Indole-3-propionic acid inhibits gut dysbiosis and endotoxin leakage to attenuate steatohepatitis in rats

Ze-Hua Zhao,Feng-Zhi Xin,Yaqian Xue,Zhimin Hu,Yamei Han,Fengguang Ma,Da Zhou,Xiao-Lin Liu,Aoyuan Cui,Zhengshuai Liu,Yuxiao Liu,Jing Gao,Qin Pan,Yu Li,Jian-Gao Fan 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Microbial metabolites have emerged as critical components that mediate the metabolic effects of the gut microbiota. Here, we show that indole-3-propionic acid (IPA), a tryptophan metabolite produced by gut bacteria, is a potent anti-non-alcoholic steatohepatitis (NASH) microbial metabolite. Here, we demonstrate that administration of IPA modulates the microbiota composition in the gut and inhibits microbial dysbiosis in rats fed a high-fat diet. IPA induces the expression of tight junction proteins, such as ZO-1 and Occludin, and maintains intestinal epithelium homeostasis, leading to a reduction in plasma endotoxin levels. Interestingly, IPA inhibits NF-κB signaling and reduces the levels of proinflammatory cytokines, such as TNFα, IL-1β, and IL-6, in response to endotoxin in macrophages to repress hepatic inflammation and liver injury. Moreover, IPA is sufficient to inhibit the expression of fibrogenic and collagen genes and attenuate diet-induced NASH phenotypes. The beneficial effects of IPA on the liver are likely mediated through inhibiting the production of endotoxin in the gut. These findings suggest a protective role of IPA in the control of metabolism and uncover the gut microbiome and liver cross-talk in regulating the intestinal microenvironment and liver pathology via a novel dietary nutrient metabolite. IPA may provide a new therapeutic strategy for treating NASH.

Transcatheter Arterial Chemoembolization Plus 131I-Labelled Metuximab versus Transcatheter Arterial Chemoembolization Alone in Intermediate/Advanced Stage Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Ze-xin Zhu,Ming-heng Liao,Xiao-xue Wang,Ji-wei Huang 대한영상의학회 2016 Korean Journal of Radiology Vol.17 No.6

Objective: The aim of the study was to compare transcatheter arterial chemoembolization (TACE) plus 131I-labelled metuximab with TACE alone for hepatocellular carcinoma (HCC). Materials and Methods: A comprehensive search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Chinese BioMedical Literature Database with published date from the earliest to February 29th, 2016. No language restrictions were applied, but only prospective randomized controlled trials (RCTs) or non-RCTs were eligible for a full-text review. The primary outcome was the overall survival (OS) and effective rate (the rate of partial atrophy or complete clearance of the tumor lesion). The odds ratios (ORs) were combined using either the fixed-effects model or random-effects model. Results: Eight trials (3 RCTs and 5 non-RCTs) were included, involving a total of 1121 patients. Patients receiving combined therapy of TACE plus 131I-labelled metuximab showed significant improvement in effective rate {OR = 4.00, (95% confidence interval [CI]: 2.40–6.66), p < 0.001}, 1-year OS (OR = 2.03 [95% CI: 1.55–2.67], p < 0.001) and 2-year OS (OR = 2.57 [95% CI: 1.41–4.66], p = 0.002]. Conclusion: TACE plus 131I-labelled metuximab is more beneficial for treating advanced HCCs than TACE alone in terms of tumor response and OS. Large, multi-center, and blinded randomized trials are required to confirm these findings.

Fabrication of Photopolymer Hierarchical Micronanostructures by Coupling Electrospinning and Photolithography for SERS Substrates

Wen-Yi Zhang,Xin-Ze Xiao,Chao Lv,Jia Zhao,Gong Wang,Xuan Gu,Ran Zhang,Bin-Bin Xu,Dan-Dan Zhang,Ai-Wu Li,Yong-Lai Zhang,Hong-Bo Sun 한국고분자학회 2013 Macromolecular Research Vol.21 No.3

Reported here is the fabrication of photopolymer hierarchical micronanostructures through a combinative process of electrospinning and subsequent photolithography. Electrospun SU-8 (epoxy-based negative photoresist)nanofiber films have been patterned into gratings with periods of 100, 200, 300, and 400 μm, respectively. Deposition of a silver nanolayer on these interlaced nanofiber films would lead to the formation of various plasmonic nanostructures,and therefore, giving rise to abundant surface-enhanced Raman scattering (SERS) “hot spots”. In the detection of Rhodamine 6G (R6G), probing molecule, the resultant SERS substrates show both high sensitivity and good reproducibility. The SERS enhancement factor could reach as high as ~108, indicating high efficiency. The fabrication of patterned, highly efficient SERS substrates may hold a great promise for the integration of SERS substrates in various microdevices such as microfluidic chips.

Deubiquitinating enzyme Josephin-2 stabilizes PHGDH to promote a cancer stem cell phenotype in hepatocellular carcinoma

Wang Ying,Li Ze-Xin,Wang Jian-Guo,Li Lu-Hao,Shen Wen-Long,Dang Xiao-Wei 한국유전학회 2023 Genes & Genomics Vol.45 No.2

Background Deubiquitinating enzymes (DUBs) have been shown to be possible targets for hepatocellular carcinoma (HCC) treatment. Objective This study was designed to reveal the effect and underlying mechanism of Josephin-2, a relatively newly defined DUB, in HCC progression. Methods SNU-387 and PLC/PRF/5 cells were used for in vitro functional assays. The levels of Josephin-2 and phosphoglycerate dehydrogenase (PHGDH) were determined using RT-qPCR and western blotting. Cell proliferation, migration and invasion were assessed by CCK-8, colony formation and Transwell. Spheroid-forming assay was performed to assess the cancer stem cell (CSC)-phenotype of HCC cells. A xenograft mice model was applied to verify the effect of Josephin-2 on HCC cell growth in vivo. Results Herein, we showed that Josephin-2 expression was negatively correlated with HCC patient survival in data from the online database. Cell experiments indicated that knockdown of Josephin-2 attenuated HCC cell malignant biological behaviors. Besides, Josephin-2 silencing also decreased the spheroid-formation while inhibited the expression of CSC biomarkers (CD133, OCT4, SOX2 and EpCAM) in HCC cells. Mechanistically, Josephin-2 had a deubiquitinating activity towards the regulation of PHGDH protein, the rate-limiting enzyme in the first step of serine biosynthesis pathway. Depletion of Josephin-2 enhanced the ubiquitination degradation of PHGDH and ultimately inhibited the proliferation and CSC-phenotype of HCC in vitro and in vivo. Conclusion Our work uncovered the regulatory effects of Josephin-2 on PHGDH protein stability and profiled its contribution in HCC malignant progression, which might provide a potential therapeutic target for HCC.

Novel Alkali-Stable, Cellulase-Free Xylanase from Deep-Sea Kocuria sp. Mn22

Chan Juan Li,Yu Zhi Hong,Zong Ze Shao,Ling Lin,Xiao Luo Huang,Peng Fu Liu,Gao Bing Wu,Xin Meng,Zi Duo Liu 한국미생물 · 생명공학회 2009 Journal of microbiology and biotechnology Vol.19 No.9

Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression

Da Zhou,Yuan-Wen Chen,Ze-Hua Zhao,Rui-Xu Yang,Feng-Zhi Xin,Xiao-Lin Liu,Qin Pan,Huiping Zhou,Jian-Gao Fan 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is wellknown that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/ insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.