55 results on '"Wen, Cong"'
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2. Psychometric Evaluation of the Malay Version of the Family Adaptability and Cohesion Evaluation Scale III for Malaysian Adolescents
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Chin Wen Cong, Chee-Seng Tan, Hooi San Noew, and Shin Ling Wu
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Circumplex Model ,psychometrics ,Brief Report ,Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,Malaysia ,Reproducibility of Results ,FACES-III ,Surveys and Questionnaires ,adolescent ,family functioning ,Humans ,Medicine ,Language - Abstract
The Family Adaptability and Cohesion Scale III (FACES-III) has been widely used to measure an individual’s family functioning in terms of cohesion and adaptability. In Malaysia, the FACES-III has been translated into the Malay language for the community, but its psychometric properties in this context remain unknown. Thus, the purpose of this research is to examine the psychometric properties of the Malay version of the FACES-III in 852 adolescents attending secondary schools in Kuala Lumpur, Malaysia. Data were randomly split into two halves: the exploration sample and the validation sample. Exploratory factor analysis was conducted on the exploration sample and a two-factor model was discovered after removing nine items that showed low factor loading. Then, confirmatory factor analysis was conducted on the validation sample to compare the one-factor models, two-factor models, and three-factor models. Results showed that the 11-item two-factor model (FACES-III-M-SF) was superior to the other competing models. Both the exploratory and confirmatory factor analyses replicated the two-factor structure of the original version of FACES-III. The reliability of the overall scale was consistently good, but the subscale results were mixed. This suggests that researchers should use the overall score, but not the subscale scores, in analyses.
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- 2022
3. The Mediating Role of Work Engagement in the Relationship between Executive Functioning Deficits and Employee Well-Being
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Chee-Seng Tan, Hira Nasir, Kai-Shuen Pheh, Chin Wen Cong, Kok-Wai Tay, and Jia-Qi Cheong
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Adult ,Creativity ,creativity ,employee ,engagement ,executive function ,job demands-resources model ,Malaysia ,workers ,well-being ,Health, Toxicology and Mutagenesis ,Surveys and Questionnaires ,Public Health, Environmental and Occupational Health ,Humans ,Cognitive Dysfunction ,Work Engagement - Abstract
Executive functioning and its related components have been found to promote well-being. However, there is a limited understanding of the underlying mechanism. Drawing from the job demands–resources and PERMA models, the present study examined the hypothetical mediating role of work engagement in the relationship between executive functioning deficit and well-being among 314 working adults in Malaysia. Participants answered a survey consisting of the Executive Skills Questionnaire-Revised (ESQ-R; a new measure of executive functioning deficits for working adults), Utrecht Work Engagement Scale, Employee Well-Being Scale, and Self-Rated Creativity Scale. Pearson correlation analysis showed that the ESQ-R score was negatively associated with all other target variables, while the latter was positively related to each other. Moreover, supporting the hypotheses, the results of mediation analysis using PROCESS macro found that work engagement mediated the negative relationship between executive functioning deficits and well-being after statistically controlling for the creativity score. The findings not only replicate the beneficial role of executive functioning in employees’ well-being but also shed light on the underlying process of the relationship. Implications and directions for future studies are discussed.
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- 2022
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4. Salt-inducible kinase inhibition sensitizes human acute myeloid leukemia cells to all-trans retinoic acid-induced differentiation
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Wen-Yue Long, Zu-Yin Yu, Xue-wen Zhang, Guo-Lin Xiong, He Xiao, Xing Shen, Feng-Jun Li, Shuang Xing, and Yu-Wen Cong
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Acute promyelocytic leukemia ,MAP Kinase Signaling System ,Retinoic acid ,Antineoplastic Agents ,Apoptosis ,Tretinoin ,Protein Serine-Threonine Kinases ,Immunophenotyping ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Differentiation therapy ,Cell Line, Tumor ,hemic and lymphatic diseases ,medicine ,Humans ,Protein Kinase Inhibitors ,neoplasms ,Protein kinase B ,Akt/PKB signaling pathway ,Kinase ,organic chemicals ,Cell Cycle ,Myeloid leukemia ,Cell Differentiation ,Hematology ,medicine.disease ,Immunohistochemistry ,biological factors ,Leukemia, Myeloid, Acute ,chemistry ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer research ,Growth inhibition ,Proto-Oncogene Proteins c-akt ,Biomarkers ,030215 immunology - Abstract
Differentiation therapies with all-trans retinoic acid (ATRA) have been successful in treating acute promyelocytic leukemia, a rare subtype of acute myeloid leukemia (AML). However, their efficacy is limited in the case of other AML subtypes. Here, we show that the combination of ATRA with salt-inducible kinase (SIK) inhibition significantly enhances ATRA-mediated AML differentiation. SIK inhibition augmented the ability of ATRA to induce growth inhibition and G1 cell cycle arrest of AML cells. Moreover, combining ATRA and SIK inhibition synergistically activated the Akt signaling pathway but not the MAPK pathway. Pharmacological blockade of Akt activity suppressed the combination-induced differentiation, indicating an essential role for Akt in the action of the combination treatment. Taken together, our study reveals a novel role for SIK in the regulation of ATRA-mediated AML differentiation, implicating the combination of ATRA and SIK inhibition as a promising approach for future differentiation therapy.
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- 2020
5. Circadian rhythms of blood pressure in hypertensive patients with cerebral microbleeds
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Yang‐Kun Chen, Wen‐Cong Liang, Shu‐Lan Yuan, Zhuo‐Xin Ni, Wei Li, Yong‐Lin Liu, and Jian‐Feng Qu
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Behavioral Neuroscience ,Case-Control Studies ,Hypertension ,Humans ,Blood Pressure ,Blood Pressure Monitoring, Ambulatory ,Cerebral Hemorrhage ,Circadian Rhythm - Abstract
Whether the circadian rhythms of blood pressure (BP) contribute to the presence of cerebral microbleeds (CMBs) remains unknown. This study aimed to assess the relationship between nocturnal BP and CMBs in hypertensive patients.This prospective case-control study recruited 51 hypertensive patients with CMBs and 51 hypertensive patients without CMBs, matched with age and gender, serving as controls. A 24-h ambulatory BP monitoring was conducted in all subjects. Differences in ambulatory BP parameters between the two groups were compared. Logistic regression analyzes were conducted to investigate the relationship between the ambulatory BP parameters and presence of CMBs.Patients with CMBs had a significant higher nocturnal mean SBP and lower relative nocturnal SBP dipping rate. Two logistic models were constructed to explore the association between ABPM indices and the presence of CMBs, adjusted with history of ischemic stroke and smoking. In model 1, higher nocturnal mean SBP positively correlated with presence of CMBs [standardized β = 0.254, odds ratio (OR) = 1.029, p = .041]. In model 2, the relative nocturnal SBP dipping rate was negatively correlated with CMBs (standardized β = -.363, OR = 0.918, p = .007). Only patients with deep CMBs had significant higher nocturnal mean SBP and lower relative nocturnal SBP dipping rate in comparison with those without CMBs.Higher nocturnal SBP and lower relative nocturnal SBP dipping rate may be associated with CMBs in hypertensive patients.
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- 2022
6. Family functioning, coping strategy, and suicidal ideation among adolescents
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Mimi Fitriana, Wu Shin Ling, and Chin Wen Cong
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Male ,Coping (psychology) ,Adolescent ,Family functioning ,Suicidal Ideation ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Adaptation, Psychological ,Independent samples ,Developmental and Educational Psychology ,medicine ,Humans ,Family ,0501 psychology and cognitive sciences ,030212 general & internal medicine ,Suicidal ideation ,Kuala lumpur ,05 social sciences ,Significant difference ,Malaysia ,Family cohesion ,Adolescent suicide ,Psychiatry and Mental health ,Clinical Psychology ,Adolescent Behavior ,Pediatrics, Perinatology and Child Health ,Female ,medicine.symptom ,Psychology ,050104 developmental & child psychology ,Clinical psychology - Abstract
Background and aim: Adolescent suicide has become a central issue around the world, including in Malaysia, which needs attention. The current study investigated the mediating effect of coping strategy in the association between family functioning and suicidal ideation among adolescents in Kuala Lumpur, Malaysia. Method: A total of 852 school-attending adolescents aged 13-17 years were recruited by multistage cluster sampling. The relationships between all the study variables were analysed using Pearson's correlation. Moreover, the mediation model was tested using SPSS PROCESS macro, while sex differences in suicidal ideation were examined using independent samples t-test. Results: Results showed that family cohesion, family flexibility, and problem-focused coping negatively correlated with adolescents' suicidal ideation. Problem-focused coping also mediated the association between family flexibility and suicidal ideation. There was a significant difference in suicidal ideation for males and females. Conclusion: Family functioning and coping strategy are related to adolescents' suicidal ideation, while problem-focused coping plays a crucial role in the relationship between family flexibility and suicidal ideation.
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- 2020
7. Effects of Low-Dose Amitriptyline on Epigastric Pain Syndrome in Functional Dyspepsia Patients
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Jian Xu, Wen-cong Zhou, Shu-Man Jiang, Yao Liu, Jing Liu, and Lin Jia
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Adult ,Male ,medicine.medical_specialty ,Physiology ,Amitriptyline ,Epigastric pain ,Pittsburgh Sleep Quality Index ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Hamd ,Humans ,Medicine ,Prospective Studies ,Dyspepsia ,Pantoprazole ,Dose-Response Relationship, Drug ,business.industry ,Therapeutic effect ,Gastroenterology ,Analgesics, Non-Narcotic ,Middle Aged ,Abdominal Pain ,Treatment Outcome ,Before Bedtime ,030220 oncology & carcinogenesis ,Anxiety ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,medicine.drug - Abstract
To observe the therapeutic effect of low-dose amitriptyline (AMT) on epigastric pain syndrome (EPS) in patients with functional dyspepsia. Sixty patients with EPS were randomly divided into the following two groups for a four-week clinical trial: routine treatment with pantoprazole (RT group) and the AMT group. The RT group was treated with 40 mg of pantoprazole once daily. The AMT group received 25 mg of AMT once daily before bedtime. The Nepean Dyspepsia Index (NDI) checklist, Hamilton Rating Scale of Anxiety/Depression (HAMA/HAMD), and Pittsburgh Sleep Quality Index (PSQI) were employed to evaluate dyspepsia symptoms, psychological distress, and sleep, respectively. All items were similar between the two groups before treatment (0 week). After 4 weeks of treatment, the NDI–symptom checklist score as well as the severity and bothersomeness of EPS in the AMT group was significantly decreased compared with those in the RT group (p
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- 2020
8. Endothelial ZEB1 promotes angiogenesis-dependent bone formation and reverses osteoporosis
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Lei Di, Rong Fu, Yan Xu, Ying Xu, Zhao-Qiu Wu, Liming Wang, Tao Lu, Xiao-Jie Chen, Wen-Cong Lv, Nan Jiang, Mu-Yun Gong, Ran Mo, and Qingqiang Yao
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0301 basic medicine ,Endothelium ,Angiogenesis ,Science ,Transgene ,Ovariectomy ,Osteoporosis ,Notch signaling pathway ,General Physics and Astronomy ,Neovascularization, Physiologic ,Mice, Transgenic ,General Biochemistry, Genetics and Molecular Biology ,Article ,Bone remodeling ,Epigenesis, Genetic ,Neovascularization ,03 medical and health sciences ,0302 clinical medicine ,Osteogenesis ,medicine ,Animals ,Humans ,Receptor, Notch1 ,lcsh:Science ,Transcription factor ,Skeleton ,Adaptor Proteins, Signal Transducing ,Aged ,Mice, Knockout ,Multidisciplinary ,business.industry ,Calcium-Binding Proteins ,Endothelial Cells ,Zinc Finger E-box-Binding Homeobox 1 ,General Chemistry ,Middle Aged ,medicine.disease ,Cell biology ,Platelet Endothelial Cell Adhesion Molecule-1 ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Epigenetics ,lcsh:Q ,medicine.symptom ,business - Abstract
Recent interest in the control of bone metabolism has focused on a specialized subset of CD31hiendomucinhi vessels, which are reported to couple angiogenesis with osteogenesis. However, the underlying mechanisms that link these processes together remain largely undefined. Here we show that the zinc-finger transcription factor ZEB1 is predominantly expressed in CD31hiendomucinhi endothelium in human and mouse bone. Endothelial cell-specific deletion of ZEB1 in mice impairs CD31hiendomucinhi vessel formation in the bone, resulting in reduced osteogenesis. Mechanistically, ZEB1 deletion reduces histone acetylation on Dll4 and Notch1 promoters, thereby epigenetically suppressing Notch signaling, a critical pathway that controls bone angiogenesis and osteogenesis. ZEB1 expression in skeletal endothelium declines in osteoporotic mice and humans. Administration of Zeb1-packaged liposomes in osteoporotic mice restores impaired Notch activity in skeletal endothelium, thereby promoting angiogenesis-dependent osteogenesis and ameliorating bone loss. Pharmacological reversal of the low ZEB1/Notch signaling may exert therapeutic benefit in osteoporotic patients by promoting angiogenesis-dependent bone formation., An endothelial cell subtype, expressing endomucin and CD31, has been reported to couple angiogenesis with osteogenesis. Here, the authors show that loss of ZEB1 in these cells epigenetically suppresses Notch signaling, leading to impaired angiogenesis and osteogenesis, and that Zeb1 delivery via liposomes ameliorates bone loss in osteoporotic mice
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- 2020
9. Knockdown of lncRNA NEAT1 suppresses proliferation and migration, and induces apoptosis of cervical cancer cells by regulating the miR-377/FGFR1 axis
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Wen-Cong Jia, Feng Geng, Tao Li, Wei Wei, and Na Li
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Cancer Research ,China ,cervical cancer ,Cell Survival ,Cell ,Primary Cell Culture ,NEAT1 ,Gene Expression ,Uterine Cervical Neoplasms ,Apoptosis ,Biochemistry ,HeLa ,Cell Movement ,Genetics ,medicine ,microRNA-377 ,Humans ,Viability assay ,Receptor, Fibroblast Growth Factor, Type 1 ,Molecular Biology ,Aged ,Cell Proliferation ,Gene knockdown ,biology ,Chemistry ,fibroblast growth factor receptor 1 ,Transfection ,Articles ,Cell cycle ,Middle Aged ,biology.organism_classification ,Molecular biology ,Gene Expression Regulation, Neoplastic ,stomatognathic diseases ,MicroRNAs ,medicine.anatomical_structure ,Oncology ,Cell culture ,Molecular Medicine ,Female ,RNA, Long Noncoding - Abstract
To investigate the role of NEAT1 and the microRNA (miR)-377/fibroblast growth factor receptor 1 (FGFR1) axis in cervical cancer (CC), the expression levels of NEAT1, FGFR1 and miR-377 were detected in CC tissues and cell lines. NEAT1 or FGFR1 was knocked down by transfection with short hairpin RNA (sh)-NEAT1 or sh-FGFR1, and miR-377 was overexpressed by transfection with miR-377 mimics in HeLa and C33A cells. Cell viability and migration were measured using MTT and Transwell assays, respectively. Cell apoptosis was determined by flow cytometry. A dual luciferase reporter assay was performed to confirm the presence of binding sites between miR-377 and FGFR1. The results revealed that the expression levels of NEAT1 and FGFR1 were significantly elevated, whereas miR-377 expression was markedly decreased in CC tissues and cell lines. In HeLa and C33A cells, after NEAT1 knockdown, miR-377 expression was increased, cell viability and migration were inhibited, and apoptosis was induced. Similarly, silencing FGFR1 inhibited cell viability and migration, and induced apoptosis of HeLa and C33A cells. A dual luciferase reporter gene assay verified a targeting relationship between NEAT1 and miR-377. Inhibition of miR-377 or overexpression of FGFR1 reversed the effects of NEAT1 knockdown on cell function in HeLa and C33A cells. Moreover, a dual luciferase reporter assay confirmed that FGFR1 was a direct target of miR-377. In conclusion, suppression of NEAT1 inhibited cell viability and migration, and promoted apoptosis of CC cells, and these effects were achieved through regulation of the miR-377/FGFR1 axis.
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- 2021
10. Validation and Measurement Invariance of the Body Appreciation Scale-2 between Genders in a Malaysian Sample
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Afi Roshezry Abu Bakar, Siew-May Cheng, Bazlin Darina Binti Ahmad Tajudin, Nor Ez-Zatul Hanani Mohamed Rosli, Muliyati Mat Alim, Chin Wen Cong, Chee-Seng Tan, Mohamad Iqbaal Bin Mohd Wazir, Alfian Bin Asmi, and Edwin Michael
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Adult ,Male ,Adolescent ,Psychometrics ,body image ,Health, Toxicology and Mutagenesis ,education ,Context (language use) ,Developmental psychology ,Young Adult ,Sex Factors ,Cronbach's alpha ,Surveys and Questionnaires ,Humans ,Measurement invariance ,selfie editing ,BAS-2 ,Analysis of covariance ,Brief Report ,Multilevel model ,Public Health, Environmental and Occupational Health ,Malaysia ,Reproducibility of Results ,Middle Aged ,Exploratory factor analysis ,Confirmatory factor analysis ,measurement invariance ,Medicine ,Female ,Factor Analysis, Statistical ,Psychology ,Incremental validity - Abstract
The 10-item Body Appreciation Scale-2 (BAS-2) is a measurement for individuals to self-report the extent to which they accept and respect their bodies. Although the BAS-2 has been translated into the Malay language and found to have promising qualities, the psychometric characteristics of the English version of BAS-2 remain unknown in the Malaysian context. The present study thus administered the English version BAS-2 and selfie-editing frequency scale to 797 individuals aged 18 to 56 years old in Malaysia. The dataset that was randomly divided into two halves were submitted to exploratory factor analysis and confirmatory factor analysis respectively. Both of the factor analyses consistently support a one-factor model. The Cronbach’s alpha and McDonald omega coefficients were greater than 0.90, indicating that the BAS-2 has good internal consistency. The incremental validity is also evident. A hierarchical multiple regression showed that the BAS-2 score had a positive relationship with selfie-editing frequency after controlling for age and gender. Moreover, the measurement invariance test supported scalar invariance between genders, and an analysis of covariance did not find significant gender differences. Overall, the findings replicate past findings and regularly support the usability of the BAS-2 in the Malaysian context. The implications of the BAS-2 and future directions are also discussed.
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- 2021
11. Neuroimaging risk factors for participation restriction after acute ischemic stroke: 1-year follow-up study
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Huo-Hua Zhong, Wen-Cong Liang, Jian-Feng Qu, Wei Li, Yang-Kun Chen, and Yong-Lin Liu
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Male ,medicine.medical_specialty ,Activities of daily living ,Neuroimaging ,Logistic regression ,Severity of Illness Index ,General Biochemistry, Genetics and Molecular Biology ,Modified Rankin Scale ,Risk Factors ,Internal medicine ,Activities of Daily Living ,medicine ,Humans ,cardiovascular diseases ,Stroke ,Ischemic Stroke ,Univariate analysis ,business.industry ,Stroke Rehabilitation ,Atrial fibrillation ,General Medicine ,medicine.disease ,Hyperintensity ,Female ,business ,Follow-Up Studies - Abstract
The aim of the present study was to determine the neuroimaging predictors of poor participation after acute ischemic stroke. A total of 443 patients who had acute ischemic stroke were assessed. At 1-year recovery, the Reintegration to Normal Living Index was used to assess participation restriction. We also assessed the Activities of Daily Living Scale and modified Rankin Scale (mRS) score. Brain MRI measurement included acute infarcts and pre-existing abnormalities such as enlarged perivascular spaces, white matter lesions, ventricular-brain ratio, and medial temporal lobe atrophy (MTLA). The study included 324 men (73.1%) and 119 women (26.9%). In the univariate analysis, patients with poor participation after 1 year were older, more likely to be men, had higher National Institutes of Health Stroke Scale (NIHSS) score on admission, with more histories of hypertension and atrial fibrillation, larger infarct volume, more severely enlarged perivascular spaces and MTLA, and more severe periventricular hyperintensities and deep white matter hyperintensities. Patients with participation restriction also had poor activities of daily living (ADL) and mRS score. Multiple logistic regression showed that, in model 1, age, male gender, NIHSS score on admission, and ADL on follow-up were significant predictors of poor participation, accounting for 60.2% of the variance. In model 2, which included both clinical and MRI variables, male gender, NIHSS score on admission, ADL on follow-up, and MTLA were significant predictors of poor participation, accounting for 61.2% of the variance. Participation restriction was common after acute ischemic stroke despite good mRS score. Male gender, stroke severity, severity of ADL on follow-up, and MTLA may be predictors of poor participation. Trial registration number ChiCTR1800016665.
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- 2021
12. Predicting factors of central lymph node metastasis and BRAFV600E mutation in Chinese population with papillary thyroid carcinoma
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Wen Cong Sun, Chao Ding, Lei Zhang, Yan Ping Guo, Yue Wu Zhao, Tao Deng, Zi Guang Xu, Ling Fei Kong, and Sheng Li Zhou
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Adult ,Male ,Proto-Oncogene Proteins B-raf ,China ,medicine.medical_specialty ,Mutation rate ,Multivariate analysis ,endocrine system diseases ,RD1-811 ,medicine.medical_treatment ,Gastroenterology ,Thyroid carcinoma ,03 medical and health sciences ,BRAFV600E mutation ,0302 clinical medicine ,Surgical oncology ,Internal medicine ,medicine ,Humans ,Thyroid Neoplasms ,Risk factor ,Central lymph node metastasis ,030223 otorhinolaryngology ,RC254-282 ,Retrospective Studies ,business.industry ,Research ,Incidence (epidemiology) ,BRAF V600E mutation ,Thyroidectomy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Tumor size ,Prognosis ,Oncology ,Thyroid Cancer, Papillary ,Papillary thyroid carcinoma ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Mutation ,Mutation (genetic algorithm) ,Surgery ,business - Abstract
Objective The aim of this study was to evaluate the predictive factors of central lymph node metastasis (CLNM) and BRAFV600E mutation in Chinese patients with papillary thyroid carcinoma (PTC). Methods A total of 943 PTC patients who underwent thyroidectomy from 2014 to 2016 at our hospital were enrolled. Those patients were divided into PTC > 10 mm and papillary thyroid microcarcinoma (PTMC) groups by tumor size. The BRAFV600E mutation was examined by quantitative real-time PCR. Univariate and multivariate analyses were used to examine risk factors associated with CLNM and the BRAFV600E mutation. Results The frequency of CLNM was 53% (505/943). Both univariate and multivariate analyses suggested that the risk factors for CLNM in PTC patients were male, younger age, and larger tumor size (P < 0.05). Coexistent Hashimoto thyroiditis (HT) was an independent protective factor against CLNM when the tumor was > 10 mm (P = 0.006). Stratified analysis revealed that male, age ≤ 30 years, and tumor size > 5 mm were independent risk factors for CLNM. The BRAFV600E mutation rate was 85%. Multivariate logistic regression analysis revealed that age (P < 0.001) and coexistent HT (P = 0.005) were independent predictive factors of BRAFV600E mutation in PTC patients. Only age was a risk factor for the BRAFV600E mutation when the tumor was > 10 mm (P = 0.004). In the PTMC group, the BRAFV600E mutation was significantly correlated with tumor size (P < 0.001) and coexistent HT (P = 0.03). Stratified analysis revealed that age > 30 years and tumor size > 5 mm were independent predictive factors of BRAFV600E mutation. Furthermore, the incidence of CLNM was significantly higher in BRAFV600E mutation-positive patients (P = 0.009) when the tumor was ≤ 5 mm. Conclusion The factors male, younger age (≤ 30 years), large tumor size (> 5 mm), and coexistent HT are independent predicative factors for CLNM. The BRAFV600E mutation is associated with both large size and without HT in PTMC patients, age > 30 years in the PTC > 10 mm group. The BRAFV600E mutation was an independent risk factor for CLNM when the tumor was ≤ 5 mm. For optimal management, these features should be comprehensively evaluated to determine the initial surgical approach for PTC patients.
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- 2021
13. Hepatic Macrophage activation and the LPS pathway in patients with different degrees of severity and histopathological patterns of drug induced liver injury
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Hui-Juan, Du, Su-Xian, Zhao, Wen, Zhao, Na, Fu, Wen-Cong, Li, Xiao-Jie, Qin, Yu-Guo, Zhang, Yue-Min, Nan, and Jing-Min, Zhao
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Adult ,Lipopolysaccharides ,Male ,Immunity, Cellular ,Membrane Glycoproteins ,Kupffer Cells ,Antigens, Differentiation, Myelomonocytic ,Receptors, Cell Surface ,Macrophage Activation ,Middle Aged ,Liver ,Antigens, CD ,Humans ,Female ,Chemical and Drug Induced Liver Injury ,Carrier Proteins ,Acute-Phase Proteins - Abstract
Inflammatory activation of hepatic macrophages plays a primary role in drug-induced liver injury (DILI). However, the exact mechanism underlying DILI remains unclear.A total of 328 DILI patients and 80 healthy individuals were prospectively enrolled in this study. The DILI patients were categorized into subgroups based on either disease severity or histopathological patterns. Plasma soluble CD163 (sCD163) and hepatic CD163 were examined to determine hepatic macrophage activation, and CD8, CD20, and MUM-1 were assessed to determine cellular immunity using immunohistochemistry. The lipopolysaccharide (LPS) pathway proteins [e.g. LPS, soluble CD14 (sCD14), and LPS-binding protein (LBP)] were measured using enzyme-linked immunosorbent assay.Plasma sCD163 levels were nine-fold higher in DILI patients than in healthy controls at the baseline, but significantly decreased at the 4-week follow-up visit after treatment. The numbers of hepatic macrophages, B cells, and plasma cells were significantly higher in the liver tissues from DILI patients than those from healthy controls. Furthermore, the baseline levels of LPS pathway proteins in the DILI patients were significantly higher than those in the controls. Notably, these proteins significantly decreased at the 4-week follow-up visit but remained significantly higher than the levels for the controls.Hepatic inflammation in DILI involves the activation of hepatic macrophages and cellular immunity, in which the LPS pathway likely plays a role, at least in part. As such, this study has improved our understanding of the pathological mechanisms for DILI and may facilitate the development of better treatments for patients with DILI.
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- 2021
14. AI detection of mild COVID-19 pneumonia from chest CT scans
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Liping Wang, Wei Li, Jie Zhang, Ya Qing Li, Di Ou, Wen Cong Chen, Dong Xu, Jin Cao Yao, Lin Yin Fan, Guang Hua Hou, Chen Yang, Qiao Dan Zhu, Lijing Wang, Tao Wang, and Kaiyuan Shi
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medicine.medical_specialty ,Artificial intelligence ,Computer-assisted diagnosis ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Deep Learning ,Region of interest ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Neuroradiology ,Retrospective Studies ,medicine.diagnostic_test ,Receiver operating characteristic ,business.industry ,SARS-CoV-2 ,Area under the curve ,Volume CT ,COVID-19 ,Interventional radiology ,General Medicine ,medicine.disease ,Pneumonia ,Feature (computer vision) ,030220 oncology & carcinogenesis ,Cohort ,Chest ,Radiology ,business ,Tomography, X-Ray Computed - Abstract
Objectives An artificial intelligence model was adopted to identify mild COVID-19 pneumonia from computed tomography (CT) volumes, and its diagnostic performance was then evaluated. Methods In this retrospective multicenter study, an atrous convolution-based deep learning model was established for the computer-assisted diagnosis of mild COVID-19 pneumonia. The dataset included 2087 chest CT exams collected from four hospitals between 1 January 2019 and 31 May 2020. The true positive rate, true negative rate, receiver operating characteristic curve, area under the curve (AUC) and convolutional feature map were used to evaluate the model. Results The proposed deep learning model was trained on 1538 patients and tested on an independent testing cohort of 549 patients. The overall sensitivity was 91.5% (195/213; p < 0.001, 95% CI: 89.2–93.9%), the overall specificity was 90.5% (304/336; p < 0.001, 95% CI: 88.0–92.9%) and the general AUC value was 0.955 (p < 0.001). Conclusions A deep learning model can accurately detect COVID-19 and serve as an important supplement to the COVID-19 reverse transcription–polymerase chain reaction (RT-PCR) test. Key Points • The implementation of a deep learning model to identify mild COVID-19 pneumonia was confirmed to be effective and feasible. • The strategy of using a binary code instead of the region of interest label to identify mild COVID-19 pneumonia was verified. • This AI model can assist in the early screening of COVID-19 without interfering with normal clinical examinations. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-021-07797-x.
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- 2020
15. Identification of inhibitors of pinellic acid generation in whole wheat bread
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Eric B. Schwartz, Wen Cong, and Devin G. Peterson
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Flour ,Aversive Agents ,01 natural sciences ,Analytical Chemistry ,chemistry.chemical_compound ,0404 agricultural biotechnology ,Tandem Mass Spectrometry ,Partial least squares regression ,Humans ,Food science ,Least-Squares Analysis ,Flavor ,Bread making ,Chromatography, High Pressure Liquid ,Triticum ,Principal Component Analysis ,OPLS ,Chemistry ,010401 analytical chemistry ,food and beverages ,04 agricultural and veterinary sciences ,General Medicine ,Bread ,Whole wheat ,040401 food science ,0104 chemical sciences ,Pinellic acid ,Schaftoside ,Apigenin ,Taste Threshold ,Fatty Acids, Unsaturated ,Food Science - Abstract
Bitterness is a common aversive flavor attribute of foods associated with low consumer acceptance. Untargeted LC–MS flavoromic profiling was utilized to identify endogenous compounds that influence the generation of the bitter compound 9,12,13-trihydroxy-trans-10-octadecenoic acid (pinellic acid) during bread making. A diverse sample set of wheat germplasm was chemically profiled. The corresponding pinellic acid concentrations after dough formation were modeled by orthogonal partial least squares (OPLS) with good fit (R2Y = 0.8) and predictive ability (Q2 = 0.6). The most predictive feature (negatively correlated), postulated to interfere with the biosynthetic pathway, was identified as schaftoside, an apigenin di-C-glycoside. Recombination experiments involving the addition of schaftoside to flour prior to breadmaking resulted in a 26% decrease in pinellic acid formation and significantly lower perceived bitterness intensity in whole wheat bread. This work provides novel understanding of bitter generation pathways in wheat products and new strategies to improve flavor profiles and consumer acceptability.
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- 2020
16. Psychometric Qualities of the McMaster Family Assessment Device–General Functioning Subscale for Malaysian Samples
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Chin Wen Cong, Chee Seng Tan, Soon Aun Tan, and Sarvarubini Nainee
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Adult ,Male ,Adolescent ,Psychometrics ,Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,Reproducibility of Results ,Middle Aged ,family assessment device ,family functioning ,general functioning ,Malaysia ,psychometrics ,Data Accuracy ,Young Adult ,Asian People ,Surveys and Questionnaires ,Humans ,Female ,Factor Analysis, Statistical - Abstract
Family functioning has been associated with psychological well-being and physical health. The 12-item McMaster Family Assessment Device–General Functioning Subscale (FAD-GF) has been widely used to assess individuals’ overall level of family functioning. However, it has shown an inconsistent factor structure across various studies. The present study investigated its psychometric qualities in two studies with two different adult samples in Malaysia. In Study 1 (N = 417, 55.3% females, 19 to 26 years old), exploratory factor analyses were conducted, and four models were found: a three-factor model with 11 items, a two-factor model with 12 items, and one-factor models with six negatively worded items and six positively worded items, respectively. Study 2 (N = 358, 65.1% females, 18 to 60 years old) compared models found in past studies and those found in Study 1 through confirmatory factor analyses on another sample of adults. Among the six competing models, the two-factor model with three positively worded and three negatively worded items (i.e., FAD-GF-SF) is preferable because it did not require modification and showed a clear-cut result of goodness of fit. The subscales demonstrated satisfactory internal consistency. In conclusion, the FAD-GF-SF is a useful instrument for measuring family functioning in the Malaysian context.
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- 2022
17. Role of serum amitriptyline concentration and CYP2C19 polymorphism in predicting the response to low-dose amitriptyline in irritable bowel syndrome
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Yao-xing Huang, Xiao-Jia Ni, Yuguan Wen, Hanbing Zhao, Dewei Shang, Guo-yuan Dou, Qi Deng, Wen-cong Zhou, Meng Yang, Lin Jia, and Yao Liu
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Male ,medicine.medical_specialty ,Amitriptyline ,CYP2C19 ,Gastroenterology ,Polymorphism, Single Nucleotide ,Severity of Illness Index ,Irritable Bowel Syndrome ,Polymorphism (computer science) ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Genotyping ,Irritable bowel syndrome ,Hepatology ,Dose-Response Relationship, Drug ,business.industry ,Low dose ,Serum concentration ,Middle Aged ,medicine.disease ,Antidepressive Agents ,Cytochrome P-450 CYP2C19 ,Female ,Nortriptyline ,business ,medicine.drug - Abstract
Background Low-dose amitriptyline (AMT) is an effective treatment for diarrhea-dominant irritable bowel syndrome (IBS-D). Its efficacy depends upon its serum concentration and the patient's CYP2C19 genotype. Aims To identify the association between serum AMT and nortriptyline (NT) concentration and CYP2C19 polymorphism and the clinical response in IBS-D patients. Methods Ninety IBS-D patients were treated of AMT for 6 weeks. Efficacy was evaluated by the results of the Adequate Relief question each week and an IBS severity scoring system (IBS-SSS) at 0, 3, and 6 weeks. CYP2C19 genotyping was performed by direct sequencing. AMT and NT steady-state serum concentrations were detected by high-performance liquid chromatography. Results The CYP2C19 polymorphism exhibited a significant influence on the NT serum concentration but did not predict the clinical efficacy of AMT for treating IBS-D. The NT steady-state and dose-corrected serum concentrations were significantly correlated with an improvement in the IBS-SSS score after 6 weeks, whereas the AMT serum concentration was not correlated with clinical improvement. The cut-off NT steady-state serum concentration of 2.91 ng/ml may help distinguish responders from non-responders. Conclusions NT serum concentration but not CYP2C19 polymorphism may be correlated with the clinical efficacy of AMT for treating IBS-D, and such a response may occur at the upper NT threshold of 2.91 ng/ml.
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- 2020
18. Diurnal Blood Pressure and Heart Rate Variability in Hypertensive Patients with Cerebral Small Vessel Disease: A Case-Control Study
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Jian-Feng Qu, Zhuo-Xin Ni, Wei-Min Xiao, Wen-Cong Liang, Yang-Kun Chen, Yong-Lin Liu, and Wei Li
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Male ,medicine.medical_specialty ,Ambulatory blood pressure ,Time Factors ,Coefficient of variation ,Diastole ,Blood Pressure ,Autonomic Nervous System ,Cardiovascular System ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Heart Rate ,Risk Factors ,Internal medicine ,medicine ,Heart rate variability ,Humans ,cardiovascular diseases ,Prospective Studies ,Stroke ,Aged ,biology ,business.industry ,Dipper ,Rehabilitation ,Case-control study ,Blood Pressure Monitoring, Ambulatory ,Middle Aged ,medicine.disease ,biology.organism_classification ,Circadian Rhythm ,Blood pressure ,Case-Control Studies ,Cerebral Small Vessel Diseases ,Hypertension ,Cardiology ,Electrocardiography, Ambulatory ,Surgery ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,circulatory and respiratory physiology - Abstract
Whether autonomic dysfunction contributes to cerebral small vessel disease (CSVD) remains unclear. This study aimed to explore the relationship between CSVD and blood pressure variability (BPV) and heart rate variability (HRV).This case-control study recruited 50 patients with CSVD and 50 non-CSVD hypertensive age- and gender-matched controls. All participants completed a 24-h ambulatory electrocardiogram recording and ambulatory BP monitoring (ABPM). Differences in HRV and BPV between the two groups were examined. BPV indices assessed by ABPM included mean systolic BP (SBP), mean diastolic BP (DBP), coefficient of variation and weighted standard deviation of SBP and DBP.CSVD patients had significant higher 24-h mean systolic BP (SBP), 24-h mean diastolic BP (DBP), daytime mean SBP, nocturnal mean SBP, and nocturnal mean DBP (P.05 for all). CSVD patients had a significant lower nocturnal SBP fall rate compared with controls (median: 1.0 versus 6.2, respectively; P.001) and were more likely to be non-dippers and reverse dippers. There were no differences in HRV variables between the two groups. Five logistic models were built to explore the correlations between BPV indices and CSVD. BPV indices were separately entered into the logistic regression models, together with hyperlipidemia, ischemic stroke history, current use of anti-hypertensive agents, and serum blood urea nitrogen. In models 1-3, 24-h mean SBP and nocturnal mean SBP and DBP were significantly correlated with CSVD (rLower nocturnal SBP fall rate is associated with CSVD. Non-dipper and reverse dipper hypertensive patients have a higher risk of CSVD.
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- 2020
19. Comparative genomic analysis reveals metabolic diversity of different Paenibacillus groups
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Yilun Hu, Gengxin Zhang, Meng Li, and Wen-Cong Huang
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DNA, Bacterial ,Carbohydrate transport ,Biology ,Applied Microbiology and Biotechnology ,Genome ,03 medical and health sciences ,Paenibacillus ,Phylogenetics ,RNA, Ribosomal, 16S ,Gene family ,Humans ,Phylogeny ,030304 developmental biology ,Genetics ,0303 health sciences ,Phylogenetic tree ,030306 microbiology ,Bacterial taxonomy ,food and beverages ,Pan-genome ,General Medicine ,Genomics ,Sequence Analysis, DNA ,biology.organism_classification ,Biotechnology - Abstract
The genus Paenibacillus was originally recognized based on the 16S rRNA gene phylogeny. Recently, a standardized bacterial taxonomy approach based on a genome phylogeny has substantially revised the classification of Paenibacillus, dividing it into 23 genera. However, the metabolic differences among these groups remain undescribed. Here, genomes of 41 Paenibacillus strains comprising 25 species were sequenced, and a comparative genomic analysis was performed considering these and 187 publicly available Paenibacillus genomes to understand their phylogeny and metabolic differences. Phylogenetic analysis indicated that Paenibacillus clustered into 10 subgroups. Core genome and pan-genome analyses revealed similar functional categories among the different Paenibacillus subgroups; however, each group tended to harbor specific gene families. A large proportion of genes in the subgroups A, E, and G are related to carbohydrate metabolism. Among them, genes related to the glycoside hydrolase family were most abundant. Metabolic reconstruction of the newly sequenced genomes showed that the Embden-Meyerhof-Parnas pathway, pentose phosphate pathway, and citric acid cycle are central pathways of carbohydrate metabolism in Paenibacillus. Further, the genomes of the subgroups A and G lack genes involved in glyoxylate cycle and D-galacturonate degradation, respectively. The current study revealed the metabolic diversity of Paenibacillus subgroups assigned based on a genomic phylogeny and could inform the taxonomy of Paenibacillus. KEY POINTS: • Paenibacillus clustered into 10 subgroups. • Genomic content variation and metabolic diversity in the subgroup A, E, and G were described. • Carbohydrate transport and metabolism is important for Paenibacillus survival.
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- 2020
20. A potent CBP/p300-Snail interaction inhibitor suppresses tumor growth and metastasis in wild-type p53-expressing cancer
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Wen-Cong Lv, Bo-Xue Ren, Hongmei Li, Yan-Ran Bi, Ying Xu, Tao Lu, Yang Li, Yadong Chen, Nan Jiang, Rong Fu, Zhao-Qiu Wu, Shui Wang, and Hui Xie
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Epithelial-Mesenchymal Transition ,Snail ,Biology ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,biology.animal ,parasitic diseases ,medicine ,Humans ,Health and Medicine ,Neoplasm Metastasis ,Psychological repression ,Research Articles ,Cancer ,030304 developmental biology ,Zinc finger transcription factor ,0303 health sciences ,Multidisciplinary ,fungi ,Wild type ,SciAdv r-articles ,medicine.disease ,CREB-Binding Protein ,In vitro ,Acetylation ,030220 oncology & carcinogenesis ,Cancer research ,Snail Family Transcription Factors ,Tumor Suppressor Protein p53 ,Research Article - Abstract
Compound CYD19 has been identified as a CBP/p300-Snail interaction inhibitor that exhibits potent anticancer efficacy., The zinc finger transcription factor Snail is aberrantly activated in many human cancers and associated with poor prognosis. Therefore, targeting Snail is expected to exert therapeutic benefit in patients with cancer. However, Snail has traditionally been considered “undruggable,” and no effective pharmacological inhibitors have been identified. Here, we found a small-molecule compound CYD19 that forms a high-affinity interaction with the evolutionarily conserved arginine-174 pocket of Snail protein. In aggressive cancer cells, CYD19 binds to Snail and thus disrupts Snail’s interaction with CREB-binding protein (CBP)/p300, which consequently impairs CBP/p300-mediated Snail acetylation and then promotes its degradation through the ubiquitin-proteasome pathway. Moreover, CYD19 restores Snail-dependent repression of wild-type p53, thus reducing tumor growth and survival in vitro and in vivo. In addition, CYD19 reverses Snail-mediated epithelial-mesenchymal transition (EMT) and impairs EMT-associated tumor invasion and metastasis. Our findings demonstrate that pharmacologically targeting Snail by CYD19 may exert potent therapeutic effects in patients with cancer.
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- 2020
21. Geographical Detection of Traffic Accidents Spatial Stratified Heterogeneity and Influence Factors
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Yuhuan Zhang, Wen-cong Qu, and Huapu Lu
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Automobile Driving ,China ,spatial analysis ,nonlinear interaction ,Health, Toxicology and Mutagenesis ,Poison control ,lcsh:Medicine ,Suicide prevention ,Article ,Occupational safety and health ,spatial statistics ,stratified heterogeneity ,03 medical and health sciences ,0302 clinical medicine ,Environmental health ,0502 economics and business ,Injury prevention ,Humans ,030212 general & internal medicine ,Driving under the influence ,050210 logistics & transportation ,Geography ,Traffic accident ,05 social sciences ,celebrities ,Responsible party ,lcsh:R ,factors ,Accidents, Traffic ,Public Health, Environmental and Occupational Health ,Human factors and ergonomics ,celebrities.reason_for_arrest ,traffic accident ,geographical detectors - Abstract
The purpose of this paper is to investigate the existence of stratification heterogeneity in traffic accidents in Shenzhen, what factors influence the casualties, and the interaction of those factors. Geographical detection methods are used for the analysis of traffic accidents in Shenzhen. Results show that spatial stratification heterogeneity does exist, and the influencing factors of fatalities and injuries are different. The traffic accident causes and types of primary responsible party have a strong impact on fatalities and injuries, followed by zones and time interval. However, road factors, lighting, topography, etc., only have a certain impact on fatalities. Drunk driving, speeding over 50%, and overloading are more likely to cause more casualties than other illegal behaviors. Speeding over 50% and speeding below 50% have significant different influences on fatalities, while the influences on injuries are not obvious, and so do drunk driving (Blood Alcohol Concentration &ge, 0.08) and driving under the influence of alcohol (0.08 >, Blood Alcohol Concentration &ge, 0.02). Both pedestrians and cyclists violating the traffic law are vulnerable to fatality. Heavy truck overloading is more likely to cause major traffic accidents than minibuses. More importantly, there are nonlinear enhanced interactions between the influencing factors, the combination of previous non-significant factors and other factors can have a significant impact on the traffic accident casualties. The findings could be helpful for making differentiated prevention and control measures for traffic accidents in Shenzhen and the method selection of subsequent research.
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- 2020
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22. Vibsanin A sensitizes human acute myeloid leukemia cells to tyrosine kinase inhibitor-induced myeloid differentiation via activation of PKC and upregulation of Lyn
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Zuyin Yu, Qin-Shi Zhao, Hong-Ling Ou, Lu Zhang, Fang-Min Wang, Xing Shen, Yu-Wen Cong, He Xiao, Xin-Ru Wang, Guo-Lin Xiong, Shuang Xing, and Ya-Jun Shan
- Subjects
0301 basic medicine ,Acute promyelocytic leukemia ,Myeloid ,medicine.drug_class ,Cellular differentiation ,Biophysics ,Enzyme Activators ,Biochemistry ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,0302 clinical medicine ,LYN ,Differentiation therapy ,Cell Line, Tumor ,hemic and lymphatic diseases ,medicine ,Humans ,Myeloid Cells ,Protein Kinase Inhibitors ,Molecular Biology ,Protein Kinase C ,Protein kinase C ,Cell Proliferation ,Chemistry ,Myeloid leukemia ,Cell Differentiation ,Cell Cycle Checkpoints ,Cell Biology ,Protein-Tyrosine Kinases ,medicine.disease ,respiratory tract diseases ,Leukemia, Myeloid, Acute ,src-Family Kinases ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Diterpenes - Abstract
Differentiation therapies have been proposed to overcome the impaired cell differentiation in acute myeloid leukemia (AML). However, thus far the all-trans retinoic acid-based differentiation therapy has been the only successful modality in treating acute promyelocytic leukemia. Here, we showed that vibsanin A, a novel protein kinase C (PKC) activator, sensitized AML cells to tyrosine kinase inhibitor (TKI)-induced differentiation. Vibsanin A augmented the ability of TKIs to induce growth inhibition and G1 cell cycle arrest of AML cells. Mechanistically, PKC activation was involved in the differentiation-inducing effects of combining vibsanin A with TKIs. Moreover, we found that vibsanin A enhanced TKI-induced Lyn expression and suppression of Lyn interfered with AML cell differentiation, indicating an essential role for Lyn expression in the combination-induced differentiation. Finally, combining vibsanin A and TKIs enhanced the activation of the Raf/MEK/ERK cascade. Together, this is the first study to evaluate the synergy of vibsanin A and TKIs in AML cell differentiation. Our study lays the foundation in assessing new opportunities for the combination of vibsanin A and TKIs as a promising approach for future differentiation therapy.
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- 2018
23. Vascular endothelial injury in severe fever with thrombocytopenia syndrome caused by the novel bunyavirus
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Wen-Cong Zhang, Xiao-Kun Li, Wu-Chun Cao, Wen Xu, Li Zhang, Pan-He Zhang, Hao Li, Wei-Wei Chen, Bo Xing, Shao-Fei Zhang, Qing-Bin Lu, and Wei Liu
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Phlebovirus ,0301 basic medicine ,Fever ,Endothelium ,Inflammation ,Biology ,Bunyaviridae Infections ,Virus ,Capillary Permeability ,Cohort Studies ,Pathogenesis ,03 medical and health sciences ,Virology ,medicine ,Humans ,Endothelial dysfunction ,Retrospective Studies ,medicine.disease ,Thrombocytopenia ,Endothelial stem cell ,Severe fever with thrombocytopenia syndrome ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Cytokines ,Endothelium, Vascular ,medicine.symptom ,Severe fever with thrombocytopenia syndrome virus - Abstract
Severe fever with thrombocytopenia syndrome virus (SFTSV) infection typically causes acute fever, thrombocytopenia and leucopenia, presenting with a high case fatality rate. The pathogenesis of SFTSV infection, however, is not well described. It was hypothesized that endothelial dysfunction might play part in the disease process. In current study, we retrospectively analyzed the clinical manifestations among a large group of confirmed SFTS cases and found evidence of plasma leakage and vascular endothelial injury. Then we established a SFTSV infection cell model and determined the infectivity and stimulation of SFTSV on vascular endothelial cells in vitro. The hyperpermeability of endothelial cells directly induced by SFTSV was confirmed by electrical resistance and dextran diffusion assay. The virus induced alterations of cell junctions and cytoskeleton was also revealed. It's suggested that vascular endothelial cell injury and barrier function damage were induced after SFTSV infection, which is a vital but neglected pathogenesis of SFTS.
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- 2018
24. High neutrophil-to-lymphocyte ratio predicts worse overall survival in patients with advanced/metastatic urothelial bladder cancer
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Ernest Wen Cong Eu, Weber Kam On Lau, Yu Guang Tan, and Hong Hong Huang
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Male ,Oncology ,medicine.medical_specialty ,Multivariate analysis ,Neutrophils ,Urology ,030232 urology & nephrology ,Kaplan-Meier Estimate ,Leukocyte Count ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Internal medicine ,medicine ,Carcinoma ,Humans ,Lymphocytes ,Neutrophil to lymphocyte ratio ,Aged ,Retrospective Studies ,Carcinoma, Transitional Cell ,Bladder cancer ,business.industry ,Proportional hazards model ,Hazard ratio ,Retrospective cohort study ,Middle Aged ,Prognosis ,medicine.disease ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Predictive value of tests ,Female ,business - Abstract
Objectives To study the role of the neutrophil-to-lymphocyte ratio in predicting survival outcomes for patients with advanced bladder cancer. Methods We retrospectively reviewed 150 patients diagnosed with advanced or metastatic bladder cancer between January 2004 and June 2014. The neutrophil-to-lymphocyte ratio was computed on diagnosis and after the first cycle of chemotherapy. A neutrophil-to-lymphocyte ratio cut-off of 3.0 was determined, with a concordance index of 0.89. Kaplan–Meier curves, log–rank tests, Cox proportional hazards and logistic regression models were used to predict the association of the neutrophil-to-lymphocyte ratio with survival outcomes. Results Just five patients were alive at the end of the study; the rest died from metastatic bladder cancer. On multivariate analysis, higher Eastern Cooperative Oncology Group status, lymphadenopathy, visceral metastases and neutrophil-to-lymphocyte ratio ≥3.0 were associated with poorer overall survival (hazard ratio 1.67, P = 0.03; hazard ratio 1.97, P =
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- 2017
25. The effects of paroxetine and amitriptyline on the upper esophageal sphincter (UES) pressure and its natural history in globus pharyngeus
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Shu-Man Jiang, Lin Jia, Dong-yun Chen, Jian Xu, Yao Liu, Jing Liu, Wen-cong Zhou, and Meng Yang
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Adult ,Male ,Manometry ,Amitriptyline ,Lansoprazole ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,Humans ,Medicine ,Prospective Studies ,Hepatology ,business.industry ,Gastroenterology ,Proton Pump Inhibitors ,Pharyngeal Diseases ,Middle Aged ,Esophageal Sphincter, Upper ,Paroxetine ,Antidepressive Agents ,Treatment period ,Clinical trial ,Natural history ,Upper esophageal sphincter ,030220 oncology & carcinogenesis ,Anesthesia ,Antidepressant ,Female ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Background Antidepressant agents have been shown to be an effective and safe treatment method for patients with globus. However, there are few clinical trials dedicated to studying the effects of antidepressant agents on the natural history and upper oesophageal sphincter (UES) pressure of treated globus patients. Aims To evaluate the effect of paroxetine and amitriptyline to prevent relapses in patients with globus, the simultaneous relationship between changes in UES pressure and improvement of globus symptoms were measured. Methods Globus patients were randomised into amitriptyline, paroxetine and lansoprazole groups for a 6-week treatment period, and follow-up was extended to 12 additional months. Efficacy was evaluated in terms of the Glasgow-Edinburgh Throat Scale (GETS), and UES pressure was measured by standard oesophageal manometry. Results Paroxetine therapy resulted in a higher withdrawal rate due to symptom relapse (15.9% vs 44.1%, P = 0.01; 15.9% vs 64.7, P = 0.001) than amitriptyline and lansoprazole. Furthermore, globus symptoms were alleviated with the decrease of UES pressure after paroxetine and amitriptyline treatment (r = 0.620, P = 0.02; r = 0.575, P = 0.03) Conclusions This follow-up study indicates that paroxetine may alter the natural history of globus and can effectively be used for the long-term management of patients with the disease. Apart from the clinical benefits, paroxetine and amitriptyline can potentially decrease UES pressure.
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- 2017
26. Emperipolesis mediated by CD8
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Su-Xian, Zhao, Wen-Cong, Li, Na, Fu, Guang-de, Zhou, Shu-Hong, Liu, Li-Na, Jiang, Yu-Guo, Zhang, Rong-Qi, Wang, Yue-Min, Nan, and Jing-Min, Zhao
- Subjects
Male ,Liver Cirrhosis, Biliary ,primary biliary cholangitis ,apoptosis ,Epithelial Cells ,Original Articles ,CD8-Positive T-Lymphocytes ,Middle Aged ,digestive system diseases ,biliary epithelial cells ,Case-Control Studies ,Humans ,Female ,Original Article ,Bile Ducts ,Emperipolesis ,CD8+ T cell ,Cell Proliferation - Abstract
Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell‐in‐cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty‐six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early‐stage PBC (stages I and II, n = 39) and late‐stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin‐eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3+ and CD8+ T cells correlated with the advancement of emperipolesis (R 2 = 0.318, P
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- 2019
27. Ginsenoside Rb3 provides protective effects against cisplatin‐induced nephrotoxicity via regulation of AMPK‐/mTOR‐mediated autophagy and inhibition of apoptosis in vitro and in vivo
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Jing-jing Xing, Ying-Ping Wang, Wen-cong Liu, Chen Chen, Jin-Gang Hou, Zhi-na Ma, Wei Li, Shen Ren, and Zi Wang
- Subjects
Male ,0301 basic medicine ,autophagy ,Ginsenosides ,ATG5 ,cisplatin ,Apoptosis ,AMP-Activated Protein Kinases ,Pharmacology ,Kidney ,Protective Agents ,medicine.disease_cause ,Blood Urea Nitrogen ,Cell Line ,Nephrotoxicity ,Acetylcysteine ,Mice ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,HEK293 cells ,Malondialdehyde ,medicine ,Animals ,Humans ,Ginsenoside Rb3 ,PI3K/AKT/mTOR pathway ,Inflammation ,Mice, Inbred ICR ,Superoxide Dismutase ,Chemistry ,nephrotoxicity ,TOR Serine-Threonine Kinases ,Autophagy ,AMPK ,Original Articles ,Cell Biology ,General Medicine ,AMPK/mTOR ,Glutathione ,Oxidative Stress ,030104 developmental biology ,Creatinine ,030220 oncology & carcinogenesis ,Original Article ,Oxidative stress ,Signal Transduction ,medicine.drug - Abstract
Objectives: Based on previous reports that ginsenosides have been shown to exert better preventive effects on cisplatin‐induced kidney injury, the present work aims to evaluate the protective effects of ginsenoside Rb3 (G‐Rb3) on cisplatin‐induced renal damage and underlying mechanisms in vivo and in vitro. Materials and methods: The protective effect of G‐Rb3 on cisplatin‐induced acute renal failure in ICR mouse model and HEK293 cell model was investigated, and the underlying possible mechanisms were also explored. For animal experiment, renal function, kidney histology, inflammation, oxidative stress, relative protein molecules involved in apoptosis and autophagy signalling pathways were assessed. In addition, rapamycin (a specific inhibitor of mTOR), compound C (a specific inhibitor of AMPK) and acetylcysteine (NAC, a specific ROS scavenger) were employed to testify the effects of AMPK/mTOR signal pathway on the protective effects of G‐Rb3 in HEK293 cells. Results: Pre‐treatment with G‐Rb3 at doses of 10 and 20 mg/kg for ten days significantly reversed the increases in serum creatinine (CRE), blood urea nitrogen (BUN) and malondialdehyde (MDA), and decrease in glutathione (GSH) content and superoxide dismutase (SOD) activity. Histopathological examination further revealed that G‐Rb3 inhibited cisplatin‐induced nephrotoxicity. G‐Rb3 diminished cisplatin‐induced increase in protein expression levels of p62, Atg3, Atg5 and Atg7, and decrease in protein expression level of p‐mTOR and the ratio of LC3‐I/LC3‐II, indicating that G‐Rb3 suppressed cisplatin‐induced activation of autophagy. Inhibition of autophagy induced inactivation of apoptosis, which suggested that autophagy played an adverse effect on cisplatin‐evoked renal damage. Further, we found that G‐Rb3 might potentially modulate the expressions of AMPK‐related signal pathways. Conclusions: These findings clearly suggested that G‐Rb3‐mediated alleviation of cisplatin‐induced nephrotoxicity was in part due to regulation of AMPK‐/mTOR‐mediated autophagy and inhibition of apoptosis in vitro and in vivo.
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- 2019
28. Validation of the energy balance approach for design of vertical lifeline systems
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Yang Miang Goh, Soo Jin Adrian Koh, Shazed Mohammad Tashrif, and Wen Cong Lim
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05 social sciences ,Public Health, Environmental and Occupational Health ,Energy balance ,030210 environmental & occupational health ,Drop test ,Calculation methods ,03 medical and health sciences ,0302 clinical medicine ,Fall from height ,Linear Models ,Environmental science ,Humans ,0501 psychology and cognitive sciences ,Accidental Falls ,Safety, Risk, Reliability and Quality ,Safety Research ,Personal protective equipment ,050107 human factors ,Energy (signal processing) ,Marine engineering - Abstract
To ensure that vertical lifeline systems (VLLSs) are well designed, calculation methods are required to estimate the extension of a personal energy absorber (PEA) (xPEA) and the total fall distance...
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- 2019
29. Arginyl-fructosyl-glucose, a Major Maillard Reaction Product of Red Ginseng, Attenuates Cisplatin-Induced Acute Kidney Injury by Regulating Nuclear Factor κB and Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathways
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Wei-Zhe Zhang, Rong-Yan Li, Xiao-Tong Yan, Wen-cong Liu, Wei Li, Chen Chen, Zi Wang, Ding Chuanbo, Yue-Ru Li, Jin-Gang Hou, and Yinan Zheng
- Subjects
inorganic chemicals ,0106 biological sciences ,Male ,Glycine ,Panax ,Inflammation ,Apoptosis ,Pharmacology ,medicine.disease_cause ,Arginine ,Kidney ,01 natural sciences ,Ginseng ,chemistry.chemical_compound ,medicine ,Animals ,Humans ,Phosphatidylinositol ,Protein kinase B ,Mice, Inbred ICR ,Chemistry ,Kinase ,010401 analytical chemistry ,NF-kappa B ,NF-κB ,General Chemistry ,Acute Kidney Injury ,female genital diseases and pregnancy complications ,0104 chemical sciences ,Maillard Reaction ,Oxidative Stress ,Glucose ,Creatinine ,medicine.symptom ,Signal transduction ,Cisplatin ,Phosphatidylinositol 3-Kinase ,General Agricultural and Biological Sciences ,Proto-Oncogene Proteins c-akt ,Oxidative stress ,010606 plant biology & botany ,Drugs, Chinese Herbal ,Signal Transduction - Abstract
Recently, although ginseng ( Panax ginseng C. A. Meyer) and its main component saponins (ginsenosides) have been reported to exert protective effects on cisplatin (CDDP)-induced acute kidney injury (AKI), the beneficial activities of non-saponin on CDDP-induced AKI is little known. This research was designed to explore the protective effect and underlying mechanism of arginyl-fructosyl-glucose (AFG), a major and representative non-saponin component generated during the process of red ginseng, on CDDP-caused AKI. AFG at doses of 40 and 80 mg/kg remarkably reversed CDDP-induced renal dysfunction, accompanied by the decreased levels of serum creatinine and blood urea nitrogen. Interestingly, all of oxidative stress indices were ameliorated after pretreatment with AFG continuously for 10 days. Importantly, AFG relieved CDDP-induced inflammation and apoptosis in part by mitigating the cascade initiation steps of nuclear factor κB signals and regulating the participation of the phosphatidylinositol 3-kinase/protein kinase B signal pathway. In conclusion, these results clearly provide strong rationale for the development of AFG to prevent CDDP-induced AKI.
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- 2019
30. Inferring novel genes related to colorectal cancer via random walk with restart algorithm
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Zhenggang Zhu, Wen-Cong Lu, and Sheng Lu
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0301 basic medicine ,Colorectal cancer ,Biology ,Novel gene ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Humans ,Protein Interaction Maps ,Molecular Biology ,Gene ,Genetic Association Studies ,Cancer ,Computational Biology ,Random walk ,medicine.disease ,digestive system diseases ,030104 developmental biology ,030220 oncology & carcinogenesis ,Molecular Medicine ,Identification (biology) ,Colorectal Neoplasms ,Dijkstra's algorithm ,Algorithm ,Protein Interaction Map ,Algorithms ,Software ,Genes, Neoplasm - Abstract
Colorectal cancer (CRC) is the third most common type of cancer. In recent decades, genomic analysis has played an increasingly important role in understanding the molecular mechanisms of CRC. However, its pathogenesis has not been fully uncovered. Identification of genes related to CRC as complete as possible is an important way to investigate its pathogenesis. Therefore, we proposed a new computational method for the identification of novel CRC-associated genes. The proposed method is based on existing proven CRC-associated genes, human protein-protein interaction networks, and random walk with restart algorithm. The utility of the method is indicated by comparing it to the methods based on Guilt-by-association or shortest path algorithm. Using the proposed method, we successfully identified 298 novel CRC-associated genes. Previous studies have validated the involvement of the majority of these 298 novel genes in CRC-associated biological processes, thus suggesting the efficacy and accuracy of our method.
- Published
- 2018
31. Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation
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Wen-Bing Zhou, Qin-Shi Zhao, Yan-Feng Zhang, Bo Dong, Yu Cui, Ya-Jun Shan, Zu-Yin Yu, Xiao-Lan Liu, He Xiao, Guo-Lin Xiong, Jian-Nan Feng, Qing-Liang Luo, Yu-Wen Cong, Yu Jing, Xing Shen, Shuang Xing, Li-Sheng Wang, Limei Wang, Wen-Feng Sun, and Lin Wang
- Subjects
Male ,0301 basic medicine ,Acute promyelocytic leukemia ,Cancer Research ,Myeloid ,Bryostatin 1 ,Cellular differentiation ,Blotting, Western ,Pharmacology ,Real-Time Polymerase Chain Reaction ,Antileukemic agent ,Mice ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,Protein Kinase C ,Protein kinase C ,business.industry ,Myeloid leukemia ,Cell Differentiation ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Xenograft Model Antitumor Assays ,Enzyme Activation ,Mice, Inbred C57BL ,Leukemia ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Leukemia, Myeloid ,030220 oncology & carcinogenesis ,Diterpenes ,business ,Phytotherapy - Abstract
All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A–induced differentiation. Mechanistically, vibsanin A–mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698–709. ©2016 AACR.
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- 2016
32. Early changes in pulmonary function and intrarenal haemodynamics and the correlation between these sets of parameters in patients with T2DM
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Zhang Lide, Lian-qun Jia, Xiao-Lin Jiang, Zhang Yi, Xin Fu, Xin-yue Cui, Wen-cong Cao, Ye-tao Ju, Jin-song Kuang, Wei Chen, J J JiaJia Yu, and He Tai
- Subjects
Blood Glucose ,Male ,Pulmonology ,Physiology ,Pulmonary Function ,Hemodynamics ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Kidney ,Biochemistry ,Pulmonary function testing ,Endocrinology ,Mathematical and Statistical Techniques ,Renal Artery ,0302 clinical medicine ,Medicine and Health Sciences ,Diabetes diagnosis and management ,Lung ,Multidisciplinary ,Statistics ,Middle Aged ,Prognosis ,Type 2 Diabetes ,medicine.anatomical_structure ,Physical Sciences ,Cardiology ,Medicine ,Female ,Anatomy ,Research Article ,Glomerular Filtration Rate ,medicine.medical_specialty ,HbA1c ,Endocrine Disorders ,Science ,Renal function ,030209 endocrinology & metabolism ,Research and Analysis Methods ,Diabetes Complications ,03 medical and health sciences ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Hemoglobin ,Statistical Methods ,Glycated Hemoglobin ,Renal Physiology ,Biology and life sciences ,business.industry ,Proteins ,Type 2 Diabetes Mellitus ,Kidneys ,Renal System ,medicine.disease ,Diagnostic medicine ,Diabetes Mellitus, Type 2 ,Metabolic Disorders ,Case-Control Studies ,Vascular resistance ,Vascular Resistance ,business ,Mathematics ,Biomarkers ,Forecasting ,Follow-Up Studies ,Kidney disease - Abstract
PurposeThe main objectives of this study were to assess the early changes in pulmonary function and intrarenal haemodynamics and to determine the correlation between pulmonary function and intrarenal haemodynamics in patients with type 2 diabetes mellitus (T2DM).Methods96 patients with T2DM (diabetes group) without diabetes kidney disease (DKD) and 33 healthy subjects (control group) were enrolled in studies intended to assess the early changes in pulmonary function and intrarenal haemodynamics associated with diabetes, as well as to determine the correlation between pulmonary function and intrarenal haemodynamics.ResultsPulmonary functional parameters were negatively correlated with HbA1c levels and diabetes duration (P< 0.05). Moreover, renal functional parameters were positively correlated with HbA1c levels and diabetes duration (PConclusionsPatients displayed changes in pulmonary function and intrarenal haemodynamics during the preclinical stages of DKD. Regulating glycaemia may improve intrarenal haemodynamics in the bilateral interlobular renal arteries. Moreover, during the preclinical stages of DKD, the right kidney RI is a effective predictor of early changes in pulmonary function in adult T2DM patients.Trial registrationClinicalTrials.gov (NCT02798198); registered 8 June 2016.
- Published
- 2019
33. A ZEB1/p53 signaling axis in stromal fibroblasts promotes mammary epithelial tumours
- Author
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Nan Jiang, Bao-An Chen, Lei Di, Tao Lu, Hong-Mei Li, Qinglong Guo, Chen-Feng Han, Yin He, Li-Juan Liu, Rong Fu, Ting Ni, Yan-Ran Bi, Wen-Cong Lv, Hui Xie, Xiaosheng Wang, Shui Wang, Zhao-Qiu Wu, and Stephen J. Weiss
- Subjects
0301 basic medicine ,Male ,Vascular Endothelial Growth Factor A ,Angiogenesis ,General Physics and Astronomy ,02 engineering and technology ,Metastasis ,Extracellular matrix ,Mice ,Breast cancer ,Tumor Microenvironment ,Breast ,Neoplasms, Glandular and Epithelial ,lcsh:Science ,Mice, Knockout ,Multidisciplinary ,021001 nanoscience & nanotechnology ,Extracellular Matrix ,Gene Expression Regulation, Neoplastic ,Cell Transformation, Neoplastic ,Female ,Fibroblast Growth Factor 2 ,Signal transduction ,0210 nano-technology ,Signal Transduction ,Cancer microenvironment ,Stromal cell ,Fibroblast Growth Factor 7 ,Science ,Breast Neoplasms ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Stroma ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Cell Proliferation ,Tumor microenvironment ,Interleukin-6 ,Cancer ,Mammary Neoplasms, Experimental ,Zinc Finger E-box-Binding Homeobox 1 ,General Chemistry ,Neoplasms, Experimental ,Fibroblasts ,medicine.disease ,030104 developmental biology ,Cancer research ,lcsh:Q ,Neoplasm Recurrence, Local ,Tumor Suppressor Protein p53 ,Gene Deletion - Abstract
Accumulating evidence indicates that the zinc-finger transcription factor ZEB1 is predominantly expressed in the stroma of several tumours. However, the role of stromal ZEB1 in tumour progression remains unexplored. In this study, while interrogating human databases, we uncover a remarkable decrease in relapse-free survival of breast cancer patients expressing high ZEB1 levels in the stroma. Using a mouse model of breast cancer, we show that ZEB1 inactivation in stromal fibroblasts suppresses tumour initiation, progression and metastasis. We associate this with reduced extracellular matrix remodeling, immune cell infiltration and decreased angiogenesis. ZEB1 deletion in stromal fibroblasts increases acetylation, expression and recruitment of p53 to FGF2/7, VEGF and IL6 promoters, thereby reducing their production and secretion into the surrounding stroma. Importantly, p53 ablation in ZEB1 stroma-deleted mammary tumours sufficiently recovers the impaired cancer growth and progression. Our findings identify the ZEB1/p53 axis as a stroma-specific signaling pathway that promotes mammary epithelial tumours., In epithelial cells Zeb1 is involved in the epithelial to mesenchymal transition. In this study, the authors show in a mouse model of breast cancer, that Zeb1 expression in stromal cells is required for tumour formation and metastasis.
- Published
- 2018
34. Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer
- Author
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Li Ding, Hai-Feng Li, Wen-Cong Ruan, and Yue-Ping Che
- Subjects
Oncology ,medicine.medical_specialty ,Bevacizumab ,Colorectal cancer ,medicine.medical_treatment ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Internal medicine ,Drug Discovery ,medicine ,Humans ,In patient ,Adverse effect ,030304 developmental biology ,Randomized Controlled Trials as Topic ,0303 health sciences ,Chemotherapy ,business.industry ,Organic Chemistry ,General Medicine ,medicine.disease ,Computer Science Applications ,030220 oncology & carcinogenesis ,Meta-analysis ,Toxicity ,business ,Colorectal Neoplasms ,Adjuvant ,medicine.drug - Abstract
Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.
- Published
- 2018
35. LW106, a novel indoleamine 2,3‐dioxygenase 1 inhibitor, suppresses tumour progression by limiting stroma‐immune crosstalk and cancer stem cell enrichment in tumour micro‐environment
- Author
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Zhao-Qiu Wu, Zhiyu Li, Tao Lu, Qinglong Guo, Li Zhao, Stephen J. Weiss, Rong Fu, Hongmei Li, Zhang Yiwei, and Wen-Cong Lv
- Subjects
0301 basic medicine ,Male ,Stromal cell ,Mice, Nude ,Antineoplastic Agents ,Kaplan-Meier Estimate ,Dioxygenases ,03 medical and health sciences ,chemistry.chemical_compound ,Immune system ,Stroma ,Cancer stem cell ,Cell Line, Tumor ,Neoplasms ,Tumor Microenvironment ,Animals ,Humans ,Indoleamine 2,3-dioxygenase ,Pharmacology ,Mice, Knockout ,Research Papers ,Mice, Inbred C57BL ,030104 developmental biology ,chemistry ,Cell culture ,Apoptosis ,Cancer research ,Neoplastic Stem Cells ,Kynurenine - Abstract
BACKGROUND AND PURPOSE: Indoleamine 2,3‐dioxygenase 1 (IDO1) is emerging as an important new therapeutic target for treatment of malignant tumours characterized by dysregulated tryptophan metabolism. However, the antitumour efficacy of existing small‐molecule inhibitors of IDO1 is still unsatisfactory and the underlying mechanism remains largely undefined. Hence, we discovered a novel potent small‐molecule inhibitor of IDO1, LW106, and studied its antitumour effects and the underlying mechanisms in two tumour models. EXPERIMENTAL APPROACH: C57BL6 mice, athymic nude mice or Ido1 (−/−) mice were inoculated with IDO1‐expressing and ‐nonexpressing tumour cells and treated with vehicle, epacadostat or increasing doses of LW106. Xenografted tumours, plasma, spleens and other vital organs were harvested and subjected to kynurenine/tryptophan measurement and flow cytometric, histological and immunohistochemical analyses. KEY RESULTS: LW106 dose‐dependently inhibited the outgrowth of xenografted tumours that were inoculated in C57BL6 mice but not nude mice or Ido1 (−/−) mice, showing a stronger antitumour efficacy than epacadostat, an existing IDO1 inhibitor. LW106 substantially elevated intratumoural infiltration of proliferative T(eff) cells, while reducing recruitment of proliferative T(reg) cells and non‐haematopoietic stromal cells such as endothelial cells and cancer‐associated fibroblasts. LW106 treatment resulted in a reduced subpopulation of cancer stem cells (CSCs) in xenografted tumours in which fewer proliferative/invasive tumour cells and more apoptotic tumour cells were observed. CONCLUSIONS AND IMPLICATIONS: LW106 inhibits tumour outgrowth by limiting stroma‐immune crosstalk and CSC enrichment in the tumour micro‐environment. LW106 has potential as a immunotherapeutic agent for use in combination with immune checkpoint inhibitors and (or) chemotherapeutic drugs for cancer treatment.
- Published
- 2018
36. Vibsanol A induces differentiation of acute myeloid leukemia cells via activation of the PKC signaling pathway and induction of ROS
- Author
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Guo-Lin Xiong, Shuang Xing, He Xiao, Fang-Min Wang, Xin-Ru Wang, Hong-Ling Ou, Yu-Wen Cong, Meng Yang, Yan-Hong Tu, Lu Zhang, Xing Shen, and Zuyin Yu
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Cancer Research ,MAP Kinase Signaling System ,Cellular differentiation ,Retinoic acid ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,hemic and lymphatic diseases ,Cell Line, Tumor ,Humans ,Protein Kinase Inhibitors ,Protein kinase C ,Chemistry ,Kinase ,Viburnum ,Myeloid leukemia ,Cell Differentiation ,Hematology ,Free Radical Scavengers ,G1 Phase Cell Cycle Checkpoints ,Cell biology ,Leukemia, Myeloid, Acute ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Signal transduction ,Diterpenes ,Drug Screening Assays, Antitumor ,Reactive Oxygen Species ,G1 phase ,Protein Kinases - Abstract
Identifying novel differentiating agents to promote leukemia-cell differentiation is a pressing need. Here, we demonstrated that vibsanol A, a vibsane-type diterpenoid, inhibited the growth of acute myeloid leukemia (AML) cells via induction of cell differentiation, which was characterized by G1 cell cycle arrest. The differentiation-inducing effects of vibsanol A were dependent upon protein kinase C (PKC) activation, and subsequent activation of the extracellular signal-regulated kinase (ERK) pathway. Furthermore, vibsanol A treatment increased reactive oxygen species (ROS) levels, and the ROS scavenger NAC reversed the vibsanol A-induced cell differentiation, indicating an important role for ROS in the action of vibsanol A. Finally, vibsanol A exhibited a differentiation-enhancing effect when used in combination with all-trans retinoic acid in AML cells. Overall results suggested that vibsanol A induces AML cell differentiation via activation of the PKC/ERK signaling and induction of ROS. Vibsanol A may prove to be an effective differentiating agent against AML.
- Published
- 2018
37. [Therapeutic Effect of Recombinant Human Stem Cell Factor on Rhesus Monkeys with Severe Acute Radiation Sickness]
- Author
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Fang-Min, Wang, Guo-Lin, Xiong, Xing, Shen, Ling, Xie, Ming, Li, Ling-Ling, Guo, Rui-Ying, Zhang, Lu, Zhang, Xin-Ru, Wang, Yu-Wen, Cong, Zu-Yin, Yu, and Shuang, Xing
- Subjects
Stem Cell Factor ,Animals ,Humans ,Radiation Injuries ,Macaca mulatta ,Recombinant Proteins ,Whole-Body Irradiation ,Hematopoiesis - Abstract
To study the therapeutic effect of rhSCF early administration on rhesus monkeys with severe acute radiation sickness(ARS).Twelve adult monkeys totally exposed to 7.0 Gy6 animals treated with rhSCF all survived, while 2 in irradiated controls survived on 40 day after radiation. rhSCF treatment promoted hematopoiesis recovery significantly, increased the nadir of white blood cells, neutrophils and platelets, and simplified supportive care in ARS rhesus monkeys.RhSCF injection soon after TBI taken shows an significant therapeutic efficiency on rhesus monkeys with severe acute radiation sickness.
- Published
- 2017
38. Role of TGF-β1 Signaling in Heart Valve Calcification Induced by Abnormal Mechanical Stimulation in a Tissue Engineering Model
- Author
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Si Chen, Jiawei Shi, Junwei Liu, Chen Deng, Nianguo Dong, Feng Shi, Xingjian Hu, and Wen-Cong-Hui Wu
- Subjects
Male ,Swine ,Pulsatile flow ,Heart Valve Diseases ,Bone Morphogenetic Protein 2 ,Stimulation ,Core Binding Factor Alpha 1 Subunit ,030204 cardiovascular system & hematology ,Biochemistry ,Bone morphogenetic protein 2 ,Polyethylene Glycols ,Smad1 Protein ,Andrology ,Transforming Growth Factor beta1 ,03 medical and health sciences ,0302 clinical medicine ,Bioreactors ,Tissue engineering ,Genetics ,medicine ,Animals ,Humans ,Von Kossa stain ,Aorta ,Aged ,Homeodomain Proteins ,Tissue Engineering ,Chemistry ,technology, industry, and agriculture ,Calcinosis ,Middle Aged ,medicine.disease ,030220 oncology & carcinogenesis ,Aortic Valve ,Alkaline phosphatase ,Female ,Immunostaining ,Calcification ,Signal Transduction - Abstract
A tissue engineering model of heart valve calcification induced in a bioreactor was established to evaluate the calcification induced by abnormal mechanical stimulation and explore the underlying molecular mechanisms. Polyethylene glycol (PEG)-modified decellularized porcine aortic leaflets seeded with human valve interstitial cells (huVICs) were mounted on a Ti-Ni alloy frame to fabricate two-leaflet and threeleaflet tissue engineered valves. The two-leaflet model valves were exposed to abnormal pulsatile flow stimulation with null (group A), low (1000 mL/min, group B), medium (2000 mL/min, group C), and high velocity (3000 mL/min, group D) for 14 days. Morphology and calcification were assessed by von Kossa staining, alkaline phosphatase (ALP) content, and Runx2 immunostaining. Leaflet calcification and mRNA and protein expression of transforming growth factor (TGF)-β1, bone morphogenetic protein 2 (BMP2), Smad1, and MSX2 were measured at different time points. ALP content was examined in two-leaflet valves seeded with BMP2 shRNA plasmid-infected huVICs and exposed to the same stimulation conditions. The results showed that during 14 days of flow stimulation, huVICs on the leaflet surface proliferated to generate normal monolayer coverage in groups A, B, and C. Under mechanical stimulation, huVICs showed a parallel growth pattern in the direction of the fluid flow, but huVICs exhibited disordered growth in the high-velocity flow environment. von Kossa staining, ALP measurement, and immunohistochemical staining for Runx2 confirmed the lack of obvious calcification in group A and significant calcification in group D. Expression levels of TGF-β1, BMP2, and MSX2 mRNA and protein were increased under fluid stimulation. ALP production by BMP2 shRNA plasmid-infected huVICs on model leaflets was significantly reduced. In conclusion, abnormal mechanical stimulation in a bioreactor induced calcification in the tissue engineering valve model. The extent of calcification correlated positively with the flow velocity, as did the mRNA and protein levels of TGF-β1, BMP2, and MSX2. These findings indicate that TGF-β1/BMP2 signaling is involved in valve calcification induced by abnormal mechanical stimulation.
- Published
- 2017
39. Caspase-Mediated Anti-Apoptotic Effect of Ginsenoside Rg5, a Main Rare Ginsenoside, on Acetaminophen-Induced Hepatotoxicity in Mice
- Author
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Wen-cong Liu, Meng-han Yan, Zi Wang, Jun-nan Hu, Wei Li, and Jing-jing Xing
- Subjects
0301 basic medicine ,Male ,Ginsenosides ,Panax ,Caspase 3 ,Apoptosis ,Pharmacology ,03 medical and health sciences ,Ginseng ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Malondialdehyde ,medicine ,Animals ,Humans ,Acetaminophen ,Caspase 8 ,Mice, Inbred ICR ,biology ,Chemistry ,General Chemistry ,CYP2E1 ,Caspase 9 ,Nitric oxide synthase ,Oxidative Stress ,030104 developmental biology ,Liver ,Ginsenoside ,030220 oncology & carcinogenesis ,biology.protein ,Tumor necrosis factor alpha ,Chemical and Drug Induced Liver Injury ,General Agricultural and Biological Sciences ,medicine.drug - Abstract
Frequent overdose of acetaminophen (APAP) is one of the most common and important incentives of acute hepatotoxicity. Prior to this work, our research group confirmed that black ginseng (Panax ginseng, BG) showed powerful protective effects on APAP-induced ALI. However, it is not clear which kind of individual ginsenoside from BG plays such a liver protection effect. The objective of the current investigation was to evaluate whether ginsenoside Rg5 (G-Rg5) protected against APAP-induced hepatotoxicity and the involved action mechanisms. Mice were administrated with G-Rg5 at two dosages of 10 or 20 mg/kg for 7 consecutive days. After the last treatment, all of the animals that received a single intraperitoneal injection of APAP (250 mg/kg) showed severe liver toxicity after 24 h, and the liver protection effects of G-Rg5 were examined. The results clearly indicated that pretreatment with G-Rg5 remarkably inhibited the production of serum tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) compared with the APAP group. Meanwhile, G-Rg5 decreased the hepatic malondialdehyde (MDA) content, the protein expression levels of 4-hydroxynonenal (4-HNE) and cytochrome P450 2E1 (CYP2E1) in the liver tissues. G-Rg5 decreased APAP caused the hepatic overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Furthermore, analysis of immunohistochemistry and Western blotting also indicated that G-Rg5 pretreatment inhibited activation of apoptotic pathways mainly via increasing the expression of Bcl-2 protein, decreasing the expression of Bax protein, proliferating cell nuclear antigen (PCNA), cytochrome c, caspase-3, caspase-8, and caspase-9. Liver histopathological observation provided further evidence that pretreatment with G-Rg5 could significantly inhibit hepatocyte necrosis, inflammatory cell infiltration, and apoptosis caused by APAP. In conclusion, the present study clearly demonstrates that G-Rg5 exerts a liver protection effect against APAP-induced acute hepatotoxicity mainly via a caspase-mediated anti-apoptotic effect.
- Published
- 2017
40. An Adult Case of Multiphasic Disseminated Encephalomyelitis Manifesting with Optic Neuritis
- Author
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Jianjun Ma, Shu-Man Feng, Hongqi Yang, and Wen-Cong Zhao
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Optic Neuritis ,Oligoclonal band ,Visual acuity ,Encephalomyelitis ,Visual Acuity ,Diagnosis, Differential ,Internal Medicine ,medicine ,Humans ,Optic neuritis ,Right optic nerve ,medicine.diagnostic_test ,business.industry ,Multiple sclerosis ,Encephalomyelitis, Acute Disseminated ,Optic Nerve ,Magnetic resonance imaging ,General Medicine ,medicine.disease ,Magnetic Resonance Imaging ,Acute disseminated encephalomyelitis ,Female ,medicine.symptom ,business - Abstract
A 25-year-old woman presented with a fever, headache, vomiting and somnolence. Cranial magnetic resonance imaging (MRI) showed multiple lesions in the cerebellum, brainstem, cerebral cortex and subcortex. Oligoclonal bands were positive in the cerebral spinal fluid (CSF). She experienced a good recovery after steroid treatment. Four months later, she developed right vision loss. Repeated MRI showed multiple cranial lesions different from those involved in the first attack in both size and distribution. An abnormal high signal was also observed in the front and intraorbital regions of the right optic nerve. The patient's vision progressively improved, and she obtained a full recovery following the administration of steroids. A diagnosis of multiphasic disseminated encephalomyelitis manifesting with optic neuritis was made.
- Published
- 2014
41. [Therapeutic Effect of Combined Cytokines on Nonhuman Primate Model of Severe Haemopoietic Acute Radiation Sickness]
- Author
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Yan-Chao, Ma, Ming, Li, Shuang, Xing, Guo-Lin, Xiong, Xing, Shen, Qiu, Chen, Yu-Wen, Cong, Jin-Xiang, Wang, Nan-Kang, Zhu, Zu-Yin, Yu, and Xue-Guang, Zhang
- Subjects
Bone Marrow Cells ,Hematopoietic Stem Cells ,Macaca mulatta ,Recombinant Proteins ,Hematopoiesis ,Random Allocation ,Thrombopoietin ,Bone Marrow ,Gamma Rays ,Granulocyte Colony-Stimulating Factor ,Animals ,Humans ,Interleukin-2 ,Radiation Injuries ,Whole-Body Irradiation - Abstract
To evaluate the therapeutic effects of combined administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-2 (rhIL-2) on radiation-induced severe haemopoietic acute radiation sickness (ARS) in rhesus monkeys, so as to provide experimental evidences for the effective clinical treatment.Seventeen rhesus monkeys were exposed to 7.0 Gy (60)Co γ-ray total body irradiation (TBI) to establish severe haemopoietic ARS model, and were randomly divided into supportive care group, rhG-CSF+rhTPO treatment group and rhG-CSF+rhTPO+rhIL-2 treatment group. Survival time, general signs such as bleeding and infections, and peripheral blood cell counts in each group were monitored. Bone marrow cells were cultivated to examine the colony formation ability. The histomorphology changes of bone marrow were observed at 45 d post irradiation.After 7.0 Gy (60)Co γ-ray TBI, monkeys of supportive care group underwent tarry stool and emesis, then died in 12~18 d. The overall survival rate in this group was 16.7%. Gastrointestinal reactions of monkeys in two combined-cytokines treatment groups were inapparent. Combined-cytokines treatment induced 100% survival. Complete blood cells declined sharply after irradiation in each group, but two combined-cytokines treatment schemes could elevate the nadir of all blood cells, shorten the duration of pancytopenia and accelerate the recovery of hemogram. Compared with rhG-CSF+ rhTPO treatment, rhG-CSF+ rhTPO+ rhIL-2 treatment could increase the counts of lymphocytes and monocytes. The colony-formation rate of haemopoietic stem/progenitor cells in bone marrow dropped markedly at 2 d after irradiation. Combined-cytokines treatment promoted the ability of colony formation on day 29. Hematopoietic cells mostly disappeared in bone marrow of animals in supportive care group, but hematopoietic functions were recovered after cytokines were administrated.rhG-CSF+ rhTPO and rhG-CSF+ rhTPO+ rhIL-2 treatment can significantly promote hematopoiesis recovery, improve the quantity of life, simplify the supportive therapy, and enhance the survival rate of rhesus monkeys with severe haemopoietic ARS induced by 7.0 Gy (60)Co γ-ray exposure. Especially the application of rhIL-2 can accelerate the recovery of lymphocytes and monocytes and restore the immunological function. Thus, combination of rhG-CSF, rhTPO and rhIL-2 on the basis of supportive care is an efficient strategy to treat severe haemopoietic ARS.
- Published
- 2016
42. Phytochemical composition and toxicity of an antioxidant extract from Pimpinella brachycarpa ( Kom. ) Nakai
- Author
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Wen Cong, Xuming Deng, Dacheng Wang, Guoren Huang, Wenhui Qian, Zhenning Wang, Shuang Guan, Jing Lu, and Linli Xu
- Subjects
Pimpinella ,Antioxidant ,Cell Survival ,Health, Toxicology and Mutagenesis ,medicine.medical_treatment ,Myristic acid ,Toxicology ,Chromosome aberration ,Antioxidants ,Mice ,chemistry.chemical_compound ,Functional food ,Cell Line, Tumor ,Toxicity Tests, Acute ,medicine ,Animals ,Humans ,Pimpinella brachycarpa ,Pharmacology ,Traditional medicine ,Mutagenicity Tests ,Plant Extracts ,Chemistry ,General Medicine ,Sitosterols ,Acute toxicity ,Biochemistry ,Toxicity ,Reactive Oxygen Species ,Micronucleus - Abstract
Pimpinella brachycarpa (Kom.) Nakai (PB) is one of the most favored edible greens grown in Asian regions. In our previously study, we found PB extract had antioxidant effects in vitro. In the present study, an EtOAc soluble extract (PBet) was isolated from PB. Then the antioxidant properties at cellular level, phytochemical composition and toxicity of PBet were examined. The results indicated that PBet (0.5-2mg/mL) could protect Bel-7404 cells from H(2)O(2) induced cell damage through scavenging of intracellular ROS. Moreover, myristic acid, 24ζ-methyl-5α-lanosta-25-one, β-sitosterol, pregnenolone and β-daucosterol were firstly isolated from PB. In addition, PBet (0.75g/kg BW, ig) had no acute toxicity and it (0.03-0.12g/kg BW, ig, 7 d) could not influence the rate of bone marrow polychromatic erythrocytes micronucleus and chromosome aberration in KM mice. All above findings suggested that PBet could be considered as a safe functional food with antioxidant activities.
- Published
- 2012
43. Dietary α-Mangostin Provides Protective Effects against Acetaminophen-Induced Hepatotoxicity in Mice via Akt/mTOR-Mediated Inhibition of Autophagy and Apoptosis
- Author
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Shen Ren, Wen-cong Liu, Yin-Shi Sun, Chen Chen, Wei Li, Zi Wang, Li-Chun Zhao, and Xiao-Tong Yan
- Subjects
Male ,0301 basic medicine ,autophagy ,Xanthones ,Caspase 3 ,acute liver injury ,Pharmacology ,α-mangostin ,Article ,Catalysis ,Garcinia mangostana ,lcsh:Chemistry ,Inorganic Chemistry ,Mice ,03 medical and health sciences ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,lcsh:QH301-705.5 ,Molecular Biology ,Protein kinase B ,Spectroscopy ,PI3K/AKT/mTOR pathway ,acetaminophen ,Mice, Inbred ICR ,Chemistry ,TOR Serine-Threonine Kinases ,apoptosis ,Organic Chemistry ,Autophagy ,General Medicine ,Computer Science Applications ,Acetaminophen ,Oxidative Stress ,030104 developmental biology ,Liver ,lcsh:Biology (General) ,lcsh:QD1-999 ,Apoptosis ,Tumor necrosis factor alpha ,Chemical and Drug Induced Liver Injury ,Signal transduction ,Microtubule-Associated Proteins ,Drugs, Chinese Herbal ,medicine.drug - Abstract
Acetaminophen overdose-induced hepatotoxicity is the most common cause of acute liver failure in many countries. Previously, alpha-mangostin (α-MG) has been confirmed to exert protective effects on a variety of liver injuries, but the protective effect on acetaminophen-induced acute liver injury (ALI) remains largely unknown. This work investigated the regulatory effect and underlying cellular mechanisms of α-MG action to attenuate acetaminophen-induced hepatotoxicity in mice. The increased serum aminotransferase levels and glutathione (GSH) content and reduced malondialdehyde (MDA) demonstrated the protective effect of α-MG against acetaminophen-induced hepatotoxicity. In addition, α-MG pretreatment inhibited increases in tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) caused by exposure of mice to acetaminophen. In liver tissues, α-MG inhibited the protein expression of autophagy-related microtubule-associated protein light chain 3 (LC3) and BCL2/adenovirus E1B protein-interacting protein 3 (BNIP3). Western blotting analysis of liver tissues also proved evidence that α-MG partially inhibited the activation of apoptotic signaling pathways via increasing the expression of Bcl-2 and decreasing Bax and cleaved caspase 3 proteins. In addition, α-MG could in part downregulate the increase in p62 level and upregulate the decrease in p-mTOR, p-AKT and LC3 II /LC3 I ratio in autophagy signaling pathways in the mouse liver. Taken together, our findings proved novel perspectives that detoxification effect of α-MG on acetaminophen-induced ALI might be due to the alterations in Akt/mTOR pathway in the liver.
- Published
- 2018
44. [Study on the effect of vibsane-type diterpenoids of Viburnum odoratissimum on human HepG2 cell growth and its underlying mechanism]
- Author
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Hai-Fang, Zhang, Lin, Wang, Jie, Liu, Wen-Bin, Zhou, Liu-Zhen, Zhang, Ya-Jun, Shan, Zu-Yin, Yu, Ping, Liu, Hong-Wei, Tang, and Yu-Wen, Cong
- Subjects
Viburnum ,Humans ,Apoptosis ,Cell Cycle Checkpoints ,Hep G2 Cells ,Diterpenes ,Cell Proliferation - Abstract
To study the antiproliferation effect on HepG2 cells and its underlying mechanism of the active chemical composition of the Viburnum Odoratissimum.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay and trypan blue dye exclusion assay were used to assess the effect of vibsane-type diterpenoids on the proliferation of various tumor cells. Alterations in cell cycle and apoptosis were determined by flowcytometry. The enzymatic activity of caspase-3/7 was measured by Apo-ONE homogeneous Caspase-3/7 Assay kit.Compound 1 #, a vibsane-type diterpenoid, was found to significantly inhibit the growth of HepG2 cells by anticancer proliferation activity screening. It was demonstrated that the modified groups on side chain coupled to C11 site affected the cell growth-inhibition activity of compounds by structure-activity analysis. In addition, HepG2 cell line was most sensitive to compound 1 #, which induced growth arrest of HepG2 cells in a dose- and time-dependent manner. Study on the mechanisms underlying these effects indicated that compound 1 # induced significant G0/G1 phase arrest of HepG2 cells in a time- and concentration-dependent manner. Meanwhile, It was found that higher concentrations of compound (5-10 micromol/L) caused evident increase in the unmber of apoptotic cells and dose-dependent activation of caspase-3/7.Vibsane-type diterpenoids could significantly inhibit the growth of HCC HepG2 cells. Induction of cell cycle arrest and apoptosis may play important roles in their anticancer effects.
- Published
- 2014
45. The protein kinase C agonist prostratin induces differentiation of human myeloid leukemia cells and enhances cellular differentiation by chemotherapeutic agents
- Author
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He Xiao, Yu-Wen Cong, Shuang Xing, Guo-Lin Xiong, Meng Yang, Yan-Feng Zhang, Yu Cui, Li-Sheng Wang, Xing Shen, Zu-Yin Yu, Xiao-Lan Liu, Yu Jing, Qing-Liang Luo, Bo Dong, and Ya-Jun Shan
- Subjects
Cancer Research ,Cellular differentiation ,Blotting, Western ,Antineoplastic Agents ,Apoptosis ,Proto-Oncogene Proteins c-myc ,chemistry.chemical_compound ,Differentiation therapy ,hemic and lymphatic diseases ,Phorbol Esters ,medicine ,Tumor Cells, Cultured ,Humans ,Prostratin ,Extracellular Signal-Regulated MAP Kinases ,Protein kinase C ,Protein Kinase C ,Cell Proliferation ,biology ,Kinase ,Cell Cycle ,Cytarabine ,Myeloid leukemia ,Cell Differentiation ,Drug Synergism ,medicine.disease ,Leukemia ,Leukemia, Myeloid, Acute ,Oncology ,chemistry ,Mitogen-activated protein kinase ,Cancer research ,biology.protein - Abstract
As acute myeloid leukemia (AML) cells are characterized by uncontrolled self-renewal and impaired cellular differentiation, induction of terminal differentiation of leukemia cells by differentiating agents has been proposed as an attractive therapeutic strategy to treat AML. Here, we demonstrated that prostratin, a potent protein kinase C (PKC) activator, inhibited the growth of myeloid leukemia cells by a predominant G1 arrest with variable induction of apoptosis. Conversely, prostratin induced significant differentiation of AML cell lines and primary AML blasts as evidenced by morphology and immunophenotyping. The effects of prostratin were PKC dependent, and activation of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/2 by PKC was required for prostratin-induced cell differentiation. Consequently, prostratin reprogrammed transcriptional factor expression, and ectopic expression of c-Myc in HL-60 cells significantly eliminated prostratin-mediated cellular differentiation and cell cycle arrest, indicating an essential role for c-Myc suppression in the differentiation-inducing effects of prostratin. Finally, prostratin was able to potentiate cellular differentiation induced by chemotherapeutic agents such as Ara-C. Together, we proposed that prostratin alone or administered with other anticancer agents may be effective in differentiation therapy of AML.
- Published
- 2014
46. [Analysis of small supernumerary marker chromosome 15q11 in four infertile males]
- Author
-
Xiang-dong, Tu, Xue-wen, Cong, Jian, Zeng, De-zhu, Zheng, Ai-zhen, Yan, Yan-hong, Lin, Li-ping, Qiu, Min, Zhang, Fuchun, Zhong, and Fenghua, Lan
- Subjects
Adult ,Genetic Markers ,Male ,Chromosomes, Human, Pair 15 ,Pregnancy ,Humans ,Female ,Infertility, Male ,Chromosome Banding - Abstract
To delineate the origins of small supernumerary marker chromosomes (sSMCs) identified in 4 infertile males.The sSMCs were analyzed with combined G-banding, N-banding, multiplex ligation-dependent probe amplification (MLPA), fluorescence in situ hybridization (FISH) and single nucleotide polymorphisms array (SNP-array) techniques.G-banding analysis has suggested a 46,X,-Y,+mar karyotype in all of the 4 cases. N-banding revealed that all of the sSMCs have possessed two satellites located on both sides. By MLPA, 1 patient showed copy number gains for 15q11.2 region. SNP-array analysis suggested that all had duplication for 15q11.1-q11.2 region, spanning 3.06 Mb, 0.9118 Mb, 1.728 Mb and 0.287 Mb, respectively. By FISH analysis, all of the sSMCs showed two hybridization signals, indicating that they were dicentric chromosomes.In all of the four cases, the marker chromosomes have derived from chromosome 15 and were bisatellited and dicentric, which gave rise to a karyotype of 47,XY,+ish,inv dup(15)(q11)(D15Z4++). sSMC 15q11 therefore may be a major cause for male infertility.
- Published
- 2013
47. [Delineation of three structural Y chromosome aberrations combined molecular techniques]
- Author
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Xiang-dong, Tu, Jian, Zeng, Xue-wen, Cong, Ai-zhen, Yan, Wu-jian, Huang, Yan-hong, Lin, De-zhu, Zheng, Min, Zhang, and Zhi-hong, Wang
- Subjects
Adult ,Genetic Markers ,Male ,Chromosomes, Human, Y ,Humans ,In Situ Hybridization, Fluorescence ,Infertility, Male ,Sex Chromosome Aberrations ,Chromosome Banding - Abstract
To delineate the structure of Y chromosome aberrations and recombinant mechanisms for three patients.Karyotype analysis, multiplex ligation dependent probe amplification (MLPA), fluorescence in situ hybridization (FISH), Y chromosome sequence tagged sites (STS) analysis, human whole genome-wide SNP array were used.The karyotypes of the three patients were 46, X, +mar. As suggested by MLPA analysis, case 1 has increased copy numbers of SRY, ZFY and UTY genes, case 2 had increased copies of SRY and ZFY genes, and deletion of UTY gene, and case 3 had decreased copies for subtelomeric regions of X/Yp and X/Yq. By STSs analysis, case 1 has retained SRY, sY84 and sY86 in the AZFa region, sY1227 in the AZFb region, whilst lost sY1228 in the AZFb region and other STSs in the AZFc region. Its breakpoint was thereby mapped between sY1227 and sY1228. Case 2 has retained SRY and sY1200 in the centromeric region, whilst has deletion of other STSs. Case 3 has retained SRY and STSs in the AZF regions. By SNP array, case 1 had duplicated Yp11.31-p11.2 and deletion of Yq11.22-q11.23 (approximately 5.18 Mb). Case 2 had duplicated Yp11.31-p11.2 and deletion of Yq11.21-q11.23 (approximately 14.644 Mb). Case 3 had single copy number deletion of p22.33 and q28 in the subtelomeric region of X/Yp and X/Yq. By FISH, cases 1 and 2 showed two signals for SRY and DYZ3 but no signal for DYZ1 on their marker chromosomes. Combining above results, the karyotypes of cases 1, 2 and 3 were determined as 46, X, idic(Y) (q11.23), 46, X, idic(Y) (q10) and 46, X, r(Y) (p11q12), respectively.Y chromosome aberrations are variable. Combined use of MLPA, STSs, FISH and SNP array is effective for revealing the breakpoints and recombinant mechanisms.
- Published
- 2013
48. [Chemistry and biological activities of Viburnum odoratissimum]
- Author
-
Jie, Liu, Wen-Bin, Zhou, Yu-Wen, Cong, and Ping, Liu
- Subjects
Flavonoids ,Plant Leaves ,Plants, Medicinal ,Molecular Structure ,Cytotoxins ,Cell Line, Tumor ,Viburnum ,Animals ,Humans ,Diterpenes ,Antineoplastic Agents, Phytogenic ,Lignans ,Triterpenes - Abstract
Viburnum odoratissimum is a folk medicinal plant, it can dredge the meridian passage and contains mainly diterpenes, triterpenes, flavonoids, sesquiterpenes, lignans, coumarin glycosides, etc. Vibsanin-type diterpenoids are the characteristic compounds of V. odoratissimum, and are divided into eleven-membered ring, seven-membered ring, and rearrangement-type. Vibsanin B, vibsanin C and neovibsanin A are the representative compounds of the three subtypes of vibsanin-type diterpenoids respectively. V. odoratissimum has cytotoxic activity, antibacterial activity, fish piscicidal activity and activity of inhibiting the growth of plants, Cytotoxic activity is the main biological activity.
- Published
- 2013
49. RhG-CSF improves radiation-induced myelosuppression and survival in the canine exposed to fission neutron irradiation
- Author
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Xiao-Lan Liu, He Xiao, Zu-Yin Yu, A-Ru-Na Han, Yan-fang Zhao, Yu-wen Cong, Qing-Liang Luo, Guo-lin Xiong, Ming Li, Ya-Jun Shan, Shuang Xing, Hong-Ling Ou, Ling Xie, and Zhen-hu Zhao
- Subjects
medicine.medical_specialty ,Neutropenia ,Cell Survival ,Neutrophils ,Health, Toxicology and Mutagenesis ,Spleen ,Granulocyte ,Gastroenterology ,Dogs ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Myeloid Cells ,Irradiation ,Neutrons ,Radiation ,Leukopenia ,business.industry ,fungi ,medicine.disease ,Recombinant Proteins ,Haematopoiesis ,Radiation Injuries, Experimental ,medicine.anatomical_structure ,Gamma Rays ,Myelopoiesis ,Bone marrow ,medicine.symptom ,Nuclear medicine ,business ,Whole-Body Irradiation - Abstract
Neutron irradiation/rhG-CSF/Myelosuppression. Fission-neutron radiation damage is hard to treat due to its critical injuries to hematopoietic and gastrointestinal systems, and so far few data are available on the ther apeutic measures for neutron-radiation syndrome. This study was designed to test the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in dogs which had r eceived 2.3 Gy mixed fission-neutron-γ irradiation with a high ratio of neutrons (~90%). Following irradiation, rhG-CSF treatment induced 100% survival versus 60% in controls. Only two of five rhG-CSF-treated dogs experienced leukopenia (white blood cells [WBC] count < 1.0 × 10 9 /L) and neutropenia (neutrophil [ANC] count < 0.5 × 10 9 /L), whereas all irradiated controls displayed a profound period of leukopenia and neutropenia. Furthermore, administration of rhG-CSF significantly delayed the onset of leukopenia and reduced th e duration of leucopenia as compared with controls. In addition, individual dogs in the rhG-CSF-treated group exhibited evident differences in rhG-CSF res ponsiveness after neutron-irradiation. Finally, histopathological evaluation of the surviving dogs revealed that the incidence and severity of bone marrow, thymus and spleen damage decreased in rhGCSF-treated dogs as compared with surviving controls. Thus, these results demonstrated that rhG-CSF administration enhanced recovery of myelopoiesis and survival after neutron-irradiation.
- Published
- 2011
50. [Effect of rhG-CSF on blood coagulation in beagles irradiated by 2.3 Gy neutron]
- Author
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Ming, Li, Qin-Fang, Han, Xiao-Lan, Liu, Shuang, Xing, Guo-Lin, Xiong, Ling, Xie, Yan-Fang, Zhao, Zu-Yin, Yu, Yi-Bo, Ding, Zhen-Hu, Zhao, Yu-Wen, Cong, and Qing-Liang, Luo
- Subjects
Leukocyte Count ,Neutron Diffraction ,Radiation Injuries, Experimental ,Dogs ,Bone Marrow ,Platelet Count ,Granulocyte Colony-Stimulating Factor ,Animals ,Humans ,Radiation Dosage ,Blood Coagulation ,Recombinant Proteins - Abstract
The aim of this study was to investigate the effect of recombinant human granulocyte stimulating factor (rhG-CSF) on blood coagulation of beagles irradiated by 2.3 Gy neutron so as to provide new therapy for blood coagulation disorder after neutron irradiation. 10 beagles were exposed to 2.3 Gy neutron, and then randomly assigned into supportive care group and rhG-CSF-treated group. The rhG-CSF-treated cohorts were injected subcutaneously with rhG-CSF (10 µg/kg·d) beginning at the day of exposure for 21 consecutive days. Peripheral blood platelet counts were examined once every two days. In vitro platelet aggregation test, thromboelastography and blood clotting tetrachoric tests were also performed. The results indicated that the blood clotting system of irradiated dogs was in hypercoagulable state in the early days after 2.3 Gy neutron irradiation, and became hypocoagulable at crisis later and were mainly on intrinsic coagulation pathway. Blood fibrinogen increased markedly during the course of disease, while platelet counts and aggregation function were decreased remarkably. rhG-CSF administered daily could correct hypercoagulable state induced by 2.3 Gy neutron irradiation at the early time post exposure, shortened the thromboplastin generation time and clotting formation, down-regulated the abnormal high fibrinogen in blood, and improved platelet aggregation function. It is concluded that rhG-CSF can improve coagulation disorders of irradiated dogs.
- Published
- 2010
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