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Calcitriol Suppressed Isoproterenol-induced Proliferation of Cardiac Fibroblasts via Integrinβ3/FAK/Akt Pathway

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Current Medical science 2023年第1期43卷 48-57页

作者： xin-feng WANG Qian LI xia SUN Li-ming ZHENG Shao-li CHENG Yan-he ZHU Department of Physiology and Pathophysiology School of Basic Medical SciencesXi’an Jiaotong University Health Science CenterXi’an710061China Department of Ultrasound the Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an710004China Basic Medical Experimental Teaching Center School of Basic Medical SciencesXi’an Jiaotong University Health Science CenterXi’an710061China Institute of Endemic Diseases School of Public HealthXi’an Jiaotong University Health Science CenterXi’an710061China

Objective Cardiac fibroblasts(CFs)proliferation and extracellular matrix deposition are important features of cardiac fibrosis.Various studies have indicated that vitamin D displays an anti-fibrotic property in chronic heart diseases.This study explored the role of vitamin D in the growth of CFs via an integrin signaling pathway.Methods MTT and 5-ethynyl-2′-deoxyuridine assays were performed to determine cell viability.Western blotting was performed to detect the expression of proliferating cell nuclear antigen(PCNA)and integrin signaling pathway.The fibronectin was observed by ELISA.Immunohistochemical staining was employed to evaluate the expression of integrinβ3.Results The PCNA expression in the CFs was enhanced after isoproterenol(ISO)stimulation accompanied by an elevated expression of integrin beta-3(β3).The blockade of the integrinβ3 with a specific integrinβ3 antibody reduced the PCNA expression induced by the ISO.Decreasing the integrinβ3 by siRNA reduced the ISO-triggered phosphorylation of FAK and Akt.Both the FAK inhibitor and Akt inhibitor suppressed the PCNA expression induced by the ISO in the CFs.Calcitriol(CAL),an active form of vitamin D,attenuated the ISO-induced CFs proliferation by downregulating the integrinβ3 expression,and phosphorylation of FAK and Akt.Moreover,CAL reduced the increased levels of fibronectin and hydroxyproline in the CFs culture medium triggered by the ISO.The administration of calcitriol decreased the integrinβ3 expression in the ISO-induced myocardial injury model.Conclusion These findings revealed a novel role for CAL in suppressing the CFs growth by the downregulation of the integrinβ3/FAK/Akt pathway.

关键词： vitamin D cardiac fibroblast proliferation integrin myocardial fibrosis

Establishment and verification of a surgical prognostic model for cervical spinal cord injury without radiological abnormality

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Neural Regeneration Research 2019年第4期14卷 713-720页

作者： Jie Wang Shuai Guo Xuan Cai Jia-Wei Xu Hao-Peng Li Second Affiliated Hospital of xi'an jiaotong university health science Center Xi'an Jiaotong University

Some studies have suggested that early surgical treatment can effectively improve the prognosis of cervical spinal cord injury without radiological abnormality, but no research has focused on the development of a prognostic model of cervical spinal cord injury without radiological abnormality. This retrospective analysis included 43 patients with cervical spinal cord injury without radiological abnormality. Seven potential factors were assessed: age, sex, external force strength causing damage, duration of disease, degree of cervical spinal stenosis, Japanese Orthopaedic Association score, and physiological cervical curvature. A model was established using multiple binary logistic regression analysis. The model was evaluated by concordant profiling and the area under the receiver operating characteristic curve. Bootstrapping was used for internal validation. The prognostic model was as follows: logit(P) =-25.4545 + 21.2576 VALUE + 1.2160SCORE-3.4224 TIME, where VALUE refers to the Pavlov ratio indicating the extent of cervical spinal stenosis, SCORE refers to the Japanese Orthopaedic Association score(0–17) after the operation, and TIME refers to the disease duration(from injury to operation). The area under the receiver operating characteristic curve for all patients was 0.8941(95% confidence interval, 0.7930–0.9952). Three factors assessed in the predictive model were associated with patient outcomes: a great extent of cervical stenosis, a poor preoperative neurological status, and a long disease duration. These three factors could worsen patient outcomes. Moreover, the disease prognosis was considered good when logit(P) ≥-2.5105. Overall, the model displayed a certain clinical value. This study was approved by the Biomedical Ethics Committee of the Second Affiliated Hospital of xi'an jiaotong university, China(approval number: 2018063) on May 8, 2018.

关键词： nerve regeneration surgical prognostic model cervical spinal cord injury retrospective study multiple binary logistic regression analysis bootstrapping internal validation multiple imputations cervical spinal stenosis duration of disease Pavlov ratio neural regeneration

Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity

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Journal of Pharmaceutical Analysis 2023年第3期13卷 262-275页

作者： Guang-Yue Li Shu-Jing Zhang Dong Xue Yue-Qi Feng Yan Li Xun Huang Qiang Cui Bo Wang Jun Feng Tao Bao Pei-Jun Liu Shao-Ying Lu Ji-Chang Wang Department of science and Technology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Department of Vascular Surgery The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Department of General Surgery The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Center for Translational Medicine The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Department of Pharmacy Xi'an Jiaotong University Health Science CenterXi'an710061China

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endothelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

关键词： Metformin Colorectal cancer Non-angiogenic Endothelial apoptosis Vascular immaturity

Remodeling the tumor microenvironment by vascular normalization and GSH-depletion for augmenting tumor immunotherapy

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Chinese Chemical Letters 2024年第2期35卷 329-334页

作者： Jin Wang Qingqing Zhang Yanchen Li xiaoyan Pan Yuanyuan Shan Jie Zhang School of Pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an 710061China Department of Pharmacy The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061China

Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and immunotherapy.Normalization of tumor vasculature as well as depletion of glutathione(GSH)can improve the TME.Here,we developed a novel therapeutic nanoparticle functional enzyme ultra QDAU5 nanoparticles(FEUQ Nps)based on a fluorescence-on and releasable strategy by combining a vascular normalization inducer,a GSH depleting agent,and an activated fluorophore.In which the cleavage of disulfide bonds releases active molecules that induce vascular normalization and improve the hypoxic microenvironment.In addition,it may deplete GSH in cancer cells,thus inducing the production of reactive oxygen species(ROS)and lipid peroxide(LPO)and promoting iron toxicity.It may also lead to endoplasmic stress and release of calmodulin,which activates the immune system.Meanwhile,quenched fluorophores are turned on in the presence of galactosidase(GLU)for tumor-specific labeling.In summary,we developed novel therapeutic agent nanoparticles with the function of vascular normalization inducers to achieve specific labeling of hepatocellular carcinoma while exerting efficient antitumor effects in vivo.

关键词： Vascular normalization Tumor microenvironment GSH depletion Ferroptosis Activated immune

A conceived model of“physician scientist”cultivation:exploring the double degrees of MD-PhD program

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Chinese Medical Journal 2020年第13期133卷 1620-1622页

作者： Wei-Jiang Dong Wen-Bin Liu Hui-Lin Gong Yan-Bin Cheng Ming Zhang Yi Lyu xiao-Jian Wu xiao-Jun Meng She-Min Lyu Li-Na Chen Qian Guo Jin-Song Zhou Hong Yan School of Basic Medical sciences Health Science Center of Xi'an Jiaotong UniversityXi'anShaanxi 710061China First Affiliated Hospital of xi'an jiaotong university Xi'anShaanxi 710061China Talent Training Office Health Science Center of Xi'an Jiaotong UniversityXi'anShaanxi 710061China health science Center of xi'an jiaotong university Xi'anShaanxi 710061China General Office Health Science Center of Xi'an Jiaotong UniversityXi'anShaanxi 710061China School of Nursing Health Science Center of Xi'an Jiaotong UniversityXi'anShaanxi 710061China

To the Editor:With the rapid economic growth and improvement of people's living standards in China,ever-greater demands for high-level health-care services hre expected.These expectations are bringing new challenges to the development of clinical doctors.However,the traditional path for doctor training is inadequate to meet these challenges,as both clinical and scientific practices are important for doctors but difficult to integrate into medical education.Thus,the current medical training system is challenged to combine scientific research training with conventional clinical training.To provide possible sol-utions,health science Center(HSC)of xian jiaotong university(XJTU)has been exploring a new mode of developing physician scientists:The Double Doctoral Program(DDP)。

关键词： doctor physician bringing

Can canines alone be used for age estimation in Chinese individuals when applying the Kvaal method?

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Forensic sciences Research 2022年第2期7卷 132-137页

作者： Mujia Li Jiamin Zhao Wenjie Chen xin Chen Guang Chu Teng Chen Yucheng Guo Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’anChina Department of Orthodontics Stomatological Hospital of Xi’an Jiaotong UniversityXi’anChina College of Medicine and Forensics Xi’an Jiaotong University Health Science CenterXi’anChina

Due to the secondary dentin formation,the dental pulp undergoes changes in shape throughout life.Based on this phenomenon,the Kvaal method has been applied to various populations for age estimation,and its usefulness has been verified.When applying the Kvaal method to Chinese subjects,we observed a relatively strong correlation between mandibular canines and age.This study notes the correlation between canines and chronological age and is the first to identify which canine is most closely related to chronological age.In addition,a new,simpler formula is determined based on canines according to Kvaal’s methodology.The radiographs of 360 individuals from northern China were selected,from which the widths and lengths of the pulp from four canines were measured according to the Kvaal method.Next,inter-and intra-observer reliabilities were analyzed in order to assess the repeatability of these measurements.The correlation between measurements and age was examined,and Chinese-specific age estimation formulae were derived.The results revealed that the ratios from the left maxillary canine exhibited the strongest correlation with age compared to the other canines,whereas the left mandibular canine showed the weakest correlation,which may contribute to the overall poor correlation of mandibular canines with age.What’s more,the formula derived from the left maxillary canine in this study displayed the highest coefficients of determination,and the formula derived from all canines showed the lowest residuals.Both of these formulae performed better than the Chinese-specific formula derived from six different types of teeth in our previous study,which had formerly possessed the highest coefficients of determination and the lowest residuals.Thus,we concluded that canines do play an important role in age estimation in the Chinese population,and the correlation between maxillary canines and chronological age is stronger than that of mandibular canines,although no distinct trend as to which side is better correlated with age was e

关键词： Forensic sciences forensic odontology age estimation canine secondary dentine Kvaal method Chinese subjects

Applications and challenges of low temperature plasma in pharmaceutical field

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Journal of Pharmaceutical Analysis 2021年第1期11卷 28-36页

作者： Lingge Gao xingmin Shi xili Wu School of Public health Medical Science CenterXi’an Jiaotong UniversityXi’an710061China Second Affiliated Hospital Xi’an Jiaotong UniversityXi’an710004China

Low temperature plasma(LTP)technology has shown an outstanding application value in the pharmaceutical filed in recent ten years.This paper reviews the research advances in LTP,including its effects on enhancing or inhibiting drug activity,its combined use with drugs to treat cancers,its effects on the improvement of drug delivery system,its use in preparation of new inactivated virus vaccines,its use with mass spectrometry for rapid detection of drug quality,and the anti-tumor and sterilization effects of plasma-activated liquids.The paper also analyzes the challenges of LTP in the pharmaceutical filed,hoping to promote related research.

关键词： Low temperature plasma Pharmacy Nanodrug Drug delivery system Plasma-activated liquids

Osteoimmunology research in rheumatoid arthritis:From single-cell omics approach

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Chinese Medical Journal 2023年第14期136卷 1642-1652页

作者： Nan Hu Jing Wang Bomiao Ju Yuanyuan Li Ping Fan xinxin Jin xiaomin Kang Shufang Wu Department of Rheumatology The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710061China Department of Physiology and Pathophysiology School of Basic Medical SciencesXi’an Jiaotong University Health Science CenterXi’anShaanxi 710061China Center for Translational Medicine The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710061China

Cellular immune responses as well as generalized and periarticular bone loss are the key pathogenic features of rheumatoid arthritis(RA).Under the pathological conditions of RA,dysregulated inflammation and immune processes tightly interact with skeletal system,resulting in pathological bone damage via inhibition of bone formation or induction of bone resorption.Singlecell omics technologies are revolutionary tools in the field of modern biological research.They enable the display of the state and function of cells in various environments from a single-cell resolution,thus making it conducive to identify the dysregulated molecular mechanisms of bone destruction in RA as well as the discovery of potential therapeutic targets and biomarkers.Here,we summarize the latest findings of single-cell omics technologies in osteoimmunology research in RA.These results suggest that single-cell omics have made significant contributions to transcriptomics and dynamics of specific cells involved in bone remodeling,providing a new direction for our understanding of cellular heterogeneity in the study of osteoimmunology in RA.

关键词： Rheumatoid arthritis Osteoimmunology Single-cell omics Single-cell RNA sequencing scATAC-seq

Cytoplasmic domain and enzymatic activity of ACE2 are not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells

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Virologica Sinica 2022年第3期37卷 380-389页

作者： Hang Yang Huijun Yuan xiaohui Zhao Meng Xun Shangrui Guo Nan Wang Bing Liu Hongliang Wang Department of Pathogen Biology and Immunology School of Basic Medical SciencesXi'an Jiaotong University Health Science CenterXi'an710061China School of Pharmacy Xi’an Jiaotong University Health Science CenterXi'an710061China BioBank The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Department of Life sciences Faculty of Natural SciencesImperial College LondonLondonSW72AZUnited Kingdom Key Laboratory of Environment and Genes Related to Diseases Xi'an Jiaotong UniversityXi'an710061China

The recent COVID-19 pandemic poses a global health emergency.Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2(ACE2).Here,by using lentivirus based pseudotypes bearing spike protein,we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis,and phosphoinositides played essential roles during this process.In addition,we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry.Finally,we showed that the current predominant Delta variant,although with high infectivity and high syncytium formation,also entered cells through clathrin-mediated endocytosis.These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.

关键词： SARS-CoV-2 Endocytosis Phosphoinositides Angiotensin converting enzyme 2(ACE2) Syncytium