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Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier

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World Journal of Gastroenterology 2017年第1期23卷 60-75页

作者： Da Zhou Qin Pan feng-zhi xin Rui-Nan Zhang Chong-xin He Guang-Yu Chen Chang Liu Yuan-Wen Chen Jian-Gao Fan Department of Gastroenterology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Clinical Epidemiology Center Shanghai Jiaotong University School of Medicine Department of Medical Microbiology and Parasito-logy Institutes of Medical SciencesShanghai Jiao Tong University School of Medicine

AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation-or metabolism-associated genes were quantified by real-time PCR. RESULTS NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-alpha, IL-1, IL-2, IL-6 and IFN-gamma in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. CONCLUSION NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.

关键词： Non-alcoholic fatty liver disease Sodium butyrate Gut microbiota Gastrointestinal barrier Endotoxin

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Folic acid attenuates high-fat diet-induced steatohepatitis via deacetylase SIRT1-dependent restoration of PPARα

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World Journal of Gastroenterology 2020年第18期26卷 2203-2220页

作者： feng-zhi xin Ze-Hua Zhao Rui-Nan Zhang Qin Pan Zi-Zhen Gong Chao Sun Jian-Gao Fan Center for Fatty Liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Shanghai Key Lab of Pediatric Gastroenterology and Nutrition Shanghai 200092China Shanghai Institute for Pediatric Research Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Pediatric Surgery Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China

BACKGROUND Folic acid has been shown to improve non-alcoholic steatohepatitis(NASH),but its roles in hepatic lipid metabolism,hepatic one-carbon metabolism,and gut microbiota are still *** To demonstrate the role of folic acid in lipid metabolism and gut microbiota in *** Twenty-four Sprague-Dawley rats were assigned into three groups:Chow diet,high-fat diet(HFD),and HFD with folic acid *** the end of 16 wk,the liver histology,the expression of hepatic genes related to lipid metabolism,one-carbon metabolism,and gut microbiota structure analysis of fecal samples based on 16 S r RNA sequencing were measured to evaluate the effect of folic *** acid-exposed Huh7 cell line was used to evaluate the role of folic acid in hepatic lipid *** Folic acid treatment attenuated steatosis,lobular inflammation,and hepatocellular ballooning in rats with HFD-induced *** related to lipid de novo lipogenesis,β-oxidation,and lipid uptake were improvedin HFD-fed folic acid-treated ***,peroxisome proliferator-activated receptor alpha(PPARα)and silence information regulation factor 1(SIRT1)were restored by folic acid in HFD-fed rats and palmitic acid-exposed Huh7 cell *** restoration of PPARαby folic acid was blocked after transfection with SIRT1 si RNA in the Huh7 cell ***,folic acid administration ameliorated depleted hepatic one-carbon metabolism and restored the diversity of the gut microbiota in rats with HFD-induced *** Folic acid improves hepatic lipid metabolism by upregulating PPARαlevels via a SIRT1-dependent mechanism and restores hepatic one-carbon metabolism and diversity of gut microbiota,thereby attenuating HFD-induced NASH in rats.

关键词： Nonalcoholic fatty liver disease Folic acid Gut microbiota PPARα SIRT1

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Trimethylamine N-oxide attenuates high-fat high-cholesterol dietinduced steatohepatitis by reducing hepatic cholesterol overload in rats

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World Journal of Gastroenterology 2019年第20期25卷 2450-2462页

作者： Ze-Hua Zhao feng-zhi xin Da Zhou Ya-Qian Xue Xiao-Lin Liu Rui-Xu Yang Qin Pan Jian-Gao Fan Center for Fatty Liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China CAS Key Laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Shanghai Key Lab of Pediatric Gastroenterology and Nutrition Shanghai 200092China

BACKGROUND Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM To determine the effect of TMAO on the progression of NASH. METHODS A rat model was induced by 16-wk high-fat high-cholesterol (HFHC) diet feeding and TMAO was administrated by daily oral gavage for 8 wk. RESULTS Oral TMAO intervention attenuated HFHC diet-induced steatohepatitis in rats. Histological evaluation showed that TMAO treatment significantly alleviated lobular inflammation and hepatocyte ballooning in the livers of rats fed a HFHC diet. Serum levels of alanine aminotransferase and aspartate aminotransferase were also decreased by TMAO treatment. Moreover, hepatic endoplasmic reticulum (ER) stress and cell death were mitigated in HFHC diet-fed TMAOtreated rats. Hepatic and serum levels of cholesterol were both decreased by TMAO treatment in rats fed a HFHC diet. Furthermore, the expression levels of intestinal cholesterol transporters were detected. Interestingly, cholesterol influxrelated Niemann-Pick C1-like 1 was downregulated and cholesterol efflux-related ABCG5/8 were upregulated by TMAO treatment in the small intestine. Gut microbiota analysis showed that TMAO could alter the gut microbial profile and restore the diversity of gut flora. CONCLUSION These data suggest that TMAO may modulate the gut microbiota, inhibit intestinal cholesterol absorption, and ameliorate hepatic ER stress and cell death under cholesterol overload, thereby attenuating HFHC diet-induced steatohepatitis in rats. Further studies are needed to evaluate the influence on CVD and define the safe does of TMAO treatment.

关键词： Gut microbiota Trimethylamine N-oxide Nonalcoholic steatohepatitis Endoplasmic reticulum stress Cholesterol

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Diagnostic accuracy of fiberoptic ductoscopy plus in vivo iodine staining for intraductal proliferative lesions

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Chinese Medical Journal 2013年第16期126卷 3124-3129页

作者： feng xin-zhi SONG Ying-hua ZHANG feng-xia JIANG Chuan-wu MEI Hong ZHAO Bin Shandong University Shandong Provincial Medical Imaging Institute Jinan Shandong 250021 China Department of Respiratory Medicine Shandong ProvincialQianfoshan Hospital Jinan Shandong 250014 China Department of Radiology Hiser Hospital of Qingdao QingdaoShandong 266033 China

Background lodine staining during endoscopy has been successfully used to detect early carcinomatous and precancerous lesions in the esophagus,cervix,and oral *** objective of this study was to determine the diagnostic accuracy of fiberoptic ductoscopy （FDS） plus in vivo iodine staining for intraductal proliferative lesions of the *** We performed periodic acid-Schiff （PAS） and in vitro iodine staining on 52 and 64 specimens of benign mammary hyperplasia,respectively,and 57 and 53 specimens of ductal carcinoma in situ （DCIS）,***,FDS was performed on 177 recurrent nipple discharge patients who were randomly divided into two *** group was iodine-staining group in which 92 patients were randomly selected to undergo iodine staining during FDS,and the remaining 85 were assigned to the control *** specimens of suspicious lesions were obtained and subjected to histopathological *** Following PAS staining,benign mammary hyperplasia lesions were positively stained,while negligible PAS positivity was observed in the DCIS lesions （P ＜0.05）.Following in vitro iodine staining,benign mammary hyperplasia specimens appeared dark brown,whereas DCIS samples appeared significantly lighter or *** with the pathological examination results,FDS with iodine staining showed an agreement rate in the diagnosis of ductal intraepithelial neoplasia （DIN）,sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,and Youden index of 97.82％,98.83％,83.33％,5.93,0.014,and 0.8216,respectively; the corresponding values for FDS without iodine staining were 88.24％,89.16％,50.00％,1.78,0.217,and 0.3916,*** FDS with iodine staining was superior to conventional FDS for the diagnosis of DIN and is valuable for breast cancer prevention.

关键词： carcinoma, ductal breast, endoscopes sensitivity and specificity

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mi R-192-5p regulates lipid synthesis in non-alcoholic fatty liver disease through SCD-1

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World Journal of Gastroenterology 2017年第46期23卷 8140-8151页

作者： Xiao-Lin Liu Hai-Xia Cao Bao-Can Wang feng-zhi xin Rui-Nan Zhang Da Zhou Rui-Xu Yang Ze-Hua Zhao Qin Pan Jian-Gao Fan Center for Fatty Liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

AIM To evaluate the levels of mi R-192-5 p in non-alcoholic fatty liver disease(NAFLD) models and demonstrate the role of mi R-192-5 p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided into three groups, which were given a standard diet, a high-fat diet(HFD), and an HFD with injection of liraglutide. At the end of 16 weeks, hepatic mi R-192-5 p and stearoyl-Co A desaturase 1(SCD-1) levels were measured. Mi R-192-5 p mimic and inhibitor and SCD-1 si RNA were transfected into Huh7 cells exposed to palmitic acid(PA). Lipid accumulation was evaluated by oil red O staining and triglyceride assays. Direct interaction was validated by dual-luciferase reporter gene *** The HFD rats showed a 0.46-fold decrease and a 3.5-fold increase in hepatic mi R-192-5 p and SCD-1 protein levels compared with controls, respectively, which could be reversed after disease remission by liraglutide injection(P < 0.01). The Huh7 cells exposed to PA also showed down-regulation and up-regulation of mi R-192-5 p and SCD-1 protein levels, respectively(P < 0.01). Transfection with mi R-192-5 p mimic and inhibitor in Huh7 cells induced dramatic repression and promotion of SCD-1 protein levels, respectively(P < 0.01). Luciferase activity was suppressed and enhanced by mi R-192-5 p mimic and inhibitor, respectively, in wild-type SCD-1(P < 0.01) but not in mutant SCD-1. Mi R-192-5 p overexpression reduced lipid accumulation significantly in PA-treated Huh7 cells, and SCD-1 si RNA transfection abrogated the lipid deposition aggravated by mi R-192-5 p inhibitor(P < 0.01).CONCLUSION This study demonstrates that mi R-192-5 p has a negative regulatory role in lipid synthesis, which is mediated through its direct regulation of SCD-1.

关键词： mi R-192-5p Stearoyl-Co A desaturase 1 High fat diet Lipid synthesis Non-alcoholic fatty liver disease

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变积分限Cauchy核与卷积核混合的完全奇异积分方程的求解

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吉林大学学报（理学版） 2013年第6期51卷 1051-1057页

作者：冯志新吉林师范大学数学学院吉林四平136000

考虑{0}函数类中,变积分限的Cauchy核与卷积核混合的完全奇异积分方程的求解问题,借助Fourier积分变换,利用Riemann边值问题和Fredholm积分方程理论,先将所讨论的方程转化为在一定可解条件下与其等价的{{0}}类中的Fredholm积分方程,再... 详细信息

考虑{0}函数类中,变积分限的Cauchy核与卷积核混合的完全奇异积分方程的求解问题,借助Fourier积分变换,利用Riemann边值问题和Fredholm积分方程理论,先将所讨论的方程转化为在一定可解条件下与其等价的{{0}}类中的Fredholm积分方程,再通过求解等价的Fredholm积分方程,得到所研究方程在{0}函数类中的可解条件及一般解.

关键词：奇异积分方程卷积核 Cauchy核 Fredholm积分方程

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Effect of Pleurotus ostreatus on Dynamics of Meloidogyne arenaria Population and Control Effectiveness

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Agricultural Sciences in China 2002年第1期1卷 86-95页

作者： XIANG Hong-qiong and feng zhi-xin(Department of Plant Protection , Guizhou University, Guiyang 550025 Laboratory of Plant Nematology, South China Agricultural University, Guangzhou 510642) Department of Plant Protection Guizhou University Guiyang 550025 Laboratory of Plant Nematology South China Agricultural University Guangzhou 510642

The control effects and application methods of Pleurotus ostreatus on the peanut root-knot nematode disease, Meloidogyne arenaria, were systematically studied in the greenhouse. Results of pot experiments showed that P. ostreatus could effectively reduce the 2nd-instar population density in the soil, and the larva reduced by 80% compared with the control. P. ostreatus could markedly lower the infecting number of the peanut root-knot nematodes, the nematode density inside the root knots declined by 40.00% -82.64%, and the peanut root knots also reduced by 86.96% - 94. 03%. The fungus could defer the initial infection of M. arenaria to the roots, the epidemic rate of the peanut root-knot nematode disease was significantly cut down, and the increase of root-knot changed from the way of Logistic curve in the control to the way of linear curve in the treatment. The final control effectiveness was about 80%. The results of pot trial also indicated that the control effectiveness is closely related to the application time and the amount of this fungus. The key factor affecting control effectiveness was the application time of P. ostreatus in the soil and the suitable time was 20 days before sowing.

关键词： Pleurotus ostreatus Meloidogyne arenaria Peanut root-knot nematode disease Biological control

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基于DOE的汽车保险杠注塑工艺参数的优化方法研究

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塑料工业 2017年第7期45卷 73-76页

作者：冯志新北京电子科技职业学院汽车工程学院北京100176

以汽车保险杠为例,研究了其注塑工艺参数的优化方法。利用Moldflow软件设计了一套具有时序控制方案的热流道注塑系统,减少了熔接痕缺陷的存在。以保险杠注塑过程中熔体温度、模具温度、保压时间为实验因子,以最大锁模力和成型后的最大... 详细信息

以汽车保险杠为例,研究了其注塑工艺参数的优化方法。利用Moldflow软件设计了一套具有时序控制方案的热流道注塑系统,减少了熔接痕缺陷的存在。以保险杠注塑过程中熔体温度、模具温度、保压时间为实验因子,以最大锁模力和成型后的最大变形量为目标变量进行了实验设计,最终得到了多目标优化的方法和参考优化方案。

关键词：汽车保险杠注塑实验设计工艺参数优化

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Construction of a telomerase-immortalized porcine tracheal epithelial cell model for swine-origin mycoplasma infection

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Journal of Integrative Agriculture 2022年第2期21卷 504-520页

作者： XIE xing HAO Fei WANG Hai-yan PANG Mao-da GAN Yuan LIU Bei-bei ZHANG Lei WEI Yan-na CHEN Rong ZHANG Zhen-zhen BAO Wen-bin BAI Yun SHAO Guo-qing XIONG Qi-yan feng zhi-xin Key Laboratory for Veterinary Bio-Product Engineering of Ministry of Agriculture and Rural Affairs Institute of Veterinary MedicineJiangsu Academy of Agricultural SciencesNanjing 210014P.R.China Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology Institute of Food Safety and NutritionJiangsu Academy of Agricultural SciencesNanjing 210014P.R.China College of Animal Science and Technology Yangzhou UniversityYangzhou 225009P.R.China

Primary porcine tracheal epithelial cells(PTECs) are an appropriate model for studying the molecular mechanism of various porcine respiratory diseases, including swine-origin mycoplasmas, which are isolated from respiratory tract of pigs and mainly found on the mucosal surface surrounding swine trachea. However, the short proliferation ability of primary PTECs greatly limits their lifespan. In this study, primary PTECs were carefully isolated and cultured, and immortal PTECs were constructed by transfecting primary PTECs with the recombinant constructed plasmid pEGFPhTERT containing human telomerase reverse transcriptase(hTERT). Immortal PTECs(hTERT-PTECs) maintained both the morphological and functional characteristics of primary PTECs, as indicated by the expression of cytokeratin 18, cellcycle analysis, proliferation assay, Western blotting, telomerase activity assay, karyotype analysis and quantitative RTPCR. Compared to primary PTECs, hTERT-PTECs had an extended replicative lifespan, higher telomerase activity, and enhanced proliferative activity. In addition, this cell line resulted in a lack of transformed and grown tumors in nude mice, suggesting that it could be safely applied in further studies. Moreover, hTERT-PTECs were vulnerable to all swineorigin mycoplasmas through quantitative analysis as indicated by 50% color changing unit(CCU_(50)) calculation, and no significant differences of adhesion ability between primary and immortal PTECs were observed. For the representative swine mycoplasma Mycoplasma hyopneumoniae(Mhp), except for DNA copies quantitative real-time PCR assay, indirect immunofluorescence assay and Western blotting analysis also depicted that hTERT-PTECs was able to adhere to different Mhp strains of different virulence. In summary, like primary PTECs, hTERT-PTECs could be widely used as an adhesion cell model for swine-origin mycoplasmas and in infection studies of various porcine respiratory pathogens.

关键词： porcine tracheal epithelial cells(PTECs) hTERT-PTECs swine-origin mycoplasmas adhesion cell model

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卡尔曼滤波在主动悬架中的仿真应用

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煤矿机械 2013年第10期34卷 68-69页

作者：冯志新吉林师范大学数学学院吉林四平136000

提出了一种应用触发子系统模块实现卡尔曼滤波器对系统进行滤波的仿真方法并详细阐述了实现过程和在主动悬架系统中的应用。该方法采用Simulink模块与M函数相结合,符合在线实时滤波的情况。

关键词：卡尔曼滤波 LQR 触发子系统仿真实现

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