127 results on '"MING ZHAO"'
Search Results
2. Trends in the distribution of socioeconomic inequalities in smoking and cessation: evidence among adults aged 18 ~ 59 from China Family Panel Studies data
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Huang, Ming Zhao, Liu, Tai Yi, Zhang, Zhong Min, Song, Fujian, and Chen, Ting
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- 2023
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3. A prospective cohort study of the risk factors for new falls and fragility fractures in self-caring elderly patients aged 80 years and over
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Zhou, Jian, Liu, Bo, Qin, Ming-Zhao, and Liu, Jin-Ping
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- 2021
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4. Liver injury caused by fenofibrate within 48 h after first administration: a case report
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He, Yu, Qin, Ming-zhao, and Chen, Yi-wen
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- 2021
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5. Proliferative diabetic retinopathy in patients with type 2 diabetes correlates with the presence of atherosclerosis cardiovascular disease
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Gao, Lu, Zhao, Wei, Yang, Jin-Kui, and Qin, Ming-Zhao
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- 2021
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6. Influence of injection rates of calibrating standard solution on monitoring pulse indicator continuous cardiac output
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Shu-Lan, Chen, Fang-Chen, Lan, Zhen-Shuang, Du, Ya-Ping, Xu, Hui-Ming, Zhao, Cui-Ping, Zeng, and Yu, Miao
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- 2018
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7. Disruption of hematopoiesis attenuates the osteogenic differentiation capacity of bone marrow stromal cells
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Changzhen Wang, Hongmei Ning, Jiao Gao, Teng Xue, Ming Zhao, Xiaoxia Jiang, Xiaoming Zhu, Ximin Guo, Hong Li, and Xiaoyan Wang
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Medicine (General) ,Hematopoietic cells ,Research ,Medicine (miscellaneous) ,Bone Marrow Cells ,Cell Differentiation ,Cell Biology ,QD415-436 ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Biochemistry ,Hematopoiesis ,Mice ,R5-920 ,Osteogenesis ,Differentiation ,Niche ,Molecular Medicine ,Mesenchymal stem cells ,Animals ,Cells, Cultured - Abstract
Background The homeostasis of mesenchymal stem cells (MSCs) is modulated by both their own intracellular molecules and extracellular milieu signals. Hematopoiesis in the bone marrow is maintained by niche cells, including MSCs, and it is indispensable for life. The role of MSCs in maintaining hematopoietic homeostasis has been fully elucidated. However, little is known about the mechanism by which hematopoietic cells reciprocally regulate niche cells. The present study aimed to explore the close relationship between MSCs and hematopoietic cells, which may be exploited for the development of new therapeutic strategies for related diseases. Methods In this study, we isolated cells from the offspring of Tie2Cre + and Ptenflox/flox mice. After cell isolation and culture, we investigated the effect of hematopoietic cells on MSCs using various methods, including flow cytometry, adipogenic and osteogenic differentiation analyses, quantitative PCR, western bloting, and microCT analysis. Results Our results showed that when the phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene was half-deleted in hematopoietic cells, hematopoiesis and osteogenesis were normal in young mice; the frequency of erythroid progenitor cells in the bone marrow gradually decreased and osteogenesis in the femoral epiphysis weakened as the mice grew. The heterozygous loss of Pten in hematopoietic cells leads to the attenuation of osteogenic differentiation and enhanced adipogenic differentiation of MSCs in vitro. Co-culture with normal hematopoietic cells rescued the abnormal differentiation of MSCs, and in contrast, MSCs co-cultured with heterozygous null Pten hematopoietic cells showed abnormal differentiation activity. Co-culture with erythroid progenitor cells also revealed them to play an important role in MSC differentiation. Conclusion Our data suggest that hematopoietic cells function as niche cells of MSCs to balance the differentiation activity of MSCs and may ultimately affect bone development.
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- 2022
8. One hundred twelve cases of 46, XY DSD patients after initial gender assignment: a short-term survey of gender role and gender dysphoria
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Chunxiu Gong, Jiajia Chen, Liping Hou, Lijun Fan, Ming Zhao, Michel Polak, Bingyan Cao, and Yonghua Cui
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Gender dysphoria ,Male ,Pediatrics ,medicine.medical_specialty ,Disorders of Sex Development ,Gene mutation ,Complete androgen insensitivity syndrome ,46, XY disorders of sex development ,Gender assignment ,medicine ,Humans ,Pharmacology (medical) ,Early childhood ,Disorders of sex development ,Gender role ,Partial androgen insensitivity syndrome ,Child ,Genetics (clinical) ,Disorder of Sex Development, 46,XY ,business.industry ,Research ,General Medicine ,medicine.disease ,Cross-Sectional Studies ,Child, Preschool ,Cohort ,Medicine ,Female ,business - Abstract
Background 46, XY disorders of sex development (46, XY DSD) are congenital disorders with 46, XY chromosomal karyotype but inconsistent gonadal/phenotypic sex. One of the biggest concerns for parents and clinicians is the gender assignment. However, there is no standard uniform of care nor consensus at present. We sought to evaluate the current treatment's rationality and provide a reference basis for the gender reassignment in 46, XY DSD patients with a specific diagnosis. Methods We conducted a cross-sectional survey of gender role with the Pre-school Activities Inventory (PSAI), the Children's Sex Role Inventory (CSRI) in 46, XY DSD patients and set up control groups comparison. Psychiatrist assessed gender dysphoria in patients ≥ 8-year-old with the criteria of diagnostic and statistical manual of mental disorders, 5th edition (DSM-5). Results A total of 112 responders of 136 patients participated in this study (82.4%, aged 2–17.8 years, median age: 4-year-old). The follow-up period was from 6 months to 10 years (median: 2 years). Twenty-five females were reassigned to the male gender after a specific diagnosis (16/25 (64%) in 5 alfa-reductase-2 deficiency (5α-RD2), 5/25 (20%) in partial androgen insensitivity syndrome (PAIS), 4/25 (16%) in NR5A1gene mutation). Male gender assignment increased from 55.3 (n = 62) to 77.7% (n = 87). The median PSAI score was similar to the control males in 5α-RD2, PAIS, and NR5A1 gene mutation groups (p > 0.05); while identical to the control females in complete androgen insensitivity syndrome (CAIS) and CYP17A1 gene mutation groups (p > 0.05). PSAI score of children raised as male was higher than those of CAIS and CYP17A1 groups raised as female (p p > 0.05). None of the patients over 8-year-old (n = 44) had gender dysphoria. Conclusion The reassigned gender in 46, XY DSD patients is consistent with their gender role during early childhood. None of them had gender dysphoria. The molecular diagnosis, gonadal function, and the gender reassignment are congruent within our Chinese cohort. Long-term follow-up and more evaluation are still required.
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- 2021
9. Mitral early-diastolic inflow peak velocity (E)-to-left atrial strain ratio as a novel index for predicting elevated left ventricular filling pressures in patients with preserved left ventricular ejection fraction
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Zhen-Ya Shen, Xin Zhao, You Zhou, Cai-Ming Zhao, and Bing-Yuan Zhou
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medicine.medical_specialty ,Diastole ,Left atrial strain ,Speckle tracking echocardiography ,Ventricular Function, Left ,Ventricular Dysfunction, Left ,Heart failure with preserved left ventricular ejection fraction ,Internal medicine ,medicine ,Diseases of the circulatory (Cardiovascular) system ,Humans ,Radiology, Nuclear Medicine and imaging ,Angiology ,Heart Failure ,Ejection fraction ,business.industry ,Research ,Area under the curve ,Stroke Volume ,General Medicine ,Odds ratio ,Confidence interval ,Preload ,RC666-701 ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Left ventricular diastolic dysfunction - Abstract
ObjectivesWe sought to explore the relationship between an index of left ventricular diastolic function parameters combined with left atrial strain and the diastolic function of patients with preserved ejection fraction.MethodsWe prospectively enrolled 388 patients with left ventricular ejection fraction (LVEF) ≥ 50%, 49 of whom underwent left heart catherization. Transthoracic echocardiography was performed within 12 h before or after the procedure. Left atrial (LA) strain was obtained by speckle tracking echocardiography. These patients served as the test group. The remaining patients (n = 339) were used to validate the diagnostic performance of the mitral early-diastolic inflow peak velocity (E)-to-left atrial reservoir strain ratio (E/LASr) in left ventricular diastolic dysfunction.ResultsInvasive measurements of LV end-diastolic pressure (LVEDP) demonstrated that the E/LASr ratio was increased in patients with elevated LVEDP [ 2.0 (1.8–2.2) vs 3.0 (2.6–4.0),p n = 49). After adjusting for age, mitral A, E/e' ratio and β-blocker use, the E/LASr ratio was an independent predictor of elevated LVEDP and showed good diagnostic performance in determining elevated LVEDP [area under the curve (AUC) 0.903, cutoff value 2.7, sensitivity 74.2%, specificity 94.4%]. In the validation group (n = 339), the E/LASr ratio also performed well in diagnosing elevated left atrial pressure (LAP) (AUC 0.904, cutoff value 3.2, sensitivity 76.5%, specificity 89.0%), while with a cut-off value of 2.7, the E/LASr ratio showed high accuracy in discriminating elevated LAP. In addition, E/LASr was a good index of excellent diagnostic utility (AUC: 0.899 to 0.996) in the categorization of diastolic dysfunction grades. Regarding the clinical relevance of this index, the E/LASr ratio could accurately diagnose HF with preserved ejection fraction (HFpEF) (0.781), especially in patients with “indeterminate” status (AUC: 0.829). Furthermore, an elevated E/LASr ratio was significantly associated with the risk of rehospitalization due to major adverse cardiac events (MACEs) within one year (odds ratio: 1.183, 95% confidence interval: 1.067, 1.312).ConclusionsIn patients with EF preservation, the E/LASr ratio is a novel index for assessing elevated left ventricular filling pressure with high accuracy.
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- 2021
10. UHRF1 downregulation promotes T follicular helper cell differentiation by increasing BCL6 expression in SLE
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Longyuan Hu, Xiaoli Min, Qianjin Lu, Haijing Wu, Limin Liu, Sujie Jia, Linxuan Yang, Du Pei, Ming Zhao, Jiali Wu, and Hai Long
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0301 basic medicine ,Epigenomics ,Male ,T Follicular Helper Cells ,Cellular differentiation ,BCL6 ,Ubiquitin-Protein Ligases ,Down-Regulation ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Systemic lupus erythematosus ,Downregulation and upregulation ,immune system diseases ,hemic and lymphatic diseases ,Genetics ,Animals ,Humans ,Lupus Erythematosus, Systemic ,Epigenetics ,UHRF1 ,Promoter Regions, Genetic ,Molecular Biology ,Transcription factor ,Genetics (clinical) ,T follicular helper cell differentiation ,biology ,Chemistry ,Research ,Cell Differentiation ,DNA Methylation ,Cell biology ,Histone Code ,030104 developmental biology ,Histone ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,DNA methylation ,Hemocyanins ,biology.protein ,CCAAT-Enhancer-Binding Proteins ,Proto-Oncogene Proteins c-bcl-6 ,Female ,Tfh cells ,Haptens ,Developmental Biology ,Transcription Factors - Abstract
Background Transcription factor B cell lymphoma 6 (BCL6) is a master regulator of T follicular helper (Tfh) cells, which play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanisms by which BCL6 expression is regulated are poorly understood. Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an important epigenetic factor that regulates DNA methylation and histone modifications. In the present study, we assessed whether UHRF1 can regulate BCL6 expression and influence the differentiation and proliferation of Tfh cells. Results Compared to healthy controls, the mean fluorescence intensity of UHRF1 (UHRF1-MFI) in Tfh cells from SLE patients was significantly downregulated, whereas that of BCL6 (BCL6-MFI) was significantly upregulated. In vitro, UHRF1 knockdown led to BCL6 overexpression and promoted Tfh cell differentiation. In contrast, UHRF1 overexpression led to BCL6 downregulation and decreased Tfh cell differentiation. In vivo, conditional UHRF1 gene knockout (UHRF1-cKO) in mouse T cells revealed that UHRF1 depletion can enhance the proportion of Tfh cells and induce an augmented GC reaction in mice treated with NP-keyhole limpet hemocyanin (NP-KLH). Mechanistically, UHRF1 downregulation can decrease DNA methylation and H3K27 trimethylation (H3K27me3) levels in the BCL6 promoter region of Tfh cells. Conclusions Our results demonstrated that UHRF1 downregulation leads to increased BCL6 expression by decreasing DNA methylation and H3K27me3 levels, promoting Tfh cell differentiation in vitro and in vivo. This finding reveals the role of UHRF1 in regulating Tfh cell differentiation and provides a potential target for SLE therapy.
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- 2021
11. A prospective cohort study of the risk factors for new falls and fragility fractures in self-caring elderly patients aged 80 years and over
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Jian Zhou, Ming-Zhao Qin, Bo Liu, and Jin-Ping Liu
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Male ,medicine.medical_specialty ,Activities of daily living ,medicine.medical_treatment ,Timed up-and-go (TUG) test ,030209 endocrinology & metabolism ,Lumbar vertebrae ,lcsh:Geriatrics ,Walking speed ,03 medical and health sciences ,Fractures, Bone ,0302 clinical medicine ,Fragility ,Risk Factors ,Activities of Daily Living ,medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Prospective cohort study ,Aged ,Aged, 80 and over ,Rehabilitation ,business.industry ,Incidence (epidemiology) ,Aged 80 years and over ,Preferred walking speed ,lcsh:RC952-954.6 ,medicine.anatomical_structure ,Physical therapy ,Falls ,Accidental Falls ,Female ,Geriatrics and Gerontology ,Risk assessment ,business ,Fragility fractures ,Research Article - Abstract
Background This study aimed to prospectively analyze the risk factors for new falls and fragility fractures in self-caring elderly patients and to find suitable evaluation tools for community screening and follow-up interventions. Methods: A total of 300 participants (187 male and 113 female), aged 80 or above and capable of caring for themselves, were enrolled in this study and observed for a period of 12 months. Their medical histories were collected, various indicators were measured, and the risk factors for new falls and fragility fractures were analyzed. Results A total of 290 participants were included in the statistical analysis. Eighty-seven participants (30%) had new falls. The incidence was negatively correlated with the activities of daily living (ADL, represented by the Barthel Index) score (P=0.008) but was positively correlated with the timed up-and-go (TUG) test score> 12 s (P=0.021). The results also revealed that 33 fragility fractures occurred in 29 patients (10.0%), which was positively correlated with new falls (P=0.000). New fragility fractures were negatively correlated with the bone mineral density (BMD) of the lumbar vertebrae (P=0.012) and walking speed (P=0.000). Conclusion TUG, walking speed, the ADL score, and the fall risk assessment scale can simply and effectively assess the risk of new falls and fragility fractures in the elderly population, and their use should be widely implemented in the community.
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- 2021
12. Bone marrow derived mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury
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Ding Liu, Jianmin Hu, Liuyang Li, Min Li, Yu-ming Qiao, Ming Zhao, Ying Guo, Li-pei Fan, Jun Liao, Yong-guang Liu, and Song Zhou
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lcsh:Biotechnology ,Bone marrow derived mesenchymal stem cells ,Pharmacology ,General Biochemistry, Genetics and Molecular Biology ,lcsh:Biochemistry ,SIRT1 ,stomatognathic system ,lcsh:TP248.13-248.65 ,Medicine ,lcsh:QD415-436 ,lcsh:QH301-705.5 ,Blood urea nitrogen ,Erythropoietin ,Kidney ,business.industry ,Research ,Mesenchymal stem cell ,Acute kidney injury ,Lung entrapment ,hemic and immune systems ,medicine.disease ,medicine.anatomical_structure ,lcsh:Biology (General) ,Apoptosis ,Bone marrow ,Stem cell ,business ,medicine.drug - Abstract
Background Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI). The main drawbacks of MSCs therapy, including the lack of specific homing after systemic infusion and early cell death in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning of MSCs promotes their therapeutic effect, however, the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO in bone marrow derived mesenchymal stem cells (BMSCs) for AKI treatment. Results We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in BMSCs, which was decreased by EPO pretreatment, indicating that EPO protected the cells from apoptosis. Further, we showed that EPO up-regulated silent information regulator 1 (SIRT1) and Bcl-2 expression and down-regulated p53 expression. This effect was partially reversed by SIRT1 siRNA intervention. The anti-apoptotic effect of EPO in pretreated BMSCs may be mediated through the SIRT1 pathway. In a rat AKI model, 24 h after intravenous infusion, GFP-BMSCs were predominantly located in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs and increased their distribution in the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-α, and a significantly higher level of IL-10 as compared to rats infused with untreated BMSCs. The administration of EPO-BMSCs after reperfusion reduced serum creatinine, blood urea nitrogen, and pathological scores in I/R-AKI rats more effectively than BMSCs treatment did. Conclusions Our data suggest that EPO pretreatment enhances the efficacy of BMSCs to improve the renal function and pathological presentation of I/R-AKI rats.
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- 2020
13. Comparative analysis of maca (Lepidium meyenii) proteome profiles reveals insights into response mechanisms of herbal plants to high-temperature stress
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Li Xuan Ma, Li Qin Zhang, Li Xiao, Zhongshan Zhang, Zhan Qi Wang, Xueting Zhong, Wei Fan, Yang Tian, Qi Ming Zhao, and Chou Fei Wu
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Chlorophyll ,Proteome ,Plant Science ,Biology ,Tandem mass tag ,Real-Time Polymerase Chain Reaction ,Lepidium ,High-temperature stress ,Molecular mechanism ,Gene Expression Regulation, Plant ,lcsh:Botany ,Gene ,Plant Proteins ,Lepidium meyenii ,Endoplasmic reticulum ,Stress response ,Herbaceous plant ,Maca ,lcsh:QK1-989 ,Cell biology ,Metabolic pathway ,Seedlings ,Signal transduction ,Heat-Shock Response ,Metabolic Networks and Pathways ,Research Article - Abstract
Background High-temperature stress (HTS) is one of the main environmental stresses that limit plant growth and crop production in agricultural systems. Maca (Lepidium meyenii) is an important high-altitude herbaceous plant adapted to a wide range of environmental stimuli such as cold, strong wind and UV-B exposure. However, it is an extremely HTS-sensitive plant species. Thus far, there is limited information about gene/protein regulation and signaling pathways related to the heat stress responses in maca. In this study, proteome profiles of maca seedlings exposed to HTS for 12 h were investigated using a tandem mass tag (TMT)-based proteomic approach. Results In total, 6966 proteins were identified, of which 300 showed significant alterations in expression following HTS. Bioinformatics analyses indicated that protein processing in endoplasmic reticulum was the most significantly up-regulated metabolic pathway following HTS. Quantitative RT-PCR (qRT-PCR) analysis showed that the expression levels of 19 genes encoding proteins mapped to this pathway were significantly up-regulated under HTS. These results show that protein processing in the endoplasmic reticulum may play a crucial role in the responses of maca to HTS. Conclusions Our proteomic data can be a good resource for functional proteomics of maca and our results may provide useful insights into the molecular response mechanisms underlying herbal plants to HTS.
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- 2020
14. A comparative study on shared-use medicines in Tibetan and Chinese medicine
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Ming-ming Zhao, Ke-ru Wang, Shi-Hong Zhong, and Rui Gu
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0106 biological sciences ,Cultural Studies ,Health (social science) ,South asia ,Traditional Chinese medicine ,Tibetan medicine ,Shared history ,01 natural sciences ,Southeast asia ,lcsh:Botany ,Medicine, Tibetan Traditional ,Medicine, Chinese Traditional ,Medical systems ,Plants, Medicinal ,Traditional medicine ,Research ,Shared-use medicines ,lcsh:Other systems of medicine ,lcsh:RZ201-999 ,lcsh:QK1-989 ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Geography ,Complementary and alternative medicine ,Medicinal herbs ,Comparative study ,General Agricultural and Biological Sciences ,010606 plant biology & botany - Abstract
Background Tibetan medicine (TM) and traditional Chinese medicine (TCM) are two independent traditional medical systems. Due to geographical factors, the development of Tibetan medicinal theory is relatively independent, but there are still many shared-use medicines in TM and TCM. However, a thorough and comparative study on those medicines is still absent. This study listed shared-use medicines by TM and TCM and analyzed the similarities and dissimilarities of these two medical systems. This paper also aimed to understand mutual influences like the shared history of TM and TCM and to roughly outline the exchanging process between them. Methods Shared-use medicines in TM and TCM were listed alphabetically. Information on the scientific name, material name, medicinal parts, and medical efficacy were extracted from publications. Shared-use medicines were grouped according to medicinal properties and medicinal parts used by TM and TCM. The historical origin and current status of clinical prescriptions of shared-use medicines were analyzed. Results A total of 136 shared-use medicines in TM and TCM were listed. Shared-use medicines that were used for a similar purpose in TM and TCM accounted for 14% of the total, while those used for different purposes accounted for 49% of the total, with some of the latter being commonly used in TCM. Shared-use medicinal herbs that originated from both Tibetan and Han regions accounted for 49% of the total, and those that were imported from South Asia and Southeast Asia were frequently observed in TM. Conclusion Owing to its unique geographical location and cultural diversity, the Tibetan region played a role as a development cradle for various traditional medicinal theories and knowledge. Medicinal knowledge was exchanged between TM and TCM during their parallel independent growth. Shared-use medicines in TM and TCM were mostly determined by flora similarity and medicinal trade, and they marked significant differences in their medicinal properties. However, medicines that were used for similar purposes in TM and TCM presented obvious commercial medicinal characteristic as well as the same chemical profile. The Tibetan region not only provided medicinal usage knowledge of TCM, but also served as a supply of medicinal resources attributing to “high altitude” locations.
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- 2019
15. Allogeneic mesenchymal stem cells as induction therapy are safe and feasible in renal allografts: pilot results of a multicenter randomized controlled trial
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Yanwen Peng, Fanhang Meng, Ning Na, Ronghua Cao, Heng Li, Qipeng Sun, Bin Miao, Jianmin Hu, Qiquan Sun, Zhengyu Huang, Liangqing Hong, Daqiang Zhao, Fei Han, and Ming Zhao
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0301 basic medicine ,Male ,lcsh:Medicine ,Pilot Projects ,Kaplan-Meier Estimate ,030230 surgery ,law.invention ,Umbilical Cord ,0302 clinical medicine ,Postoperative Complications ,Randomized controlled trial ,law ,Medicine ,DGF ,Mesenchymal stem cell ,Incidence (epidemiology) ,General Medicine ,Tissue Donors ,medicine.anatomical_structure ,Treatment Outcome ,Acute rejection ,Female ,Glomerular Filtration Rate ,Adult ,medicine.medical_specialty ,Urology ,Renal function ,Mesenchymal Stem Cell Transplantation ,General Biochemistry, Genetics and Molecular Biology ,MSC ,03 medical and health sciences ,medicine.artery ,Humans ,Transplantation, Homologous ,Renal artery ,Adverse effect ,Vein ,business.industry ,Research ,lcsh:R ,Renal transplantation ,Delayed graft function ,Mesenchymal Stem Cells ,Kidney Transplantation ,Transplantation ,030104 developmental biology ,Feasibility Studies ,business ,Follow-Up Studies - Abstract
Background Kidneys from deceased donors are being used to meet the growing need for grafts. However, delayed graft function (DGF) and acute rejection incidences are high, leading to adverse effects on graft outcomes. Optimal induction intervention should include both renal structure injury repair and immune response suppression. Mesenchymal stem cells (MSCs) with potent anti-inflammatory, regenerative, and immune-modulatory properties are considered a candidate to prevent DGF and acute rejection in renal transplantation. Thus, this prospective multicenter paired study aimed to assess the clinical value of allogeneic MSCs as induction therapy to prevent both DGF and acute rejection in deceased donor renal transplantation. Methods Forty-two renal allograft recipients were recruited and divided into trial and control groups. The trial group (21 cases) received 2 × 106/kg human umbilical-cord-derived MSCs (UC-MSCs) via the peripheral vein before renal transplantation, and 5 × 106 cells via the renal artery during the surgical procedure. All recipients received standard induction therapy. Incidences of DGF and biopsy-proven acute rejection were recorded postoperatively and severe postoperative complications were assessed. Graft and recipient survivals were also evaluated. Results Treatment with UC-MSCs achieved comparable graft and recipient survivals with non-MSC treatment (P = 0.97 and 0.15, respectively). No increase in postoperative complications, including DGF and acute rejection, were observed (incidence of DGF: 9.5% in the MSC group versus 33.3% in the non-MSC group, P = 0.13; Incidence of acute rejection: 14.3% versus 4.8%, P = 0.61). Equal postoperative estimated glomerular filtration rates were found between the two groups (P = 0.88). All patients tolerated the MSCs infusion without adverse clinical effects. Additionally, a multiprobe fluorescence in situ hybridization assay revealed that UC-MSCs administered via the renal artery were absent from the recipient’s biopsy sample. Conclusions Umbilical-cord-derived MSCs can be used as clinically feasible and safe induction therapy. Adequate timing and frequency of UC-MSCs administration may have a significant effect on graft and recipient outcomes. Trial registrationNCT02490020. Registered on June 29 2015
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- 2018
16. The role of 18F-FDG uptake features in the differential diagnosis of solitary pulmonary lesions with PET/CT
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Ling Yuan, Zhihua Wei, Ming Zhao, Hongxing Jin, Rongrong Tian, Baolin Chang, and Hongtao Yu
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Adult ,Male ,medicine.medical_specialty ,China ,Lung Neoplasms ,PET/CT ,Standardized uptake value ,Diagnosis, Differential ,Text mining ,Fluorodeoxyglucose F18 ,Statistical significance ,Solitary pulmonary lesions ,medicine ,Humans ,Aged ,Neoplasm Staging ,Aged, 80 and over ,PET-CT ,Solitary pulmonary nodule ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,Research ,Solitary Pulmonary Nodule ,Middle Aged ,medicine.disease ,Prognosis ,18F-FDG ,Oncology ,ROC Curve ,Positron emission tomography ,Positron-Emission Tomography ,Surgery ,Female ,Radiology ,Differential diagnosis ,Radiopharmaceuticals ,business ,Nuclear medicine ,Tomography, X-Ray Computed - Abstract
Background The aim of this study is to evaluate the value of 18F-FDG uptake features in the diagnosis of solitary pulmonary lesions. Methods One hundred thirty-nine patients with solitary pulmonary lesions were divided into full uptake, circular uptake, multi-focus uptake, mild uptake, and no-uptake groups according to the uptake features of 18F-FDG in solitary pulmonary lesions. The incidence of benign and malignant lesions and the false-positive and false-negative rates in each group were analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the method using 18F-FDG uptake features combined with maximum standard uptake value (SUVmax) (SUV method) in the differential diagnosis of solitary pulmonary lesions were evaluated. Results There were 89 malignant and 50 benign lesions. (1) The malignant incidence of the full uptake group was 84.0 % (63/75), and there were significant differences when compared with the other groups except the circular uptake group (16/23) (all P = 0.0001). The benign incidence of the multi-focus and no-uptake groups was 83.3 % (10/12) and 82.4 % (14/17), respectively, and there were significant differences when compared with the full uptake and the circular uptake groups, respectively (all P 0.05). No statistical significance was found between either two of the no-uptake, mild uptake, and multi-focus uptake groups (all P > 0.05). (2) In cases with SUVmax ≥2.5, the false-positive rate in the multi-focus uptake group was 83.3 % (10/12), which was significantly higher than in the full uptake (12/75) or circular uptake group (7/23) (all P
- Published
- 2015
17. Down-regulation of MBD4 contributes to hypomethylation and overexpression of CD70 in CD4+ T cells in systemic lupus erythematosus.
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Wei Liao, Mengying Li, Haijing Wu, Sujie Jia, Nu Zhang, Yong Dai, Ming Zhao, and Qianjin Lu
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SYSTEMIC lupus erythematosus ,CD4 antigen ,GENETIC overexpression - Abstract
Background: Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by lymphocytic infiltration and overproduction of autoantibodies, leading to significant morbidity and mortality. However, the pathogenesis of this disorder has not yet been completely elucidated. It has been reported that CD70, a B cell costimulatory molecule encoded by the gene TNFSF7 (tumor necrosis factor ligand superfamily member 7), is overexpressed in CD4
+ T cells from patients with SLE due to the demethylation of its promoter. We aimed to investigate the expression patterns of MBD4 (methyl-CpG binding domain protein 4) in CD4+ T cells and its contribution to the pathogenesis of SLE by increasing CD70 expression through epigenetic regulation. Results: Our results showed that the expression of MBD4 was significantly decreased in CD4+ T cells from SLE patients. We verified that transfection of MBD4 siRNA into healthy CD4+ T cells upregulated expression of CD70 and decreased the methylation level of the CD70 promoter. Overexpression of MBD4 inhibited CD70 expression and enhanced the DNA methylation level of CD70 in CD4+ T cells of SLE patients. Conclusion: Our results indicated that downregulation of MBD4 contributed to overexpression and hypomethylation of the CD70 gene in SLE CD4+ T cells. This modulation of MBD4 may provide a novel therapeutic approach for SLE. [ABSTRACT FROM AUTHOR]- Published
- 2017
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18. Radix Puerariae and Fructus Crataegi mixture inhibits renal injury in type 2 diabetes via decreasing of AKT/PI3K.
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Zhengyue Chen, Yanyan Yuan, Xinrong Zou, Mengqi Hong, Ming Zhao, Yu Zhao, Yuanping Liu, Guofu Li, Yabin Zhu, Lin Luo, Beiyan Bao, and Shizhong Bu
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KIDNEY disease prevention ,ANIMAL experimentation ,DIABETIC nephropathies ,HERBAL medicine ,POLYMERASE chain reaction ,RATS - Abstract
Background: Radix puerariae (RP) is a herbal medicines for diabetes, mainly because of anti-oxidative, insulin resistance and hypoglycemic effect. Fructus crataegi (FC) also possesses strong antioxidant activity in vitro. This study focused on the effects of herbal mixture of RP and FC (RPFC) on renal protection through a diabetic rat model. Methods: Type 2 Diabetic model was established with high fat diet followed by injecting rats a low dose of STZ (25 mg/kg body weight). Rats were randomly divided into five groups: normal, high fat diet, diabetes mellitus, high fat diet plus RPFC prevention, and RPFC prevention before diabetes mellitus. RPFC was given to rats daily by intragastric gavage. The blood bio-chemical index and renal pathological changes were examined. The later includes hematoxylin and eosin staining, periodic acid schiff staining, and Masson trichrome staining. Protein levels of were determined by Western blot and immunohistochemical staining. mRNA levels were detected by RT-PCR. Results: Rats prevented with RPFC resulted in decreasing blood glucose with corresponding vehicle treated rats. Glomerulus mesangial matrix expansion, renal capsule constriction, and renal tubular epithelial cell edema were less severe following RPFC prevention. Moreover, RPFC prevention reduced protein levels of PI3K, AKT, a-SMA and collagen IV in the kidney of diabetic rats. Conclusion: Combined prevention with RPFC may inhibit the PI3K/AKT pathway in the kidney, thereby prevent renal injury in diabetic rats. [ABSTRACT FROM AUTHOR]
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- 2017
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19. Selinexor (KPT-330) demonstrates anti-tumor efficacy in preclinical models of triple-negative breast cancer.
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Arango, Natalia Paez, Yuca, Erkan, Ming Zhao, Evans, Kurt W., Scott, Stephen, Kim, Charissa, Gonzalez-Angulo, Ana Maria, Janku, Filip, Ueno, Naoto T., Tripathy, Debu, Akcakanat, Argun, Aung Naing, Meric-Bernstam, Funda, Zhao, Ming, and Naing, Aung
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BREAST cancer treatment ,ANTINEOPLASTIC agents ,DRUG efficacy ,CANCER cell proliferation ,CANCER chemotherapy - Abstract
Background: Selinexor (KPT-330) is an oral agent that has been shown to inhibit the nuclear exporter XPO1. Given the pressing need for novel therapies for triple-negative breast cancer (TNBC), we sought to determine the antitumor effects of selinexor in vitro and in vivo.Methods: Twenty-six breast cancer cell lines of different breast cancer subtypes were treated with selinexor in vitro. Cell proliferation assays were used to measure the half-maximal inhibitory concentration (IC50) and to test the effects in combination with chemotherapy. In vivo efficacy was tested both as a single agent and in combination therapy in TNBC patient-derived xenografts (PDXs).Results: Selinexor demonstrated growth inhibition in all 14 TNBC cell lines tested; TNBC cell lines were more sensitive to selinexor (median IC50 44 nM, range 11 to 550 nM) than were estrogen receptor (ER)-positive breast cancer cell lines (median IC50 > 1000 nM, range 40 to >1000 nM; P = 0.017). In multiple TNBC cell lines, selinexor was synergistic with paclitaxel, carboplatin, eribulin, and doxorubicin in vitro. Selinexor as a single agent reduced tumor growth in vivo in four of five different TNBC PDX models, with a median tumor growth inhibition ratio (T/C: treatment/control) of 42% (range 31 to 73%) and demonstrated greater antitumor efficacy in combination with paclitaxel or eribulin (average T/C ratios of 27% and 12%, respectively).Conclusions: Collectively, these findings strongly suggest that selinexor is a promising therapeutic agent for TNBC as a single agent and in combination with standard chemotherapy. [ABSTRACT FROM AUTHOR]- Published
- 2017
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20. GATA3 is a sensitive marker for primary genital extramammary paget disease: an immunohistochemical study of 72 cases with comparison to gross cystic disease fluid protein 15.
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Ming Zhao, Lixin Zhou, Li Sun, Yan Song, Yunquan Guo, Xun Zhang, Feng Zhao, Peng Wang, Junqiu Yue, Dongfeng Niu, Zhongwu Li, Xiaozheng Huang, Qiang Kang, Lin Jia, Jinping Lai, and Dengfeng Cao
- Subjects
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OSTEITIS deformans , *BREAST cancer , *IMMUNOHISTOCHEMISTRY , *METASTASIS , *ADENOCARCINOMA - Abstract
Background: GATA-binding protein 3 (GATA3) has been identified as a sensitive marker for breast carcinoma but its sensitivity in primary genital extramammary Paget diseases (EMPDs) has not been well studied. Methods: Here we investigated immunohistochemical expression of GATA3 in 72 primary genital EMPDs (35 from female, 37 from male; 45 with intraepithelial disease only, 26 with both intraepithelial disease and invasive adenocarcinoma including 14 also metastasis, 1 with metastatic adenocarcinoma only for study). We also compared GATA3 to gross cystic disease fluid protein 15 (GCDFP15) for their sensitivity. Results: Positive GATA3 staining was seen in all 71 (100%) intraepithelial diseases, 25/26 (96%; female 10/10, male 15/16) invasive adenocarcinomas and 14/15 (93%; female 3/3, male 11/12) metastatic adenocarcinomas, respectively. Positive GCDFP15 staining was seen in 46/71 (65%; female 28/34 or 82%, male 18/37 or 49%) intraepithelial diseases, 20/26 (77%; female 9/10, male 11/16) invasive adenocarcinomas, and 12/15 (80%; female 2/3, male 10/12) metastatic adenocarcinomas, respectively (GATA3 versus GCDFP15: p < 0.01 for both intraepithelial disease and invasive adenocarcinoma, p = 0.28 for metastatic adenocarcinoma). In positive-stained cases, GATA3 stained more tumor cells than GCDFP15 (79% versus 25% for intraepithelial disease, 71% vs 34% for invasive adenocarcinoma, 73% vs 50% for metastatic adenocarcinoma, p < 0.01forall3components). Conclusions: Our findings indicate that GATA3 is a very sensitive marker for primary genital EMPDs and is more sensitive than GCDFP15. [ABSTRACT FROM AUTHOR]
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- 2017
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21. Buformin inhibits the stemness of erbB-2-overexpressing breast cancer cells and premalignant mammary tissues of MMTV-erbB-2 transgenic mice.
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Parris, Amanda B., Qingxia Zhao, Howard, Erin W., Ming Zhao, Zhikun Ma, and Xiaohe Yang
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GENETICS of breast cancer ,METFORMIN ,GENETIC overexpression ,MAMMARY gland cancer ,TRANSGENIC mice - Abstract
Background: Metformin, an FDA-approved drug for the treatment of Type II diabetes, has emerged as a promising anti-cancer agent. Other biguanide analogs, including buformin and phenformin, are suggested to have similar properties. Although buformin was shown to reduce mammary tumor burden in carcinogen models, the anti-cancer effects of buformin on different breast cancer subtypes and the underlying mechanisms remain unclear. Therefore, we aimed to investigate the effects of buformin on erbB-2-overexpressing breast cancer with in vitro and in vivo models. Methods: MTT, cell cycle, clonogenic/CFC, ALDEFLUOR, tumorsphere, and Western blot analyses were used to determine the effects of buformin on cell growth, stem cell populations, stem cell-like properties, and signaling pathways in SKBR3 and BT474 erbB-2-overexpressing breast cancer cell lines. A syngeneic tumor cell transplantation model inoculating MMTV-erbB-2 mice with 78617 mouse mammary tumor cells was used to study the effects of buformin (1.2 g buformin/kg chow) on tumor growth in vivo. MMTV-erbB-2 mice were also fed buformin for 10 weeks, followed by analysis of premalignant mammary tissues for changes in morphological development, mammary epithelial cell (MEC) populations, and signaling pathways. Results: Buformin significantly inhibited SKBR3 and BT474 cell growth, and in vivo activity was demonstrated by considerable growth inhibition of syngeneic tumors derived from MMTV-erbB-2 mice. In particular, buformin suppressed stem cell populations and self-renewal in vitro, which was associated with inhibited receptor tyrosine kinase (RTK) and mTOR signaling. Consistent with in vitro data, buformin suppressed mammary morphogenesis and reduced cell proliferation in MMTV-erbB-2mice. Importantly, buformin decreased MEC populations enriched with mammary reconstitution units (MRUs) and tumor-initiating cells (TICs) from MMTV-erbB-2 mice, as supported by impaired clonogenic and mammosphere formation in primary MECs. We further demonstrated that buformin-mediated in vivo inhibition of MEC stemness is associated with suppressed activation of mTOR, RTK, ER, and β-catenin signaling pathways. Conclusions: Overall, our results provide evidence for buformin as an effective anti-cancer drug that selectively targets TICs, and present a novel prevention and/or treatment strategy for patients who are genetically predisposed to erbB-2-overexpressing breast cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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22. Increased Set1 binding at the promoter induces aberrant epigenetic alterations and up-regulates cyclic adenosine 5'-monophosphate response element modulator alpha in systemic lupus erythematosus.
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Qing Zhang, Shu Ding, Huilin Zhang, Hai Long, Haijing Wu, Ming Zhao, Vera Chan, Chak-Sing Lau, and Qianjin Lu
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CYCLIC adenylic acid ,LUPUS erythematosus ,IMMUNOPRECIPITATION - Abstract
Background: Up-regulated cyclic adenosine 5'-monophosphate response element modulator α (CREMα) which can inhibit IL-2 and induce IL-17A in T cells plays a critical role in the pathogenesis of systemic lupus erythematosus (SLE). This research aimed to investigate the mechanisms regulating CREMα expression in SLE. Results: From the chromatin immunoprecipitation (ChIP) microarray data, we found a sharply increased H3 lysine 4 trimethylation (H3K4me3) amount at the CREMα promoter in SLE CD4+ T cells compared to controls. Then, by ChIP and real-time PCR, we confirmed this result. Moreover, H3K4me3 amount at the promoter was positively correlated with CREMα mRNA level in SLE CD4+ T cells. In addition, a striking increase was observed in SET domain containing 1 (Set1) enrichment, but no marked change in mixed-lineage leukemia 1 (MLL1) enrichment at the CREMα promoter in SLE CD4+ T cells. We also proved Set1 enrichment was positively correlated with both H3K4me3 amount at the CREMα promoter and CREMα mRNA level in SLE CD4+ T cells. Knocking down Set1 with siRNA in SLE CD4+ T cells decreased Set1 and H3K4me3 enrichments, and elevated the levels of DNMT3a and DNA methylation, while the amounts of H3 acetylation (H3ac) and H4 acetylation (H4ac) didn't alter greatly at the CREMα promoter. All these changes inhibited the expression of CREMα, then augmented IL-2 and down-modulated IL-17A productions. Subsequently, we observed that DNA methyltransferase (DNMT) 3a enrichment at the CREMα promoter was down-regulated significantly in SLE CD4+ T cells, and H3K4me3 amount was negatively correlated with both DNA methylation level and DNMT3a enrichment at the CREMα promoter in SLE CD4+ T cells. Conclusions: In SLE CD4+ T cells, increased Set1 enrichment up-regulates H3K4me3 amount at the CREMα promoter, which antagonizes DNMT3a and suppresses DNA methylation within this region. All these factors induce CREMα overexpression, consequently result in IL-2 under-expression and IL-17A overproduction, and contribute to SLE at last. Our findings provide a novel approach in SLE treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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23. Neuroprotective effect of a novel Chinese herbal decoction on cultured neurons and cerebral ischemic rats.
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Chui-Fun Ip, Fanny, Yu-Ming Zhao, Kim-Wan Chan, Yee-Ling Cheng, Elaine, Pui-Sze Tong, Estella, Chandrashekar, Oormila, Guang-Miao Fu, Zhong-Zhen Zhao, and Yuk-Yu Ip, Nancy
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ANALYSIS of variance ,ANIMAL experimentation ,DOSE-effect relationship in pharmacology ,ELECTROPHYSIOLOGY ,HERBAL medicine ,HIGH performance liquid chromatography ,IMMUNOHISTOCHEMISTRY ,CHINESE medicine ,RATS ,RESEARCH funding ,STATISTICS ,T-test (Statistics) ,WESTERN immunoblotting ,DATA analysis ,NEUROPROTECTIVE agents ,STROKE rehabilitation ,DESCRIPTIVE statistics ,IN vitro studies ,IN vivo studies ,PHARMACOKINETICS - Abstract
Background: Historically, traditional Chinese medicine has been widely used to treat stroke. Based on the theory of Chinese medicine and the modern pharmacological knowledge of herbal medicines, we have designed a neuroprotective formula called Post-Stroke Rehabilitation (PSR), comprising seven herbs -- Astragalus membranaceus (Fisch.) Bunge, Salvia miltiorrhiza Bunge, Paeonia lactiflora Pall., Cassia obtusifolia L., Ligusticum chuanxiong Hort., Angelica sinensis (Oliv.) Diels, and Glycyrrhiza uralensis Fisch. We aim to examine the neuroprotective activity of PSR in vitro and in vivo, and to explore the underlying molecular mechanisms, to better understand its therapeutic effect and to further optimize its efficacy. Methods: PSR extract or vehicle was applied to primary rat neurons to examine their survival effects against N- methyl-D-aspartate (NMDA)-elicited excitotoxicity. Whole-cell patch-clamp recording was conducted to examine the NMDA-induced current in the presence of PSR. ERK- and CREB-activation were revealed by western blot analysis. Furthermore, PSR was tested for CRE promoter activation in neurons transfected with a luciferase reporter. The protective effect of PSR was then studied in the rat middle cerebral artery occlusion (MCAO) model. MCAO rats were either treated with PSR extract or vehicle, and their neurobehavioral deficit and cerebral infarct were evaluated. Statistical differences were analyzed by ANOVA or t-test. Results: PSR prominently reduced the death of cultured neurons caused by NMDA excitotoxicity in a dose-dependent manner, indicating its neuroprotective property. Furthermore, PSR significantly reduced NMDA-evoked current reversibly and activated phosphorylation of ERK and CREB with distinct time courses, with the latter's kinetics slower. PSR also triggered CRE-promoter activity as revealed by the increased expression of luciferase reporter in transfected neurons. PSR effectively reduced cerebral infarct and deficit in neurological behavior in MCAO rats when PSR decoction was administered starting either 6 days before or 6 h after onset of ischemia. Conclusions: PSR is neuroprotective both in vitro and in vivo -- it protects cultured neurons against NMDA excitotoxicity, and effectively reduces ischemic injury and neurobehavioral deficit in MCAO rats in both the pre- and post-treatment regimens. The underlying neuroprotective mechanisms may involve inhibition of NMDA receptor current and activation of ERK and CREB. This study provides important preclinical data necessary for the further development of PSR for stroke treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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24. High expression of long non-coding RNA SBF2-AS1 promotes proliferation in nonsmall cell lung cancer.
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Junjie Lv, Mantang Qiu, Wenjia Xia, Chao Liu, Youtao Xu, Jie Wang, Xuechun Leng, Su Huang, Rong Zhu, Ming Zhao, Fengqing Ji, Lin Xu, Keping Xu, and Rong Yin
- Subjects
NON-coding RNA ,CELL proliferation ,LUNG cancer ,EPIGENETICS ,IMMUNOPRECIPITATION - Abstract
Background: Recent evidence has proven that long noncoding RNAs (lncRNAs) play important roles in cancer biology, while few lncRNAs have been characterized in NSCLC. Here, we characterized a novel lncRNA, SBF2 antisense RNA 1 (SBF2-AS1), in non-small cell lung cancer (NSCLC). Methods: Quantitative real-time PCR was used to quantify SBF2-AS1 expression in NSCLC tissues and cell lines. The correlation of SBF2-AS1 expression with clinicopathologic features was analyzed in a cohort NSCLC patient. Loss of function and gain of function studies were performed to determine the effects of SBF2-AS1 on proliferation and metastasis of NSCLC cells. RNA immunoprecipitation and chromosome immunoprecipitation assay was performed to confirm the interaction between SBF2-AS1 with protein and chromosome. Results: We confirmed that SBF2-AS1 was significantly upregulated in NSCLC compared with corresponding non-tumor tissues, and a high expression level of SBF2-AS1 was correlated with lymph node metastasis and advanced TNM stage. Using siRNAs specifically targeting SBF2-AS1 and plasmid vector, we successfully silenced and overexpressed SBF2-AS1 in NSCCLC cell lines and investigated its biological function both in vitro and in vivo. After the silencing of SBF2-AS1, the metastasis of NSCLC cells was significantly inhibited, the silencing of SBF2-AS1 decreased the proliferation of NSCLC cells, and the cell cycle was arrested at the G1 phase; while overexpression promoted proliferation ability. Xenograft tumor models revealed that the silencing of SBF2-AS1 inhibited tumor growth in vivo. We speculated that SBF2-AS1 might negatively regulate P21. RNA immunoprecipitation discovered that SBF2-AS2 could bind with a core component of polycomb repressive complex2, SUZ12. Additionally chromatin immunoprecipitation assay demonstrated that, after silencing SBF2-AS1, the enrichment of SUZ12 and trimethylation of histone 3 lysine 27 decreased at the promoter region of P21. Conclusions: We demonstrated that SBF2-AS1 is upregulated in NSCLC and promotes proliferation of NSCLC tumor cells. SBF2-AS1 may serve as a novel biomarker and potential therapeutic target for NSCLC patients. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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25. PU.1 controls the expression of long noncoding RNA HOTAIRM1 during granulocytic differentiation.
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Shuyong Wei, Ming Zhao, Xiaoling Wang, Yizhen Li, and Kankan Wang
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MYELOID leukemia , *TRETINOIN , *TRANSCRIPTION factors , *RNA , *CHROMATIN - Abstract
Background: Long noncoding RNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) has been characterized as a critical factor in all-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) cells. However, the essential transcription factor for gene expression of HOTAIRM1 is still unknown. Findings: Chromatin immunoprecipitation (ChIP) assays revealed that PU.1 constitutively bound to the regulatory region of HOTAIRM1. Co-expression of PU.1 led to the transactivation of the regulatory region of HOTAIRM1 in a reporter assay. Detailed analysis showed that two PU.1 motifs, which were located around +1100 bp downstream of the transcriptional start site of the HOTAIRM1 promoter, were responsible for the PU.1-dependent transactivation. The induction of HOTAIRM1 by ATRA was dependent on PU.1, and ectopic expression of PU.1 significantly up-regulated HOTAIRM1. Furthermore, low HOTAIRM1 expression was observed in APL cells, which was attributed to the reduced PU.1 expression rather than the repression by PML-RARα via the direct binding. Conclusion: PU.1 directly activates the expression of HOTAIRM1 through binding to the regulatory region of HOTAIRM1 during granulocytic differentiation. The reduced PU.1 expression, rather than PML-RARα itself, results in the low expression of HOTAIRM1 in APL cells. Our findings enrich the knowledge on the regulation of lncRNAs and the underlying mechanisms of the abnormal expression of lncRNAs involved in APL. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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26. Applicability of visceral adiposity index in predicting metabolic syndrome in adults with obstructive sleep apnea: a cross-sectional study.
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Gong-Ping Chen, Jia-Chao Qi, Bi-Ying Wang, Xin Lin, Xiao-Bin Zhang, Jian-Ming Zhao, Xiao Fang Chen, Ting Lin, Dong-Dong Chen, Qi-Chang Lin, Chen, Gong-Ping, Qi, Jia-Chao, Wang, Bi-Ying, Lin, Xin, Zhang, Xiao-Bin, Zhao, Jian-Ming, Chen, Xiao Fang, Lin, Ting, Chen, Dong-Dong, and Lin, Qi-Chang
- Subjects
SLEEP apnea syndromes ,HYPNAGOGIA ,METABOLIC syndrome ,POLYSOMNOGRAPHY ,METABOLIC disorders ,ADIPOSE tissues ,HIGH density lipoproteins ,LONGITUDINAL method ,OBESITY ,TRIGLYCERIDES ,LOGISTIC regression analysis ,BODY mass index ,CROSS-sectional method ,RETROSPECTIVE studies ,SEVERITY of illness index ,RECEIVER operating characteristic curves ,WAIST circumference - Abstract
Background: Obstructive sleep apnea (OSA) is severely affected by visceral adiposity (VA) that correlates to another disorder-metabolic syndrome (MetS). However, little is known concerning the relation of visceral adiposity index (VAI)-a novel and simple indicator of VA, with OSA and MetS. The objective of the study was to analyze the association of VAI with both disorders and applicability to identify OSA patients at risk of MetS.Methods: Consecutive individuals undergoing polysomnography and biochemical tests were enrolled, and differences in all subjects grouped by apnea-hypopnea index (AHI) were analyzed. Spearman correlation was performed for assessing the relationship between VAI, OSA-related indices and metabolic score-total number of the positive diagnostic criteria of MetS. Receiver operating characteristic (ROC) curve was conducted to obtain a cut-off value of VAI for predicting incident MetS by sex. Then, the risk of MetS in OSA patients according to the cut-offs was attained by logistic regression.Results: A total of 411 individuals were enrolled. Of whom, 361 subjects were diagnosed OSA (mild in 67 patients, moderate in 89 and severe in 205, respectively). A significant increasing trend based on AHI was observed in the variables of blood pressure, triglycerides, fasting glucose, incident MetS, metabolic score and VAI (all p < 0.05). Irrespective of gender, VAI was all significantly correlated with PSG characteristics as AHI, mean nocturnal oxygen saturation, the lowest oxygen saturation, metabolic score(all p < 0.05). A VAI of 2.282, 2.105, 2.511 (for all subjects, males and females, separately) were calculated to determine the occurrence of MetS. According to the cut-offs, OSA patients tended to suffer from greater risk in MetS (odds ratio [OR] = 10.237, p = 0.000; OR = 13.556, p = 0.000; OR = 21.458, p = 0.000).Conclusions: The present study suggested that VAI was significantly associated with MetS and OSA. As a simple and alternative approach obtained in everyday practice, it may offer a powerful tool to identify patients with OSA at risk of MetS. [ABSTRACT FROM AUTHOR]- Published
- 2016
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27. MicroRNA-26a suppresses epithelial-mesenchymal transition in human hepatocellular carcinoma by repressing enhancer of zeste homolog 2.
- Author
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De-Ning Ma, Zong-Tao Chai, Xiao-Dong Zhu, Ning Zhang, Di-Hua Zhan, Bo-Gen Ye, Cheng-Hao Wang, Cheng-Dong Qin, Yi-Ming Zhao, Wei-Ping Zhu, Man-Qing Cao, Dong-Mei Gao, Hui-Chuan Sun, and Zhao-You Tang
- Subjects
MICRORNA ,LIVER cancer ,MACROPHAGES ,CANCER cells ,CANCER cell migration ,GENETIC overexpression ,GENETICS - Abstract
Background: Our previous study reported that microRNA-26a (miR-26a) inhibited tumor progression by inhibiting tumor angiogenesis and intratumoral macrophage infiltration in hepatocellular carcinoma (HCC). The direct roles of miR-26a on tumor cell invasion remain poorly understood. In this study, we aim to explore the mechanism of miR- 26a in modulating epithelial-mesenchymal transition (EMT) in HCC. Methods: In vitro cell morphology and cell migration were compared between the hepatoma cell lines HCCLM3 and HepG2, which were established in the previous study. Overexpression and down-regulation of miR-26a were induced in these cell lines, and Western blot and immunofluorescence assays were used to detect the expression of EMT markers. Xenograft nude mouse models were used to observe tumor growth and pulmonary metastasis. Immunohistochemical assays were conducted to study the relationships between miR-26a expression and enhancer of zeste homolog 2 (EZH2) and E-cadherin expression in human HCC samples. Results: Down-regulation of miR-26a in HCCLM3 and HepG2 cells resulted in an EMT-like cell morphology and high motility in vitro and increased in tumor growth and pulmonary metastasis in vivo. Through down-regulation of EZH2 expression and up-regulation of E-cadherin expression, miR-26a inhibited the EMT process in vitro and in vivo. Luciferase reporter assay showed that miR-26a directly interacted with EZH2 messenger RNA (mRNA). Furthermore, the expression of miR-26a was positively correlated with E-cadherin expression and inversely correlated with EZH2 expression in human HCC tissue. Conclusions: miR-26a inhibited the EMT process in HCC by down-regulating EZH2 expression. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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28. Protective effects of extracts from Pomegranate peels and seeds on liver fibrosis induced by carbon tetrachloride in rats.
- Author
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Xiang-lan Wei, Ru-tang Fang, Yong-hua Yang, Xue-yuan Bi, Guo-xia Ren, A-li Luo, Ming Zhao, and Wei-jin Zang
- Subjects
SEEDS ,POMEGRANATE ,ANIMAL experimentation ,ANTIOXIDANTS ,ASPARTATE aminotransferase ,BIOLOGICAL models ,COLLAGEN ,HYALURONIC acid ,HYDROCARBONS ,LIVER diseases ,MEMBRANE proteins ,OXIDOREDUCTASES ,PROLINE ,RATS ,RESEARCH funding ,SUPEROXIDE dismutase ,T-test (Statistics) ,PLANT extracts ,OXIDATIVE stress ,FIBROSIS ,ALANINE aminotransferase ,DESCRIPTIVE statistics ,MANN Whitney U Test ,THERAPEUTICS - Abstract
Background: Liver fibrosis is a feature in the majority of chronic liver diseases and oxidative stress is considered to be its main pathogenic mechanism. Antioxidants including vitamin E, are effective in preventing liver fibrogenesis. Several plant-drived antioxidants, such as silymarin, baicalin, beicalein, quercetin, apigenin, were shown to interfere with liver fibrogenesis. The antioxidans above are polyphenols, flavonoids or structurally related compounds which are the main chemical components of Pomegranate peels and seeds, and the antioxidant activity of Pomegranate peels and seeds have been verified. Here we investigated whether the extracts of pomegranate peels (EPP) and seeds (EPS) have preventive efficacy on liver fibrosis induced by carbon tetrachloride (CCl
4 ) in rats and explored its possible mechanisms. Methods: The animal model was established by injection with 50 % CCl4 subcutaneously in male wistar rats twice a week for four weeks. Meanwhile, EPP and EPS were administered orally every day for 4 weeks, respectively. The protective effects of EPP and EPS on biochemical metabolic parameters, liver function, oxidative markers, activities of antioxidant enzymes and liver fibrosis were determined in CCl4 -induced liver toxicity in rats. Results: Compared with the sham group, the liver function was worse in CCl4 group, manifested as increased levels of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin. EPP and EPS treatment significantly ameliorated these effects of CCl4 . EPP and EPS attenuated CCl4 --induced increase in the levels of TGF-β1, hydroxyproline, hyaluronic acid laminin and procollagen type III. They also restored the decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and inhibited the formation of lipid peroxidized products in rats treated with CCl4 . Conclusion: The EPP and EPS have protective effects against liver fibrosis induced by CCl4 , and its mechanisms might be associated with their antioxidant activity, the ability of decreasing the level of TGF-β1 and inhibition of collagen synthesis. [ABSTRACT FROM AUTHOR]- Published
- 2015
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29. Mucinous tubular and spindle cell renal cell carcinoma: a review of clinicopathologic aspects.
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Ming Zhao, Xiang-lei He, and Xiao-dong Teng
- Subjects
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RENAL cell carcinoma , *MUCINOUS adenocarcinoma , *TUMOR classification , *IMMUNOHISTOCHEMISTRY , *MOLECULAR genetics , *CELL differentiation - Abstract
Mucinous tubular and spindle cell renal cell carcinoma is a rare, recently described variant of renal cell carcinoma characterized by an admixture of cuboidal cells in tubules and sheets of spindle cells, and variable amounts of mucinous stroma. It has been recognized as a distinct entity in the 2004 World Health Organization tumor classification. Since then, several dozen of these tumor have been reported with additional complementary morphologic characteristics, immunohistochemical profile, and molecular genetic features that have further clarified its clinicopathologic aspects. Although originally considered as a low grade renal cell carcinoma on the basis of its bland appearing nuclear features and indolent clinical course, mucinous tubular and spindle cell renal cell carcinoma has currently been proven to be a tumor that has a histological spectrum ranging from low to high grade that includes sarcomatoid differentiation. In this review, we present a detailed summary of the current knowledge regarding the clinicopathologic, immunohistochemical, molecular genetic, and prognostic characteristics, as well as differential diagnoses of mucinous tubular and spindle cell renal cell carcinoma. [ABSTRACT FROM AUTHOR]
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- 2015
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30. Alveolar soft part sarcoma of lung: report of a unique case with emphasis on diagnostic utility of molecular genetic analysis for TFE3 gene rearrangement and immunohistochemistry for TFE3 antigen expression.
- Author
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Ming Zhao, Qiu Rao, Cuiyun Wu, Zhongsheng Zhao, Xianglei He, and Guoqing Ru
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ALVEOLAR soft part sarcomas , *LUNG cancer , *MOLECULAR genetics , *GENE rearrangement , *IMMUNOHISTOCHEMISTRY , *ANTIGENS , *GENE expression - Abstract
Alveolar soft part sarcoma (ASPS) is a rare, malignant mesenchymal tumor of distinctive clinical, morphologic, ultrastructural, and cytogenetical characteristics. It typically arises in the extremities of adolescents and young adults, but has also been documented in a number of unusual sites, thus causing diagnostic confusions both clinically and morphologically. The molecular signature of ASPS is a specific der(17)t(X;17)(p11.2;q25) translocation, which results in the fusion of TFE3 transcription factor gene at Xp11.2 with ASPL at 17q25. Recent studies have shown that the ASPL-TFE3 fusion transcript can be identified by reverse-transcriptase polymerase chain reaction analysis and TFE3 gene rearragement can be detected using a dual-color, break apart fluorescence in situ hybridization assay in paraffin-embedded tissue, and the resultant fusion protein can be detected immunohistochemically with antibody directed to the carboxy terminal portion of TFE3. Herein, we report a unique case of ASPS presenting as an asymptomatic mass in the lung of a 48 year-old woman without evidence of a primary soft tissue tumor elsewhere at the time of initial diagnosis. To the best of our knowledge, this is the third report of such cases appearing in the English language literature to date. We emphasize the differential diagnoses engendered by ASPS including a series of tumors involving the lung that have nested and alveolar growth patterns, and both clear and eosinophilic cytoplasm, and demonstrate the utility of molecular genetic analysis for TFE3 rearrangement and immunohistochemistry for TFE3 antigen expression for arriving at accurate diagnosis. [ABSTRACT FROM AUTHOR]
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- 2015
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31. The role of 18F-FDG uptake features in the differential diagnosis of solitary pulmonary lesions with PET/CT.
- Author
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Ming Zhao, Baolin Chang, Zhihua Wei, Hongtao Yu, Rongrong Tian, Ling Yuan, and Hongxing Jin
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SOLITARY pulmonary nodule , *LUNG tumors , *PRECANCEROUS conditions , *LUNG disease diagnosis , *BENIGN tumors , *PROGNOSIS , *DIAGNOSIS - Abstract
Background: The aim of this study is to evaluate the value of 18F-FDG uptake features in the diagnosis of solitary pulmonary lesions. Methods: One hundred thirty-nine patients with solitary pulmonary lesions were divided into full uptake, circular uptake, multi-focus uptake, mild uptake, and no-uptake groups according to the uptake features of 18F-FDG in solitary pulmonary lesions. The incidence of benign and malignant lesions and the false-positive and false-negative rates in each group were analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the method using 18F-FDG uptake features combined with maximum standard uptake value (SUVmax) (SUV method) in the differential diagnosis of solitary pulmonary lesions were evaluated. Results: There were 89 malignant and 50 benign lesions. (1) The malignant incidence of the full uptake group was 84.0 % (63/75), and there were significant differences when compared with the other groups except the circular uptake group (16/23) (all P = 0.0001). The benign incidence of the multi-focus and no-uptake groups was 83.3 % (10/12) and 82.4 % (14/17), respectively, and there were significant differences when compared with the full uptake and the circular uptake groups, respectively (all P < 0.05). The benign incidence of the mild uptake group was 58.3 % (7/12), and there were no significant differences when compared with the others except the full uptake group (all P > 0.05). No statistical significance was found between either two of the no-uptake, mild uptake, and multi-focus uptake groups (all P > 0.05). (2) In cases with SUVmax ≥2.5, the false-positive rate in the multi-focus uptake group was 83.3 % (10/12), which was significantly higher than in the full uptake (12/75) or circular uptake group (7/23) (all P < 0.05). In cases with SUVmax <2.5, the false-negative rates in the mild and no-uptake groups were 41.7 and 17.6 % (P = 0.218). (3) The sensitivity, specificity, accuracy, PPV, and NPV of the method using 18F-FDG uptake features combined with SUVmax and the single SUV method were 88.7 %/91.0 %, 62.0 %/42.0 %, 79.1 %/ 73.4 %, 80.6 %/73.6 %, and 75.6 %/72.4 %, respectively. Conclusions: The method using uptake features of 18F-FDG combined with SUVmax can improve the diagnostic specificity and accuracy of solitary pulmonary lesions. The multi-focus uptake feature maybe a benign sign, which still needs more researches to confirm. [ABSTRACT FROM AUTHOR]
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- 2015
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32. Systems infection biology: a compartmentalized immune network of pig spleen challenged with Haemophilus parasuis
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Hui Jin, Xinyun Li, Ming Zhao, Hongbo Chen, Rui Zhou, Shuhong Zhao, Mengjin Zhu, and Xiangdong Liu
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Haemophilus Infections ,Swine ,Systems biology ,Spleen ,Network ,Biology ,Proteomics ,Haemophilus parasuis ,Immune system ,Haemophilus ,Genetics ,medicine ,Animals ,Humans ,Scale-free, C1R ,Swine Diseases ,Systems Biology ,Immune network ,biology.organism_classification ,Pig model ,Immunogenome ,Immunity, Innate ,medicine.anatomical_structure ,Quantitative topology ,Immunology ,DNA microarray ,Biological network ,Biotechnology ,Research Article - Abstract
Background Network biology (systems biology) approaches are useful tools for elucidating the host infection processes that often accompany complex immune networks. Although many studies have recently focused on Haemophilus parasuis, a model of Gram-negative bacterium, little attention has been paid to the host's immune response to infection. In this article, we use network biology to investigate infection with Haemophilus parasuis in an in vivo pig model. Results By targeting the spleen immunogenome, we established an expression signature indicative of H. parasuis infection using a PCA/GSEA combined method. We reconstructed the immune network and estimated the network topology parameters that characterize the immunogene expressions in response to H. parasuis infection. The results showed that the immune network of H. parasuis infection is compartmentalized (not globally linked). Statistical analysis revealed that the reconstructed network is scale-free but not small-world. Based on the quantitative topological prioritization, we inferred that the C1R-centered clique might play a vital role in responding to H. parasuis infection. Conclusions Here, we provide the first report of reconstruction of the immune network in H. parasuis-infected porcine spleen. The distinguishing feature of our work is the focus on utilizing the immunogenome for a network biology-oriented analysis. Our findings complement and extend the frontiers of knowledge of host infection biology for H. parasuis and also provide a new clue for systems infection biology of Gram-negative bacilli in mammals.
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- 2013
33. The docking protein p130Cas regulates cell sensitivity to proteasome inhibition
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Kristiina Vuori and Ming Zhao
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Sequestosome-1 Protein ,Physiology ,Integrin ,Plant Science ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Focal adhesion ,Growth factor receptor ,Structural Biology ,Animals ,lcsh:QH301-705.5 ,Ecology, Evolution, Behavior and Systematics ,Paxillin ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,Cell Biology ,Fibroblasts ,eye diseases ,humanities ,Cell biology ,Crk-Associated Substrate Protein ,lcsh:Biology (General) ,embryonic structures ,biology.protein ,Signal transduction ,General Agricultural and Biological Sciences ,human activities ,Proteasome Inhibitors ,Intracellular ,Developmental Biology ,Biotechnology ,Research Article - Abstract
Background The focal adhesion protein p130Cas (Cas) activates multiple intracellular signaling pathways upon integrin or growth factor receptor ligation. Full-length Cas frequently promotes cell survival and migration, while its C-terminal fragment (Cas-CT) produced upon intracellular proteolysis is known to induce apoptosis in some circumstances. Here, we have studied the putative role of Cas in regulating cell survival and death pathways upon proteasome inhibition. Results We found that Cas-/- mouse embryonic fibroblasts (MEFs), as well as empty vector-transfected Cas-/- MEFs (Cas-/- (EV)) are significantly resistant to cell death induced by proteasome inhibitors, such as MG132 and Bortezomib. As expected, wild-type MEFs (WT) and Cas-/- MEFs reconstituted with full-length Cas (Cas-FL) were sensitive to MG132- and Bortezomib-induced apoptosis that involved activation of a caspase-cascade, including Caspase-8. Cas-CT generation was not required for MG132-induced cell death, since expression of cleavage-resistant Cas mutants effectively increased sensitivity of Cas-/- MEFs to MG132. At the present time, the domains in Cas and the downstream pathways that are required for mediating cell death induced by proteasome inhibitors remain unknown. Interestingly, however, MG132 or Bortezomib treatment resulted in activation of autophagy in cells that lacked Cas, but not in cells that expressed Cas. Furthermore, autophagy was found to play a protective role in Cas-deficient cells, as inhibition of autophagy either by chemical or genetic means enhanced MG132-induced apoptosis in Cas-/- (EV) cells, but not in Cas-FL cells. Lack of Cas also contributed to resistance to the DNA-damaging agent Doxorubicin, which coincided with Doxorubicin-induced autophagy in Cas-/- (EV) cells. Thus, Cas may have a regulatory role in cell death signaling in response to multiple different stimuli. The mechanisms by which Cas inhibits induction of autophagy and affects cell death pathways are currently being investigated. Conclusion Our study demonstrates that Cas is required for apoptosis that is induced by proteasome inhibition, and potentially by other death stimuli. We additionally show that Cas may promote such apoptosis, at least partially, by inhibiting autophagy. This is the first demonstration of Cas being involved in the regulation of autophagy, adding to the previous findings by others linking focal adhesion components to the process of autophagy.
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- 2011
34. DNA methylation profiling of the X chromosome reveals an aberrant demethylation on CXCR3 promoter in primary biliary cirrhosis.
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Lleo, Ana, Weici Zhang, Ming Zhao, Yixin Tan, Bernuzzi, Francesca, Bochen Zhu, Qian Liu, Qiqun Tan, Malinverno, Federica, Valenti, Luca, Tingting Jiang, Lina Tan, Wei Liao, Coppel, Ross, Invernizzi, Pietro, Qianjin Lu, Adams, David H., and Gershwin, M. Eric
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DNA methylation ,X chromosome ,DEMETHYLATION ,BILIARY liver cirrhosis ,AUTOIMMUNITY - Abstract
Background: Although the etiology of primary biliary cirrhosis (PBC) remains enigmatic, there are several pieces of data supporting the thesis that a strong genetic predisposition and environmental factors interact to produce a selective loss of tolerance. The striking female predominance of PBC has suggested that this sex predisposition may be secondary to epigenetic alterations on the X chromosome. In the present study, we rigorously defined the X chromosome methylation profile of CD4, CD8, and CD14 cells from 30 PBC patients and 30 controls. Genomic DNA from sorted CD4, CD8, and CD14 subpopulations was isolated, sonicated, and immunoprecipitated for analysis of methylation. All products were hybridized to a custom-tiled four-plex array containing 27,728 CpG islands annotated by UCSC and 22,532 well-characterized RefSeq promoter regions. Furthermore, bisulfite sequencing was then used for validation on a subsequent group of independent samples from PBC patients and controls. Thence, expression levels of selected X-linked genes were evaluated by quantitative real-time PCR with cDNA samples from all subjects. Results: We report herein that a total of 20, 15, and 19 distinct gene promoters reflected a significant difference in DNA methylation in CD4+ T, CD8+ T, and CD14+ cells in patients with PBC. Interestingly, there was hypermethylation of FUNDC2 in CD8+ T cells and a striking demethylation of CXCR3 in CD4+ T cells, which inversely correlated with CXCR3 expression levels in CD4+ T cells from early-stage PBC patients. Conclusions: Our data provides a set of genes with epigenetic alteration likely to be indicators of autoimmunity and emphasizes the role of CXCR3 in the natural history of PBC. [ABSTRACT FROM AUTHOR]
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- 2015
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35. The role of microRNA-1246 in the regulation of B cell activation and the pathogenesis of systemic lupus erythematosus.
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Shuangyan Luo, Yu Liu, Gongping Liang, Ming Zhao, Haijing Wu, Yunsheng Liang, Xiangning Qiu, Yixin Tan, Yong Dai, Susan Yung, Tak-Mao Chan, and Qianjin Lu
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- 2015
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36. Hypomethylation and overexpression of ITGAL (CD11a) in CD4+ T cells in systemic sclerosis.
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YaoYao Wang, Ye Shu, YangFan Xiao, Qing Wang, Takuro Kanekura, YaPing Li, JiuCun Wang, Ming Zhao, QianJin Lu, and Rong Xiao
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- 2014
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37. Seroprevalence, risk factors and genotyping of Toxoplasma gondii in domestic geese (Anser domestica) in tropical China.
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Guang Rong, Han-Lin Zhou, Guan-Yu Hou, Jun-Ming Zhao, Tie-Shan Xu, and Song Guan
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SEROPREVALENCE ,TOXOPLASMA gondii ,GEESE ,LIVESTOCK diseases ,TOXOPLASMA ,DISEASES ,DISEASE risk factors ,DIAGNOSIS - Abstract
Background Little information is available about the seroprevalence of Toxoplasma gondii infection in geese (Anser domestica) in China. In the present investigation, the seroprevalence, risk factors and genotyping of T. gondii in geese were investigated in Hainan province, tropical China. Findings A total of 600 serum samples and 150 brain tissue samples were collected from six administrative regions in tropical China, and assayed for T. gondii antibodies by Indirect Haemagglutination (IHA) test. Genomic DNA was extracted from the 30 brain tissues of seropositive geese and T. gondii B1 gene was amplified using a semi-nested PCR. DNA samples giving positive B1 amplification were then genetically characterized using multilocus PCR-RFLP. Overall, 17% (95% CI: 14-20) of the animals were positive for T. gondii antibodies. Presence of cats in the household (odds ratio, OR 3), hygiene (OR 2.3) and presence of stray cat around the house (OR 2.3) were considered as main risk factors associated with T. gondii infection. Of 30 DNA samples, three were positive for the T. gondii B1 gene, two showed complete genotyping results. Only one genotype (type II) was identified. Conclusions The results of the present survey indicated the presence of T. gondii infection in geese in tropical China. Therefore, it is imperative that improved integrated measures be carried out to prevent and control T. gondii infection in geese in this province. This is the first report documenting the occurrence of T. gondii genotype in geese in China. [ABSTRACT FROM AUTHOR]
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- 2014
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38. Norcantharidin inhibits tumor growth and vasculogenic mimicry of human gallbladder carcinomas by suppression of the PI3-K/MMPs/ Ln-5γ2 signaling pathway.
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Jing-Tao Zhang, Wei Sun, Wen-Zhong Zhang, Chun-Yan Ge, Zhong-Yan Liu, Ze-Ming Zhao, Xing-Sui Lu, and Yue-Zu Fan
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GALLBLADDER cancer ,HETEROCYCLIC compounds ,CELLULAR signal transduction ,PHOSPHATIDYLINOSITOL 3-kinases ,MATRIX metalloproteinases ,ANTINEOPLASTIC agents ,DONOR blood supply - Abstract
Background: Vasculogenic mimicry (VM) is a novel tumor blood supply in some highly aggressive malignant tumors. Recently, we reported VM existed in gallbladder carcinomas (GBCs) and the formation of the special passage through the activation of the PI3K/MMPs/Ln-5γ2 signaling pathway. GBC is a highly aggressive malignant tumor with disappointing treatments and a poor prognosis. Norcantharidin (NCTD) has shown to have multiple antitumor activities against GBCs, etc; however the exact mechanism is not thoroughly elucidated. In this study, we firstly investigated the anti-VM activity of NCTD as a VM inhibitor for GBCs and its underlying mechanisms. Methods: In vitro and in vivo experiments to determine the effects of NCTD on proliferation, invasion, migration, VM formation, hemodynamic and tumor growth of GBC-SD cells and xenografts were respectively done by proliferation, invasion, migration assays, H&E staining and CD31-PAS double stainings, optic/electron microscopy, tumor assay, and dynamic micro-MRA. Further, immunohistochemistry, immunofluorescence, Western blotting and RT-PCR were respectively used to examine expression of VM signaling-related markers PI3-K, MMP-2, MT1-MMP and Ln-5γ2i n GBC-SD cells and xenografts in vitro and in vivo. Results: After treatment with NCTD, proliferation, invasion, migration of GBC-SD cells were inhibited; GBC-SD cells and xenografts were unable to form VM-like structures; tumor center-VM region of the xenografts exhibited a decreased signal in intensity; then cell or xenograft growth was inhibited. Whereas all of untreated GBC-SD cells and xenografts formed VM-like structures with the same conditions; the xenograft center-VM region exhibited a gradually increased signal; and facilitated cell or xenograft growth. Furthermore, expression of MMP-2 and MT1-MMP products from sections/supernates of 3-D matrices and the xenografts, and expression of PI3-K, MMP-2, MM1-MMP and Ln-5γ2 proteins/mRNAs of the xenografts were all decreased in NCTD or TIMP-2 group; (all P<0.01, vs. control group); NCTD down-regulated expression of these VM signaling-related markers in vitro and in vivo. Conclusions: NCTD inhibited tumor growth and VM of human GBCs in vitro and in vivo by suppression of the PI3-K/MMPs/Ln-5γ2 signaling pathway. It is firstly concluded that NCTD may be a potential anti-VM agent for human GBCs. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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39. Norcantharidin inhibits tumor growth and vasculogenic mimicry of human gallbladder carcinomas by suppression of the PI3-K/MMPs/Ln-5γ2 signaling pathway.
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Jing-Tao Zhang, Wei Sun, Wen-Zhong Zhang, Chun-Yan Ge, Zhong-Yan Liu, Ze-Ming Zhao, Xing-Sui Lu, and Yue-Zu Fan
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GALLBLADDER cancer ,TUMOR growth ,PHOSPHATIDYLINOSITOL 3-kinases ,VASCULOGENIC mimicry ,MATRIX metalloproteinases ,LAMININS ,MICRORNA - Abstract
Background: Vasculogenic mimicry (VM) is a novel tumor blood supply in some highly aggressive malignant tumors. Recently, we reported VM existed in gallbladder carcinomas (GBCs) and the formation of the special passage through the activation of the PI3K/MMPs/Ln-5γ2 signaling pathway. GBC is a highly aggressive malignant tumor with disappointing treatments and a poor prognosis. Norcantharidin (NCTD) has shown to have multiple antitumor activities against GBCs, etc; however the exact mechanism is not thoroughly elucidated. In this study, we firstly investigated the anti-VM activity of NCTD as a VM inhibitor for GBCs and its underlying mechanisms. Methods: In vitro and in vivo experiments to determine the effects of NCTD on proliferation, invasion, migration, VM formation, hemodynamic and tumor growth of GBC-SD cells and xenografts were respectively done by proliferation, invasion, migration assays, H&E staining and CD31-PAS double stainings, optic/electron microscopy, tumor assay, and dynamic micro-MRA. Further, immunohistochemistry, immunofluorescence, Western blotting and RT-PCR were respectively used to examine expression of VM signaling-related markers PI3-K, MMP-2, MT1-MMP and Ln-5γ2 in GBC-SD cells and xenografts in vitro and in vivo. Results: After treatment with NCTD, proliferation, invasion, migration of GBC-SD cells were inhibited; GBC-SD cells and xenografts were unable to form VM-like structures; tumor center-VM region of the xenografts exhibited a decreased signal in intensity; then cell or xenograft growth was inhibited. Whereas all of untreated GBC-SD cells and xenografts formed VM-like structures with the same conditions; the xenograft center-VM region exhibited a gradually increased signal; and facilitated cell or xenograft growth. Furthermore, expression of MMP-2 and MT1-MMP products from sections/supernates of 3-D matrices and the xenografts, and expression of PI3-K, MMP-2, MM1-MMP and Ln-5γ2 proteins/mRNAs of the xenografts were all decreased in NCTD or TIMP-2 group; (all P < 0.01, vs. control group); NCTD down-regulated expression of these VM signaling-related markers in vitro and in vivo. Conclusions: NCTD inhibited tumor growth and VM of human GBCs in vitro and in vivo by suppression of the PI3-K/MMPs/Ln-5γ2 signaling pathway. It is firstly concluded that NCTD may be a potential anti-VM agent for human GBCs. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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40. Superparamagnetic iron oxide nanoparticles mediated 131I-hVEGF siRNA inhibits hepatocellular carcinoma tumor growth in nude mice.
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Jing Chen, Shu Zhu, Liangqian Tong, Jiansha Li, Fei Chen, Yunfeng Han, Ming Zhao, and Wei Xiong
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SUPERPARAMAGNETIC materials ,IRON oxides ,SMALL interfering RNA ,LIVER cancer ,TUMOR growth ,LABORATORY mice ,NANOMEDICINE ,GENE therapy ,RADIOTHERAPY - Abstract
Background Hepatocellular carcinoma (HCC) is a primary liver tumor and is the most difficult human malignancy to treat. In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously. This was achieved through targeting HCC with superparamagnetic iron oxide nanoparticles (SPIOs) carrying small interfering RNA with radiolabled iodine 131 (
131 I) against the human vascular endothelial growth factor (hVEGF). Methods hVEGF siRNA was labeled with131 I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs.131 I-hVEGF siRNA/SilenceMag was then subcutaneously injected into nude mice with HCC tumors exposed to an external magnetic field (EMF). The biodistribution and cytotoxicity of131 I-hVEGF siRNA/SilenceMag was assessed by SPECT (Single-Photon Emission Computed Tomography) and MRI (Magnetic Resonance Imaging) studies and blood kinetics analysis. The body weight and tumor size of nude mice bearing HCC were measured daily for the 4-week duration of the experiment. Results I-hVEGF siRNA/SilenceMag was successfully labeled; with a satisfactory radiochemical purity (>80%) and biological activity in vitro. External application of an EMF successfully attracted and retained more131 I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with131 I-hVEGF siRNA/SilenceMag grew nearly 50% slower in the presence of EMF than those without EMF and the control. Immunohistochemical assay confirmed that the tumor targeted by131 I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control. Conclusions EMF-guided131 I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of131 I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging. [ABSTRACT FROM AUTHOR]- Published
- 2014
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41. STRAD pseudokinases regulate axogenesis and LKB1 stability.
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Veleva-Rotse&, Biliana O., Smart, James L., Baas, Annette F., Edmonds, Benjamin, Zi-ming Zhao, Brown, Allyson, Klug, Lillian R., Hansen, Kelly, Reilly, Gabrielle, Gardner, Alexandria P., Krishnaveni Subbiah, Gaucher, Eric A., Clevers, Hans, and Barnes, Anthony P.
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MORPHOGENESIS ,NEURAL development ,THREONINE ,NEOPLASTIC cell transformation ,PROTEIN stability ,PROTOPLASMIC streaming - Abstract
Background Neuronal polarization is an essential step of morphogenesis and connectivity in the developing brain. The serine/threonine kinase LKB1 is a key regulator of cell polarity, metabolism, tumorigenesis, and is required for axon formation. It is allosterically regulated by two related and evolutionarily conserved pseudokinases, STe20-Related ADapters (STRADs) α and β. The roles of STRADα and STRADβ in the developing nervous system are not fully defined, nor is it known whether they serve distinct functions. Results We find that STRADα is highly spliced and appears to be the primal STRAD paralog. We report that each STRAD is sufficient for axogenesis and in promoting cell survival in the developing cortex. We also reveal a reciprocal protein-stabilizing relationship in vivo between LKB1 and STRADα, whereby STRADα specifically maintains LKB1 protein levels via cytoplasmic compartmentalization. Conclusions We demonstrate a novel role for STRADβ in axogenesis and also show for the first time in vivo that STRADα, but not STRADβ, is responsible for LKB1 protein stability. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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42. Prevalence of chronic kidney disease across levels of glycemia among adults in Pudong New Area, Shanghai, China.
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Yi Zhou, Echouffo-Tcheugui, Justine B., Jian-jun Gu, Xiao-nan Ruan, Gen-ming Zhao, Wang-hong Xu, Li-ming Yang, Hong Zhang, Hua Qiu, Narayan, K. M. Venkat, and Qiao Sun
- Subjects
KIDNEY diseases ,GLYCEMIC index ,BLOOD pressure ,CONFIDENCE intervals ,BODY mass index - Abstract
Background Few population-based studies have examined the relationship between glycemic status and chronic kidney disease (CKD) in China. We examined the prevalence of CKD across categories of glycemia [diagnosed diabetes, undiagnosed diabetes (fasting plasma glucose [FPG] ⩾ 126 mg/dL), prediabetes (FPG 100-126 mg/dL) and normal glycemia (FPG <100 mg/dL)] among Chinese adults and assessed the relative contribution of dysglycemia (prediabetes and/or diabetes) to the burden of CKD. Methods 5,584 Chinese adults aged 20-79 years were selected from the Pudong New Area of Shanghai through a multistage random sampling. Demographic and lifestyle characteristics, anthropometry and blood pressure were measured. Biochemical assays included FPG, serum creatinine and lipids, urinary creatinine and albumin. Prevalence of albuminuria [urine albumin-to-creatinine ratio (ACR) ⩾ 30 mg/g], decreased kidney function and CKD (either decreased kidney function or albuminuria) across levels of glycemia were estimated. Results The prevalence of albuminuria, decreased kidney function and CKD each increased with higher glycemic levels (P < 0.001). Based on the MDRD Study equation, the unadjusted CKD prevalence was 30.9%, 28.5%, 14.1% and 9.2% in those with diagnosed diabetes, undiagnosed diabetes, prediabetes and normoglycemia, respectively. The corresponding age-, gender- and hypertension-adjusted CKD prevalence were 25.8%, 25.0%, 12.3% and 9.1%, respectively. In a multivariable analysis, the factors associated with CKD were hypertension (Odds ratio [OR] 1.70, 95% confidence interval [CI]: 1.42-2.03), dysglycemia (OR 1.65, 95% CI: 1.39-1.95), female gender (OR 1.48, 95% CI: 1.25-1.75), higher triglycerides (OR 1.14, 95% CI: 1.08-1.20 per mmol/L), higher body mass index (OR 1.08, 95% CI: 1.05-1.10 per kg/m2), and older age (OR 1.02, 95% CI: 1.01 -1.03 per year). The population attributable risks (PARs) associated with diabetes, prediabetes, dysglycemia (diabetes and prediabetes) and hypertension were 18.4%, 19.7%, 30.3% and 44.5% for CKD as defined by the MDRD study equation, and 15.8%, 24.4%, 29.2% and 10.0% with the CKD-EPI equation. Estimates of prevalence and ORs of the relative contribution of various risk factors to CKD obtained with the CKD-EPI equation were similar. Conclusions As much as 30% of the CKD burden may be associated with dysglycemia among Chinese adults, independent of age, gender and hypertension status. Prevention and control of diabetes and prediabetes should be a high priority in reducing the CKD burden in China. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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43. Detecting early-warning signals of type 1 diabetes and its leading biomolecular networks by dynamical network biomarkers.
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Xiaoping Liu, Rui Liu, Xing-Ming Zhao, and Luonan Chen
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TYPE 1 diabetes ,MOUSE diseases ,BLOOD sugar analysis ,BIOMARKERS ,DISEASE progression ,GENE expression in mammals ,HYPERGLYCEMIA - Abstract
Background: Type 1 diabetes (T1D) is a complex disease and harmful to human health, and most of the existing biomarkers are mainly to measure the disease phenotype after the disease onset (or drastic deterioration). Until now, there is no effective biomarker which can predict the upcoming disease (or pre-disease state) before disease onset or disease deterioration. Further, the detail molecular mechanism for such deterioration of the disease, e.g., driver genes or causal network of the disease, is still unclear. Methods: In this study, we detected early-warning signals of T1D and its leading biomolecular networks based on serial gene expression profiles of NOD (non-obese diabetic) mice by identifying a new type of biomarker, i.e., dynamical network biomarker (DNB) which forms a specific module for marking the time period just before the drastic deterioration of T1D. Results: Two dynamical network biomarkers were obtained to signal the emergence of two critical deteriorations for the disease, and could be used to predict the upcoming sudden changes during the disease progression. We found that the two critical transitions led to peri-insulitis and hyperglycemia in NOD mices, which are consistent with other independent experimental results from literature. Conclusions: The identified dynamical network biomarkers can be used to detect the early-warning signals of T1D and predict upcoming disease onset before the drastic deterioration. In addition, we also demonstrated that the leading biomolecular networks are causally related to the initiation and progression of T1D, and provided the biological insight into the molecular mechanism of T1D. Experimental data from literature and functional analysis on DNBs validated the computational results. [ABSTRACT FROM AUTHOR]
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- 2013
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44. Chimeric antigen receptor containing ICOS signaling domain mediates specific and efficient antitumor effect of T cells against EGFRvIII expressing glioma.
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Chan-Juan Shen, Yu-Xiu Yang, Han, Ethan Q., Na Cao, Yun-Fei Wang, Yi Wang, Ying-Ying Zhao, Li-Ming Zhao, Jian Cui, Gupta, Puja, Wong, Albert J., and Shuang-Yin Han
- Subjects
T cells ,GLIOMAS ,EPIDERMAL growth factor ,ANTIGENS ,XENOGRAFTS ,LENTIVIRUSES ,CYTOKINES - Abstract
Background: Adoptive transfer of chimeric antigen receptor (CAR)-modified T cells appears to be a promising immunotherapeutic strategy. CAR combines the specificity of antibody and cytotoxicity of cytotoxic T lymphocytes, enhancing T cells' ability to specifically target antigens and to effectively kill cancer cells. Recent efforts have been made to integrate the costimulatory signals in the CAR to improve the antitumor efficacy. Epidermal growth factor receptor variant III (EGFRvIII) is an attractive therapeutic target as it frequently expresses in glioma and many other types of cancers. Our current study aimed to investigate the specific and efficient antitumor effect of T cells modified with CAR containing inducible costimulator (ICOS) signaling domain. Methods: A second generation of EGFRvIII/CAR was generated and it contained the EGFRvIII single chain variable fragment, ICOS signaling domain and CD3ζ chain. Lentiviral EGFRvIII/CAR was prepared and human CD3
+ T cells were infected by lentivirus encoding EGFRvIII/CAR. The expression of EGFRvIII/CAR on CD3+ T cells was confirmed by flow cytometry and Western blot. The functions of EGFRvIII/CAR+ T cells were evaluated using in vitro and in vivo methods including cytotoxicity assay, cytokine release assay and xenograft tumor mouse model. Results: Chimeric EGFRvIIIscFv-ICOS-CD3ζ (EGFRvIII/CAR) was constructed and lentiviral EGFRvIII/CAR were made to titer of 106 TU/ml. The transduction efficiency of lentiviral EGFRvIII/CAR on T cells reached around 70% and expression of EGFRvIII/CAR protein was verified by immunoblotting as a band of about 57 kDa. Four hour51 Cr release assays demonstrated specific and efficient cytotoxicity of EGFRvIII/CAR+ T cells against EGFRvIII expressing U87 cells. A robust increase in the IFN-γ secretion was detected in the co-culture supernatant of the EGFRvIII/CAR+ T cells and the EGFRvIII expressing U87 cells. Intravenous and intratumor injection of EGFRvIII/CAR+ T cells inhibited the in vivo growth of the EGFRvIII expressing glioma cells. Conclusions: Our study demonstrates that the EGFRvIII/CAR-modified T cells can destroy glioma cells efficiently in an EGFRvIII specific manner and release IFN-γ? in an antigen dependent manner. The specific recognition and effective killing activity of the EGFRvIII-directed T cells with ICOS signaling domain lays a foundation for us to employ such approach in future cancer treatment. [ABSTRACT FROM AUTHOR]- Published
- 2013
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45. Association between socioeconomic status and obesity in a Chinese adult population.
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Yuanyuan Xiao, Naiqing Zhao, Hao Wang, Jie Zhang, Qingfang He, Danting Su, Ming Zhao, Lixin Wang, Xinwei Zhang, Weiwei Gong, Ruying Hu, Min Yu, Gangqiang Ding, Liming Cong, and Zhen Ye
- Subjects
SOCIOECONOMIC factors ,OBESITY ,BODY mass index ,REGRESSION analysis - Abstract
Background: Existing studies which regarding to the association between individual socioeconomic status (SES) and obesity are still scarce in developing countries. The major aim of this study is to estimate such association in an adult population which was drawn from an economically prosperous province of China. Methods: Study population was determined by multilevel randomized sampling. Education and income were chosen as indicators of individual SES, general obesity and abdominal obesity were measured by body mass index (BMI) and waist circumference (WC). Descriptive statistical methods were used to depict overall and factor-specific distributions of general and abdominal obesity among 16,013 respondents. Two-step logistic regression models were fitted on gender basis. Results: The age-and-sex adjusted rates of general overweight, general obesity, abdominal overweight and abdominal obesity in study population were 28.9% (95%CI: 27.9%-29.9%), 7.5% (95%CI: 7.0%-8.1%), 32.2% (95%CI: 31.2%-33.3%) and 12.3% (95%CI: 11.6%-13.1%), respectively. Based on model fitting results, a significant inverse association between education and obesity only existed in women, while in men, income rather than education was positively related to obesity. Conclusions: The atypical SES-obesity relationship we found reflected the on-going social economy transformation in affluent regions of China. High-income men and poorly-educated women were at higher risk of obesity in Zhejiang province, thus merit intense focuses. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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46. Spatial-temporal variations of Schistosoma japonicum distribution after an integrated national control strategy: a cohort in a marshland area of China.
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Yi-Biao Zhou, Song Liang, Geng-Xin Chen, Chris Rea, Shi-Min Han, Zong-Gui He, Yuan-Pei Li, Jian-Guo Wei, Gen-Ming Zhao, and Qing-Wu Jiang
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SCHISTOSOMA japonicum ,SPATIAL variation ,BIOLOGICAL variation ,COHORT analysis ,STATISTICAL correlation ,INFECTIOUS disease transmission - Abstract
Background: Schistosomiasis transmission is typically focal. Understanding spatial variations of Schistosoma infections and their associated factors is important to help to invent site-specific intervention strategies. Methods: A five-year longitudinal study was carried out prospectively in 12 natural villages, Guichi district of Anhui province. A GIS-based spatial analysis was conducted to identify geographic distribution patterns of schistosomiasis infections at the household scale. Results: The results of the spatial autocorrelation analysis for 2005 showed that there were significant spatial clusters of human infections at the household level, and these results were in agreement with that of the spatial scan statistic. As prevalence of infections in humans decreased over the course of control, the spatial distribution of these infections became less heterogeneous. Conclusions: The findings imply that it may be necessary to re-assess risk factors of S. japonicum transmission over the course of control and to adjust accordingly control measures in the communities. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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47. Chromosomal evolution of Escherichia coli for the efficient production of lycopene.
- Author
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Yun-Yan Chen, Hong-Jie Shen, Yan-Yan Cui, Shang-Guang Chen, Zhi-Ming Weng, Ming Zhao, and Jian-Zhong Liu
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GENE expression ,ESCHERICHIA coli ,PLASMIDS ,BIOMARKERS ,LYCOPENE - Abstract
Background: Plasmid-based overexpression of genes has been the principal strategy for metabolic engineering. However, for biotechnological applications, plasmid-based expression systems are not suitable because of genetic instability, and the requirement for constant selective pressure to ensure plasmid maintenance. Results: To overcome these drawbacks, we constructed an Escherichia coli lycopene production strain that does not carry a plasmid or an antibiotic marker. This was achieved using triclosan-induced chromosomal evolution, a high gene copy expression system. The engineered strain demonstrated high genetic stability in the absence of the selective agent during fermentation. The replacement of native appγ promoter with a T5 promoter, and the deletion of the iclR gene in E. coli CBW 12241 further improved lycopene production. The resulting strain, E. coli CBW 12241(ΔiclR, PT5-appγ), produced lycopene at 33.43 mg per gram of dry cell weight. Conclusions: A lycopene hyper-producer E. coli strain that does not carry a plasmid or antibiotic marker was constructed using triclosan-induced chromosomal evolution. The methods detailed in this study can be used to engineer E. coli to produce other metabolites. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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48. Systems infection biology: a compartmentalized immune network of pig spleen challenged with Haemophilus parasuis.
- Author
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Ming Zhao, Liu, Xiang-dong, Li, Xin-yun, Chen, Hong-bo, Jin, Hui, Rui Zhou, Zhu, Meng-jin, and Zhao, Shu-hong
- Subjects
- *
SWINE diseases , *GENE expression , *IMMUNOGENETICS , *HAEMOPHILUS diseases , *SYSTEMS biology , *SPLEEN , *GRAM-negative bacteria , *QUANTITATIVE research - Abstract
Background: Network biology (systems biology) approaches are useful tools for elucidating the host infection processes that often accompany complex immune networks. Although many studies have recently focused on Haemophilus parasuis, a model of Gram-negative bacterium, little attention has been paid to the host's immune response to infection. In this article, we use network biology to investigate infection with Haemophilus parasuis in an in vivo pig model. Results: By targeting the spleen immunogenome, we established an expression signature indicative of H. parasuis infection using a PCA/GSEA combined method. We reconstructed the immune network and estimated the network topology parameters that characterize the immunogene expressions in response to H. parasuis infection. The results showed that the immune network of H. parasuis infection is compartmentalized (not globally linked). Statistical analysis revealed that the reconstructed network is scale-free but not small-world. Based on the quantitative topological prioritization, we inferred that the C1R-centered clique might play a vital role in responding to H. parasuis infection. Conclusions: Here, we provide the first report of reconstruction of the immune network in H. parasuis-infected porcine spleen. The distinguishing feature of our work is the focus on utilizing the immunogenome for a network biology-oriented analysis. Our findings complement and extend the frontiers of knowledge of host infection biology for H. parasuis and also provide a new clue for systems infection biology of Gram-negative bacilli in mammals. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
49. Exploring drug combinations in genetic interaction network.
- Author
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Yin-Ying Wang, Ke-Jia Xu, Jiangning Song, and Xing-Ming Zhao
- Subjects
GENETICS ,DRUG efficacy ,ATROPINE ,PRALIDOXIME compounds ,DOSAGE forms of drugs ,DROSOPHILA - Abstract
Background: Drug combination that consists of distinctive agents is an attractive strategy to combat complex diseases and has been widely used clinically with improved therapeutic effects. However, the identification of efficacious drug combinations remains a non-trivial and challenging task due to the huge number of possible combinations among the candidate drugs. As an important factor, the molecular context in which drugs exert their functions can provide crucial insights into the mechanism underlying drug combinations. Results: In this work, we present a network biology approach to investigate drug combinations and their target proteins in the context of genetic interaction networks and the related human pathways, in order to better understand the underlying rules of effective drug combinations. Our results indicate that combinatorial drugs tend to have a smaller effect radius in the genetic interaction networks, which is an important parameter to describe the therapeutic effect of a drug combination from the network perspective. We also find that drug combinations are more likely to modulate functionally related pathways. Conclusions: This study confirms that the molecular networks where drug combinations exert their functions can indeed provide important insights into the underlying rules of effective drug combinations. We hope that our findings can help shortcut the expedition of the future discovery of novel drug combinations. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
50. The drug cocktail network.
- Author
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Ke-Jia Xu, Jiangning Song, and Xing-Ming Zhao
- Subjects
DRUG side effects ,DRUG interactions ,DRUG development ,DRUG administration ,DRUG therapy ,DRUG utilization - Abstract
Background: Combination of different agents is widely used in clinic to combat complex diseases with improved therapy and reduced side effects. However, the identification of effective drug combinations remains a challenging task due to the huge number of possible combinations among candidate drugs that makes it impractical to screen putative combinations. Results: In this work, we construct a 'drug cocktail network' using all the known effective drug combinations extracted from the Drug Combination Database (DCDB), and propose a network-based approach to investigate drug combinations. Our results show that the agents in an effective combination tend to have more similar therapeutic effects and share more interaction partners. Based on our observations, we further develop a statistical approach termed as DCPred (Drug Combination Predictor) to predict possible drug combinations by exploiting the topological features of the drug cocktail network. Validating on the known drug combinations, DCPred achieves the overall AUC (Area Under the receiver operating characteristic Curve) score of 0.92, indicating the predictive power of our proposed approach. Conclusions: The drug cocktail network constructed in this work provides useful insights into the underlying rules of effective drug combinations and offer important clues to accelerate the future discovery of new drug combinations. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
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