Publications by authors named "Mingliang Cheng"

31 Publications

Survival analysis of patients with primary breast duct carcinoma and lung adenocarcinoma: a population-based study from SEER.

Sci Rep 2021 Jul 20;11(1):14790. Epub 2021 Jul 20.

Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The appeal to enroll patients with primary breast and lung cancer in clinical trials is increasing, but survival of these two primary cancers remains to be elucidated. This study analyzed the prognosis of primary breast duct carcinoma with subsequent lung adenocarcinoma (BCLA) and primary breast duct carcinoma with prior lung adenocarcinoma (LABC). Cohorts of 3,515 patients with BCLA and 654 patients with LABC were identified from the Surveillance, Epidemiology, and End Results database. Patients were classified into simultaneous two primary cancer (sTPC), metachronous two primary cancer (mTPC1), or mTPC2 groups when the interval times between breast and lung cancer were within 6 months, between 7 and 60 months, or over 60 months, respectively. The propensity score matching program (PSM) was applied to determine the survival of BCLA/LABC relative to single breast/lung cancer. Cox proportional hazard regression model and competing risk modes were performed to identify confounders associated with all-cause and cancer-specific death, respectively. Survival of patients with LABC/BCLA relative to single breast/lung cancer was accessed via median survival time. The survival of patients with BCLA/LABC was generally poor compared with the survival of those with single breast cancer. The PSM-estimated HR in the sTPC group with BCLA and in the mTPC1 and mTPC2 groups with LABC were 0.75 (95% CI 0.62-0.90), 0.52 (95% CI 0.27-0.98), and 0.36 (95% CI 0.20-0.65), respectively, whereas the SHRs were 0.80 (95% CI 0.66-0.97), 0.68 (95% CI 0.34-1.34), and 0.46 (95% CI 0.27-0.80), respectively, compared with those in the single lung cancer group. By contrast, the survival rates of the remaining patients did not differ. The median survival times since secondary malignancy were 42, 23, and 20 months in the sTPC, mTPC1, and mTPC2 groups with BCLA, respectively, and 18, 60, and 180 months in those with LABC, respectively. For patients with BCLA, the adjusted Cox regression suggested incidences of all-cause deaths in mTPC1group were statically higher than those in sTPC group, whereas the incidences of all-cause and cancer-specific death in the mTPC1 and mTPC2 groups were statistically lower than those in the sTPC group. The prognosis of patients with breast cancer and subsequent lung cancer of over 18 months was not significantly different than that of single lung cancer, which supported the profound appeal to increase the involvement of these two primary cancers in potential beneficial clinical trials. For patients with lung cancer and prior breast cancer of within 6 months and subsequent breast cancer of over 18 months, prognosis was improved relative to single lung cancer. Therefore, additional attention is needed to eliminate the potential bias may when these patients are recruited in the clinical trials.
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http://dx.doi.org/10.1038/s41598-021-94357-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292419PMC
July 2021

Thymosin beta 4 alleviates non-alcoholic fatty liver by inhibiting ferroptosis via up-regulation of GPX4.

Eur J Pharmacol 2021 Jul 16;908:174351. Epub 2021 Jul 16.

Department of Blood Transfusion, The Affliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China. Electronic address:

Thymosin beta 4 (Tβ4) can improve the liver fibrosis and reduce inflammation, while the role of Tβ4 in non-alcoholic fatty liver disease (NAFLD) whether mediated by ferroptosis remains unclear. A rat model of NAFLD was established on a high-fat diet (HFD), and rats were assigned ferroptosis inducer erastin and inhibitor Ferrostatin 1 (Fer-1). Subsequently, histopathology of the liver and the expression of ferroptosis-related genes in rat liver were detected. The steatosis of LO2 cells was induced by palmitic acid (PA) to reproduce the results of the rat experiment. The small interfering RNA (siRNA) was used to interfere with GPX4 expression to explore the influence on Tβ4 function. Tβ4 improved the inflammation, biochemical and lipid metabolism indexes, increased the antioxidant level, and inhibited abnormal accumulation of intracellular reactive oxygen species in HFD-induced NAFLD rats. Also, Tβ4 improved PA-induced LO2 damage and inhibited apoptosis of PA-induced LO2 cells. Both in vivo and in vitro, Tβ4 regulated expression of genes associated with ferroptosis, and Fer-1 treatment exaggerated the above effects of Tβ4, while erastin attenuated the protective effect of Tβ4. Moreover, siRNA GPX4 attenuated the protective effect of Tβ4 on the rat liver and on the mitochondrial membrane integrity of LO2 cells. Interfered expression of GPX4 with siRNA also regulated the expression of Bcl-2, Bax, Caspase-3 and SOD1, which attenuated therapeutic effect of Tβ4 on rat liver and LO2 cells. This study revealed that Tβ4 protects hepatocytes by inhibiting the GPX4-mediated ferroptosis pathway, which provides a new strategy and target for the treatment of NAFLD.
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http://dx.doi.org/10.1016/j.ejphar.2021.174351DOI Listing
July 2021

Association of central obesity with hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy.

Aliment Pharmacol Ther 2021 Aug 22;54(3):329-338. Epub 2021 Jun 22.

Guangzhou, China.

Background: Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB).

Aim: To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy.

Methods: We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body-mass index (BMI). Central obesity was evaluated by waist circumference, waist-to-hip ratio and waist-to-height ratio.

Results: A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5-year cumulative incidence of HCC was 2.9%. Waist-to-height ratio performed better in predicting HCC development than BMI, waist circumference or waist-to-hip ratio. Patients with central obesity (defined as waist-to-height ratio >0.5) had significantly higher 5-year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist-to-height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12-3.13, P = 0.017).

Conclusions: Central obesity, evaluated by the waist-to-height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease.
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http://dx.doi.org/10.1111/apt.16469DOI Listing
August 2021

Waterfall Forest Environment Regulates Chronic Stress via the NOX4/ROS/NF-κB Signaling Pathway.

Front Neurol 2021 18;12:619728. Epub 2021 Mar 18.

Department of Infectious Diseases, Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Forest therapy has been proven to have beneficial effects on people with depression and anxiety. However, it remains unknown whether the waterfall forest environment (WF) affects the physical and psychological health of patients with chronic fatigue and how the WF regulates chronic stress. Twenty-four patients with chronic fatigue were randomly divided into two groups: the WF group and the urban (U) group. Scores on the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Fatigue Scale-14 (FS-14) were evaluated before and after environmental intervention. Detection of physiological indexes and inflammatory factor levels and immunological analysis were also performed. In addition, the chronic stress rat model was constructed, and the effects of the WF on hopelessness and liver damage of rats were investigated. Patients with chronic fatigue in the WF group showed a significant decrease in FS-14, HAMA, and HAMD scores compared with the U group. The expression levels of glutathione peroxidase and superoxide dismutase were remarkably higher in the WF group than in the U group. However, the expression levels of malondialdehyde and inflammatory factors (IL-1β, TNF-α, IL-6, and IL-10) were remarkably decreased after the intervention of the WF. In addition, animal experiments confirmed that the WF improved hopelessness, liver damage, and excitability of neurons of chronic stress rats. Mechanistically, the WF reduced the liver damage caused by chronic stress in rats by inhibiting the NOX4/ROS/NF-κB signaling pathway. Collectively, the WF had a positive effect on immune enhancement and physical and psychological health in patients with chronic fatigue and might inhibit chronic stress by regulating the NOX4/ROS/NF-κB signaling pathway.
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http://dx.doi.org/10.3389/fneur.2021.619728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044934PMC
March 2021

Integrative proteomic and lipidomic analysis of Kaili Sour Soup-mediated attenuation of high-fat diet-induced nonalcoholic fatty liver disease in a rat model.

Nutr Metab (Lond) 2021 Mar 10;18(1):26. Epub 2021 Mar 10.

Department of Infectious Diseases, Affiliated Hospital of Guizhou Medical University, 28 Guiyi Street, Guiyang City, 550004, Guizhou Province, China.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and is characterized by excessive fat accumulation. Kaili Sour Soup, a food typical of Guizhou Province, is believed to have significant health benefits. Thus, we aimed to identify and assess the impact of Kaili Sour Soup on NAFLD and its underlying mechanism using integrative proteomic and lipidomic analysis.

Methods: A high-fat diet and male Wistar rats were used to construct a NAFLD rat model. Haematoxylin and eosin (HE) and Oil Red O staining analyses were used to perform the histologic examination. Proteomic analysis was utilized to systematically identify the global protein profile in NAFLD with and without Kaili Sour Soup treatment. Western blot assays were used to verify the expression of proteins screened by proteomic analysis. Lipidomic analysis was performed to screen lipid metabolism in NAFLD with and without Kaili Sour Soup treatment.

Results: Kaili Sour Soup alleviated high-fat diet (HFD)-induced fatty liver and had a normalizing effect on physiological and biochemical indicators of NAFLD, including body weight, liver weight, liver index, total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and insulin resistance level of homeostasis model assessment (HOMA-IR). Kaili Sour Soup decreased the levels of 13 proteins (Tmem44, Rnaseh2b, Gstm6l, LOC100910877, Rufy4, Slc12a2, Pcif1, P4503A1, Sult1e1, Nop53, AABR07065656.4, AABR07065789.3) that were upregulated by HFD and increased the levels of 3 proteins (Sult1c2, Sult1c2a, Snrnp48) that were downregulated by HFD. Kaili Sour Soup attenuated the HFD-induced increase in acyl carnitine (AcCa) and enhanced the HFD-induced decreases in gangliosides (GM3) and lysophosphatidylserine (LPS) in the NAFLD rat model.

Conclusions: Altogether, this study revealed that Kaili Sour Soup attenuated HFD-induced fatty liver and systematically identified abnormal proteins and lipids involved in the role of Kaili Sour Soup in a NAFLD rat model.
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http://dx.doi.org/10.1186/s12986-021-00553-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945315PMC
March 2021

Fecal transplantation alleviates acute liver injury in mice through regulating Treg/Th17 cytokines balance.

Sci Rep 2021 Jan 15;11(1):1611. Epub 2021 Jan 15.

Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyang Street, Guiyang, 550002, Guizhou, China.

Changes in intestinal microecology during acute liver failure (ALF) directly affect the occurrence and development of the disease. The study aimed to investigate the relationship between the intestinal microbiota and the key immune cells. Fecal microbiota transplantation (FMT) was used to determine whether ALF can balance Th17/Treg cytokines. The relationship between gut microbiota and clinical indicators was analyzed. BALB/c mice were treated with D-galactosamine (D-GalN) to induce a murine ALF model. FMT to D-GalN mice was conducted to test for liver function indicators. Results showed that the proportions of Lachnospiraceae, Prevotella, S24-7, Odoribacter and Rikenellaceae in D-GalN mice with intestinal microbiota disorder were restored after FMT. Further, CIA analysis showed that bacteria had a covariant relationship with clinical indicators. Microbiota could account for changes in 49.9% of the overall clinical indicators. Adonis analysis showed that Ruminococcus, and Enterococcus have a greater impact on clinical indicators. FMT down-regulated the expression of IL-17A, TNF-α, and TGF-β, while up-regulated IL-10 and IL-22. Transplantation of feces from Saccharomyces boulardii donor mice improved GalN-induced liver damage. These findings indicate that FMT attenuates D-GalN-induced liver damage in mice, and a clinical trial is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with ALF.
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http://dx.doi.org/10.1038/s41598-021-81263-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810881PMC
January 2021

Resveratrol contributes to the inhibition of liver fibrosis by inducing autophagy via the microRNA‑20a‑mediated activation of the PTEN/PI3K/AKT signaling pathway.

Int J Mol Med 2020 Dec 9;46(6):2035-2046. Epub 2020 Oct 9.

Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China.

Liver fibrosis (LF) is a healing response to wounds resulting in liver injury that can cause liver failure or even cancer without functional prevention. Resveratrol (RSV) has been suggested to exert biological effects against various human diseases. MicroRNA‑20a (miRNA/miR‑20a) has been shown to promote disease progression. The present study aimed to assess the mechanisms through which RSV induces autophagy and activates the miR‑20a‑mediated phosphatase and tensin homolog (PTEN)/PI3K/AKT signaling pathway in LF. First, a rat model of carbon tetrachloride (CCL4)‑induced LF and a cell model of platelet‑derived growth factor (PDGF)‑BB‑stimulated HSC‑T6 cells were established for use in subsequent experiments. Subsequently, RSV at a range of concentrations was injected into the model rats with LF. Indicators related to liver injury, oxidative stress and fibrosis were determined in the rats with LF. The RSV‑treated HSC‑T6 cells were subjected to transfection with miR‑20a mimic and PTEN overexpression plasmid to assess the levels of liver injury and LF. A dual‑luciferase reporter gene assay was performed to verify the binding sites between PTEN and miR‑20a. RSV was found to alleviate LF in rats, and autophagy was enhanced in the rats with LF following RSV treatment. Furthermore, the activation of the PTEN/PI3K/AKT axis attenuated LF, which was reversed by transfection with miR‑20a mimic. RSV reversed the inhibitory effects of miR‑20a on PTEN expression, reducing miR‑20a expression and promoting PTEN, PI3K and p‑AKT protein expression, thus attenuating LF. On the whole, the present study demonstrates that RSV induces autophagy and activates the miR‑20a‑mediated PTEN/PI3K/AKT signaling pathway to attenuate LF. These findings may lead to the development of potential therapeutic strategies for LF.
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http://dx.doi.org/10.3892/ijmm.2020.4748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595670PMC
December 2020

A tRNA-derived fragment (tRF-3001b) aggravates the development of nonalcoholic fatty liver disease by inhibiting autophagy.

Life Sci 2020 Sep 20;257:118125. Epub 2020 Jul 20.

Department of infectious disease, The Affiliated Hospital of Guizhou Medical University, No. 28, Guiyi Street, Guiyang 550001, Guizhou, China.

Aim: Nonalcoholic fatty liver disease (NAFLD) is a growing health problem worldwide. Impaired autophagy has been linked to NAFLD pathogenesis. Whether transfer RNA (tRNA)-derived fragments (tRFs) regulate the progression of NAFLD via autophagy is not clear. Here, we aimed to identify autophagy- or adipogenesis-related tRFs and investigate their roles in NAFLD.

Methods: Small RNA sequencing was performed on NAFLD and control mice, and candidate tRFs were validated using quantitative reverse transcription PCR (qRT-PCR). The role of a key tRF was investigated using Oil red O staining, western blotting, qRT-PCR and a luciferase reporter assay.

Key Findings: In NAFLD mice, the expression of p62 was increased and the ratio of LC3B-II/LC3-I was decreased compared to control mice. We identified nine differentially expressed tRFs, among which tRF-3001b was found to be significantly upregulated in NAFLD mice compared to the control liver tissues. Autophagy was decreased in FA (fatty acids)-induced LO2 cells, while silencing of tRF-3001b significantly abrogated the decrease in autophagy and increase in lipid formation. Moreover, chloroquine (CQ) dramatically abrogated the effect of tRF-3001b inhibition on lipid formation. Mechanistically, tRF-3001b targeted and inhibited the expression of the autophagy-related gene Prkaa1. In vivo, tRF-3001b silencing significantly improved pathology and decreased the levels of triglycerides and cholesterol in NAFLD mice, while CQ dramatically abrogated the effect of tRF-3001b deficiency.

Significance: tRF-3001b may aggravate the development of NAFLD by inhibiting autophagy via targeting Prkaa1.
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http://dx.doi.org/10.1016/j.lfs.2020.118125DOI Listing
September 2020

Baseline Characteristics and Treatment Patterns of the Patients Recruited to the China Registry of Hepatitis B.

J Clin Transl Hepatol 2019 Dec 20;7(4):322-328. Epub 2019 Dec 20.

Department of Infectious Diseases, Xinjiang Changji Prefecture People's Hospital, Changji, Xinjiang, China.

Chronic hepatitis B virus (HBV) infection remains a major public health problem globally. Here, we describe the baseline characteristics and treatment profiles of HBV-infected patients recruited to the China Registry of Hepatitis B. Inclusion criteria were patients with different stages of chronic HBV infection and complete key data. Exclusion criteria were patients with hepatocellular carcinoma. The baseline clinical, laboratory and treatment profiles were analyzed. Finally, 40,431 patients were included. The median age was 43 years, with 65.2% being men and 51.3% being positive for hepatitis B e antigen (HBeAg). The most common initial diagnosis was chronic hepatitis B (81.0%), followed by cirrhosis (9.3%), inactive carrier of hepatitis B surface antigen (HBsAg) (6.7%), and immune tolerant phase of hepatitis B infection (3.0%). Among the 21,228 patients who were on treatment, 88.0%, 10.0% and 2.0% received nucleos(t)ide analogues (NAs), interferon or combination of NAs and interferon, respectively. The proportion of patients who received preferred NAs (entecavir or tenofovir disoproxil fumarate) had increased from 13.5% in 2003 to 79.7% in 2016. We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study. About half of the patients were HBeAg-positive. NAs were the most commonly used therapy, and use of the preferred NAs had steadily increased in the past decade.
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http://dx.doi.org/10.14218/JCTH.2019.00052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943209PMC
December 2019

Outcomes of Long-term Treatment of Chronic HBV Infection With Entecavir or Other Agents From a Randomized Trial in 24 Countries.

Clin Gastroenterol Hepatol 2020 02 12;18(2):457-467.e21. Epub 2019 Jul 12.

Department of Infectious Diseases, Henan Provincial People's hospital, Zhengzhou, China.

Background & Aims: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response.

Methods: Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response.

Results: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events.

Conclusions: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.
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http://dx.doi.org/10.1016/j.cgh.2019.07.010DOI Listing
February 2020

AST to ALT ratio and arterial stiffness in non-fatty liver Japanese population:a secondary analysis based on a cross-sectional study.

Lipids Health Dis 2018 Dec 3;17(1):275. Epub 2018 Dec 3.

Department of Immunology and Microbiology, Guiyang College of Traditional Chinese Medicine, 84# ShiDong Road, Guiyang, 550001, Guizhou, China.

Background: Previous studies have revealed that triglyceride to high-density lipoprotein cholesterol (HDL-C) ratio (henceforth TG/HDL-C) is one of the major risk factors for cardiovascular disease, insulin resistance and metabolism syndrome. However, there are fewer investigations of the correlations between the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio and brachial ankle pulse wave velocity (baPWV). This study was undertaken to investigate the relationship between the AST to ALT ratio and brachial-ankle pulse wave velocity (baPWV) in a Japanese population.

Methods: The present study was a cross-sectional study. A total of 646 Japanese men and women without fatty liver, aged 24-84 years old, received a health medical check-up programme including the results from baPWV inspection and various standardized questionnaires in a health examination centre in Japan. Main outcome measures included AST/ALT ratio, baPWV, fatty liver and postmenopausal status. Abdominal ultrasonography was used to diagnose fatty liver. A postmenopausal state was defined as beginning 1 year following the cessation of menses.

Results: After adjusting for potential confounders (age, sex, BMI, SBP, DBP, AST, ALT, GGT, uric acid, fasting glucose, TC, LDL, eGFR, smoking and exercise statuses, fatty liver, alcohol consumption and ABI), a non-linear relationship was detected between AST/ALT and baPWV, which had an inflection point of 5.6. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 12.7 (1.9 to 23.5) and - 16.7 (- 36.8 to 3.3), respectively. Subgroup analysis in participants with excessive alcohol consumption (more than 280 g/week) showed that AST/ALT had a negative correlation with baPWV (β = - 30.7, 95%CI (- 53.1, - 8.4)), and the P value for the interaction was less than 0.05.

Conclusion: The relationship between AST/ALT and baPWV is non-linear. AST/ALT was positively correlated with baPWV when AST/ALT was less than 5.6. In addition, the trend was the opposite in subjects who consumed excessive amounts of alcohol.
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http://dx.doi.org/10.1186/s12944-018-0920-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278163PMC
December 2018

Thymosin-β4 Mediates Hepatic Stellate Cell Activation by Interfering with CircRNA-0067835/miR-155/FoxO3 Signaling Pathway.

Cell Physiol Biochem 2018 27;51(3):1389-1398. Epub 2018 Nov 27.

Peking University Health Science Center, Beijing, China.

Background/aims: Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis. Our study proved that thymosin beta 4 (Tβ4) has anti-fibrogenic effects in HSCs through PI3K/AKT pathway. However, the underlying mechanisms are not fully elucidated. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of in liver fibrosis is still unknown. Therefore, we hypothesize that Tβ4 influences circRNAs in liver fibrosis.

Methods: Circular RNA microarray was conducted to identify Tβ4-related circRNAs. Pathway analysis and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in liver fibrosis. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in liver fibrosis. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in liver fibrosis.

Results: A total of 644 differentially expressed circRNAs were identified between the Tβ4-depleted LX-2 cells and the control LX2 cells. The expression of circRNA-0067835 was significantly increased in the Tβ4-depleted LX-2 cells compared with control. Knockdown of circRNA-0067835 observably decreased LX-2 cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay.

Conclusion: Our experiments showed that circRNA-0067835 regulated liver fibrosis progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with liver fibrosis.
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http://dx.doi.org/10.1159/000495556DOI Listing
January 2019

Blueberry, combined with probiotics, alleviates non-alcoholic fatty liver disease via IL-22-mediated JAK1/STAT3/BAX signaling.

Food Funct 2018 Dec;9(12):6298-6306

Department of Infection, Affiliated Hospital of Guizhou Medical University, No. 28, Guiyang Street, Guiyang 550001, Guizhou, China.

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent diseases worldwide. Blueberry, combined with probiotics (BP), might be a potential candidate for NAFLD treatment, due to its anti-inflammatory and anti-apoptotic properties. Here, we investigated whether the anti-inflammatory cytokine, IL-22, was involved in the therapeutic process of BP, using cell and rat models of NAFLD. Results indicated that BP significantly reduced lipid droplets and triglyceride (TG) accumulation in NAFLD cells. However, when IL-22 was deficient, the lipid droplets and TG content were significantly increased. In vivo, the serum parameters and pathological degree of NAFLD rats were significantly improved by BP, while IL-22 silencing significantly abolished the BP effect. Immunohistochemistry, immunofluorescence, qRT-PCR, and western blotting showed that the NAFLD group expressed significantly lower levels of IL-22, JAK1, and STAT3, and higher levels of BAX, than the normal group. Furthermore, BP significantly elevated the levels of IL-22, JAK1 and STAT3, and reduced the level of BAX in NAFLD, while IL-22 silencing prevented BP from restoring the expression of JAK1, STAT3, and BAX. We conclude that IL-22 is vital for the therapeutic effect of BP, and acts via activation of JAK1/STAT3 signaling and inhibition of the apoptosis factor BAX, which makes IL-22 a promising target for therapy of NAFLD.
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http://dx.doi.org/10.1039/c8fo01227jDOI Listing
December 2018

Thymosin-β4 inhibits proliferation and induces apoptosis of hepatic stellate cells through PI3K/AKT pathway.

Oncotarget 2017 Sep 28;8(40):68847-68853. Epub 2017 Jun 28.

Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.

Liver fibrosis is a necessary stage for chronic liver diseases, and serious threat to human health. Hepatic fibrosis is a necessary stage for chronic liver diseases. Hepatic stellate cells (HSCs) are the primary cell type responsible for fibrosis. Thymosin beta 4 (Tβ4) has a potential role in the pathogenesis of liver fibrosis and that it is especially associated with the activation of HSCs, however, the underlying mechanisms are not fully elucidated. Herein, we investigated the potential role of Tβ4 in liver fibrosis by describing the effects of Tβ4, and we discuss the possible signaling pathway regulated by Tβ4. The expression of Tβ4 was significantly decreased in human HSC cell line LX-2 and CCl4-treated mouse liver. The depletion of Tβ4 significantly associated with the activation of HSCs via the enhanced expression of α-SMA and vimentin. Tβ4 significantly suppressed the viability and migration of HSCs. Understanding the potential effects and regulatory mechanism of Tβ4 in liver fibrosis might help to provide a novel treatment for patients with liver fibrosis.
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http://dx.doi.org/10.18632/oncotarget.18748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620301PMC
September 2017

Baicalin Ameliorates Liver Injury Induced by Chronic plus Binge Ethanol Feeding by Modulating Oxidative Stress and Inflammation via CYP2E1 and NRF2 in Mice.

Oxid Med Cell Longev 2017 16;2017:4820414. Epub 2017 Aug 16.

Department of Clinical Microbiology and Immunology, Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Yunyan District, Guiyang City, Guizhou Province 550004, China.

Alcoholic liver injury leads to serious complication including death. The potential role of baicalin at the transcription level in mice model of alcohol injury is not known yet. In this study, we examined the effect of baicalin against chronic plus binge ethanol model in mice and understanding the mechanism of protection. Liver function, histology, steatosis, inflammation, NF-B activity, oxidative stress sources, nuclear translocation of NRF2 transcription factor, and cell death were assessed. Treatment with baicalin ameliorated ethanol-induced oxidative stress, inflammation, and cell death. Baicalin attenuated ethanol-induced proinflammatory molecules such as TNF-, IL-1, MIP-2, and MCP-1 and reversed redox-sensitive transcription factor NF-B activation. Baicalin also modulated Kupffer cell activation in vitro. Baicalin inhibited ethanol-induced expression of reactive oxygen species (ROS) generating enzymes NOX2, p67phox, xanthine oxidase, and iNOS in addition to CYP2E1 activities. Baicalin also enhanced ethanol-induced NRF2 nuclear translocation and increased downstream target gene HO-1 as antioxidant defense. Finally, baicalin reduced significant apoptotic and necrotic cell death. Our study suggests that baicalin ameliorates chronic plus binge ethanol-induced liver injury involving molecular crosstalk of multiple pathways at the transcriptional level and through upregulation of antioxidant defense mechanism.
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http://dx.doi.org/10.1155/2017/4820414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603751PMC
May 2018

CXCL10 accelerates EMT and metastasis by MMP-2 in hepatocellular carcinoma.

Am J Transl Res 2017 15;9(6):2824-2837. Epub 2017 Jun 15.

Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College28 Guiyi Street, Guiyang 550004, Guizhou, China.

Human malignant hepatocellular carcinoma (HCC) is a common tumor, which severely threatens human health and shortens longevity. The poor prognosis of HCC is primarily attributed to distant metastases. C-X-C motif chemokine 10 (CXCL10) regulates the control of several cellular and developmental processes including tumor cell proliferation, apoptosis, and cell metastasis. Previous studies have confirmed that CXCL10 functions as an oncogene in several cancers. However, the expression and biological functions of CXCL10 in HCC, especially with regard to metastasis, need further investigation. In this study, CXCL10 was found to be over expressed in invasive HCC cells and HCC clinical samples. While the over-expression of CXCL10 enhanced migration, invasion, and metastasis of HCC cells in vitro as well as in vivo, silencing of CXCL10 resulted in inhibition of HCC cell metastasis. Further, CXCL10 was found to accelerate epithelial-mesenchymal transition of HCC cells. The microarray analysis indicated that matrix metallopeptidase-2 (MMP-2) functions as a downstream factor of CXCL10. This study demonstrates that CXCL10 partakes in the metastasis of HCC by activating MMP-2 expression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489884PMC
June 2017

The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α.

Nutrients 2017 Feb 27;9(3). Epub 2017 Feb 27.

Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China.

Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets ( < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models ( < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) ( < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway via PPAR-α.
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http://dx.doi.org/10.3390/nu9030198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372861PMC
February 2017

The combination of blueberry juice and probiotics reduces apoptosis of alcoholic fatty liver of mice by affecting SIRT1 pathway.

Drug Des Devel Ther 2016 12;10:1649-61. Epub 2016 May 12.

Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang, People's Republic of China.

Purpose: To explore the effects of the combination of blueberry juice and probiotics on the apoptosis of alcoholic fatty liver disease (AFLD).

Methods: Healthy C57BL/6J mice were used in the control group (CG). AFLD mice models were established with Lieber-DeCarli ethanol diet and evenly assigned to six groups with different treatments: MG (model), SI (SIRT1 [sirtuin type 1] small interfering RNA [siRNA]), BJ (blueberry juice), BJSI (blueberry juice and SIRT1 siRNA), BJP (blueberry juice and probiotics), and BJPSI (blueberry juice, probiotics, and SIRT1 siRNA). Hepatic tissue was observed using hematoxylin and eosin (HE) and Oil Red O (ORO) staining. Biochemical indexes of the blood serum were analyzed. The levels of SIRT1, caspase-3, forkhead box protein O1 (FOXO1), FasL (tumor necrosis factor ligand superfamily member 6), BAX, and Bcl-2 were measured by reverse transcription-polymerase chain reaction and Western blotting.

Results: HE and ORO staining showed that the hepatocytes were heavily destroyed with large lipid droplets in MG and SI groups, while the severity was reduced in the CG, BJ, and BJP groups (P<0.05). The levels of superoxide dismutase (SOD), reduced glutathione (GSH), and high-density lipoprotein-cholesterol (HDL-C) were increased in BJ and BJP groups when compared with the model group (P<0.05). In contrast, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total triglycerides (TGs), total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and malondialdehyde (MDA) were lower in BJ and BJP groups than in the model group (P<0.05). The level of SIRT1 was increased, while the levels of FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase-3, BAX, and Bcl-2 were decreased in CG, BJ, and BJP groups (P<0.05). Meanwhile, SIRT1 silence resulted in increase of the levels of FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase-3, BAX, and Bcl-2.

Conclusion: The combination of blueberry juice and probiotics reduces apoptosis in AFLD by suppressing FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase-3, BAX, and Bcl-2 via the upregulation of SIRT1.
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http://dx.doi.org/10.2147/DDDT.S102883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869661PMC
May 2017

[Effects of blueberry on apoptosis and expression of Bcl-2 and Bax in HSC-T6].

Zhonghua Yi Xue Za Zhi 2015 Aug;95(31):2560-4

Department of Infectious Diseases, Guiyang Medical College, Guiyang 550004, China.

Objective: To investigate the effects of blueberry on the apoptosis, expression of Bcl-2 and Bax in rat hepatic stellate cell (HSC-T6).

Methods: 10% blueberry serum at low, middle and high dose, 10% Fu-Fang-Bie-Jia-Ruan-Gan tablet serum and 10% saline serum were prepared by method of serum pharmacology. Subcultured HSC-T6 was divided into saline serum control group, blueberry serum at low, middle, high dose and Fu-Fang-Bie-Jia-Ruan-Gan tablet serum group, and then was respectively incubated at different dose of 10% blueberry serum, 10% Fu-Fang-Bie-Jia-Ruan-Gan tablet serum and 10% saline serum for 72 hours.Apoptosis of HSC-T6 was detected using flow cytometry with annexin V FITC/PI double staining. The expression of Bcl-2 and Bax in HSC-T6 were examined using immunocytochemistry and Western blotting, respectively.

Result: There was no significant difference for HSC-T6 Bax protein expression in the low, middle and high dose blueberry serum groups, compared with saline serum control group, respectively.In the high-dose blueberry serum group HSC-T6 early and total apoptosis rate increased significantly compared with the saline serum control group (5.55% ± 0.98% vs 2.53% ± 0.46%, 7.01% ± 1.05% vs 2.96% ± 0.81%, both P<0.05); Bcl-2 protein expression was significantly decreased (A value, 82 ± 35 vs 51 ± 13, P<0.05); Bcl-2/Bax ratio was significantly decreased (0.26 ± 0.02 vs 0.46 ± 0.03, P<0.05); HSC-T6 early and total apoptosis rate, Bcl-2 expression and Bcl-2/Bax ratio in the low and the middle dose blueberry serum group showed no significant difference with the saline serum control group.

Conclusion: Blueberry can induce HSC-T6 apoptosis by down-regulating Bcl-2 expression and decreasing the ratio of Bcl-2/Bax in HSC-T6 cells, so it may have potential interference effects on hepatic fibrosis.
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August 2015

Loss of FGF21 in diabetic mouse during hepatocellular carcinogenetic transformation.

Am J Cancer Res 2015 15;5(5):1762-74. Epub 2015 Apr 15.

Chinese-American Research Institute for Diabetic Complications Ruian Center, The Department of Endocrinology, The Third Affiliated Hospital of Wenzhou Medical University Ruian, Zhejiang 325200, China ; Kosair Children's Hospital Research Institute, The Department of Pediatrics of The University of Louisville Louisville, KY 40202.

Diabetes associated metabolic syndrome has been shown to be an independent risk factor for the development of hepatocellular carcinoma (HCC). Cirrhosis, in fact, was not always a prerequisite of HCC development and this might particularly apply to the metabolic abnormality associated HCC. This study was to investigate diabetes associated HCC and the potential role of FGF21 during carcinogenetic transformation of HCC. Dimethylnitrosamine (DEN) was used to induce HCC in the diabetic OVE26 mice. Pronounced damage characterized by steatohepatitis was found in the liver of diabetic mice. Steatohepatitis accompanied by constant cell proliferation and tumor cell growth were also found in the hepatic tissues of diabetic OVE26 mice when DEN being administrated. FGF21 protein level increased in liver tissues at an early stage along with steatohepatitis in diabetic OVE26 mice, but decreased in liver tissues later when HCC was developed. In addition, decreased FGF21 protein level was associated with cancerous hyper-proliferation and aberrant p53 and TGF-β/Smad signaling during HCC development. Loss of FGF21 may play an important role in HCC carcinogenetic transformation during metabolic liver injury in diabetic animals. The present finding calls attention to the need to control metabolic disorders associated with diabetes and may further develop a protective strategy against HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497442PMC
July 2015

ER stress and autophagy dysfunction contribute to fatty liver in diabetic mice.

Int J Biol Sci 2015 2;11(5):559-68. Epub 2015 Apr 2.

3. Chinese-American Research Institute for Diabetic Complications RuiAn Center, the Department of Endocrinology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang, China, 325200 ; 4. Kosair Children's Hospital Research Institute, the Department of Pediatrics of the University of Louisville, Louisville, KY 40202, USA.

Diabetes mellitus and nonalcoholic fatty liver disease (NAFLD) are often identified in patients simultaneously. Recent evidence suggests that endoplasmic reticulum (ER) stress and autophagy dysfunction play an important role in hepatocytes injury and hepatic lipid metabolism, however the mechanistic interaction between diabetes and NAFLD is largely unknown. In this study, we used a diabetic mouse model to study the interplay between ER stress and autophagy during the pathogenic transformation of NAFLD. The coexist of inflammatory hepatic injury and hepatic accumulation of triglycerides (TGs) stored in lipid droplets indicated development of steatohepatitis in the diabetic mice. The alterations of components for ER stress signaling including ATF6, GRP78, CHOP and caspase12 indicated increased ER stress in liver tissues in early stage but blunted in the later stage during the development of diabetes. Likewise, autophagy functioned well in the early stage but suppressed in the later stage. The inactivation of unfolded protein response and suppression of autophagy were positively related to the development of steatohepatitis, which linked to metabolic abnormalities in the compromised hepatic tissues in diabetic condition. We conclude that the adaption of ER stress and impairment of autophagy play an important role to exacerbate lipid metabolic disorder contributing to steatohepatitis in diabetes.
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http://dx.doi.org/10.7150/ijbs.10690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400387PMC
January 2016

Adipose-derived stem cell-based treatment for acute liver failure.

Stem Cell Res Ther 2015 Mar 21;6:40. Epub 2015 Mar 21.

Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchangzhong Road, Shanghai, 200072, P.R. China.

Introduction: Acute liver failure (ALF) is a highly lethal disease, for which effective therapeutic methods are limited. Although allogeneic liver transplantation is a viable treatment method for ALF, there is a serious shortage of liver donors. Recent studies suggest that stem cell transplantation is a more promising alternative. Hence, we investigate whether human adipose-derived stem cells (ASCs) have the therapeutic potential for ALF in this study based on the studies of rat models.

Methods: Sprague Dawley rats were used to establish ALF models by D-galactosamine injection. These rats were randomly divided into a human ASC-treated group and a phosphate-buffered saline (PBS) control group. The human ASCs or PBS was transplanted through the spleen of rats. The indices of hepatic function and hepatic histology were dynamically detected, and the survival rates of rats were also counted. Double-fluorescence immunohistochemistry was employed to detect the ASC fate after transplantation. Moreover, both concentrated ASC conditional media and ASC lysates were transplanted through the femoral vain of rats to investigate the therapeutic potential for ALF.

Results: The ASC transplantation group showed improved viability in comparison with the sham control. Histological and biochemical analysis suggested that liver morphology and function were improved in terms of cell proliferation and apoptosis. Although a plethora of ASCs persist in the spleen, the improvement in liver function was obvious. However, ASCs did not differentiate into hepatocytes after engrafting to livers within 3 days. In addition, both concentrated serum-free ASC conditional media and ASC lysates, characterized by high levels of hepatocyte growth factor and vascular endothelial growth factor, demonstrated obvious improvement in terms of high survival rates of ALF rats.

Conclusion: Our data suggest that ASC transplantation has the potential for ALF treatment partly by the mechanism of secreting growth factors contributing to liver regeneration.
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http://dx.doi.org/10.1186/s13287-015-0040-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425851PMC
March 2015

Zinc treatment prevents type 1 diabetes-induced hepatic oxidative damage, endoplasmic reticulum stress, and cell death, and even prevents possible steatohepatitis in the OVE26 mouse model: Important role of metallothionein.

Toxicol Lett 2015 Mar 21;233(2):114-24. Epub 2015 Jan 21.

Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, China. Electronic address:

Whether zinc is able to improve diabetes-induced liver injury remains unknown. Transgenic type 1 diabetic (OVE26) mice develop hyperglycemia at 3 weeks old; therefore therapeutic effect of zinc on diabetes-induced liver injury was investigated in OVE26 mice. Three-month old OVE26 and age-matched wild-type mice were treated by gavage with saline or zinc at 5mg/kg body-weight every other day for 3 months. Hepatic injury was examined by serum alanine aminotransferase (ALT) level with liver histopathological and biochemical changes. OVE26 mice at 6 months old showed significant increases in serum ALT level and hepatic oxidative damage, endoplasmic reticulum stress and associated cell death, mild inflammation, and fibrosis. However, all these hepatic morphological and functional changes were significantly prevented in 3-month zinc-treated OVE26 mice. Mechanistically, zinc treatment significantly increased hepatic metallothionein, a protein with known antioxidant activity, in both wild-type and OVE26 mice. These results suggest that there were significantly functional, structural and biochemical abnormalities in the liver of OVE26 diabetic mice at 6 months old; however, all these changes could be prevented with zinc treatment, which was associated with the upregulation of hepatic metallothionein expression.
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http://dx.doi.org/10.1016/j.toxlet.2015.01.010DOI Listing
March 2015

Dietary blueberry and bifidobacteria attenuate nonalcoholic fatty liver disease in rats by affecting SIRT1-mediated signaling pathway.

Oxid Med Cell Longev 2014 27;2014:469059. Epub 2014 Nov 27.

Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, 28 Guiyi Street, Guiyang, Guizhou 550004, China.

NAFLD model rats were established and divided into NAFLD model (MG group), SIRT1 RNAi (SI group), blueberry juice (BJ group), blueberry juice + bifidobacteria (BJB group), blueberry juice + SIRT1 RNAi (BJSI group), and blueberry juice + bifidobacteria + SIRT1 RNAi groups (BJBSI group). A group with normal rats was a control group (CG). BJB group ameliorated NAFLD, which was better than BJ group (P < 0.05). The lipid accumulation was lower in CG, BJ, and BJB groups than that in MG, SI, BJSI, and BJBSI groups (P < 0.05). The levels of SIRT1 and PPAR-α were higher in CG, BJ, and BJB groups than those in MG, SI, BJSI, and BJBSI groups (P < 0.05). The levels of SREBP-1c were lower in CG, BJ, and BJB groups than those in MG, SI, BJSI, and BJBSI groups (P < 0.05). The biochemical indexes SOD, GSH, and HDL-c were improved from CG to BJB group (P < 0.05). Inversely, the levels of AST and ALT, TG, TC, LDL-c, and MDA were decreased from CG to BJB group (P < 0.05). These changes enhance antioxidative capability and biochemical index of rats. Blueberry juice and bifidobacteria improve NAFLD by activating SIRTI-mediating signaling pathway.
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http://dx.doi.org/10.1155/2014/469059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265704PMC
August 2015

[Natural clearance of hepatitis C virus in 96 patients with infection acquired by blood transfusion from a single donor in Guizhou].

Zhonghua Gan Zang Bing Za Zhi 2014 Apr;22(4):251-4

Department of Infectious Diseases, the Qiannan People's Hospital in Guizhou Province, Guizhou Qiannan 558000, China.

Objective: To investigate the clinical features and rate of natural viral clearance in patients with hepatitis C virus (HCV) infection acquired by blood transfusion from a single donor.

Methods: Ninety-six patients who acquired HCV infection between January 1998 and December 2002, upon receipt of donated blood from a single infected individual in Guizhou,were included in this retrospective cross-sectional study. Patients were clinically assessed to determine levels of anti-HCV antibodies, HCV RNA and biochemical indicators of liver function,as well as features of liver structure (by abdominal B ultrasonography and elastography). HCV genetic testing was used to determine the virus genotype. Measurement data were expressed as mean ± standard deviation. Count data were analyzed by the x² test,with P less than 0.05 indicating statistical significance.

Results: All 96 patients tested positive for antiHCV antibodies. The majority of patients (70%; 34:33 male:female) had HCV RNA more than or equal to 1.0 * 103 copies/ml. All patients carried the same HCV genotype as the single blood donor:genotype lb. The overall rate of natural HCV clearance was 30.2%. but males had a significantly lower rate (19.0% (8/42) vs. females:38.9% (21/54);x²=4.41,P=0.023) as did older patients (more than 40 years-old:16.1% (5/31) vs .less than or equal to 40 years-old:36.9% (24/65);x²=4.30,P=0.028). The overall rate of chronic HCV infection (CHC) was 69.8%,but the rate was significantly lower in younger patients (less than or equal to 40 years-old:63.1% (41/65) vs. more than 40 years-old:83.9% (26/31);x²=6.67,P=0.028). Among the 67 patients with CHC,12 had symptoms of mild weakness,anorexia and abdominal distention,11 had elevated serum alanine aminotransferase (116.25 +/- 24.65 U/L) and stage 3 or 4 fibrosis (liver elasticity values more than or equal to 5.1 kPa),and three had mildly abnormal serum bilirubin (32.56 ± 5.28 mumol/L). Fifteen patients showed signs of chronic hepatitis and one patient showed signs of cirrhosis by abdominal B ultrasonography. None of the patients showed signs of hepatocellular carcinoma.

Conclusion: The course of blood transfusion acquired HCV infection is largely unknown and natural viral clearance rate may be associated with sex-and age-related factors.
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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2014.04.003DOI Listing
April 2014

[A case-control study on the risk factors of hepatocellular carcinoma in Guizhou Province].

Zhonghua Gan Zang Bing Za Zhi 2014 Jan;22(1):33-7

Department of Infectious Disease, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China.

Objective: To determine the risk factor of HCC in Guizhou.

Methods: A group case-control study design was conducted between 762 cases and 798 controls in Guizhou province. The main related-factors were analyzed with unconditional logistic regression model and evaluated by odds ratio (OR) and 95% confidence interval (95% CI).

Results: There are significant differences between cases and controls in regarding to cigarette smoking 210 (27.6%),non-alcoholic fatty liver disease 336 (44.1%), alcoholic liver disease 245 (32.2%), family history of HCC 141 (16.5%), alcohol consumption 300 (39.4%), HBV infection 436 (57.2%), pickled food 290 (38.1%), and economic status 5 years ago 420 (55.1%) in cases,and cigarette smoking 116 (14.5%),non-alcoholic fatty liver disease 160 (20.1%), alcoholic liver disease 101 (12.7%), family history of HCC 40 (5.0%), alcohol consumption 180 (22.6%), HBV infection 82 (10.3%), pickled food 225 (28.2%), and economic status 5 years ago 647 (81.1%) in controls, with OR of each variable was 3.520, 2.464, 4.330, 2.219, 2.451, 19.245, 6.212, 0.174 respectively, P less than 0.01.

Conclusion: HBV infection and pickled food were the most common risks for HCC in Guizhou. Alcohol consumption excessively and cigarette smoking may increase the risk too.
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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2014.01.008DOI Listing
January 2014

Maotai ameliorates diethylnitrosamine-initiated hepatocellular carcinoma formation in mice.

PLoS One 2014 1;9(4):e93599. Epub 2014 Apr 1.

Guiyang Medical College Hospital, GuiYang, Guizhou, China.

Consumption of alcohol is closely related to liver disease, such as hepatic fibrosis or even hepatocellular carcinoma (HCC). However, epidemiological and experimental studies indicated that consumption of Maotai, one of the famous liquors in China, exhibits no significant correlation with hepatic fibrosis or cirrhosis as other beverage sources do. This study detected the relationship of Maotai consumption and HCC development in a diethylnitrosamine (DEN)-initiated HCC animal model. DEN was given to mice at a dose of 100 mg/kg, ip, and 50 mg/kg, ip in the following week. Mice were simultaneously given Maotai or an equal amount of ethanol (53%, 5 ml/kg/day, 5 days/week for up to 35 weeks). At 3-week and 35- week of the experiment, serum and livers were collected for biochemical and histopathological examination of liver injury and incidence of HCC. Real-time RT-PCR, immunohistochemistry and Western blotting were used to examine the expression of metallothionein-1/2 (MT-1/2), NF-E2-related factor 2 (Nrf2), glutamate-cysteine ligase catalytic subunit (GCLC) and modified subunit (GCLM). We identified tissue damage and dysfunction of liver in ethanol + DEN-treated mice, whereas the extent of injury was reduced in Maotai+ DEN -treated mice. Significant Glypican-3(GPC3) expression and precancerous injury or HCC were seen in approximately 50% of mice with ethanol+ DEN, but barely be seen in Maotai + DEN-treated mice. A higher expression of MT-1/2, Nrf2 and GCLC could be seen in Maotai + DEN-treated mice. Thus, Maotai liquor ameliorates the formation of DEN-induced HCC in mice, and the protection mechanism is possibly related with the activation of anti-oxidation factors, such as MTs, Nrf2 and GCLC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093599PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972115PMC
June 2015

Effect of Maotai liquor on P53 gene in primary hepatocellular carcinoma induced by compound factors in rats.

Chin Med J (Engl) 2014 ;127(2):378-80

Department of Infectious Disease, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, China.

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January 2015

Novel host genetic variations associated with spontaneous clearance of a single-source outbreak of HCV1b infections.

BMJ Open Gastroenterol 2014 6;1(1):e000010. Epub 2015 Feb 6.

Liver Research Center , Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University , Beijing , China.

Background And Aims: A total of 105 patients were identified as accidentally infected with hepatitis C virus genotype 1b (HCV1b) through blood transfusion from a single blood donor. This group provides a unique patient population to study host factors involved in the spontaneous clearance of HCV and disease progression.

Methods: Clinical markers, HCV RNA and eight single nucleotide polymorphisms (SNPs) of interleukin-28B (IL-28B) were detected. Exome capture and sequencing were analysed for association with HCV clearance.

Results: Among the 85 patients with the positive HCV antibody, 27 cases (31.8%) were HCV RNA negative over a period of 9-12 years. Of the 58 patients with positive HCV RNA, 22.4% developed chronic hepatitis, and 5.2% developed cirrhosis. Age was found to be associated with HCV1b clearance. IL-28 rs10853728 CC showed the trend. By exon sequencing, 39 SNPs were found to be significantly different in spontaneous clearance patients (p<0.001). Two SNPs in the tenascin receptor (TNR), five in the transmembrane protease serine 11A (TMPRSS11A), and one in the serine peptidase inhibitor kunitz type 2 (SPINT2) showed the closest associations (p<10(-5)).

Conclusions: Host genetic analyses on the unique, single source HCV1b-infected patient population has suggested that age and mutations in TNR, TMPRSS11A and SPINT2 genes may be factors associated with HCV clearance.
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http://dx.doi.org/10.1136/bmjgast-2014-000010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533326PMC
October 2015

Dietary supplementation of blueberry juice enhances hepatic expression of metallothionein and attenuates liver fibrosis in rats.

PLoS One 2013 12;8(3):e58659. Epub 2013 Mar 12.

Department of Clinical Microbiology and Immunology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou Province, China.

Aim: To investigate the effect of blueberry juice intake on rat liver fibrosis and its influence on hepatic antioxidant defense.

Methods: Rabbiteye blueberry was used to prepare fresh juice to feed rats by daily gastric gavage. Dan-shao-hua-xian capsule (DSHX) was used as a positive control for liver fibrosis protection. Liver fibrosis was induced in male Sprague-Dawley rats by subcutaneous injection of CCl4 and feeding a high-lipid/low-protein diet for 8 weeks. Hepatic fibrosis was evaluated by Masson staining. The expression of α-smooth muscle actin (α-SMA) and collagen III (Col III) were determined by immunohistochemical techniques. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenates were determined. Metallothionein (MT) expression was detected by real-time RT-PCR and immunohistochemical techniques.

Results: Blueberry juice consumption significantly attenuates CCl4-induced rat hepatic fibrosis, which was associated with elevated expression of metallothionein (MT), increased SOD activity, reduced oxidative stress, and decreased levels of α-SMA and Col III in the liver.

Conclusion: Our study suggests that dietary supplementation of blueberry juice can augment antioxidative capability of the liver presumably via stimulating MT expression and SOD activity, which in turn promotes HSC inactivation and thus decreases extracellular matrix collagen accumulation in the liver, and thereby alleviating hepatic fibrosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058659PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595269PMC
October 2013
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