle ,Cancer ,General Medicine ,Astragalus Plant ,Cell cycle ,Saponins ,medicine.disease ,biology.organism_classification ,Xenograft Model Antitumor Assays ,Astragalus ,Retraction Note ,Cancer research ,Heterografts ,Female ,business ,Adjuvant ,lcsh:RB1-214 - Abstract
Astragalus memebranaceus is a traditional Chinese herbal medicine used in treatment of common cold, diarrhea, fatigue, anorexia and cardiac diseases. Recently, there are growing evidences that Astragalus extract may be a potential anti-tumorigenic agent. Some research showed that the total saponins obtained from Astragalus membranaceus possess significant antitumorigenic activity. Gastric cancer is one of the most frequent cancers in the world, almost two-thirds of gastric cancer cases and deaths occur in less developed regions. But the effect of Astragalus membranaceus on proliferation, invasion and apoptosis of gastric cancer BGC-823 cells remains unclear. Astragalus saponins were extracted. Cells proliferation was determined by CCK-8 assay. Cell cycle and apoptosis were detected by the flow cytometry. Boyden chamber was used to evaluate the invasion and metastasis capabilities of BGC-823 cells. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. The results demonstrated that total Astragalus saponins could inhibit human gastric cancer cell growth both in vitro and in vivo, in additional, Astragalus saponins deceased the invasion ability and induced the apoptosis of gastric cancer BGC-823 cells. Total Astragalus saponins inhibited human gastric cancer cell growth, decreased the invasion ability and induced the apoptosis. This suggested the possibility of further developing Astragalus as an alternative treatment option, or perhaps using it as adjuvant chemotherapeutic agent in gastric cancer therapy.
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- 2017
33. Adverse reactions of targeted therapy in cancer patients: a retrospective study of hospital medical data in China.
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Ruofei Du, Xin Wang, Lixia Ma, Larcher, Leon M., Han Tang, Huiyue Zhou, Changying Chen, Tao Wang, Du, Ruofei, Wang, Xin, Ma, Lixia, Tang, Han, Zhou, Huiyue, Chen, Changying, and Wang, Tao
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CANCER patients ,CANCER treatment ,OLDER patients ,PATIENT education ,TREATMENT effectiveness - Abstract
Background: The adverse reactions (ADRs) of targeted therapy were closely associated with treatment response, clinical outcome, quality of life (QoL) of patients with cancer. However, few studies presented the correlation between ADRs of targeted therapy and treatment effects among cancer patients. This study was to explore the characteristics of ADRs with targeted therapy and the prognosis of cancer patients based on the clinical data.Methods: A retrospective secondary data analysis was conducted within an ADR data set including 2703 patients with targeted therapy from three Henan medical centers of China between January 2018 and December 2019. The significance was evaluated with chi-square test between groups with or without ADRs. Univariate and multivariate logistic regression with backward stepwise method were applied to assess the difference of pathological characteristics in patients with cancer. Using the univariate Cox regression method, the actuarial probability of overall survival was performed to compare the clinical outcomes between these two groups.Results: A total of 485 patients were enrolled in this study. Of all patients, 61.0% (n = 296) occurred ADRs including skin damage, fatigue, mucosal damage, hypertension and gastrointestinal discomfort as the top 5 complications during the target therapy. And 62.1% of ADRs were mild to moderate, more than half of the ADRs occurred within one month, 68.6% ADRs lasted more than one month. Older patients (P = 0.022) and patients with lower education level (P = 0.036), more than 2 comorbidities (P = 0.021), longer medication time (P = 0.022), drug combination (P = 0.033) and intravenous administration (P = 0.019) were more likely to have ADRs. Those with ADRs were more likely to stop taking (P = 0.000), change (P = 0.000), adjust (P = 0.000), or not take the medicine on time (P = 0.000). The number of patients with recurrence (P = 0.000) and metastasis (P = 0.006) were statistically significant difference between ADRs and non-ADRs group. And the patients were significantly poor prognosis in ADRs groups compared with non-ADRs group.Conclusion: The high incidence of ADRs would affect the treatment and prognosis of patients with cancer. We should pay more attention to these ADRs and develop effective management strategies. [ABSTRACT FROM AUTHOR]- Published
- 2021
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34. Inhibition of TGFβ improves hematopoietic stem cell niche and ameliorates cancerrelated anemia.
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Boyan Wang, Yi Wang, Hainan Chen, Senyu Yao, Xiaofan Lai, Yuan Qiu, Jianye Cai, Yinong Huang, Xiaoyue Wei, Yuanjun Guan, Tao Wang, Jiancheng Wang, and Andy Peng Xiang
- Subjects
STEM cell niches ,STROMAL cells ,PROGENITOR cells ,ANEMIA ,LABORATORY mice ,HEMATOPOIETIC stem cells ,COLONY-forming units assay - Abstract
Background: Cancer cachexia is a wasting syndrome that is quite common in terminal-stage cancer patients. Cancer-related anemia is one of the main features of cancer cachexia and mostly results in a poor prognosis. The disadvantages of the current therapies are obvious, but few new treatments have been developed because the pathological mechanism remains unclear. Methods: C57BL/6 mice were subcutaneously injected with Lewis lung carcinoma cells to generate a cancerrelated anemia model. The treated group received daily intraperitoneal injections of SB505124. Blood parameters were determined with a routine blood counting analyzer. Erythroid cells and hematopoietic stem/progenitor cells were analyzed by flow cytometry. The microarchitecture changes of the femurs were determined by microcomputed tomography scans. Smad2/3 phosphorylation was analyzed by immunofluorescence and Western blotting. The changes in the hematopoietic stem cell niche were revealed by qPCR analysis of both fibrosis-related genes and hematopoietic genes, fibroblastic colony-forming unit assays, and lineage differentiation of mesenchymal stromal cells. Results: The mouse model exhibited hematopoietic suppression, marked by a decrease of erythrocytes in the peripheral blood, as well as an increase of immature erythroblasts and reduced differentiation of multipotent progenitors in the bone marrow. The ratio of bone volume/total volume, trabecular number, and cortical wall thickness all appeared to decrease, and the increased osteoclast number has led to the release of latent TGFß and TGFß signaling over-activation. Excessive TGFß deteriorated the hematopoietic stem cell niche, inducing fibrosis of the bone marrow as well as the transition of mesenchymal stromal cells. Treatment with SB505124, a smallmolecule inhibitor of TGFß signaling, significantly attenuated the symptoms of cancer-related anemia in this model, as evidenced by the increase of erythrocytes in the peripheral blood and the normalized proportion of erythroblast cell clusters. Meanwhile, hindered hematopoiesis and deteriorated hematopoietic stem cell niche were also shown to be restored with SB505124 treatment. Conclusion: This study investigated the role of TGFß released by bone remodeling in the progression of cancerrelated anemia and revealed a potential therapeutic approach for relieving defects in hematopoiesis. [ABSTRACT FROM AUTHOR]
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- 2021
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35. Metagenomic mining pectinolytic microbes and enzymes from an apple pomace-adapted compost microbial community
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Lina Gao, Jie Gu, Huijun Yin, Xin Lü, Man Zhou, Cheng Cai, Peng Guo, and Tao Wang
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0301 basic medicine ,CAZy ,Microorganism ,Management, Monitoring, Policy and Law ,Applied Microbiology and Biotechnology ,Enrichment culture ,complex mixtures ,Pectinolytic microbes and enzymes ,03 medical and health sciences ,Metagenomic ,Lignocellulosic biofuel ,Compost habitat ,biology ,Renewable Energy, Sustainability and the Environment ,business.industry ,Research ,Bacteroidetes ,biology.organism_classification ,Pectin ,Biotechnology ,030104 developmental biology ,General Energy ,Microbial population biology ,Metagenomics ,Proteobacteria ,business ,Bacteria - Abstract
Background Degradation of pectin in lignocellulosic materials is one of the key steps for biofuel production. Biological hydrolysis of pectin, i.e., degradation by pectinolytic microbes and enzymes, is an attractive paradigm because of its obvious advantages, such as environmentally friendly procedures, low in energy demand for lignin removal, and the possibility to be integrated in consolidated process. In this study, a metagenomics sequence-guided strategy coupled with enrichment culture technique was used to facilitate targeted discovery of pectinolytic microbes and enzymes. An apple pomace-adapted compost (APAC) habitat was constructed to boost the enrichment of pectinolytic microorganisms. Results Analyses of 16S rDNA high-throughput sequencing revealed that microbial communities changed dramatically during composting with some bacterial populations being greatly enriched. Metagenomics data showed that apple pomace-adapted compost microbial community (APACMC) was dominated by Proteobacteria and Bacteroidetes. Functional analysis and carbohydrate-active enzyme profiles confirmed that APACMC had been successfully enriched for the targeted functions. Among the 1756 putative genes encoding pectinolytic enzymes, 129 were predicted as novel (with an identity
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- 2017
36. Diagnostic value of microRNA-143 in predicting in-stent restenosis for patients with lower extremity arterial occlusive disease
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Hai-Tao Wang, Zhi-Hai Yu, and Can Tu
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0301 basic medicine ,Male ,medicine.medical_specialty ,Computed Tomography Angiography ,medicine.medical_treatment ,Blood sugar ,Arterial Occlusive Diseases ,030204 cardiovascular system & hematology ,Logistic regression ,Coronary Angiography ,Real-Time Polymerase Chain Reaction ,Coronary Restenosis ,03 medical and health sciences ,0302 clinical medicine ,Restenosis ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Lower extremity arterial occlusive disease ,MicroRNA-143 ,Diagnostic value ,Aged ,Receiver operating characteristic ,medicine.diagnostic_test ,business.industry ,Research ,Area under the curve ,Stent ,General Medicine ,Middle Aged ,medicine.disease ,Femoral Artery ,MicroRNAs ,030104 developmental biology ,Logistic Models ,ROC Curve ,Angiography ,Cardiology ,Female ,Stents ,business - Abstract
Purpose This study was conducted to explore the diagnostic value of microRNA-143 (miRNA-143) in predicting in-stent restenosis (ISR) of lower extremity arterial occlusive disease (LEAOD). Methods From February 2012 to March 2015, 165 patients (112 males and 53 females) with LEAOD undergoing interventional treatment were enrolled in this study. Serum miRNA-143 expression was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Patients were assigned into the restenosis and non-restenosis groups according to routine surveillance postoperative angiography. A logistic regression analysis was conducted to analyze the risk factors for ISR in LEAOD patients. A receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic value of miRNA-143 in predicting ISR for LEAOD patients. Results There were 74 and 91 patients in the restenosis and non-restenosis groups, respectively. Before the treatment, there were significant differences in history of diabetes, smoking status, blood sugar level (BSL) at admission, low-density lipoprotein cholesterol (LDL-C) level, and stent diameter between the restenosis and non-restenosis groups (all P
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- 2017
37. LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner
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Zhen Hua Chen, Wen-Tao Wang, Bo He, Yue-Qin Chen, Hua Ye, Bo-Wei Han, and Pan-Pan Wei
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0301 basic medicine ,Small interfering RNA ,Cancer Research ,Receptors, CXCR4 ,HULC ,medicine.medical_treatment ,Cell ,Biology ,lcsh:RC254-282 ,CXCR4 ,Cholangiocarcinoma ,03 medical and health sciences ,Chemokine receptor ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,Migration and invasion ,Neoplasm Invasiveness ,Inflammation response ,Molecular Biology ,Inflammation ,lcsh:RC633-647.5 ,Competing endogenous RNA ,Interleukin-6 ,Research ,Cell migration ,lcsh:Diseases of the blood and blood-forming organs ,Hematology ,ceRNA ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Oxidative Stress ,030104 developmental biology ,medicine.anatomical_structure ,Cytokine ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Disease Progression ,RNA, Long Noncoding - Abstract
Background Long non-coding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, associated with chronic inflammation and damage to the biliary epithelium. The aim of the study is to identify if any lncRNA might associate with inflammation or oxidative stress in CCA and regulate the disease progression. Methods In this study, RNA-seqs datasets were used to identify aberrantly expressed lncRNAs. Small interfering RNA and overexpressed plasmids were used to modulate the expression of lncRNAs, and luciferase target assay RNA immunoprecipitation (RIP) was performed to explore the mechanism of miRNA-lncRNA sponging. Results We firstly analyzed five available RNA-seqs datasets to investigate aberrantly expressed lncRNAs which might associate with inflammation or oxidative stress. We identified that two lncRNAs, H19 and HULC, were differentially expressed among all the samples under the treatment of hypoxic or inflammatory factors, and they were shown to be stimulated by short-term oxidative stress responses to H2O2 and glucose oxidase in CCA cell lines. Further studies revealed that these two lncRNAs promoted cholangiocyte migration and invasion via the inflammation pathway. H19 and HULC functioned as competing endogenous RNAs (ceRNAs) by sponging let-7a/let-7b and miR-372/miR-373, respectively, which activate pivotal inflammation cytokine IL-6 and chemokine receptor CXCR4. Conclusions Our study revealed that H19 and HULC, up-regulated by oxidative stress, regulate CCA cell migration and invasion by targeting IL-6 and CXCR4 via ceRNA patterns of sponging let-7a/let-7b and miR-372/miR-373, respectively. The results suggest that these lncRNAs might be the chief culprits of CCA pathogenesis and progression. The study provides new insight into the mechanism linking lncRNA function with CCA and may serve as novel targets for the development of new countermeasures of CCA. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0348-0) contains supplementary material, which is available to authorized users.
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- 2016
38. LINC02418 promotes malignant behaviors in lung adenocarcinoma cells by sponging miR-4677-3p to upregulate KNL1 expression.
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Tao Wang, Ruiren Zhai, Xiuhua Lv, Ke Wang, Junqing Xu, Wang, Tao, Zhai, Ruiren, Lv, Xiuhua, Wang, Ke, and Xu, Junqing
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CELL motility ,NON-coding RNA ,CELL migration ,CELLS ,POTENTIAL functions - Abstract
Background: Lung adenocarcinoma (LAD) is a prevalent type of bronchogenic malignant tumor and one of the most critical factors related to human death. Long noncoding RNAs (lncRNAs) are involved in many complex biological processes and have been emerged as extremely important regulators of various cancers. LINC02418, a novel lncRNA, hasn't been mentioned in previous studies on cancer development. Therefore, it's important to define the potential function of LINC02418 in LAD.Methods: Gene expression was examined by RT-qPCR or western blot. CCK-8, colony formation, TUNEL, and transwell assays were utilized to study the role of LINC02418 in LAD. The interaction of miR-4677-3p with LINC02418 (or KNL1) was verified through luciferase reporter, RIP and RNA pull-down assays.Results: High expression of LINC02418 was observed in LAD specimens and cells. Downregulation of LINC02418 obstructed the proliferation and motility of LAD cells. Moreover, LINC02418 negatively modulated miR-4677-3p expression and miR-4677-3p overexpression could repress cell proliferation and migration. Moreover, kinetochore scaffold 1 (KNL1) expression was negatively modulated by miR-4677-3p but positively regulated by LINC02418. Furthermore, miR-4677-3p could bind with LINC02418 (or KNL1). Finally, KNL1 overexpression reversed the inhibitory function of LINC02418 deficiency in the malignant behaviors of LAD cells.Conclusions: LINC02418 contributes to the malignancy in LAD via miR-4677-3p/KNL1 signaling, providing a probable therapeutic direction for LAD. [ABSTRACT FROM AUTHOR]- Published
- 2020
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39. Upregulation of DARS2 by HBV promotes hepatocarcinogenesis through the miR-30e-5p/MAPK/NFAT5 pathway.
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Xian Qin, Changsheng Li, Tao Guo, Jing Chen, Hai-Tao Wang, Yi-Tao Wang, Yu-Sha Xiao, Jun Li, Pengpeng Liu, Zhi-Su Liu, and Quan-Yan Liu
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HEPATITIS B ,LIVER cancer ,CANCER risk factors ,NUCLEAR factor of activated T-cells ,PROTEIN expression ,GENE expression - Abstract
Background: Infection with the hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC). The osmoregulatory transcription factor nuclear factor of activated T-cells 5 (NFAT5) has been shown to play an important role in the development of many types of human cancers. The role of NFAT5 in HBV-associated HCC has never previously been investigated. Methods: We compared expression profiles of NFAT5, DARS2 and miR-30e-5p in HCC samples, adjacent nontumor tissues and different hepatoma cell lines by quantitative real-time polymerase chain reaction and /or Western blot. Clinical data of HCC patients for up to 80 months were analyzed. The regulatory mechanisms upstream and convergent downstream pathways of NFAT5 in HBV-associated HCC were investigated by ChIP-seq, MSP, luciferase report assay and bioinformation anaylsis. Results: We first found that higher levels of NFAT5 expression predict a good prognosis, suggesting that NFAT5 is a potential tumor-suppressing gene, and verified that NFAT5 promotes hepatoma cell apoptosis and inhibits cell growth in vitro. Second, our results showed that HBV could suppress NFAT5 expression by inducing hypermethylation of the AP1-binding site in the NFAT5 promoter in hepatoma cells. In addition, HBV also inhibited NFAT5 through miR-30e-5p targeted MAP4K4, and miR-30e-5p in turn inhibited HBV replication. Finally, we demonstrated that NFAT5 suppressed DARS2 by directly binding to its promoter. DARS2 was identified as an HCC oncogene that promotes HCC cell cycle progression and inhibits HCC cell apoptosis. Conclusion: HBV suppresses NFAT5 through the miR-30e-5p/mitogen-activated protein kinase (MAPK) signaling pathway upstream of NFAT5 and inhibits the NFAT5 to enhance HCC tumorigenesis via the downstream target genes of DARS2. [ABSTRACT FROM AUTHOR]
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- 2017
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40. Evaluation of recombinant multi-epitope proteins for diagnosis of goat schistosomiasis by enzyme-linked immunosorbent assay
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Tao Wang, Chao Lv, Xiaodan Cao, Zhang Zuhang, Yuanxi Shen, Hao Li, Yang Hong, Bingguang Jia, Qian Han, Jinli Zai, Zhiqiang Fu, Xuefeng Dou, Chuangang Zhu, Ke Lu, Jintao Feng, Rui Xu, and Jiaojiao Lin
- Subjects
0301 basic medicine ,Veterinary Medicine ,030231 tropical medicine ,Antibodies, Helminth ,Helminth genetics ,Schistosomiasis ,Enzyme-Linked Immunosorbent Assay ,Biology ,Cross Reactions ,Sensitivity and Specificity ,Epitope ,law.invention ,03 medical and health sciences ,Epitopes ,0302 clinical medicine ,Goat schistosomiasis ,Antigen ,law ,Diagnosis ,medicine ,Animals ,Goat Diseases ,Clinical Laboratory Techniques ,Research ,Goats ,medicine.disease ,Virology ,Recombinant Proteins ,030104 developmental biology ,Infectious Diseases ,Parasitology ,Antigens, Helminth ,Immunology ,biology.protein ,Recombinant DNA ,ELISA ,Antibody ,Recombinant multi-epitope proteins - Abstract
Background Schistosomiasis is a huge threat to human and animal health. Apart from bovines, goats play an important role in the transmission of schistosomiasis in some endemic areas of China. An accessible, quality-assured goat schistosomiasis diagnostic technique is needed. Recently, our laboratory identified two recombinant diagnostic antigens, SjPGM and SjRAD23 via an immuno-proteomic method. The application of these two recombinant antigens to develop a higher sensitivity and specificity technique for the sheep schistosomiasis diagnosis is urgently needed. Methods Epitopes of SjPGM and SjRAD23 were predicted and three polypeptides, two from SjRAD23 and one from SjPGM, were selected. Recombinant plasmids containing two to three DNA sequences encoding predicted polypeptides or large hydrophilic region of Sj23 (LHD-Sj23) were constructed and expressed. Eight recombinant schistosome antigens including four multi-epitope proteins and four recombinant single-molecule antigens as well as SEA, were assessed by ELISA in 91 sera from schistosome-infected goats, 44 sera from non-infected goats, 37 sera from Orientobilharzia-infected goats, and 12 from Haemonchus contortus-infected goats. Results ELISA tests showed that three multi-epitope proteins had higher sensitivity than the four single-molecule antigens (rSjRAD23, rSjPGM, rBSjRAD23-1, rBSj23) and the multi-epitope protein rBSjPGM-BSjRAD23-1-BSj23 had the highest sensitivity (97.8 %, 89/91) and maintained good specificity (100 %, 44/44) as well as low cross-reactivity with haemonchosis (8.33 %, 3/12) and orientobilharziasis (13.51 %, 5/37) in the diagnosis of goat schistosomiasis. In contrast, when SEA was applied as a diagnosis antigen, it had 100 % (91/91) sensitivity, 75 % (33/44) specificity, 25 and 83.78 % cross-reactivity with haemonchosis (3/12) and orientobilharziasis (31/37), respectively. Conclusions The application of recombinant multi-epitope proteins may increase the sensitivity of diagnosis technique and retain high specificity of single-molecule antigens for schistosomiasis, and the recombinant antigen rBSjPGM-BSjRAD23-1-BSj23 has the potential to be used as a diagnosis antigen for goat schistosomiasis.
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- 2016
41. Characterization of Sarcoptes scabiei cofilin gene and assessment of recombinant cofilin protein as an antigen in indirect-ELISA for diagnosis
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Yu Zheng, Ran He, Weimin Lai, Xuerong Peng, Guangyou Yang, Manli He, Xiaobin Gu, and Tao Wang
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0301 basic medicine ,medicine.medical_specialty ,030231 tropical medicine ,Blotting, Western ,Enzyme-Linked Immunosorbent Assay ,macromolecular substances ,Sarcoptes scabiei ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Medical microbiology ,Antigen ,law ,medicine ,Scabies ,Escherichia coli ,Animals ,Antigens ,Cloning, Molecular ,Gene ,biology ,integumentary system ,Cofilin ,Allergens ,biology.organism_classification ,medicine.disease ,Virology ,Immunohistochemistry ,Recombinant Proteins ,030104 developmental biology ,Infectious Diseases ,Parasitology ,Actin Depolymerizing Factors ,Immunology ,Recombinant DNA ,ELISA ,Rabbits ,Research Article - Abstract
Background Scabies impairs the health of humans and animals and causes heavy economic losses. Traditional diagnostic methods for scabies are inefficient and ineffective, and so far there is no commercial immunodiagnostic or molecular based test for scabies. Methods Here, we used recombinant Sarcoptes scabiei cofilin protein as an antigen to establish indirect ELISA. S. scabiei cofilin is highly homologous to Dermatophagoides farinae Der f 31 allergen (90 % identity). The S. scabiei cofilin gene was cloned and expressed in Escherichia coli to obtain recombinant protein. Western blotting and fluorescence immunohistochemistry were carried out, and we established an indirect ELISA method and detected 33 serum samples from scabies infected rabbits and 30 serum samples from naïve rabbits. Results Western blotting demonstrated that S. scabiei cofilin possessed good immunogenicity and fluorescence immunohistochemistry showed the S. scabiei cofilin is widespread in the splanchnic area of mites. In ELISA, a cut-off value of 0.188 was determined to judge experimental positive and negative serum values. Specificity and sensitivity of the ELISA were 87.9 and 83.33 %, respectively. Conclusions Recombinant S. scabiei cofilin showed potential value as a diagnostic antigen. The ELISA method established could be used in clinical diagnosis and provide experimental information in minimal or asymptomatic infection.
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- 2016
42. Lithium protects dopaminergic cells from rotenone toxicity via autophagy enhancement
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Xiaoyun Xu, Jie Li, Nian Xiong, Chao-dong Han, Ling Liu, Lingling Hou, Tao Wang, Guoxin Zhang, Jinsha Huang, and Zhicheng Lin
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Lithium (medication) ,Cell Survival ,Drug Evaluation, Preclinical ,Apoptosis ,Mitochondrion ,Lithium ,Neuroprotection ,Antiparkinson Agents ,Cellular and Molecular Neuroscience ,Parkinsonian Disorders ,Lysosome ,Cell Line, Tumor ,Rotenone ,Mitophagy ,medicine ,Autophagy ,Humans ,chemistry.chemical_classification ,Reactive oxygen species ,business.industry ,General Neuroscience ,Dopaminergic Neurons ,SH-SY5Y Cells ,Matrix Metalloproteinases ,Cell biology ,Mitochondria ,medicine.anatomical_structure ,Neuroprotective Agents ,chemistry ,Parkinson’s disease ,business ,Lithium Chloride ,Reactive Oxygen Species ,Neuroscience ,medicine.drug ,Research Article - Abstract
Background Previous studies have indicated that enhancement of autophagy lysosome pathway may be beneficial for Parkinson’s disease (PD), in which aberrant accumulation of aggregated/misfolded proteins and mitochondrial dysfunction are considered as crucial pathogenesis. Recently, a number of studies have suggested the neuroprotective effects of lithium in models of several neurodegenerative diseases including PD. However, the exact mechanisms underlying this neuroprotection remain unclear. In our study, rotenone-exposed SH-SY5Y cells were used as an in vitro parkinsonian model to assess the autophagy-enhancing effect of lithium and the underlying mechanisms were further investigated. Results Similar to the common used autophagy enhancer rapamycin (Rap, 0.2 μM), lithium (LiCl, 10 mM) significantly recovered the shrinkage of SH-SY5Y cells, and alleviated rotenone-induced cell apoptosis, mitochondrial membrane potential reduction and reactive oxygen species accumulation. Furthermore, the protective effects induced by LiCl were partially blocked by the co-treatment of autophagy inhibitors such as 3-methyladenine (3-MA, 10 mM) or chloroquine (CHL, 10 μM). Moreover, 3-MA or Chl suppressed LiCl-induced autophagy in the immunoblot assay. In addition, the co-localization of LC3 and mitochondria and the preservation of mitochondrial function within LiCl-treated cells were observed, confirming that the damaged mitochondria were cleared through autophagy (mitophagy). Conclusions These findings suggested that lithium exerted neuroprotection against rotenone-induced injuries partially through the autophagy pathway. Pharmacologically induction of autophagy by lithium may represent a novel therapeutic strategy as a disease-modifier in PD.
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- 2015
43. Long-term efficacy of subtotal splenectomy due to portal hypertension in cirrhotic patients
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Haibo Chu, Feng-Guo Jian, Yongbo Xu, Jianhua Zhao, Lei Wang, Weihua Zhang, Tao Wang, and Wei Han
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Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Splenectomy ,Splenic artery ,Esophageal and Gastric Varices ,Gastroenterology ,Shunt ,Hypersplenism ,Subtotal splenectomy ,Superior vena cava ,Internal medicine ,White blood cell ,medicine.artery ,Hypertension, Portal ,medicine ,Humans ,Portal hypertension ,Survival rate ,Retrospective Studies ,business.industry ,Platelet Count ,Portal Vein ,Retrospective cohort study ,General Medicine ,medicine.disease ,Surgery ,Survival Rate ,medicine.anatomical_structure ,Treatment Outcome ,Regional Blood Flow ,Hemostasis ,Splenomegaly ,Female ,business ,Gastrointestinal Hemorrhage ,Splenic Artery ,Research Article - Abstract
Background Portal hypertension (PHT) requires invasive measures to prevent rupture and bleeding of esophagogastric varices; however, the long-term results of subtotal splenectomy plus fixation of the retrosternal omentum majus (SSFROM) have not been reported. Specifically, the advantages and disadvantages of surgery that preserves the spleen and the long-term hematologic effects have not been described. Study design Our studies relating to SSFROM commenced in February 1999. As of April 2014 we have performed 256 subtotal splenectomies The records of 65 patients with PHT who underwent SSFROM were reviewed retrospectively. Results Four patients died within 4 years of surgery, with a 4-year survival rate of 94 %; the 11-year survival rate was 60 %. Eleven patients (17 %) had re-bleeding from esophagogastric varices. The white blood cell and platelet counts were higher 6 and 11 years post-operatively compared with pre-operative values (P 0.05). DSA demonstrated that 15 cases formed collateral circulations between the portal vein and superior vena cava. Conclusion SSFROM provide long-term hemostasis for esophagogastric variceal bleeding in PHT and corrected hypersplenism. SSFROM is an effective treatment for patients with PHT in whom long-term survival is expected.
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- 2015
44. Randomized phase III trial of radiotherapy or chemoradiotherapy with topotecan and cisplatin in intermediate-risk cervical cancer patients after radical hysterectomy
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Juan Wang, Tao Wang, Hongwei Chen, Wenze Sun, Fan Shi, Yingbing Zhang, Jinli Lu, Zi Liu, Beina Hui, and Jiquan Wang
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Oncology ,Risk ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Uterine Cervical Neoplasms ,Hysterectomy ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Genetics ,medicine ,Adjuvant therapy ,Humans ,Cervical cancer ,business.industry ,Chemoradiotherapy ,Chemoradiotherapy, Adjuvant ,Middle Aged ,medicine.disease ,Radiation therapy ,Clinical trial ,Treatment Outcome ,Topotecan ,Female ,Intermediate-risk ,Cisplatin ,business ,medicine.drug ,Research Article - Abstract
Background In cervical cancer patients with intermediate-risk factors, the optimal adjuvant therapy is still controversial. We undertook a randomized trial (ClinicalTrials.gov Identifier: NCT01418859) to compare the efficacy and toxicity of concurrent chemoradiotherapy with topotecan and cisplatin with radiotherapy alone in intermediate-risk cervical cancer patients. Methods Eligible patients were randomly assigned to one of three treatment arms including arm A (radiotherapy only,RT), arm B(concurrent chemoradiotherapy only, CCRT), and arm C (concurrent chemoradiotherapy with following consolidation chemotherapy, CCRT + CT). All eligible patients completed external RT (IMRT or 3D-CRT), receiving 45-50Gy /25f uniformly to the pelvis. Concurrent chemotherapy regimen was topotecan 0.75 mg/m2 for days 1, 2 and 3, followed by cisplatin 25 mg/m2 for days 1, 2 and 3. Three cycles of consolidation chemotherapy regimen was topotecan 1.5 mg/m2 for days 1 and 2, and 0.75 mg/m2 for day 3; followed by cisplatin 25 mg/m2 for days 1, 2 and 3, repeated every 21 days. Adverse events of each group were investigated and compared. Results Thirty-nine patients enrolled onto the remaining regimens: 14 to RT, 15 to CCRT and 10 to CCRT + CT. Six patients (15.4%) did not complete the protocol treatment. Hematologic toxicity was more frequent and more severe in the CCRT and CCRT + CT arms compared with the RT arm. The incidence of grade 3-4 neutropenia was significantly different statistically between the RT, CCRT and CCRT + RT groups (15.4%, 46.7% and 100%, respectively; P = 0.002). Specially, three patients in CCRT + CT arm of all six patients who did not complete the protocol treatment discontinued planned therapy because of persistent grade 4 neutropenia. However, there were no significant differences in grade 3-4 non-hematologic toxicities between the three groups(all P > 0.05). Recurrence-free survival and overall survival of each group were not analyzed on account of a median follow-up of only 16 months. Conclusions Concurrent chemoradiotherapy with topotecan and cisplatin showed severe hematologic toxicity in intermediate-risk cervical cancer patients after radical hysterectomy. Thus, the study was closed ahead of schedule. Trial registration ClinicalTrials.gov Identifier: NCT01418859.
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- 2015
45. Determination of reference intervals for metabolic profile of Hanwoo cows at early, middle and late gestation periods
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Renato Sa Vega, Da Chuan Piao, Sang Ki Kang, Hong-Gu Lee, Yun-Jaie Choi, Jae-Sung Lee, and Tao Wang
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media_common.quotation_subject ,Hanwoo cows ,Metabolic profile ,Reference intervals ,Wagyu cows ,Biology ,Biochemistry ,chemistry.chemical_compound ,Animal science ,medicine ,media_common ,chemistry.chemical_classification ,Creatinine ,Research ,Metabolic disorder ,Albumin ,Fatty acid ,medicine.disease ,chemistry ,Hanwoo ,Urea ,Animal Science and Zoology ,Reproduction ,Food Science ,Biotechnology - Abstract
Background: Metabolic profile was initially designed as a presymptomatic diagnostic aid based on statistical analyses of blood metabolites to provide an early warning of certain types of metabolic disorder. However, there is little metabolic profile data available about Korean Hanwoo cows. Therefore, this study aimed to determine the reference intervals of metabolic profile for Korean Hanwoo cows. Methods: Healthy animals (2,205) were selected and divided into early (day 1 to 95), middle (day 96 to 190) and late (day 191 to 285) period according to their gestating period. Metabolic profile including total protein (TP), albumin (Alb), urea (UREA), glucose (Glu), total cholesterol (T-Cho), long-chain fatty acid (LCFA), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), creatinine (Crea), calcium (Ca), inorganic phosphorous (iP) and magnesium (Mg) were analyzed using a TBA-40FR automatic biochemical analyzer. The data of Korean Hanwoo cows were then compared to those of the Japanese Wagyu cows. Results: Most of the data of the Korean Hanwoo cows were relatively higher than those of Japanese Wagyu cows, with the exception of Glu and GGT. This may indicate that the nutritional level of feed for the Korean Hanwoo cows was higher than that of the Japanese Wagyu cows because of the different feeding system. In particular, relatively higher levels of UREA and LCFA were observed in the Korean Hanwoo cows, and this may also contribute to the low reproduction efficiency. Conclusions: These findings may provide some theoretical basis for understanding the reproductive and feeding situation of Korean Hanwoo cows.
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- 2015
46. Elevated autocrine EDIL3 protects hepatocellular carcinoma from anoikis through RGD-mediated integrin activation
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Ying Fu, Jianren Gu, Tao Wang, Wenxin Qin, Qiang Xia, Zhigang Zhang, Mingxuan Feng, Feng Xue, Ming-Ze Ma, Jun Li, and Jianjun Zhang
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Male ,Cancer Research ,Hepatocellular carcinoma ,Carcinogenesis ,medicine.disease_cause ,Integrin activation ,Extracellular matrix ,Anoikis ,Portal Vein ,Liver Neoplasms ,Middle Aged ,Prognosis ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Epidermal growth factor-like repeats and discoidin I-like domains 3 ,Autocrine Communication ,Oncology ,Gene Knockdown Techniques ,Molecular Medicine ,Anoikis resistance ,Female ,Signal transduction ,Oligopeptides ,Signal Transduction ,Carcinoma, Hepatocellular ,Integrin ,Mice, Nude ,Biology ,Cell Line, Tumor ,medicine ,Cell Adhesion ,Animals ,Humans ,Cell adhesion ,Autocrine signalling ,neoplasms ,Cell Proliferation ,Tumor microenvironment ,Research ,Calcium-Binding Proteins ,Reproducibility of Results ,Thrombosis ,Integrin alphaV ,digestive system diseases ,Cancer research ,biology.protein ,Carrier Proteins ,Cell Adhesion Molecules - Abstract
Background A remolded microenvironment in hepatocellular carcinoma (HCC) caused by abnormally expressed matricellular proteins could promote HCC progression. The cell-matrix interactions mediated by integrins play an important role in tumor microenvironment. Epidermal Growth Factor-like repeats and Discoidin I-Like Domains 3 (EDIL3), an extracellular matrix (ECM) protein with angiogenic and anti-inflammatory effects, is abnormally highly expressed in HCC. Here we aim to analyze its expression in liver and HCC tissues, investigate the underlined mechanisms accounted for HCC progression. Methods EDIL3 expression level is examined in normal liver, cirrhotic liver and HCC at both mRNA and protein level. The association between EDIL3 and clinical outcomes is analyzed. The pattern of EDIL3 expression and location is examined using Immunofluorescence and ELISA. Overexpression or knock-down of EDIL3 in a panel of cell lines are subjected to assays related to proliferation, invasion, and anoikis to investigate the mechanisms of this matrix protein in HCC progression. Recombinant EDIL3 treatment is applied to confirm the results. Results Compared with normal liver and cirrhotic liver, EDIL3 is elevated in HCC. High level of EDIL3 protein is much more commonly in patients with larger tumor or portal vein tumor thrombus (PVTT) formation, associated with poor prognosis. EDIL3 is abundantly expressed in HCC cells and secreted by cancer cells. In vitro and in vivo studies indicate that EDIL3, probably in an autocrine manner, inhibits anoikis and promotes anchorage-independent growth of HCC cells. Further mechanistic studies suggest integrin ligation by EDIL3 and thus that the sustained activation of the FAK-Src-AKT signal is responsible for the anoikis resistance and anchorage independence. Both the administration of cilengitide, a RGD-containing integrin antagonist, and silencing of integrin αV, an important RGD-binding integrin, results in the blockade of anoikis-resistance induced by EDIL3. Conclusion Our study suggests that high levels of autocrine EDIL3 may contribute to a receptive microenvironment for the survival of detached HCC cells and may involve in cancer cell spreading. We also highlight the importance of interaction between EDIL3 and integrin αV and suggest disrupting the ligation of EDIL3 to integrins via RGD-blocking in selected patients may bear potential therapeutic value. Electronic supplementary material The online version of this article (doi:10.1186/1476-4598-13-226) contains supplementary material, which is available to authorized users.
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- 2014
47. Generation and characterization of UL41 null pseudorabies virus variant in vitro and in vivo.
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Chao Ye, Jing Chen, Tao Wang, Jingjing Xu, Hao Zheng, Jiqiang Wu, Guoxin Li, Zhiqing Yu, Wu Tong, Xuefei Cheng, Shasha Zhou, and Guangzhi Tong
- Abstract
Background: The alphaherpesvirus virion host shutoff (vhs) gene, UL41, can induce degradation of host mRNAs and shut off host protein synthesis. The roles of vhs in HSV-1 and HSV-2 have been studied extensively in previous studies, however, relatively little is known about the vhs protein of PRV. Methods: A novel method combining CRISPR/Cas9 and Gibson assembly was developed to generate UL41 null PRV variant. The properties of UL41 null PRV in vitro and in vivo were further characterized. And the vhs activity of UL41 protein of PRV variant was evaluated by luciferase assay, Western-blot and RT-qPCR. Results: Gibson assembly based on homologous recombination can accomplish one-step insertion of viral DNA fragments into donor plasmids efficiently (> 80%). Cas9/gRNA further largely enhanced the efficiency of homologous recombination. Using this method we were able to rapidly generate the UL41 null and revertant viruses of PRV variant. Compared to wild type (JS-2012), the UL41 null virus showed significantly smaller plaques and lower titers in Vero cells and impaired lethality and neuroinvasion in mice. Further the UL41 protein from different PRV strains exhibited unequal vhs activity in vitro, which of JS-2012 showed significantly weaker vhs activity than that of European-American strains. In addition UL41 null virus can also significantly decrease the expression of host genes during the early period of infection, which suggests other viral factors may be also involved in host shutoff. Conclusions: CRISPR/Cas9 combined with Gibson assembly efficiently generated UL41 null PRV. Compared to wild type, UL41 null PRV showed impaired both replication capability in vitro and neuroinvasion in vivo. Further UL41 protein of PRV variant showed significantly weaker vhs activity than that of PRV SC (European-American-like strain), suggesting the deficiency of vhs activity by the PRV variant UL41 protein. [ABSTRACT FROM AUTHOR]
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- 2018
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48. Association of APEX1 and OGG1 gene polymorphisms with breast cancer risk among Han women in the Gansu Province of China.
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Tao Wang, Haitao Wang, Suisheng Yang, Hongyun Guo, Binming Zhang, Huan Guo, Lan Wang, Gongjian Zhu, Yongdong Zhang, Haihong Zhou, Xiuli Zhang, Haining Li, and Haixiang Su
- Abstract
Background: Genetic variations in key DNA repair genes may influence DNA repair capacity, DNA damage and breast carcinogenesis. The current study aimed to estimate the association of APEX1 and OGG1 polymorphisms with the risk of breast cancer development. Methods: A total of 518 patients with histopathologically confirmed breast cancer and 921 region- and age-matched cancer-free controls were genotyped for the APEX1 polymorphisms rs3136817 and rs1130409 and the OGG1 polymorphisms rs1052133 and rs2072668 using a QuantStudio™ 12 K Flex Real-Time PCR System. Results: The rs3136817 heterozygous TC genotype along with the rs3136817 dominant model (TC + CC) was strongly associated with breast cancer susceptibility (odds ratio [OR] = 0.670, 95% confidence interval [95% CI]: 0.513 - 0.873, P = 0.003; OR = 0.682, 95% CI: 0.526 - 0.883, P = 0.004, respectively). No significant associations were observed among rs1130409, rs1052133, rs2072668 and breast cancer risk. Furthermore, an allele combination analysis revealed that APEX1 haplotypes containing C-T (alleles rs3136817 and rs1130409) conferred a significantly lower risk (corrected P < 0.001). Conclusion: This research is the latest report showing that an APEX1 rs3136817 heterozygous genotype may have a positive influence on DNA repair capacity in patients with breast cancer and thus may have a potential protective effect for Chinese Han women. [ABSTRACT FROM AUTHOR]
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- 2018
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49. The efficacy and feasibility of total reconstruction versus nontotal reconstruction of the pelvic floor on short-term and long-term urinary continence rates after radical prostatectomy: a meta-analysis.
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Yu-Peng Wu, Ning Xu, Shi-Tao Wang, Shao-Hao Chen, Yun-Zhi Lin, Xiao-Dong Li, Qing-Shui Zheng, Yong Wei, and Xue-Yi Xue
- Subjects
PELVIC floor ,PROSTATECTOMY ,TREATMENT effectiveness ,EVIDENCE-based medicine ,URINATION ,SURGERY - Abstract
Background: Recently, total pelvic floor reconstruction (TR) has been the treatment of choice for improving urinary incontinence (UI) after radical prostatectomy (RP). However, the superiority of TR with respect to urinary continence recovery following RP remains controversial. This study identified the effect of TR versus nonTR of the pelvic floor on short-term and long-term continence rates after RP. Methods: A literature search was performed in November 2017 using the PubMed, Embase, and Web of Science databases. Only comparative research or clinical studies reporting urinary continence outcomes was included in the meta-analysis, and the quality of evidence was evaluated using the 2011 Level of Evidence for therapy research. Results: We analyzed ten studies reporting urinary continence rates after RP at one or more postoperative time points (1, 2, 4, 12, 24, and 52 weeks). TR was associated with significantly better urinary continence outcomes at 1 week (OR 2. 76, 95% CI 1.58-4.84, P < 0.001), 2 weeks (OR 2.57, 95% CI 1.74-3.80, P < 0.001), 4 weeks (OR 2.61, 95% CI 1.56-4.38, P < 0.001), 12 weeks (OR 4.33, 95% CI 2.01-9.33, P < 0.001), 24 weeks (OR 3.83, 95% CI 1.54-9.55, P = 0.004), 52 weeks (OR 4. 10, 95% CI 1.80-9.38, P < 0.001) after RP. There was no difference in the rate of complications between the two arms (OR 0.54, 95% CI 0.19-1.54, P = 0.25). Conclusions: Compared with nonTR, TR is significantly and positively associated with a return to continence but not with complication rate in men following RP, suggesting that TR may be useful for decreasing the urinary incontinence rate after surgery. [ABSTRACT FROM AUTHOR]
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- 2017
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50. New methods for estimating follow-up rates in cohort studies.
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Xiaonan Xue, Agalliu, Ilir, Kim, Mimi Y., Tao Wang, Juan Lin, Ghavamian, Reza, Strickler, Howard D., Xue, Xiaonan, Wang, Tao, and Lin, Juan
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PROSTATE cancer patients ,CANCER relapse ,KAPLAN-Meier estimator ,COHORT analysis ,MEASUREMENT errors ,BIG data - Abstract
Background: The follow-up rate, a standard index of the completeness of follow-up, is important for assessing the validity of a cohort study. A common method for estimating the follow-up rate, the "Percentage Method", defined as the fraction of all enrollees who developed the event of interest or had complete follow-up, can severely underestimate the degree of follow-up. Alternatively, the median follow-up time does not indicate the completeness of follow-up, and the reverse Kaplan-Meier based method and Clark's Completeness Index (CCI) also have limitations.Methods: We propose a new definition for the follow-up rate, the Person-Time Follow-up Rate (PTFR), which is the observed person-time divided by total person-time assuming no dropouts. The PTFR cannot be calculated directly since the event times for dropouts are not observed. Therefore, two estimation methods are proposed: a formal person-time method (FPT) in which the expected total follow-up time is calculated using the event rate estimated from the observed data, and a simplified person-time method (SPT) that avoids estimation of the event rate by assigning full follow-up time to all events. Simulations were conducted to measure the accuracy of each method, and each method was applied to a prostate cancer recurrence study dataset.Results: Simulation results showed that the FPT has the highest accuracy overall. In most situations, the computationally simpler SPT and CCI methods are only slightly biased. When applied to a retrospective cohort study of cancer recurrence, the FPT, CCI and SPT showed substantially greater 5-year follow-up than the Percentage Method (92%, 92% and 93% vs 68%).Conclusions: The Person-time methods correct a systematic error in the standard Percentage Method for calculating follow-up rates. The easy to use SPT and CCI methods can be used in tandem to obtain an accurate and tight interval for PTFR. However, the FPT is recommended when event rates and dropout rates are high. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
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