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Calcium signaling of pancreatic acinar cells in the pathogenesis of pancreatitis

World Journal of Gastroenterology 2014年第43期20卷 16146-16152页

作者： Jun li Rui Zhou Jian Zhang zong-fang li National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy the Second Affiliated Hospital of Xi’an Jiaotong University College of Medicine Department of General Surgery National Local Joint Engineering Research Center of Biodiagnostics and Biotherapythe Second Affiliated Hospital of Xi’an Jiaotong University College of Medicine

Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca2+) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca2+ overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca2+ signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca2+ elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca2+ from stores in the intracellular endoplasmic reticulum and/or increased Ca2+ entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca2+ by the sarco/endoplasmic reticulum Ca2+-activated ATPase and plasma membrane Ca2+-ATPase pumps, which contribute to Ca2+ overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca2+ signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. Research is currently underway to establish the mechanisms and interactions of Ca2+ signals in the pathogenesis of pancreatitis.

关键词： Pancreatitis Calcium signaling Pancreatic acinar cells Overload Cell injury

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Perspectives of traditional Chinese medicine in pancreas protection for acute pancreatitis

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World Journal of Gastroenterology 2017年第20期23卷 3615-3623页

作者： Jun li Shu Zhang Rui Zhou Jian Zhang zong-fang li National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy the Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy Department of General Surgerythe Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine

Acute pancreatitis(AP)is one of the most common *** is associated with significant morbidity and mortality,but it lacks specific and effective *** Chinese medicine(TCM)is one of the most popular complementary and alternative medicine modalities worldwide for the treatment of *** current evidence from basic research and clinical studies has shown that TCM has good therapeutic effects on *** review summarizes the widely used formulas,single herbs and monomers that are used to treat AP and the potential underlying mechanisms of *** of the abundance,low cost,and safety of TCM as well as its ability to target various aspects of the pathogenesis,TCM provides potential clinical benefits and a new avenue with tremendous potential for the future treatment of AP.

关键词： Acute pancreatitis Traditional Chinese medicine Alternative therapy Pancreas protection Anti-inflammatory

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Induction of apoptosis and cell cycle arrest in human HCC MHCC97H cells with Chrysanthemum indicum extract

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World Journal of Gastroenterology 2009年第36期15卷 4538-4546页

作者： zong-fang li Zhi-Dong Wang Yuan-Yuan Ji Shu Zhang Chen Huang Jun li Xian-Ming Xia Department of General Surgery The Second Affiliated Hospital School of Medicine Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China Scientific Research and Experiment Center The Second Affiliated Hospital School of Medicine Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China Key Laboratory of Environment and Genes Related to Diseases of the Education Ministry School of Medicine Xi'an Jiaotong University Xi'an710061 Shaanxi Province China

AIM： To investigate the effects of Chrysanthemum indicum extract （CIE） on inhibition of proliferation and on apoptosis, and the underlying mechanisms, in a human hepatocellular carcinoma （HCC） MHCC97H cell line. METHODS： Viable rat hepatocytes and human endothelial ECV304 cells were examined by trypan blue exclusion and MTT assay, respectively, as normal controls. The proliferation of MHCC97H cells was determined by MTT assay. The cellular morphology of MHCC97H cells was observed by phase contrast microscopy. Flow cytometry was performed to analyze cell apoptosis with annexin V/propidium iodide （PI）, mitochondrial membrane potential with rhodamine 123 and cell cycle with PI in MHCC97H cells. Apoptotic proteins such as cytochrome C, caspase-9, caspase-3 and cell cycle proteins, including P21 and CDK4, were measured by Western blotting. RESULTS： CIE inhibited proliferation of MHCC97H cells in a timeand dose-dependent manner without cytotoxicity in rat hepatocytes and human endothelial ceils. CIE induced apoptosis of MHCC97H cells in a concentration-dependent manner, as determined by flow cytometry. The apoptosis was accompanied by a decrease in mitochondrial membrane potential, release of cytochrome C and activation of caspase-9 and caspase-3. CIE arrested the cell cycle in the S phase by increasing P21 and decreasing CDK4 protein expression. CONCLUSION： CIE exerted a significant apoptotic effect through a mitochondrial pathway and arrested the cell cycle by regulation of cell cycle-related proteins in MHCC97H cells without an effect on normal cells. The cancer-specific selectivity shown in this study suggests that the plant extract could be a promising novel treatment for human cancer.

关键词： Apoptosis Cell cycle Chinese traditionalmedicine Chrysanthemum indicum Hepatocellularcarcinoma Herbal medicine

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Inhibitory effects of saikosaponin-d on CCl_4-induced hepatic fibrogenesis in rats

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World Journal of Gastroenterology 2007年第4期13卷 557-563页

作者： Shuang-Suo Dang Bao-Feng Wang Yan-An Cheng Ping Song Zhen-Guo liu zong-fang li Department of Infectious Diseases Second Hospital of Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China Department of Surgery Second Hospital of Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China

AIM： To investigate the suppressive effect of saikosaponin-d （SSd） on hepatic fibrosis in rats induced by CCh injections in combination with alcohol and high fat, low protein feeding and its relationship with the expression of nuclear factor-κB （NF-κB）, tumor necrosis factor-alpha （TNF-α） and interleukins-6 （IL-6）. METHODS： Hepatic fibrosis models were induced by subcutaneous injection of CCh at a dosage of 3 mL/kg in rats. At the same time, rats in treatment groups were injected intraperitoneally with SSd at different doses （1.0, 1.5 and 2.0 mg/kg） once daily for 6 wk in combination with CCh, while the control group received olive oil instead of CCh. At the end of the experiment, rats were anesthetized and killed （except for 8 rats which died during the experiment; 2 from the model group, 3 in high-dose group, 1 in medium-dose group and 2 in lowdose group）. Hernatoxylin and eosin （HE） staining and Van Gieson staining were used to examine the changes in liver pathology. The levels of alanine aminotransferase （ALT）, triglyeride （TG）, albumin （ALB）, globulin （GLB）, hyaluronic acid （HA） and larninin （LN） in serum and the content of hydroxyproline （HYP） in liver were measured by biochemical examinations and radioimmuneoassay, respectively. In addition, the expression of TNF-α and IL-6 in liver homogenate was evaluated by enzymelinked immunosorbent assay （EliSA） and the levels of NF-κBp65 and I-κBa in liver tissue were analyzed by Western blotting. RESULTS： Both histological examination and Van Gieson staining demonstrated that SSd could attenuate the area and extent of necrosis and reduce the scores of liver fibrosis. Similarly, the levels of ALT, TG, GLB, HA, and LN in serum, and the contents of HYP, TNF-α and IL-6 in liver were all significantly increased in model group in comparison with those in control group. Whereas, the treatment with SScl markedly reduced all the above parameters compared with the model group, especially in the medium group （ALT： 412 ± 94.5 IU/L

关键词： Saikosaponin-d Hepatic fibrosis Tumornecrosis factor Interleukins-6 Nuclear factor-KB Inhibitory κB alpha

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Changes in count and function of splenic lymphocytes from patients with portal hypertension

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World Journal of Gastroenterology 2008年第15期14卷 2377-2382页

作者： zong-fang li Shu Zhang Gao-Bo Lv Ying Huang Wei Zhang Song Ren Jun Yang Shuang-Suo Dang Department of General Surgery in Cadres Ward the Second Affiliated Hospital School of Medicine Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China Department of Pathology the Second Affiliated Hospital School of Medicine Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China Department of Infectious Diseases the Second Affiliated Hospital School of Medicine Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China

AIM: To investigate changes in numbers and proliferative function of splenic lymphocytes in patients with hypersplenism due to portal hypertension (PH), to provide evidence for further study of immune status of the spleen during PH. METHODS: Twelve spleens from patients with hypersplenism due to PH served as the PH group, and four spleens from cases of traumatic spleen rupture were regarded as the control group. After weighing the spleen, lymphocytes were separated and counted using a cell counting plate to calculate the lymphocyte count per gram of spleen tissue (relative quantity) and total lymphocyte count in whole spleen (absolute quantity). The immunohistochemical SP method was used to observe the density and distribution of lymphocytes in the spleen. The MTT method was used to observe changes in lymphocyte proliferative function. RESULTS: As compared to the control group, the splenic lymphocytes in the PH group showed that: (1) There was no difference in distribution but a significant decreasein density; (2) the number of lymphocytes per gram of spleen (relative quantity) decreased significantly (0.822 ± 0.157) × 108 vs (1.174 ± 0.254) × 108, P liferative function of lymphocytes was enhanced: T lymphocytes, (0.022 ± 0.005 vs 0.015 ± 0.003, P liferating function. With respect to changes in lymphocytes, PH spleens may still have immune function, although it may be disordered. However, complete evaluation of the immune function of the sple

关键词： Portal hypertension Spleen Lymphocyte Immune function

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Scutellaria barbate extract induces apoptosis of hepatoma H22 cells via the mitochondrial pathway involving caspase-3

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World Journal of Gastroenterology 2008年第48期14卷 7321-7328页

作者： Zhi-Jun Dai Xi-Jing Wang zong-fang li zong-Zheng Ji Hong-Tao Ren Wei Tang Xiao-Xu liu Hua-Feng Kang Hai-Tao Guan ling-Qin Song Department of Oncology the Second Affiliated Hospital Medical School of Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China Department of General Surgery the Second Affiliated Hospital Medical School of Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China Department of life Science Shaanxi Normal University Xi'an 710061 Shaanxi Province China

AIM： To study the growth inhibitory and apoptotic effects of Scutellaria barbata *** （S. barbata） and to determine the underlying mechanism of its antiturnor activity in mouse liver cancer cell line ***： Proliferation of H22 cells was examined by MTT assay. Cellular morphology of PC-2 cells was observed under fluorescence microscope and transmission electron microscope （EM）. Mitochondrial transmembrane potential was determined under laser scanning confocal microscope （LSCM） with rhodamine 123 staining. Flow cytometry was performed to analyze the cell cycle of H22 cells with propidium iodide staining. Protein level of cytochrome C and caspase-3 was measured by semi-quantitive RT-PCR and Western blot analysis. Activity of caspase-3 enzyme was measured by ***： M-I-I- assay showed that extracts from S. barbata （ESB） could inhibit the proliferation of H22 cells in a time-dependent manner. Among the various phasesof cell cycle, the percentage of cells in S phase was significantly decreased, while the percentage of cells in G1 phase was increased. Flow cytometry assay also showed that ESB had a positive effect on apoptosis. Typical apoptotic morphologies such as condensation and fragmentation of nuclei and blebbing membrane of apoptotic cells could be observed under transmission electron microscope and fluorescence microscope. To further investige the molecular mechanism behind ESB-induced apoptosis, ESB-treated cells rapidly lost their mitochondrial transmembrane potential, released mitochondrial cytochrome C into cytosol, and induced caspase-3 activity in a dose-dependent manner. CONCLUSION： ESB can effectively inhibit the proliferation and induce apoptosis of H22 cells involving loss of mitochondrial transmembrane potential, release of cytochrome C, and activation of caspase-3.

关键词： Scute/laria barbate Hepatoma Apoptosis Mitochondrial transmembrane potential Serum pha-rmacology

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Protection mechanism of deacetylase inhibitor on spleen of rats with severe hemorrhagic shock

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Asian Pacific Journal of Tropical Medicine 2016年第6期9卷 553-558页

作者： Gao-Rong Deng Qiang ling Bing-Hua Wu Yu-Ying Dong Xiang Gao Tai-Qiang li Xin Miu zong-fang li The Second Affiliated Hospital of Xi'an Jiaotong University Department of Orthopedics Nanchang University Fourth Affiliated Hospital

Objective: To explore the protection and molecular mechanism of histone deacetylase inhibitors(HDACIs) on the spleen of rats with hemorrhagic shock. Methods: A total of 60 SPF male SD rats were selected for the modeling of severe hemorrhagic shock using the method of arterial and venous cannulation with the time-divided bleeding. The measurement of mean arterial blood pressure and blood lactic acid was used to verify the modeling. The modeled rats were randomly divided into shock group, shock+suberoylanilide hydroxamic acid(SAHA) group, shock+autogenous transfusion group, and shock+SAHA+autogenous transfusion group. Three hours after the treatment, the spleen of rats was collected and TUNEL method was employed to detect the apoptosis of spleen cells in each group. Afterwards, real-time PCR and western blot were employed to detect the expression of BCL-2, BAX, and caspass3 in the spleen of rats in each group. Results: A total of 55 rats had successful modeling of severe hemorrhagic shock, with success rate of 92%. Cell apoptosis in the severe hemorrhagic model group was the most serious. After the intervention of HDACIs and the autogenous transfusion, the tissue injury was a bit recovered. Cell apoptosis was least in the shock+SAHA+autogenous transfusion group(P<0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BCL-2 was significantly increased(P<0.05), with highest relative expression of BCL-2 in shock+SAHA+autogenous transfusion group(P<0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BAX was significantly decreased(P<0.05), with lowest relative expression of BAX in the intervention group of single HDACIs. The change in the expression of caspass3 was similar to BAX, namely the relative expression of caspass3 was significantly decreased after the intervention of HDACIs and the autogenous transfusion(P<0.05). Conclusions: HDACIs and autogenous transfusion can all protec

关键词： Hemorrhagic shock HDACIs Apoptosis Histone acetylation

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Exogenous phosphatidylethanolamine induces apoptosis of human hepatoma HepG2 cells via the bcl-2/bax pathway

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World Journal of Gastroenterology 2009年第14期15卷 1751-1758页

作者： Yu Yao Chen Huang zong-fang li Ai-Ying Wang li-Ying liu Xiao-Ge Zhao Yu Luo Lei Ni Wang-Gang Zhang Tu-Sheng Song Department of Oncology First Affiliated Hospital of Medical College of Xi'an Jiaotong University Xi'an 710061 Shaanxi Province China Department of Genetics and Molecular Biology Medical School Xi'an Jiaotong University/Key Laboratory of Environment and Genes Related to Diseases Ministry of Education Xi'an 710061 Shaanxi Province China Second Affiliated Hospital of Xi'an Jiaotong University/Key Laboratory of Environment and Genes Related to Diseases Ministry of Education Xi'an 710004 Shaanxi Province China

AIM: To investigate the signaling pathways implicated in phosphatidylethanolamine (PE)-induced apoptosis of human hepatoma HepG2 cells. METHODS: Inhibitory effects of PE on human hepatoma HepG2 cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle, apoptosis and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry. Immunocytochemical assay and Western blotting were used to examine Bcl-2, Bax and caspase-3 protein levels in HepG2 cells treated with PE. RESULTS: PE inhibited the growth of HepG2 cells in a doseand timedependent manner. It did notaffect the cell cycle, but induced apoptosis. PE significantly decreased ΔΨm at 0.25, 0.5 and 1 mmol/L, respectively, suggesting that PE induces cell apoptosis by decreasing the mitochondrial transmembrane potential. The Bcl-2 expression level induced by different concentrations of PE was lower than that in control groups. However, the Bax expression level induced by PE was higher than that in the control group. Meanwhile, PE increased the caspase-3 expression in a doseand time-dependent manner. CONCLUSION: Exogenous PE induces apoptosis of human hepatoma HepG2 cells via the bcl-2/bax pathway.

关键词： Apoptosis Bcl-2 Bax Caspase-3 Phosphatidylethanolamine Human hepatoma HepG2 cell

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Emodin and baicalein inhibit sodium taurocholate-induced vacuole formation in pancreatic acinar cells

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World Journal of Gastroenterology 2018年第1期24卷 35-45页

作者： jun li rui zhou bei-bei bie na huang ying guo hai-yan chen meng-jiao shi jun yang jian zhang zong-fang li National and Local Joint Engineering Research Center of Biodiagnostics and Biotherapy the Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina

AIM To investigate the effects of combined use of emodin and baicalein(CEB) at the cellular and organism levelsin severe acute pancreatitis(SAP) and explore the underlying *** SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in 48 male SD rats. Pancreatic histopathology score, serum amylase activity, and levels of tumour necrosis factor alpha(TNf-α), interleukin 6(IL-6), and IL-10 were determined to assess the effects of CEB at 12 h after the surgery. The rat pancreatic acinar cells were isolated from healthy male SD rats using collagenase. The cell viability, cell ultrastructure, intracellular free Ca2+ concentration, and inositol(1,4,5)-trisphosphate receptor(IP3 R) expression were investigated to assess the mechanism of *** Pancreatic histopathology score(2.07 ± 1.20 vs 6.84 ± 1.13, P lity, inhibited cytosolic Ca2+ concentration, and significantly ameliorated intracellular vacuoles and IP3 m RNA expression compared with those in the SAP group(P 0.05).CONCLUSION These results at the cellular and organism levels reflect a preliminary mechanism of CEB in SAP and indicate that CEB is a suitable approach for SAP treatment.

关键词： inositol(1,4,5)-trisphosphate receptor Severe acute pancreatitis Calcium overload Emodin Baicalein Pancreatic acinar cell

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Transmission patterns of COVID-19 in the mainland of China and the efficacy of different control strategies: a data-and model-driven study

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Infectious Diseases of Poverty 2020年第4期9卷 21-34页

作者： Jian Zu Miao-Lei li zong-fang li Ming-Wang Shen Yan-Ni Xiao Fan-Pu Ji School of Mathematics and Statistics Xi'an Jiaotong UniversityXi'an 710049China National&Local Joint Engineering Research Center of Biodiagnosis and Biotherapy The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710004China Key Laboratory of Environment and Genes Related to Diseases Xi'an Jiaotong UniversityMinistry of Education of ChinaXi'an 710061China School of Public Health Health Science CenterXi'an Jiaotong UniversityXi'an 710061China Department of Infectious Diseases The Second Affiliated Hospital of Xi'an Jiaotong University157 Xi Wu RoadXi'an 710004Shaanxi ProvincePR China

Background:The coronavirus disease 2019(COVID-19)outbreak has seriously endangered the health and lives of Chinese *** this study,we predicted the COVID-19 epidemic trend and estimated the efficacy of several intervention strategies in the mainland of ***:According to the COVID-19 epidemic status,we constructed a compartmental *** on reported data from the National Health Commission of People's Republic of China during January 10-February 17,2020,we estimated the model *** then predicted the epidemic trend and transmission risk of *** a sensitivity analysis method,we estimated the efficacy of several intervention ***:The cumulative number of confirmed cases in the mainland of China will be 86763(95%CI:86067-87460)on May 2,*** until March 15,2020,the case fatality rate increased to 6.42%(95%CI:6.16-6.68%).On February 23,2020,the existing confirmed cases reached its peak,with 60890 cases(95%CI:60350-61431).On January 23,2020,the effective reproduction number was 2.620(95%CI:2.567-2.676)and had dropped below 1.0 since February 5,*** to governmental intervention,the total number of confirmed cases was reduced by 99.85%on May 2,*** the isolation been relaxed from February 24,2020,there might have been a second peak of ***,relaxing the isolation after March 16,2020 greatly reduced the number of existing confirmed cases and *** total number of confirmed cases and deaths would increase by 8.72 and 9.44%,respectively,due to a 1-day delayed diagnosis in non-isolated infected ***,if the coverage of close contact tracing was increased to 100%,the cumulative number of confirmed cases would be decreased by 88.26%on May 2,***:The quarantine measures adopted by the Chinese government since January 23,2020 were necessary and *** the relaxation of isolation,early diagnosis,patient isolation,broad close-contact tracing,and strict monitoring of infe

关键词： SARS-CoV-2 COVID-19 Transmission dynamics Prevalence Effective reproduction number Intervention strategy

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