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1.
Acta Pharmaceutica Sinica B ; (6): 3847-3856, 2021.
Article in English | WPRIM | ID: wpr-922445

ABSTRACT

Bile acids (BAs) are amphipathic molecules important for metabolism of cholesterol, absorption of lipids and lipid soluble vitamins, bile flow, and regulation of gut microbiome. There are over 30 different BA species known to exist in humans and mice, which are endogenous modulators of at least 6 different membrane or nuclear receptors. This diversity of ligands and receptors play important roles in health and disease; however, the full functions of each individual BA

2.
Article in Chinese | WPRIM | ID: wpr-754588

ABSTRACT

Objective To study the effects of different hemodialysis modes on growth factor-15 (GDF-15) and left ventricular function in uremic patients undergoing maintenance hemodialysis (MHD). Methods One hundred and twenty uremic patients with chronic renal failure whose MHD > 3 months admitted to Guiyang Second People's Hospital from June 2017 to June 2018 were enrolled, and they were divided into a hemodialysis (HD)+ hemofiltration (HDF)+hemoperfusion (HP) group (HD 8 times per month, HDF 4 times per month, HP 1 time per month), a HD+HDF group (HD 8 times per month, HDF 1 time per month) and a HD group (HD 8 times a month) according to different dialysis modes, each group 40 cases. The patients' venous blood was collected before treatment and 6 months and 1 year after treatment, serum was separated, and the GDF-15 levels in the three groups were detected; the left ventricular end-diastolic dimension (LVDD), left ventricular end-systolic dimension (LVDS), left ventricular end-diastolic volume (LVVD), left ventricular end-systolic volume (LVVS), left ventricular posterior wall thickness (LVPWT), ventricular septal thickness (LVST), maximum blood flow ratio (E/A) of early to late diastole and left ventricular ejection fraction (LVEF) in three groups were detected by echocardiography. Results After treatment, the GDF-15 levels and LVDD, LVDS, LVVD, LVVS, LVPWT, LVST and E/A in the three groups were significantly lower than those before treatment, while LVEF was significantly higher than that before treatment (all P < 0.05); the changes after treatment in the HD+HDF+HP group were more significant than those in the HD+HDF group and HD group [GDF-15 (ng): 853.78±78.80 vs. 921.73±72.54, 971.07±72.05, LVDD (mm): 48.25±1.25 vs. 50.67±1.26, 51.69±1.33, LVDS (mm): 35.21±1.01 vs. 37.84±0.90, 38.91±0.83, LVVD (mL): 101.44±4.40 vs. 109.27±6.47, 115.11±5.46, LVVS (mL): 35.75±1.52 vs. 37.75±1.70, 39.48±1.48, LVPWT (mm): 8.26±0.77 vs. 10.24±0.98, 11.22±0.91, LVST (mm): 9.07±0.48 vs. 10.47±0.61, 11.60±0.58, E/A: 1.03±0.05 vs. 1.07±0.06, 1.15±0.08, LVEF: 0.64±0.03 vs. 0.59±0.03, 0.51±0.04, all P <0.05]. Conclusion The combined hemo- dialysis with different hemodialysis modes can effectively reduce the level of GDF-15 in uremic patients with chronic renal failure and MHD and improve their left ventricular function, thus the incidence of cardiovascular events and mortality in such patients can be decreased.

3.
Acta Pharmaceutica Sinica B ; (6): 702-710, 2019.
Article in English | WPRIM | ID: wpr-774950

ABSTRACT

Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesity-related metabolic disorders. The modulation of gut microbiota, bile acids and the farnesoid X receptor (FXR) axis is correlated with obesity-induced insulin resistance and hepatic steatosis in mice. However, the interactions among the gut microbiota, bile acids and FXR in metabolic disorders remained largely unexplored in hamsters. In the current study, hamsters fed a 60% high-fat diet (HFD) were administered vehicle or an antibiotic cocktail by gavage twice a week for four weeks. Antibiotic treatment alleviated HFD-induced glucose intolerance, hepatic steatosis and inflammation accompanied with decreased hepatic lipogenesis and elevated thermogenesis in subcutaneous white adipose tissue (sWAT). In the livers of antibiotic-treated hamsters, cytochrome P450 family 7 subfamily B member 1 (CYP7B1) in the alternative bile acid synthesis pathway was upregulated, contributing to a more hydrophilic bile acid profile with increased tauro--muricholic acid (TMCA). The intestinal FXR signaling was suppressed but remained unchanged in the liver. This study is of potential translational significance in determining the role of gut microbiota-mediated bile acid metabolism in modulating diet-induced glucose intolerance and hepatic steatosis in the hamster.

4.
The Journal of Practical Medicine ; (24): 2443-2447, 2017.
Article in Chinese | WPRIM | ID: wpr-611916

ABSTRACT

Objective To investigate the level of plasma GDF-15 in patients with COPD and its clinical value in the diagnosis of COPD in the stable stage and in acute exacerbation stage. Methods From 2015 to 2016, 58 cases of patients with COPD were enrolled ,including COPD patients in the stable stage and in acute exacerba-tion stage. 29 cases of COPD patients diagnosed in our hospital were enrolled in the experimental group ,and 29 cases of age-,gender and body mass index-matched healthy people were enrolled in the control group. Compared and analyzed the blood cell count ,determination of plasma GDF-15 and C-reactive protein were performed and ana-lyzed. Spearman correlation analysis was conducted to compare levels of GDF-15 and C-reactive protein between pa-tients with the stable stage of COPD and those with acute exacerbation stage of COPD. The diagnostic efficacy was compared between GDF-15 and C-reactive protein in differentiatingthe COPD in acute exacerbation period and in the stable period. Results Level of GDF-15 in the stable COPD patients was significantly increased compared with that in the control group. The plasma GDF-15 level was significantly increased in acute exacerbation COPD patients compared to patient with the stable COPD(P<0.001). For the stable COPD patients,GDF-15 level and C-reactive protein level was positively correlated(r = 0.776,P < 0.001). In acute exacerbation COPD patients, GDF-15 level and C-reactive protein level was positively correlated (r = 0.877,P < 0.001). The ROC curves showed that the GDF-15 level on the diagnosis of acute exacerbation COPD patients with an AUC was 0.783(95%CI,0.666~0.900,P<0.001)and with the diagnostic accuracy was 69%. C-reactive protein in the acute exacer-bation of AUC diagnosis of COPD was 0.686(95%CI:0.549~0.823,P<0.01)and the diagnostic accuracy rate was 59%. Conclusion The plasma level of GDF-15 was significantly increased in COPD patients compared with people in the healthy control group. Plasma GDF-15 and C- reactive protein were highly correlated in the stable stage of COPD patients and in acute exacerbation stage of COPD patients. The diagnostic accuracy of GDF in patients with the stable stage of COPD and with acute exacerbation stage of COPD was higher than C-reactive pro tein.

5.
Acta Pharmaceutica Sinica B ; (6): 93-98, 2015.
Article in English | WPRIM | ID: wpr-329688

ABSTRACT

The liver is unique in regenerative potential, which could recover the lost mass and function after injury from ischemia and resection. The underlying molecular mechanisms of liver regeneration have been extensively studied in the past using the partial hepatectomy (PH) model in rodents, where 2/3 PH is carried out by removing two lobes. The whole process of liver regeneration is complicated, orchestrated event involving a network of connected interactions, which still remain fully elusive. Bile acids (BAs) are ligands of farnesoid X receptor (FXR), a nuclear receptor of ligand-activated transcription factor. FXR has been shown to be highly involved in liver regeneration. BAs and FXR not only interact with each other but also regulate various downstream targets independently during liver regeneration. Moreover, recent findings suggest that tissue-specific FXR also contributes to liver regeneration significantly. These novel findings suggest that FXR has much broader role than regulating BA, cholesterol, lipid and glucose metabolism. Therefore, these researches highlight FXR as an important pharmaceutical target for potential use of FXR ligands to regulate liver regeneration in clinic. This review focuses on the roles of BAs and FXR in liver regeneration and the current underlying molecular mechanisms which contribute to liver regeneration.

6.
Acta Pharmaceutica Sinica B ; (6): 99-105, 2015.
Article in English | WPRIM | ID: wpr-329687

ABSTRACT

The human body is now viewed as a complex ecosystem that on a cellular and gene level is mainly prokaryotic. The mammalian liver synthesizes and secretes hydrophilic primary bile acids, some of which enter the colon during the enterohepatic circulation, and are converted into numerous hydrophobic metabolites which are capable of entering the portal circulation, returned to the liver, and in humans, accumulating in the biliary pool. Bile acids are hormones that regulate their own synthesis, transport, in addition to glucose and lipid homeostasis, and energy balance. The gut microbial community through their capacity to produce bile acid metabolites distinct from the liver can be thought of as an "endocrine organ" with potential to alter host physiology, perhaps to their own favor. We propose the term "sterolbiome" to describe the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. The affinity of secondary bile acid metabolites to host nuclear receptors is described, the potential of secondary bile acids to promote tumors, and the potential of bile acids to serve as therapeutic agents are discussed.

7.
Acta Pharmaceutica Sinica B ; (6): 151-157, 2015.
Article in English | WPRIM | ID: wpr-329680

ABSTRACT

The liver is the central organ involved in lipid metabolism. Dyslipidemia and its related disorders, including non-alcoholic fatty liver disease (NAFLD), obesity and other metabolic diseases, are of increasing public health concern due to their increasing prevalence in the population. Besides their well-characterized functions in cholesterol homoeostasis and nutrient absorption, bile acids are also important metabolic regulators and function as signaling hormones by activating specific nuclear receptors, G-protein coupled receptors, and multiple signaling pathways. Recent studies identified a new signaling pathway by which conjugated bile acids (CBA) activate the extracellular regulated protein kinases (ERK1/2) and protein kinase B (AKT) signaling pathway via sphingosine-1-phosphate receptor 2 (S1PR2). CBA-induced activation of S1PR2 is a key regulator of sphingosine kinase 2 (SphK2) and hepatic gene expression. This review focuses on recent findings related to the role of bile acids/S1PR2-mediated signaling pathways in regulating hepatic lipid metabolism.

8.
Acta Pharmaceutica Sinica B ; (6): 158-167, 2015.
Article in English | WPRIM | ID: wpr-329679

ABSTRACT

Alcoholic liver disease (ALD) is one of the major causes of liver morbidity and mortality worldwide. Chronic alcohol consumption leads to development of liver pathogenesis encompassing steatosis, inflammation, fibrosis, cirrhosis, and in extreme cases, hepatocellular carcinoma. Moreover, ALD may also associate with cholestasis. Emerging evidence now suggests that farnesoid X receptor (FXR) and bile acids also play important roles in ALD. In this review, we discuss the effects of alcohol consumption on FXR, bile acids and gut microbiome as well as their impacts on ALD. Moreover, we summarize the findings on FXR, FoxO3a (forkhead box-containing protein class O3a) and PPARα (peroxisome proliferator-activated receptor alpha) in regulation of autophagy-related gene transcription program and liver injury in response to alcohol exposure.

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