Effect of mycophenolate mofetil alleviates carbon tetrachloride-induced liver fibrosis in mice / 中南大学学报(医学版)

OBJECTIVES@#Hepatic fibrosis is a serious pathological consequence of chronic liver disease. Mycophenolate mofetil (MMF) is a commonly used immunosuppressant after organ transplant. However, the relationship between MMF and hepatic fibrosis remains unclear. This study aims to explore the effect of MMF on hepatic fibrosis in mice and the potential mechanism.@*METHODS@#A total of 24 mice (male, 8-week old, C57BL/6) were randomly divided into a control group, a MMF group, a carbon tetrachloride (CCl4) group and a CCl4+MMF group (n=6 in each group). After the mice were sacrificed, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected. The liver tissues were taken up for Masson staining and collagen I (COL1) immunohistochemistry. The levels of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) were detected by Western blotting. Finally, the levels of mRNA for TGF-β1, α-SMA, and COL1 were detected using real-time PCR.@*RESULTS@#Compared with the CCl4 group, the ALT and AST levels were lower (both P<0.05), the degree of liver fibrosis was alleviated, and the deposition of COL1 in the liver was significantly decreased (P<0.01) in the CCl4+MMF group. Compared with the CCl4 group, the protein expression levels of TGF-β1 and α-SMA were significantly decreased (both P<0.05) and the relative expression levels of TGF-β1, α-SMA and COL1 mRNA in the liver were significantly decreased (all P<0.05) in the CCl4+MMF.@*CONCLUSIONS@#MMF could reduce CCl4-induced hepatic fibrosis, which might be related to the inhibition of TGF-β1. This study is expected to provide a target for the treatment of hepatic fibrosis.

Protective effect and mechanism of baicalein on hypoxia-induced cortical neuron injury in rats / 中国药房

OBJECTIVE To explore the protective effect and possible mechanism of baicalein on hypoxia-induced cortical neuron injury in rats. METHODS The cortical neurons of rats （RN-C cells） were studied and cultured under hypoxic conditions （5%CO2， 94% N2， 1%O2） for 24 hours； the effects of different concentrations of baicalein （0.01， 0.1， 1， 10， 100 μmol/L） on the survival rate of hypoxic RN-C cells were investigated； the effects of baicalein （0.1 μmol/L） on the activities of lactate dehydrogenase （LDH） and superoxide dismutase （SOD）， the content of malondialdehyde （MDA）， migration rate， apoptotic rate， cell cycle and the expressions of cleaved caspase-3， B-cell lymphoma-2 （Bcl-2） and Bcl-2 X protein （Bax） were all detected. RESULTS Compared with control group， the survival rate of cells in the hypoxia group was significantly reduced （P＜0.01）； 0.01， 0.1 and 1 μmol/L baicalein could reverse survival rate of hypoxia-induced cortical neurons （P＜0.05 or P＜0.01）. Scratch experiments showed that baicalein significantly increased the migration rate of hypoxic RN-C cells （P＜0.01）. Compared with control group， the activity of LDH in the supernatant and the content of MDA in the cells， apoptotic rate and the proportion of cells in G1 phase， were significantly increased in the hypoxia group， while SOD activity and the proportion of cells in G2+S phase was decreased significantly （P＜0.01）. The protein expressions of cleaved caspase-3 were increased significantly， while the ratio of Bcl-2/Bax in cells was significantly reduced （P＜0.05 or P＜0.01）. Compared with hypoxia group， the above indexes were all reversed significantly in baicalein group （P＜0.01）. CONCLUSIONS Baicalein can promote the proliferation and migration of cortical neurons， improve hypoxia-induced cell apoptosis and cell cycle distribution， decrease the activity of LDH in supernatant and the level of cellular lipid peroxidation， and improve antioxidant levels. Its mechanism may be related to regulating the caspase- 3/Bax/Bcl-2 pathway.

Effect of crocin on myocardial injury and energy metabolism in rats with chronic heart failure / 中华老年心脑血管病杂志

Objective To determine the effect of crocin regulating miR-139-5p/ATF4 axis on myo-cardial injury and energy metabolism in rats with CHF.Methods A total of 84 male SPF SD rats were randomly divided into sham operation group,model group,crocin low-,medium-and high-dose groups,captopril group and crocin+miR-139-5p inhibitor group,with 12 in each group.Car-diac function indexes,myocardial histomathological morphology,apoptotic rate,myocardial injury indexes,heart failure indexes,inflammatory indexes,oxidative stress indexes,myocardial ATP content,SDH activity,and miR-139-5p and ATF4 mRNA expression levels were detected in rats.The targeting relationship between miR-139-5p and ATF4 was verified.Results Compared with the conditions in the model group,crocin treatment at different doses reduced apoptotic rate of cardiomyocytes,decreased MDA content,LVEDD and LVESD values and cTnI,cTnT,CK-MB,NT-proBNP,TNF-α and IL-1β levels,and declined ATF4 mRNA level,and increased LVEF and LVFS values,SOD activity,ATP content,SDH activity and miR-139-5p level(P＜0.05).Com-pared with the crocin high-dose group,the crocin+miR-139-5p inhibitor group had higher apop-totic rate of cardiomyocytes[(22.68±3.25)％vs(11.94±1.38)％,P＜0.05],increased LVEDD and LVESD value,raised MAD content and cTnI,cTnT,CK-MB,NT-proBNP,TNF-α and IL-1βlevel,and elecated ATF4 mRNA level,and decreased LVEF and LVFS value,SOD activity,ATP content,SDH activity and miR-139-5p level(P＜0.05).There was a targeting relationship be-tween miR-139-5p and ATF4.Conclusion Crocin can improve myocardial injury and energy me-tabolism in CHF rats,which may be related to its regulation of miR-139-5p/ATF4 axis.

Protective effect of Saussurea involucrata flavone capsule on myocardial injury induced by hypoxia at high altitude in mice / 药学实践与服务

Objective To study the protective effect and mechanism of Saussurea involucrata flavone capsule on the myocardial tissue of mice in simulated plateau hypoxia environment. Methods 64 Balb/c mice were randomly divided into normal control group, hypoxia model group, positive control group and Xuelian flavonoid capsule group. Myocardial tissue was observed microscopically and ultra-structurally, and the changes of hypoxia-related indexes were detected. The changes in the transcription levels of hypoxia-related genes were detected by RT-PCR, and the changes in the protein expressions of hypoxia-related genes were detected by Western blotting to study the mechanism of action of Xuelian flavone capsules. Results Saussurea involucrata flavone capsule had significantly alleviated the pathological damage to the myocardium of mice caused by simulated altitude hypoxia, increased the activity of T-AOC in myocardial tissue, reduced the accumulation of LD, and also reduced the expression levels of HIF-1α and VEGF mRNA in myocardial tissue, increased the SOD, CAT mRNA and protein expression levels. Conclusion Saussurea involucrata flavone capsule have good anti-altitude hypoxia effect, which could protect myocardial tissue structure and function, regulate energy metabolism, and improve antioxidant capacity. The mechanism might be related to improving the antioxidant capacity, regulating energy metabolism, and affecting the protein expression of HIF-1α, VEGF, SOD and CAT mRNA in high altitude hypoxic mice.

Application value of cardiovascular MR T 1 mapping in patients recovered from COVID-19 / 中华放射学杂志

Objective:To explore the value of cardiovascular MR (CMR) T 1 mapping in evaluating myocardial injury in patients recovered from COVID-19. Methods:The clinical and image data of 15 patients with COVID-19 (9 with moderate clinical manifestation, 6 with severe clinical manifestation) who underwent CMR screening at 3 months after being discharged from the Second People′s Hospital of Fuyang City during May 2020 to June 2020 were prospective collected. Fifteen COVID-19 patients were selected as case group, and another 11 healthy volunteers were selected as control group. A standardized CMR protocol included cine, native and enhanced T 1 mapping, late gadolinium enhancement (LGE). Cardiac functional parameters, native T 1 value of left ventricular and extracellular volume fraction (ECV) were measured. One way ANOVA was used to assess the difference between CMR parameters among moderate and severe manifestation groups and control group, and LSD- t was used to assess the difference between the three groups. Results:LGE value was negative in all subjects. ECV values were higher in recovered COVID-19 patients with either moderate (27.9%±2.7%) or severe manifestation (30.0%±3.7%) than control group (23.2±1.9%) ( P<0.05); there was no significant difference of ECV values between recovered COVID-19 patients with moderate and severe manifestation ( P=0.100). There was no difference of native T 1 values and other functional and morphologic parameters of left ventricular and right ventricular among recovered COVID-19 patients with moderate and severe manifestation and control group ( P>0.05). Conclusion:CMR myocardial tissue ECV increase in patients who recovered from COVID-19, suggesting subclinical myocardial injury.

Expression of serum ADAM33 in patients with different severity of asthma and the relation to airway chronic inflammation / 医学研究生学报

Objective A distintegrin and metalloproteinase 33 (ADAM33) is one of the asthma susceptibility gene, which is closely related to the pathogenesis of asthma and airway hyperreactivity.The aim of this study was to evaluate the expression of serum ADAM33 in patients with different severity of asthma and the relation to airway chronic inflammation through clinical trials.MethodsPatients diagnosed as mild-to-moderate asthma (n=54), severe asthma (n=35) and healthy controls (n=30) were recruited from May 2015 to May 2016.The serum IgE, ADAM33, IL-4 and IL-13 1evels and Eosinophil (EOS) in peripheral blood were detected, and the correlation analysis was performed Results The serum levels of ADAM33 in mild-to-moderate asthma group, severe asthma group and healthy control group were 23.8±6.21pg/mL,64.8±12.8pg/mL and 18.3±4.49pg/mL, respectively.The ADAM33 levels in mild-to-moderate asthma group and severe asthma group were higher than those in control group (P<0.05).The ADAM33 levels in severe asthma group were higher than those in mild to moderate asthma group.(P<0.05).The correlation analysis showed that ADAM33 had positive correlation with IL-4 and IL-13(r=0.79 and r=0.81), but no correlation with EOS and IgE(r=0.54 and r=0.46).Conclusion The expression of serum ADAM33 was up-regulated in asthmatic patients along with the severity of asthma.ADAM33 was positively correlated with serum IL-4 and IL-13, implying that the expression of ADAM33 may be regulated by Th2 type cytokines.

Dose-Response Relationship between Alanine Aminotransferase Levels within the Reference Interval and Metabolic Syndrome in Chinese Adults

PURPOSE: Elevation in serum alanine aminotransferase (ALT) levels is a biomarker for metabolic syndrome (MS); however, the relationship has not been fully investigated within the reference interval of ALT levels. Our objective was to explore the relationship between serum ALT levels within the reference interval and MS in Chinese adults. MATERIALS AND METHODS: This cross-sectional study included 16028 adults, who attended routine health check-ups at Shengli Oilfield Central Hospital from January 2006 to March 2012. The reference interval of serum ALT level was defined as less than 40 U/L. Logistic regression models and restricted cubic spline were used to evaluate the association of ALT with MS. RESULTS: The prevalence of MS in the total population was 13.7% (6.4% for females and 18.4% for males). Multiple logistic regression showed that ALT levels were positively associated with MS after adjustment for potential confounding factors. The odds ratio of MS in the top quartile was 4.830 [95% confidence interval (CI): 2.980–7.829] in females and 3.168 (95% CI: 2.649–3.790) in males, compared with the ALT levels in the bottom quartile. The restricted cubic spline models revealed a positive non-linear dose-response relationship between ALT levels and the risk of MS in women (p for nonlinearity was 0.0327), but a positive linear dose-response relationship in men (p for nonlinearity was 0.0659). CONCLUSION: Serum ALT levels within the reference interval are positively associated with MS in a dose-response manner. Elevated ALT levels, even within the reference interval, may reflect early dysmetabolic changes.

Association between serum direct bilirubin with metabolic syndrome and its components based on a longitudinal health check-up study / 中华流行病学杂志

Objective To investigate the association between serum direct bilirubin (DBIL) with metabolic syndrome (MS) and its components.Methods A dynamic health check-up cohort study was set up from 2006 to 2011.5 258 participants who satisfied the two basic rules:1) being free of MS at the 1st health check-up program;2) having at least two intact health checks were included in this study.With generalized estimating equation (GEE) model,after adjusting for items as age,gender,smoking,drinking,alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase,uric acid,blood urea nitrogen and white blood cells,the multivariable relative risks (RRs) of DBIL with MS and their components were analyzed.Results The RRs of DBIL for MS was 0.722 (95％ CI:0.654-0.797),which showing a dose-response.Serum DBIL was negatively associated with obesity and hyperlipidemia.Taking factors as gender and age into account,in the ＜45 years and 45-55 years groups,the RRs of DBIL for MS in females appeared as 0.516 (95％CI:0.349-0.761) and 0.435 (95％CI:0.256-0.740).And in males of ＜45 years and 45-55 years,the RRs of DBIL for MS were 0.738 (95％ CI:0.644-0.846) and 0.790 (95％ CI:0.667-0.937),respectively.Conclusions The elevated DBIL levels in serum appeared an early biomarker for MS and its components (obesity and hyperlipidemia).In particular,they may play a role in reducing the risk of MS in both females and males before 55 years of age.

A primary survey of the histopathological characteristic in nontuberculous mycobacteria lymphadenitis / 医学研究生学报

Objective:To approach the distinctive histopathological chages of nontuberculous mycobacteria lymphadenitis. Methods: The experimental animal model of nontuberculous mycobacteria lymphadenitis was developed and the histopathological changes were observed under the light microscope.Results:The distinctive histopathological changes of nontuberculous mycobacteria lymphadenitis were identified as following: ①Granulomas were found in lymph nodes which were infected with nontuberculous mycobacteria.The coagulation necrosis was located at the center of the granuloma and it was not caseation.Neutrophils were distributed over the necrosis area.Surrounding the center necrosis area,many epithelioid cells,lymphocytes and mononuclear cells could be found.The periphery of the granuloma was surrounded by the fibrous tissues.Outside the granuloma,Langhans giant cells could be found.②Serpiginous necrosis was found in the lymph nodes which were infected with nontuberculous mycobacteria.The shape of serpiginous necrosis was a long strip.In the center area,the strip of coagulation necrosis and the strip of the space which was remnant after the desquamation of necrosis tissues could be found.Many neutrophils were distributed over the necrosis area.Around the center necrosis area,many epithelioid cells,lymphocytes and mononuclear cells could be found.The fibrous tissues were in the borderline.Conclusion:Serpiginous necrosis was one of the distinctive histopathological change of nontuberculous mycobacteria lymphadenitis.