Deubiquitinase BRCC36 protects heart against chronic pressure overload-induced cardiac remodeling in mice / 中国病理生理杂志

Emerging evidence has indicated that BRCC 36-mediated K63-linked ubiquitination modification was involved in diverse cellular functions , including endocytosis , apoptosis and DNA damage repair .We previously showed that activation of cGMP/PKG pathway con-tributed to the binding of BRCC36 and the pro-fibrotic factor Smad3.The current study tested the hypothesis that BRCC 36 functions as a negative regulator of transforming growth factor-beta ( TGF-β)/Smad3 pathway and participates in cardiac remodeling .In isolated adult mouse cardiac fibroblasts , we have demonstrated that TGF-β1 treatment significantly increased the expression of BRCC 36.Over-expression BRCC36 suppressed TGF-β1-induced Smad3 phosphorylation, nuclear translocation, extracellular matrix molecular expres-sion and cell proliferation .On the contrary, silencing BRCC36 by transfection of adenovirus-carrying BRCC36 shRNA potentiated to enhance the pro-fibrotic effect of TGF-β.In vivo, under chronic pressure overload condition-induced by transverse aortic constriction , myocardial pro-survival protein Bcl-2 and Mcl-1 expression were significantly decreased and the pro-apoptosis protein Puma was in-creased.However, the cardiac-specific over-expression of BRCC36 significantly increased myocardial Bcl-2 and Mcl-1 and inhibited Puma expression .Interestingly , we also found that sustained pressure overload resulted in a significant myocardial DNA injury in wild type mice, which was characterized by the increase of γH2AX level.However, cardiac-specific BRCC36 over-expression significantly decreased the level of γH2AX in the pressure overloaded heart in the transgenic mice , while effectively enhanced myocardial RAD 51 expression, a marker of DNA damage repair.Furthermore, BRCC36 over-expression effectively attenuated TAC-induced cardiac fibro-sis and remodeling in the transgenic mice , compared with the wild type mice .Collectively , the results have suggested that BRCC 36 ef-fectively protected heart against chronic pressure overload-induced cardiac remodeling though antagonizing TGF-β/Smad3 pathway and enhancing myocardial DNA injury repair response .

Relationship Between Thyroid Hormone and Atrial Fibrillation Prevalence in Patients With Chronic Heart Failure / 中国循环杂志

Objective: To investigate the impact of thyroid hormone on atrial ifbrillation (AF) prevalence in patients with chronic heart failure (CHF). Methods: A total of 322 non-valvular heart disease CHF patients treated in our hospital from 2011-0-01 to 2012-10-01 were retrospectively studied. Based on previous history and the ECG at admission, the patients were divided into 2 groups: AF group,n=187 and Sinus rhythm group,n=135. The proifle of serum levels of free thyroxine (FT4), free triiodothyronine (FT3), hyroid stimulating hormone (TSH) and LDL-C were examined within 24 hours of admission; 12 lead ECG and echocardiography were conducted to analyze the related factor for AF occurrence. Results: Compared with Sinus rhythm group, AF group had increased FT4 level as 14.52 (12.74, 15.85) pmol/L vs 13.11 (11.68, 14.85) pmol/L,P Conclusion: High serum level of FT4 may increase the risk AF occurrence in CHF patients.

Advance in function of deubiquitination enzyme BRCC36 / 中国病理生理杂志

The protein of BRCC36 is a kind of enzyme specifically hydrolyzing K 63-linked poly-ubiquitin chain and widely found in a variety of eukaryotic cells .BRCC36 recognizes diverse substrate proteins , and participates in various kinds of pathophysiological responses such as DNA damage repair , cell signal transduction and cell cycle control .It plays an important role in the process of cancer , angiogenesis and cardiac injury .This review discusses the progress in the inves-tigation on BRCC36 protein to provide the necessary information for searching new therapeutic targets of many diseases .

Effects of endotoxin on liver Smac apoptosis channel / 华中科技大学学报（医学）（英德文版）

To study the effect of endotoxin on liver apoptosis, L02 liver cells were cultured and passaged in vitro, and then stimulated by endotoxin at 10 mg/mL for 4, 8, 16 and 24 h respectively. Liver apoptosis was flow cytometrically and fluorescently detected. Immunohistochemistry was used to detect the delivery of smac and caspase9. The delivery of liver cell smac and the activity of caspase3 were measured by caspase3 assay kit. The hepatic failure models of rats were established by using D-galactosamine. The blood serum and liver tissues were collected for the detection of the liver function, the level of endotoxin and the activity of caspase3 by using chromogenic substrate limulus amebocyte lysate method (LAL) and caspase3 active assay kit. The expression of smac and caspase9 in liver cells was detected by Western blotting. With in vitro study, the L02 cells stimulated by LPS condensed into conglobation and formed apoptotic bodies. After those cells were stained by hoechst, the apoptotic cells displayed blue color under the fluorescent microscope. The apoptosis rate was increased over time and the apoptosis was mainly of advanced stage. Meanwhile, the rate of smac delivery and activity of caspase9 and caspase3 were increased on L02 cell membrane. In vivo, hepatic failure and obvious endotoxemia were induced by injection of more than 200 mg/kg D-GalN. Hepatic mitochondria smac was reduced with dosage of D-GalN and, on the contrary, the activity of caspase3 was increased. D-GalN at 200 mg/kg increased Caspase9 while D-GalN at 300 mg/kg decreased caspase9. Mitochondria signal channel plays an important role in the endotoxin-induced apoptosis of hepatic cells by promoting the release of smac from mitochondria to cytoplasm and activating caspase9 and caspase3 in its low-level channel.

Myocardial fibrosis: A chronic inflammatory process / 中国组织工程研究

OBJECTIVE:The pathophysiology of myocardial fibrosis during hypertension is complicated.Recently,it has been shown that inflammatory response plays an important role in the pathophysiology of myocardial fibrosis.This review describes the relationships among hemodynamic stress,hormonal factors and inflammatory factors,and emphasizes the important position of inflammation during the progress of myocardial fibrosis.DATA SOURCES:Using the terms of "hypertension,myocardial fibrosis,inflammatory response,angiotensin,cytokines" in English and Chinese respectively,we searched Medline database,Chinese Biological Medicine Database (CBM) and CNKI to identify English and Chinese articles of clinical researches and experiments related to the effects of inflammatory response on myocardial fibrosis during hypertension published from January 1991 to May 2007.STUDY SELECTION:The articles were primarily checked.Only articles that reported inflammatory response and myocardial fibrosis were included.The repeated researches and experiments and Meta analysis were deleted.DATA EXTRACTION:A total of 641 articles have been selected.The titles of all the articles and most of the abstracts have been read,and 162 articles met the inclusive criteria whereas the other 479 articles were deleted.42 articles have been analyzed.DATA SYNTHESIS:During hypertension,the extracellular matrix expands because of reactive and reparative fibrosis,which at last results in myocardial fibrosis.Previous clinical and experimental studies showed that hemodynamic stress and hormonal factors affected the progress of myocardial fibrosis.While recently,there are growing evidences indicating that the immune system.related with hemodynamic stress and hormonal factors is activated during hypertension in the progress of myocardial fibrosis.Then the recruitment of inflammatory cells and factors,including chemoattractant proteins,adhesion molecules and cytokines,informing cytokines cascade response,in turn accelerate the progress of myocardial fibrosis.CONCLUSION:Inflammatory response may play an important role in the pathophysiology of myocardial fibrosis during hypertension and then accelerate the progress of heart failure.

Experience of Percutanous Coronary Intervention in 57 Cases with Chronical Total Occlusion / 中国慢性病预防与控制

Objective To explore clinical characteristics of chronic total occlusion(CTO) in population with routine coronary angiography,and to cumulate therapeutic experience.Methods Retrospective analysis was performed on clinical data of 57 cases with CTO selected from 825 patients undergone coronary angiography.Results Among 57 cases,the percentage of male,myocaridial infarction,diabetes mellitus,hyperlipidermia and left ventricular dysfunction was 73.7%,84.2%,22.8%,73.7% and 22.8%,respectively.The types of lesions included single branch(n=11),double branches(n=29) and three branches(n=17).Of 70 branches lesion vessels,44 were TIMI 0 of blood flow classification and 26 were TIMI1.The position of lesions occurred at left anterior descending branch(n=32),left circumflex branch(n=16),right coronary artery(n=22).The occlusion time was less than three months(n=41) and more than three months(n=29).The lengths of lesion was divided into less than 20 mm(n=43) and more than 20 mm(n=27).The shapes of terminal lesion looked like rat-tail(n=42) and blaze knife-edge(n=28).The coronary stents were performed at 57 lesions among 70 branches and the successful rate of operation was 82.9%.Conclusions Timely coronary angiography and selecting suitable treatment on different kinds of lesions for male patients with myocardial infraction,especially complicated with diabetes mellitus,might play important roles in prevention of CTO and in improvement of the successful rate of percutanous coronary intervention for the complex lesion.

Effect of shuxuetong in preventing restenosis after intracoronary stenting / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the effect of shuxuetong (SXT) in preventing restenosis after intracoronary stenting.</p><p><b>METHODS</b>Sixty-eight patients, accepted intracoronary stenting, were divided into two groups, the SXT group and the control group, both of them were treated with conventional treatment, and to the SXT group, SXT was given additionally. The condition of treated coronary artery restenosis in the two groups was compared by way of quantitative coronary angiography and a 6-month follow-up study was adopted.</p><p><b>RESULTS</b>Follow-up study was completed in 43 patients (23 cases in the SXT group, and 20 in the control group). The angina recurrence rate in the SXT group (3 cases, 13%) was significantly lower than that in the control group (7 cases, 35%, P < 0.05). Quantitative coronary angiography showed the restenosis degree of operated artery in the SXT group was significantly milder than that in the control group, with the last lumen losing and index in the SXT group (0.46 +/- 0.25 mm, 24.26 +/- 8.64%) less than those in the control group (0.75 +/- 0.33 mm, 31.25 +/- 11.03%). The net gain lumen and the net gain index in the SXT group (1.23 +/- 0.30 mm, 58.96 +/- 24.68%) were greater than those in the control group (0.98 +/- 0.33 mm, 42.68 +/- 29.51%), all P < 0.05. But the restenosis rate in the two groups was insignificantly different (P > 0.05).</p><p><b>CONCLUSION</b>SXT might has some definite effect in preventing restenosis after intracoronary stenting.</p>

The effect of Ca~(2+) preconditioning and ischemic preconditioning on Ca~(2+) paradox injury in rat Heart / 中国介入心脏病学杂志

Repeated calcium depletion and repletion of short term duration Ca2+ preconditioning CPC is hypothesized to protect the heart from lethal injury after exposing it to the Ca2+ paradox (Ca2+ PD). Hearts were preconditioned with five cycles of Ca2+ depletion (1 minute) and Ca2+ repletion (5 minutes). These hearts were then subjected to Ca2+ PD,ie,one cycle of Ca2+ depletion (ten minutes) and Ca2+ repletion (ten minutes). Hearts subjected to the Ca2+ PD underwent rapid and severely injury. CPC showed remarkable protection against the Ca2+ PD injury. Protein release from the perfusated heart was significantly reduced in CPC hearts compared with nopreconditioned Ca2+ PD hearts (0. 56 + 0. 10 and 1. 23 + 0. 10 mg/ml respectively ,P

Effects of pentoxifylline on ventricular remodeling and cardiac function of dilated cardiomyopathy rats / 中国病理生理杂志

AIM:To explore the effects of pentoxifylline (PTX) on ventricular remodeling and cardiac function in dilated cardiomyopathy (DCM) rats.METHODS: Lewis rats were randomly allocated to a myocin-induced dilated cardiomyopathy (DCM) group receiving saline (n=10), a DCM group receiving PTX (PTX group; 25 mg?kg-1?d-1, ip, for 30 days, n=10) or healthy control group (n=10). The levels of tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6) and IL-10 in the blood plasma were analyzed by ELISA. The extent of fibrosis was estimated using Masson's staining and immunohistochemistry analyses. Cardiac structure and function were measured by echocardiography.RESULTS: PTX decreased plasma levels of TNF-? and IL-6, and increased IL-10 level in DCM animals compared with DCM group [TNF-?: (7.21?0.24) ?g/L vs (19.30?1.31) ?g/L, P

Roles of PKC and ERK in the mechanism of delayed protection of anoxia preconditioning in rat cardiac myocytes / 中国病理生理杂志

AIM: To investigate the roles of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) in delayed protection mechanism of anoxia preconditioning (APC) in rat cardiomyocytes.METHODS: The anoxia/reoxygention (A/R) injury, APC and PMA (an activator of PKC) preconditioning models were established in cultured neonatal rat cardiomyocytes and the effects of PKC and ERK blokers on the models were observed. ERK activity was assayed at 10 min after preconditioning in every group. The cellular MDA, SOD, cell viability and LDH release were measured at the end of the study. RESULTS: Compared with the cardiomyocyte in A/R group, the percentage of viable cells and SOD activity were greatly increased (P