Isoquercitrin attenuates the progression of non-alcoholic steatohepatitis in mice by modulating galectin-3-mediated insulin resistance and lipid metabolism.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a global health problem with no effective treatment. Isoquercitrin (IQ) alters hepatic lipid metabolism and inhibits adipocyte differentiation. The underlying regulatory mechanisms of IQ in regulating insulin resistance (IR) and lipid metabolism remain unclear. PURPOSE: This study was aimed at investigating the effects of IQ on NASH and deciphering whether the underlying mechanisms are via modulation of galectin-3 mediated IR and lipid metabolism. METHODS: IR-HepG2 cell lines were used to demonstrate the ability of IQ to modulate galectin-3-mediated glucose disposal and lipid metabolism. A 20-week high-fat diet (HFD)-induced NASH model was established in C57BL/6J mice, and the protective effect of IQ on lipid disposal in the liver was verified. Further, the mRNA and protein levels of glucose and lipid metabolism were investigated, and lysophosphatidylcholine (LPC) and acylcarnitine (AC) profiling were performed to characterize the changes in endogenous substances associated with mitochondrial function and lipid metabolism in serum and cells. Furthermore, the pharmacokinetic features of IQ were explored in a rat model of NASH. RESULTS: IQ restored liver function and ameliorated inflammation and lipid accumulationin NASH model mice. Notably, significant regulation of the proteins included fatty acid-generating and transporting, cholesterol metabolism enzymes, nuclear transcription factors, mitochondrial metabolism, and IR-related enzymes was noted to be responsible for the therapeutic mechanisms of IQ against experimental NASH. Serum lipid metabolism-related metabolomic assay confirmed that LPC and AC biosynthesis mostly accounted for the therapeutic effect of IQ in mice with NASH and that IQ maintained the homeostasis of LPC and AC levels. CONCLUSION: This is the first study showing that IQ protects against of NASH by modulating galectin-3-mediated IR and lipid metabolism. The mechanisms responsible for liver protection and improved lipid metabolic disorder by IQ may be related to the suppression of IR and regulation of mitochondrial function and lipid metabolism. Galectin-3 down-regulation represents a potentially novel approach for the treatment and prevention of NASH.

Evaluation of characteristic metabolites of aromatic amino acids in patients with HIV infection at different stages of disease.

BACKGROUND: Acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV) infection, and antiretroviral therapy are usually associated with metabolic disorders. Screening for biomarkers to evaluate the progression of metabolic disorders is important for the diagnosis and treatment of HIV infection. This study aimed to establish and validate a method to quantify serum aromatic amino acid (AAA) metabolites as biomarkers of metabolic disorders in patients with HIV. METHODS: The AAAs and metabolites were analyzed using high-performance liquid chromatography-tandem mass spectrometry. Pearson's correlation, heatmap, and receiver operating characteristic curve analyses were used for statistical analysis. RESULTS: Under optimal detection conditions, the lower limits of phenylalanine (Phe), tryptophan (Trp), kynurenine (Kyn), tyrosine, phenylacetylglutamine (PAGln), and 5-hydroxytryptamine quantification reached 0.02, 0.02, 0.01, 0.02, 0.01, and 0.002 µg/ml, respectively, and the precision of intra- and inter-day was stay below 10.30%. Serum samples were stable for at least 6 months when stored at -80°C. The inter-group differences and associations between the biomarkers exhibited a particular volatility trend in PAGln, Trp, and Kyn metabolism in HIV-infected patients with metabolic syndrome. CONCLUSIONS: The developed method can be used for rapid and sensitive quantification of the AAA metabolism profile in vivo to further appraise the process of HIV infection, evaluate intervening measures, conduct mechanistic investigations, and further study the utility of PAGln, a characteristic metabolite of AAA, as a biomarker of HIV infection coupled with metabolic syndrome.

Different frequency of acupoint thread-embedding for overweight/obesity of spleen deficiency and dampness retention: a randomized controlled trial / 中国针灸

OBJECTIVES@#To compare the effect of different frequency of acupoint thread-embedding on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention.@*METHODS@#A total of 126 subjects with overweight/obesity of spleen deficiency and dampness retention were randomized into a 2-week group(63 cases, 13 cases dropped out)and a 3-week group(63 cases, 11 cases dropped out, 1 case was eliminated). The two groups were treated with acupoint thread-embedding once every 2 weeks and once every 3 weeks respectively, Zhongwan(CV 12), Shuifen(CV 9), Qihai(CV 6), Guanyuan(CV 4) and bilateral Zhangmen(LR 13), Tianshu(ST 25), Liangmen(ST 21), Daheng(SP 15), Fujie(SP 14), Pishu(BL 20), Yinlingquan(SP 9)were selected. Four times were required in the two groups. Before and after treatment, follow-up after 2 months of treatment completion, the body mass index(BMI), body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, fat percentage(F%), skin fold thickness were observed in the two groups.@*RESULTS@#After treatment and in follow-up, the BMI, body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, F%, skin fold thickness in the two groups were decreased compared with those before treatment (P<0.001, P<0.01), the changes of BMI, body weight, obesity degree, F%, skin fold thickness in the 2-week group were larger than those in the 3-week group(P<0.05, P<0.01, P<0.001).@*CONCLUSIONS@#The effect of acupoint thread-embedding once every 2 weeks on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention is superior to that once every 3 weeks.

The combination of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair alleviated inflammation in liver fibrosis.

Objective: To explore the active components and epigenetic regulation mechanism underlying the anti-inflammatory effects of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair (LFP) in carbon tetrachloride (CCl4)-induced rat liver fibrosis. Methods: The main active ingredients and disease-related gene targets of LFP were determined using TCMSP and UniProt, and liver fibrosis disease targets were screened in the GeneCards database. A network was constructed with Cytoscape 3.8.0 and the STRING database, and potential protein functions were analyzed using bioinformatics analysis. Based on these analyses, we determined the main active ingredients of LFP and evaluated their effects in a CCl4-induced rat liver fibrosis model. Serum biochemical indices were measured using commercial kits, hepatocyte tissue damage and collagen deposition were evaluated by histopathological studies, and myofibroblast activation and inflammation were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. High-performance liquid chromatography-mass spectrometry was performed to determine the levels of homocysteine, reduced glutathione, and oxidized glutathione, which are involved in inflammation and oxidative stress. Results: The main active components of LFP were quercetin, kaempferol, and luteolin, and its main targets were α-smooth muscle actin, cyclooxygenase-2, formyl-peptide receptor-2, prostaglandin-endoperoxide synthase 1, nuclear receptor coactivator-2, interleukinß, tumor necrosis factor α, CXC motif chemokine ligand 14, and transforming growth factor ß1. A combination of quercetin, kaempferol, and luteolin alleviated the symptoms of liver fibrosis. Conclusion: The results of this study support the role of LFP in the treatment of liver fibrosis, and reveal that LFP reduces collagen formation, inflammation, and oxidative stress. This study suggests a potential mechanism of action of LFP in the treatment of liver fibrosis.

Evaluation of lipid metabolism imbalance in HIV-infected patients with metabolic disorders using high-performance liquid chromatography-tandem mass spectrometry.

Human immunodeficiency virus (HIV) infection and highly active antiretroviral therapy use are associated with the disruption of lipid and glucose metabolism. Herein, a sensitive and robust high-performance liquid chromatography-tandem mass spectrometry method for the quantitation of lysophosphatidylcholines (LPCs) and acylcarnitines (ACs) in human blood serum was developed and validated to investigate them as markers of metabolic disorders in HIV-infected patients. Under optimal extraction and detection conditions, the lower limits of quantification reached 5 ng/mL (LPCs) and 0.1 ng/mL (ACs), and precision and accuracy for both intra- and inter-day analyses were generally below 15%. Serum samples were stable for at least six months when stored at - 80 °C and for at least 12 h when stored at 4 °C or 25 °C. We investigated inter-group differences and associations between the biomarkers and observed a particular volatilitytrend of LPCs and ACs for HIV-infected patients with metabolic disorders. Thus, the developed method can be used for the rapid and sensitive quantitation of LPCs and ACs in vivo to further appraise the process of HIV infection, evaluate interveningmeasures, conduct mechanistic investigations, and further study the utility of LPCs and ACs as biomarkers of HIV infection coupled with metabolic disorders.

Quercetin 7-rhamnoside protects against alpha-naphthylisothiocyanate (ANIT)-induced in cholestatic hepatitis rats by improving biliary excretion and inhibiting inflammatory responses.

Objective: To explore the pharmacological effects and molecular mechanism of quercetin 7-rhamnoside (Q7R) in the treatment of cholestatic hepatitis induced by alpha-naphthylisothiocyanate (ANIT). Methods: ANIT-induced cholestatic hepatitis rat model was used to investigate the hepatoprotective effects of three different doses of Q7R (1.25 mg/kg; 2.5 mg/kg; 5 mg/kg). Serum biochemical indices were detected using commercial kits. H&E and masson staining were used to observe hepatic tissue damage and collagen deposition in hepatocytes. The metabolism of bile acid-related substances was detected via HPLC-MS/MS by 5-(diisopropylamino) amylamine (DIAAA) derivative method. Hepatocyte injury, cholestasis, and inflammation were detected at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, respectively. Results: Q7R can decrease the level of CYP7A1, and increase FXR, CYP27A1 so then improving abnormal bile acid secretion. Furthermore, Q7R can also ameliorating inflammation by reduce TNF-α, IL-1ß, PTGS1, PTGS2, NCOA2, NF-κB level. Therefore, Q7R had an effective therapeutic effect on ANIT-induced cholestatic hepatitis, improving abnormal bile acid secretion, and inhibiting inflammatory responses. Conclusion: The results demonstrated that Q7R treat cholestatic hepatitis by regulating bile acid secretion and alleviating inflammation.

Characteristics of lymphocyte phenotypes in HBV transgenic mice and the effect of interferon-α: a preliminary study / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the characteristics of lymphocyte phenotypes in hepatitis B virus (HBV) transgenic mice and the effect of exogenous interferon-α on virological profiles and lymphocytes phenotypes of the mice.</p><p><b>METHODS</b>HBV transgenic mice and wild-type (WT) mice were examined for serum levels of HBsAg, HBcAb, IL-21, and IL-6 using ELISA. The frequencies of CD4(+)T and CD19(+)B cells separated from the liver, spleen, and peripheral blood were detected by flow cytometry. Nine HBV transgenic mice were injected subcutaneously with recombinant mouse interferon alpha (rmIFN-α) and another 9 transgenic mice were injected with PBS, and their HBsAg, HBV DNA, IL-6, and IL-21 levels and frequencies of peripheral blood CD4(+)T and CD19(+)B cells were detected.</p><p><b>RESULTS</b>HBV transgenic mice showed a high level of HBsAg with a detectable level of HBcAb and significantly increased serum levels of IL-21 and IL-6 as compared with WT mice (P<0.05). The transgenic mice had a significantly lower frequency of CD4(+) T cells in the peripheral blood, liver and spleen (P<0.05) but a significantly higher frequency of CD19(+) B cells in the liver (P<0.05). An inverse correlation between intrahepatic CD4(+) T cell frequency and serum HBsAg level while a positive correlation between intrahepatic CD19(+) B cell frequency and HBcAb level were found in HBV transgenic mice. Administration of rmIFN-α significantly increased the frequencies of CD4(+) T and CD19(+) B cells in the peripheral blood and the serum level of IL-6 in HBV transgenic mice (P<0.05).</p><p><b>CONCLUSION</b>HBV transgenic mice have lymphocyte subset dysregulation and exogenous interferon-α can modulate the immune function of the mice by regulating the frequencies of lymphocyte subsets.</p>

Effects of Se-riched soybean peptide on antioxidant function in rats of fatty liver caused by high-fat diet / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effect of Se-riched soybean peptide (SSP) on antioxidant function in rats of fatty liver caused by high-fat diet.</p><p><b>METHODS</b>Forty Wistar rats were divided into 4 groups randomly and fed with standard diet and water (NC), high-fat diet and water (HC), high-fat diet and SSP (0.1 g/d) (SeH), standard diet and SSP (0.1 g/d) (SeN) respectively. After 10 weeks, the rats were killed to investigate the pimelosis level in liver tissues by Sudan III staining and the expression of hepatic GRP78 by immunohistochemical analysis. We also analyzed the changes of liver function, blood lipid, the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in livers and serum.</p><p><b>RESULTS</b>The pimelosis level, total cholesterol (TC), triglyceride (TG), MDA contents and the expression of GRP78 in HC group were significantly higher than those in NC, SeN, SeH groups. The activities of GSH-Px and SOD in liver and serum were markedly up-regulated in SeH (P < 0.01). There was no significant difference between NC and SeN groups.</p><p><b>CONCLUSION</b>SSP can improve liver cell injury and the antioxidant functions in rats with fatty liver effectively and decrease the expression of GRP78 in liver.</p>

Effect of acupuncture on target action of ligustrazine in treatment of toxic deafness induced by gentamicin in guinea pigs / 中国针灸

<p><b>OBJECTIVE</b>To explore an effective method for treating Gentamicin-induced deafness and the mechanism.</p><p><b>METHODS</b>Guinea pigs were randomly divided into 5 groups: normal control group (group A), model group (group B), Ligustrazine group (group C), acupuncture group (group D) and Ligustrazine plus acupuncture group (group E). The group C, D and E were treated respectively by simple Ligustrazine, simple acupuncture at "Tinggong" (SI 19), "Yifeng" (TE 17), and "Waiguan" (TE 5), and Ligustrazine plus acupuncture. Ten days later, the auditory brainstem response (ABR) thresholds for the wave III , apoptosis and expressions of Bcl-2 and Bax proteins in the organ of Corti of the guinea pig were detected.</p><p><b>RESULTS</b>In the group E, the ABR threshold was significantly lower than that in the group C (P<0.05), and apoptotic cells, the expression of Bax protein and the ratio of Bax/Bcl-2 were lower than those in the group C and D in the organ of Corti, and Bcl-2 protein expression was increased.</p><p><b>CONCLUSION</b>Acupuncture at "Tinggong" (SI 19), "Yifeng" (TE 17), and "Waiguan" (TE 5) has a certain target-synergistic action on Ligustrazine and can increase therapeutic effect of Ligustrazine on Gentamicin-induced deafness, which are possible related with the inhibition of apoptosis, down-regulation of Bax expression and up-regulation of Bcl-2 expression.</p>

Human papillomaviruses infections among village women in Henan province / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of Human papillomaviruses (HPVs) among village women in Henan and to determine its relevant risk factors.</p><p><b>METHODS</b>A population based cross-sectional study on cervical cancer was conducted among village women in Xinmi, Henan. Women aged 20 - 54 who had sexual intercourse experiences were enrolled in this study. Self-sampling and direct-sampling were used in collecting women's vaginal discharge. 13 high-risk HPVs were tested with HC2 for all of the specimens. Then women with abnormal results did colposcopy and biopsy. The biopsy results were regarded as the golden standard.</p><p><b>RESULTS</b>There were 881 women enrolled in this paper and 881 self-sampling and 880 direct-sampling specimens were collected. The HPVs prevalence rates for the self-sampling and direct-sampling were 13.05% and 12.27%, respectively. Age-specific prevalence rates were 10.57% (20-), 9.60% (25-), 12.00% (30-), 9.52% (35-), 17.60% (40-), 13.74% (45-) and 12.80% (50 - 54). HPV prevalence rates were increased with progression of cervical disease (chi(2) = 200.69, P = 0.00). And HPV prevalence rates were higher in women with more advanced education background (chi(2) = 11.05, P = 0.01). HPV infection rate in women whose husbands have more than one sexual partner was 18.02% and whose husbands have only one sexual partner was 10.88% (chi(2) = 6.37, P = 0.01).</p><p><b>CONCLUSION</b>The infection rate of high-risk HPVs in this area is high. The relationship of HPV infection with age has not been observed in this study, but the the sexual activity is the major risk factor for cervical cancer.</p>