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.

Dietary inflammatory index and risk of gynecological cancers: a systematic review and meta-analysis of observational studies

Ze-ying Liu,Xu-ping Gao,Sui Zhu,Yan-hua Liu,Li-jun Wang,Chun-xia Jing,Fang-fang Zeng 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.3

Objective: There has been growing body of literatures showing that chronic inflammation might play an important role in cancer development. This meta-analysis aimed to assess the association between the dietary inflammation index (DII) score and gynecological cancers. Methods: A systematic search of PubMed, EMBASE and Web of Science up until October 20, 2018 was carried out to retrieve all related cohort and case-control studies. The summary risk assessments were pooled using random-effects models. The dose-response relationship was estimated by linear relationship model. Results: Twelve case-control studies (10,774 cases/15,958 controls) and six prospective cohort studies (330,363 participants/23,133 incident cases) were included in this meta-analysis. The pooled adjusted relative risk (RR) of gynecological cancers for the highest DII category compared to the lowest category was 1.38, (95% confidence intervals [CIs], 1.21–1.56, p<0.001]. A positive dose-response relationship was also noticed. Stratified by study design indicated that, the pooled RRs was significantly higher for case-control studies than cohort studies (p for interaction<0.001), for studies conducted among participants with body mass index (BMI) ≥25 kg/m2 than participants with BMI <25 kg/m2 (p for interaction=0.026), among participants with ovarian cancer and endometrial cancer than participants with breast cancer (p for interaction = 0.038). Meta-regression analysis further confirmed that study design significantly contributed to inter-study heterogeneity (p<0.001). Conclusion: This meta-analysis suggests that elevated DII is independently associated with a higher risk of gynecological cancers, especially patients with ovarian cancer and endometrial cancer and among obese participants.

An Innovative Analytical Method for Estrogen Sulfates without Deconjugation Procedure

Ze-hua Liu,Yoshinori Kanjo 대한토목학회 2012 KSCE Journal of Civil Engineering Vol.16 No.6

Before analysis with GC-MS, deconjugation of estrogen conjugates with acid-catalyzed solvolysis or enzymatic hydrolysis is regarded as the indispensable procedure. However, in our study we found in the first time that estrogen sulfates (Estrone-3-sulfate,E1-3S; Estradiol-3-sulfate, E2-3S; Estriol-3-sulfate, E3-3S) could be directly analyzed with GC-MS, and the deconjugation procedure can be omitted. In the procedure, estrogen sulfates could be directly derivatized to their corresponding free estrogen derivatives, in which mixture solution of N, O-bis-(trimethylsilyl) trifluoroacetamide (BSTFA) plus 1% trimethylchlorosilane (TMCS)was used as the derivatization reagent, and the derivatization conditions were determined at 80oC for 90 min. Possible mechanism of the direct derivatization of estrogen sulfates by BSTFA plus 1% TMCS was suggested. This finding indicated a latent favorable analytical method of estrogen sulfates for environmental samples.

Single-cell RNA sequencing reveals B cell–related molecular biomarkers for Alzheimer’s disease

Xiong Liu-Lin,Xue Lu-Lu,Du Ruo-Lan,Niu Rui-Ze,Chen Li,Chen Jie,Hu Qiao,Tan Ya-Xin,Shang Hui-Fang,Liu Jia,Yu Chang-Yin,Wang Ting-Hua 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

In recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.

Separation Technology, Thermodynamics : A new model for predicting solute solubility in supercritical fluids based on the Wilson equation

( Bao Hua Wang ),( Qun Sheng Li ),( Ze Ting Zhang ),( Jin Miao Yang ),( Yan Cheng Liu ) 한국화학공학회 2006 Korean Journal of Chemical Engineering Vol.23 No.1

FSCB phosphorylation in mouse spermatozoa capacitation

( Shun Li Liu ),( Bing Ni ),( Xiang Wei Wang ),( Wen Qian Huo ),( Jun Zhang ),( Zhi Qiang Tian ),( Ze Min Huang ),( Yi Tian ),( Jun Tang ),( Yan Hua Zheng ),( Feng Shuo Jin ),( Yan Feng Li ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.8

It is generally accepted that spermatozoa capacitation is associated with protein kinase A-mediated tyrosine phosphorylation. In our previous study, we identified the fibrous sheath CABYR binding protein (FSCB), which was phosphorylated by PKA. However, the phosphorylation status of FSCB protein during spermatozoa capacitation should be further investigated. To this aim, in this study, we found that phosphorylation of this 270-kDa protein occurred as early as 1 min after mouse spermatozoa capacitation, which increased over time and remained stable after 60 min. Immunoprecipitation assays demonstrated that the tyrosine and Ser/Thr phosphorylation of FSCB occurred during spermatozoa capacitation. The extent of phosphorylation and was closely associated with the PKA activity and spermatozoa motility characteristics. FSCB phosphorylation could be induced by PKA agonist DB-cAMP, but was blocked by PKA antagonist H-89.Therefore, FSCB contributes to spermatozoa capacitation in a tyrosine-phosphorylated format, which may help in further elucidating the molecular mechanism of spermatozoa capacitation. [BMB reports 2011; 44(8): 541-546]

LncRNA TMPO-AS1 promotes esophageal squamous cell carcinoma progression by forming biomolecular condensates with FUS and p300 to regulate TMPO transcription

Luo Xiao-Jing,He Ming-Ming,Liu Jia,Zheng Jia-Bo,Wu Qi-Nian,Chen Yan-Xing,Meng Qi,Luo Kong-Jia,Chen Dong-Liang,Xu Rui-Hua,Zeng Zhao-Lei,Liu Ze-Xian,Luo Hui-Yan 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Esophageal squamous cell carcinoma (ESCC) is one of the most life- and health-threatening malignant diseases worldwide, especially in China. Long noncoding RNAs (lncRNAs) have emerged as important regulators of tumorigenesis and tumor progression. However, the roles and mechanisms of lncRNAs in ESCC require further exploration. Here, in combination with a small interfering RNA (siRNA) library targeting specific lncRNAs, we performed MTS and Transwell assays to screen functional lncRNAs that were overexpressed in ESCC. TMPO-AS1 expression was significantly upregulated in ESCC tumor samples, with higher TMPOAS1 expression positively correlated with shorter overall survival times. In vitro and in vivo functional experiments revealed that TMPO-AS1 promotes the proliferation and metastasis of ESCC cells. Mechanistically, TMPO-AS1 bound to fused in sarcoma (FUS) and recruited p300 to the TMPO promoter, forming biomolecular condensates in situ to activate TMPO transcription in cis by increasing the acetylation of histone H3 lysine 27 (H3K27ac). Targeting TMPO-AS1 led to impaired ESCC tumor growth in a patient-derived xenograft (PDX) model. We found that TMPO-AS1 is required for cell proliferation and metastasis in ESCC by promoting the expression of TMPO, and both TMPO-AS1 and TMPO might be potential biomarkers and therapeutic targets in ESCC.

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.

Molecular characterization and expression analysis of putative odorant carrier proteins in Adelphocoris lineolatus

Yong Xiao,Liang Sun,Qi Wang,Qiang Zhang,Shao-Hua Gu,Adel Khashaveh,Ze-Wen Liu,Yong-Jun Zhang 한국응용곤충학회 2018 Journal of Asia-Pacific Entomology Vol.21 No.3

The alfalfa plant bug Adelphocoris lineolatus (Goeze) (Hemiptera: Miridae), a serious pest of several agricultural crops, is extremely attracted by flowering plants to perform season host switching. Generally, chemoreception of A. lineolatus plays a crucial role in detecting food sources, locating mates and oviposition sites. In addition, odorant carrier proteins are believed to participate in the initial chemical communication and perception in insects. In this work, we identified 31 putative odorant carrier protein genes from the antennal transcriptomes of A. lineolatus, including 17 new odorant binding proteins (OBPs), 10 new chemosensory proteins (CSPs) and four Niemann-Pick type C2 proteins (NPC2s). Phylogenetic analysis demonstrated that the OBP and CSP genes from four mirid bug species (A. lineolatus, Adelphocoris suturalis, Apolygus lucorum and Lygus lineolaris) had a relatively close evolutionary relationship. Regular patterns and key conserved motifs of OBPs and CSPs in Hemiptera insects are also identified by using Multiple EM for Motif Elicitation (MEME) tool. Tissue expression profiles analysis showed that nine of the 17 OBPs, 10 CSPs and two of the four NPC2s were primarily or uniquely expressed in the adult antennae suggesting their putative roles in chemoreception. Our study provides the first insight into the roles of odorant carrier proteins in chemoreception of A. lineolatus, which will help to facilitate biological functions of odorant carrier proteins and develop novel insect behavioral regulation strategy

Effects of a traditional Chinese medicine formula and its extraction on muscle fiber characteristics in finishing pigs, porcine cell proliferation and isoforms of myosin heavy chain gene expression in myocytes

Yu, Qin Ping,Feng, Ding Yuan,He, Xiao Jun,Wu, Fan,Xia, Min Hao,Dong, Tao,Liu, Yi Hua,Tan, Hui Ze,Zou, Shi Geng,Zheng, Tao,Ou, Xian Hua,Zuo, Jian Jun Asian Australasian Association of Animal Productio 2017 Animal Bioscience Vol.30 No.11

Objective: This study evaluated the effects of a traditional Chinese medicine formula (TCMF) on muscle fiber characteristics in finishing pigs and the effects of the formula's extract (distilled water, ethyl acetate and petroleum ether extraction) on porcine cell proliferation and isoforms of myosin heavy chain (MyHC) gene expression in myocytes. Methods: In a completely randomized design, ninety pigs were assigned to three diets with five replications per treatment and six pigs per pen. The diets included the basal diet (control group), TCMF1 (basal diet+2.5 g/kg TCMF) and TCMF2 (basal diet+5 g/kg TCMF). The psoas major muscle was obtained from pigs at the end of the experiment. Muscle fiber characteristics in the psoas major muscle were analyzed using myosin ATPase staining. Cell proliferation was measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye and cytometry. Isoforms of MyHC gene expression were detected by real-time quantitative polymerase chain reaction. Results: The final body weight and carcass weight of finishing pigs were increased by TCMF1 (p<0.05), while the psoas major muscle cross-sectional area was increased by TCMF (p<0.05). The cross-sectional area and diameter of psoas major muscle fiber Ι, IIA, and IIB were increased by TCMF2 (p<0.05). The cross-sectional area and fiber diameter of psoas major muscle fiber IIA and IIB were increased by diet supplementation with TCMF1 (p<0.05). Psoas major muscle fiber IIA and IIB fiber density from the pigs fed the TCMF1 diet and the type IIB fiber density from the pigs fed the TCMF2 diet were lower compared to pigs fed the control diet (p<0.05). Pigs fed TCMF2 had a higher composition of type Ι fiber and a lower percentage of type IIB fiber in the psoas major muscle (p<0.05). The expression levels of MyHC Ι, MyHC IIa, and MyHC IIx mRNA increased and the amount of MyHC IIb mRNA decreased in the psoas major muscle from TCMF2, whereas MyHC Ι and MyHC IIx mRNA increased in the psoas major muscle from TCMF1 (p<0.05). Peroxisome proliferator-activated receptor ${\gamma}$ $coactivator-1{\alpha}$ and CaN mRNA expression in the psoas major muscle were up-regulated by TCMF (p<0.05). Porcine skeletal muscle satellite cell proliferation was promoted by $4{\mu}g/mL$ and $20{\mu}g/mL$ TCMF water extraction (p<0.05). Both $1{\mu}g/mL$ and $5{\mu}g/mL$ of TCMF water extraction increased MyHC IIa, MyHC IIb, and MyHC IIx mRNA expression in porcine myocytes (p<0.05), while MyHC Ι mRNA expression in porcine myocytes was decreased by $5{\mu}g/mL$ TCMF water extraction (p<0.05). Porcine myocyte MyHC Ι and MyHC IIx mRNA expression were increased, and MyHC IIa and MyHC IIb mRNA expression were down-regulated by $5{\mu}g/mL$ TCMF ethyl acetate extraction (p<0.05). MyHC Ι and MyHC IIa mRNA expression in porcine myocytes were increased, and the MyHC IIb mRNA expression was decreased by $1{\mu}g/mL$ TCMF ethyl acetate extraction (p<0.05). Four isoforms of MyHC mRNA expression in porcine myocytes were reduced by $5{\mu}g/mL$ TCMF petroleum ether extraction (p<0.05). MyHC IIa mRNA expression in porcine myocytes increased and MyHC IIb mRNA expression decreased by $1{\mu}g/mL$ in a TCMF petroleum ether extraction (p<0.05). Conclusion: These results indicated that TCMF amplified the psoas major muscle cross-sectional area through changing muscle fiber characteristics in finishing pigs. This effect was confirmed as TCMF extraction promoted porcine cell proliferation and affected isoforms of MyHC gene expression in myocytes.