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Upregulation of Zip14 correlates with induction of endoplasmic reticulum stress(ERS)in hypertrophied hearts of Dahl saltsensitive rats

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BIOCELL 2022年第3期46卷 667-675页

作者： JINYONG HUANG TIANMING TENG BO BIAN YUCHEN XUE LONGFEI HUANG ZHELONG XU QING YANG YUEMIN SUN department of Cardiology Tianjin Medical University General HospitalTianjin300052China department of Physiology&pathophysiology Tianjin Medical UniversityTianjin300070China

Zinc is a trace element involved in maintaining cellular structure and *** zinc is associated with left ventricular hypertrophy(LVH),there have been few reports on this *** study aimed to evaluate the correlation between Zip14 and expression of endoplasmic reticulum stress(ERS)associated molecules in hypertrophied hearts of *** salt-sensitive rats were fed a high salt diet to establish a left ventricular hypertrophy(LVH)rat ***-PCR was used to determine Zip14,activating transcription factor(ATF4),ATF6,x-box-binding protein 1(xBP1),C/EBP homologous protein(CHOP),immunoglobulin-binding protein(BiP)mRNA *** blotting was used to evaluate Zip14,BiP,CHOP,GAPDH *** levels were measured by Inductively Coupled Plasma Optical Emission *** results indicated that compared with the Control group,Zip14 mRNA and protein expression in LVH rat hearts were markedly increased(P<0.01).Zinc content in rat heart tissue was significantly increased in the LVH group compared with the Control group(P<0.05).ATF4,ATF6,xBP1 mRNA expressions were increased in LVH rat hearts compared with Control hearts(P<0.001).Compared with the Control group,CHOP and BiP mRNA and protein expression were markedly increased in LVH rat hearts(P<0.05,P<0.01).Linear regression models showed that Zip14 mRNA expressions were positively correlated with zinc concentration,ATF4 and ATF6 mRNA expressions in Control hearts(P=0.0005,P=0.0052,P=0.0026,respectively)and LVH rat hearts(P<0.0001,P=0.0119,P=0.0033,respectively).In conclusion,upregulation of Zip14 in LVH rat hearts correlated with zinc accumulation and induction of ERS.

关键词： Zinc Zip14 Endoplasmic reticulum stress(ERS) Left ventricular hypertrophy(LVH) Rat hearts

TRANSFORMING GROWTH FACTOR-β1 AND SMAD4 SIGNALING PATHWAY DOWN-REGULATES RENAL EXTRACELLULAR MATRIX DEGRADATION IN DIABETIC RATS

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Chinese Medical Sciences Journal 2007年第4期22卷 243-249页

作者： Qin Yang Ru-jia Xie Ting Yang Li Fang Bing Han Guo-zhong Zhang Ming-liang Cheng department of pathophysiology Guiyang Medical College Guiyang 550004 department of Infectious Diseases Affiliated Hospital of Guiyang Medical College Guiyang 550004

Objective To investigate the role of transforming growth factor-131 （TGF-β1）/Smad4 pathway in development of renal fibrosis in streptozotocin （STZ）-induced diabetic nephropathy （DN） rats and explore its possible mechanism. Methods Male Wistar rats weighing 180-220 g were divided into 5 groups： group A （ normal control）, group B [ diabetes mellitus （DM） 2 weeks ], group C （ DM 4 weeks）, group D （ DM 8 weeks）, and group E （ DM 16 weeks）. Except for the normal control group, other groups were induced DM by single injection of STZ （55 mg/kg） respectively. Blood glucose level, serum creatinine, and 24-hour urine protein were examined. Expressions of TGF-β1 and Smad4 protein and mRNA in kidney were detected using immunohistochemical technique, Western blot, and real-time PCR. mRNA expressions of stromelysin-1 （ MMP-3 ）, tissue inhibitor of metalloproteinase-1 （ TIMP-1 ）, and collagen Ⅲ in kidney were also detected by real-time PCR. Results The levels of blood glucose, serum creatinine, and 24-hour urine protein in rats of group B, C, D, and E were higher than those of the control group. With the progression of renal fibrosis, the expressions of TGF-β1 and Smad4 protein and mRNA in kidney of diabetic rats elevated. In addition, the renal MMP-3 mRNA expression diminished in diabetic rats, while TIMP-1 and collagen Ⅲ mRNA increased. Conclusions In STZ-induced diabetic rats, the TGF-β1/Smad4 appears to play an important role in renal fibrosis of DN. The increased expression of TGF-β1 and Smad4 might result in the transcriptional regulation of downstream target genes of TGF-β1/Smad4 pathway, which contributes to the progression of renal fibrosis in diabetic rats.

关键词： transforming growth factor-β1 Smad4 diabetes mellitus renal fibrosis

Efficiency of adenoviral vector mediated CTLA4Ig gene delivery into mesenchymal stem cells

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Chinese Medical Journal 2003年第11期116卷 1649-1654页

作者：邓宇斌郭小荑原清涛李树浓 department of Pathopbysiology Zhongshan Medical College Sun Yat-sen University Guangzhou 510080 China department of pathophysiology Zhongshan Medical College Sun Yat-sen University Guangzhou 510080 China

Objective To prevent Graft-versus-host disease (GVHD) in rat model, we evaluated the feasibility of mesenchymal stem cells (MSCs) as a gene transfer target and studied the efficiency of recombinant adenovirus mediated gene therapy.Methods We constructed the recombinant adenovirus containing CTLA4lg gene. Rat MSCs of passages 3-5 were infected by the adenovirus, and the transfection efficiency was monitored by GFP markers. We performed flow cytometric analysis, immunohistochemical and Western blotting analysis to identify the CTLA4lg expression. The gene transferred MSCs were tested for their ability to inhibit the allogeneic lymphocyte response in vitro and to prevent GVHD in a rat model.Results Recombinant adenovirus pAd-CTLA4lg was correctly constructed and confirmed. After MSCs were infected by the adenovirus, the CTLA4lg protein was detected not only in transgenic MSCs, but also in the culture medium. In a mixed lymphocytes response (MLR) test, the transgenic MSCs could significantly inhibit the allogeneic lymphocyte response compared with the control groups (P < 0. 05) . A model of GVHD was developed by transplanting bone marrow cells and spleen lymphocytes of F344 rats to lethally irradiated SD rats. The onset of GVHD could be ameliorated or prevented by co-administration of transgenic MSCs. All the rats in the control groups suffered severe acute GVHD. CTLA4lg expression was observed in the liver, intestine, kidney and spleen 30 days post- transplantation.Conclusions Our results indicate that adenoviral vectors could efficiently transfer CTLA4lg gene into MSCs and sustain long-term stable expression in vitro and in vivo.

关键词： CTLA4Ig · adenoviral vector · mesenchymal stem cells · mixed lymphocytes response

MEMBRANE STABILIZATION ACTION OF METALLOTHIONEIN ON RAT HEPATIC LYSOSOMES

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Chinese Science Bulletin 1990年第6期35卷 509-512页

作者：唐朝枢李兆萍苏静怡程时 department of pathophysiology Beijing Medical University Beijing 100083 PRC department of Biophysics Beijing Medical University Beijing 100083 PRC

It is known that the synthesis of metallothionein (MT) is significantly augmented under stress conditions such as intoxication, infection, trauma, inflammation and radiation injury.

关键词： metallothionein lysosome hypoxia.

Newborns' sleep-wake cycle development on amplitude integrated electroencephalography

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World Journal of Pediatrics 2016年第3期12卷 327-334页

作者： Xu-Fang Li Yan-Xia Zhou Lian Zhang department of Neonatology Guangzhou Women and Children's Medical CenterGuangzhouChina department of Electro-neurophysiology Guangzhou Women and Children's Medical CenterGuangzhouChina

Background:To observe the development of neonatal sleep among healthy infants of different conceptional age(CA)by analyzing the amplitude-integrated electroencephalography(aEEG)of their sleep-wake cycles(SWC).Methods:Bedside aEEG monitoring was carried out for healthy newborns from 32 to 46 weeks CA between September 1,2011 and August 30,*** each aEEG tracing,mean duration of every complete SWC,number of SWC repetition within 12 hours,mean duration of each narrow and broadband of SWC,mean voltage of the upper edge and lower edge of SWC,mean bandwidth of SWC were counted and *** of the correlations between voltages or bandwidth of SWC and CA was performed to assess the developmental changes of central nervous system of newborns with different ***:The SWC of different CA on aEEG showed clearly identifiable trend after 32 weeks of *** occurrence of SWC gradually increases from preterm to post-term infants;term infants had longer SWC *** voltage of upper edge of the broadband decreased at 39 weeks,while the lower edge voltage increases and the bandwidth of broadband declined along with the growing *** upper edge of the narrowband dropped while the lower edge rised gradually,especially in preterm *** width of the narrowband narrowed down while CA ***:The SWC on aEEG of 32-46 weeks infants showed a continuous,dynamic and developmental *** appearance of SWC and the narrowing bandwidth of narrowband is the main indicator to identify the CA-dependent SWC from the preterm to the late preterm *** lower edge of the broadband identifi es the term to post-term period.

关键词： amplitude-integrated electroencephalography conceptional age development newborn sleep-wake cycle

ETIOLOGICAL ROLE OF ALTERNARIA ALTERNATA IN HUMAN ESOPHAGEAL CANCER

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中华医学杂志(英文版) 1992年第5期105卷 394-400页

作者：刘桂亭钱玉珍张鹏董伟华祁园明郭洪涛 department of pathophysiology Henan Medical University Zhengzhou.

In this paper,the mutagenicity andcarcinogenicity of alternariol monomethyl ether(AME),alternariol(AOH),and their relevance to theetiology of human esophageal cancer were *** mycotoxins were produced by Alternariaalternata which was the main contaminating fungi iso-lated from the grain in Linxian County,an area withhigh incidence of esophageal *** study dem-onstrated that:*** and AOH might cause cellmutagenicity and transformation;*** and AOHcould combine with the DNA isolated from humanfetal esophageal epithelium,activate the oncogens,c-H-ras and c-mys in it,and promote proliferation ofhuman fetal esophageal epithelium in vitro;*** cell carcinoma of the fetal esophagus couldbe induced by *** to the results of thestudies of AME and AOH mentioned above,we con-sider that Alternaria alternata plays an important rolein the etiology of human esophageal cancer.

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A Preliminary Study of The Short Circuit Current(I_(sc)) Responses of Endometria from Estrum and Bilateral Ovariectomy Female Rats

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Journal of Reproduction and Contraception 2010年第4期21卷 203-212页

作者： Jing-dong XU Li-sheng LI Hua GUO Xiao-li HOU Yue ZhANG Xiao-suo FU Jin-xia ZHU department of Physiology and pathophysiology Basic Medical College Capital Medical University Beijing 100069 China

Objective To investigate the property of the endometrium ion transport in the normal estruation and ovariectomize rats. Methods The basic electrophysiological property of the endometrium was carried out by mean of the short circuit current （Isc） recording with the rats. Results The baseline Lsc and the transepithelial resistance （Rte） were different between the estruation and ovariectomized groups. Apical application of Na＋ channel blocker, amiloride （10 μmol/L）, or CFTR Cl- channel agonist, forskolin （10 μmol/L） did not significantly affect the Lc in the two groups. However, the 1sc in the model group was more sensitive to the CFTR Cl- channel blocker （glibenclamide, 1 mmol/L, apical） decreased about 27.0% （P〈0.05, n=6）, no remarkably changes in the estruation rats. While apical application CA CC CI-channel blocker, DIDS （4, 4 ＇-diisothiocyanostilbene- 2,2 ＇-disulfonic, 100 μmol/L）, the Isc was much more sensitive, percentage almost to 36.52% （P〈0.01） in the model group than that in the control Furthermore, basolateral application of bumetanide （100μmol/L）, a blocker of Na＋-K＋-2Cl- cotransport, didn＇t significantly reduce the Lc in the two groups. Conclusion The baseline Lsc and membrane resistance in the ovariectomize group is much higher than that in the normal estruation group, and the endometrial epithelium CI- secretion may be mediated by predominantly calcium-dependent CI- channels （CACC） and activating adenylate cyclase and apical cAMP-dependent Cl- channels （CFTR） in the model group with minor contributions in the control. Furthermore, the endometrial epithelium responses to different stimulants exists difference in the control and model group a likely mechanism for the ovary hormone.

关键词： endometrial epithelium short-circuit current ovariectomized rat

Crosstalk between gut microbiota and sepsis

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Burns & Trauma 2021年第1期9卷 145-156页

作者： Mengwei Niu Peng Chen department of pathophysiology Guangdong Provincial Key Laboratory of ProteomicsSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

Sepsis is an overwhelming inflammatory response to microbial *** management remains a clinical *** role of the gut microbiome in sepsis has gained some *** evidence has demonstrated that gut microbiota regulate host physiological homeostasis mediators,including the immune system,gut barrier function and disease susceptibility ***,maintenance or restoration of microbiota and metabolite composition might be a therapeutic or prophylactic target against critical *** microbiota transplantation and supplementation of probiotics are microbiota-based treatment methods that are somewhat limited in terms of evidence-based *** review focuses on the importance of the crosstalk between the gastrointestinal ecosystem and sepsis to highlight novel microbiota-targeted therapies to improve the outcomes of sepsis treatment.

关键词： Sepsis Microbiota Immune Gut barrier Liver Fecal microbiota transplantation Probiotics

Epigenetic and metabolic regulation of breast cancer stem cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2015年第1期16卷 10-17页

作者： Hui-xin LIU Xiao-li LI Chen-fang DONG department of Pathology and pathophysiology School of Medicine Zhejiang University

Breast cancer has a relatively high mortality rate in women due to recurrence and metastasis. Increasing evidence has identified a rare population of cells with stem cell-like properties in breast cancer. These cells, termed cancer stem cells （CSCs）, which have the capacity for self-renewal and differentiation, contribute significantly to tumor progression, recurrence, drug resistance and metastasis. Clarifying the mechanisms regulating breast CSCs has important implications for our understanding of breast cancer progression and therapeutics. A strong connection has been found between breast CSCs and epithelial mesenchymal transition （EMT）. In addition, recent studies suggest that the maintenance of the breast CSC phenotype is associated with epigenetic and metabolic regulation. In this review, we focus on recent discoveries about the connection between EMT and CSC, and advances made in under- standing the roles and mechanisms of epigenetic and metabolic reprogramming in controlling breast CSC properties.

关键词： Cancer stem cells (CSCs) Epithelial mesenchymal transition (EMT) Epigenetic modification Metabolicreprogramming Breast cancer