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Wang P, Yin Q, Ding K, Zhong H, Jia Q, Xiao Z, Xiong H. Comparing machine learning models for osteoporosis prediction in Tibetan middle aged and elderly women. Sci Rep 2025; 15:10960. [PMID: 40164752 PMCID: PMC11958675 DOI: 10.1038/s41598-025-95707-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 03/24/2025] [Indexed: 04/02/2025] Open
Abstract
The aim of this study was to establish the optimal prediction model by comparing the prediction effect of 6 kinds of prediction models containing biochemical indexes on the risk of osteoporosis in middle-aged and elderly women in Tibet. This study adopted a multi-stage cluster random sampling cross-sectional survey method. From January 2022 to January 2024, we obtained biochemical and bone mineral density (BMD) data from high altitudes in Tibet. We built a predictive model of osteoporosis in three steps. First, we performed feature selection to identify factors associated with osteoporosis. Next, the eligible participants were randomly divided into a training set and a test set in a ratio of 8:2. Then, the prediction model of osteoporosis was established based on Random Forest, ANN, XGB, and SVM. Finally, we compared the performance of the prediction models using sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) to select the best prediction model. Correlation analysis was used to screen indicators with statistical differences from T-score. Finally, Age (P < 0.01), LDL-C (P < 0.05), UA (P < 0.01), AST (P < 0.05), CREA (P < 0.01), BMI (P < 0.01), ALT (P < 0.01) were associated with osteoporosis. In train set, the order of AUC from highest to lowest is Random Forest (1.000), XGB (0.887), SVM (0.868), regression (0.801), ANN (0.793) and OSTA (0.739). In test set, the order of AUC from highest to lowest is XGB (0.848), regression (0.801), Random Forest (0.772), SVM (0.755), OSTA (0.739), ANN (0.732). SVM and XGB algorithm models had better screening effect on osteoporosis than OSTA in middle-aged and elderly Tibetan residents in Tibet. Compared with Random Forest, ANN and SVM, the established XGB model had the best prediction ability and can be used to predict the risk of osteoporosis on biochemical indexes. The model needs to be further improved through large sample research.
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Affiliation(s)
- Peng Wang
- School of Medicine, Tibet University, Lhasa, 850000, China
| | - Qiang Yin
- School of Ecology and Environment, Tibet University, Lhasa, 850000, China
| | - Kangzhi Ding
- School of Medicine, Tibet University, Lhasa, 850000, China
| | - Huaichang Zhong
- Hospital Infection Management Department, The First People's Hospital of Shuangliu District, West China Airport Hospital of Sichuan University, Chengdu, 610200, China
| | - Qundi Jia
- School of Medicine, Tibet University, Lhasa, 850000, China
| | - Zhasang Xiao
- School of Medicine, Tibet University, Lhasa, 850000, China.
| | - Hai Xiong
- School of Medicine, Tibet University, Lhasa, 850000, China.
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Zhang J, Hu Y, Xu J, Shao H, Zhu Q, Si H. Genetically predicted immune cells mediate the association between gut microbiota and autoimmune liver diseases. Front Microbiol 2024; 15:1442506. [PMID: 39736991 PMCID: PMC11684339 DOI: 10.3389/fmicb.2024.1442506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 11/18/2024] [Indexed: 01/01/2025] Open
Abstract
Background Increasing evidence suggests an association between gut microbiota and Autoimmune Liver Diseases (AILDs). However, causal inference remains controversial due to confounding bias in observational studies. Additionally, there is currently no clear evidence indicating that immune cells act as intermediate phenotypes in the pathogenesis of AILDs. This study utilizes the Mendelian Randomization (MR) method to investigate the causal relationships among gut microbiota, immune cells, and AILDs. Methods Initially, we conducted a two-sample MR analysis to predict the causal relationships among 412 gut microbiota, 731 immune phenotypes, and AILDs. Subsequently, a series of sensitivity analyses were performed to validate the initial MR results and reverse MR analysis was conducted to exclude reverse causality. Finally, a two-step MR analysis was utilized to quantify the proportion of the impact of gut microbiota on AILDs mediated by immune cells. Results Following rigorous MR analysis, our findings indicate that increased involvement of the gut microbiome in the superpathway of L-tryptophan biosynthesis is positively associated with an elevated risk of Autoimmune Hepatitis (AIH). The effect is partially mediated by the CD14+ CD16+ monocyte Absolute Count, which accounts for 17.47% of the total effect. Moreover, the species Ruminococcus obeum appears to mediate the development of Primary Sclerosing Cholangitis (PSC) through CD62L-CD86+ myeloid Dendritic Cell %Dendritic Cell, contributing to 32.47% of the total observed effect. Conclusion Our study highlights the potential mediating mechanisms of immune cells in the causal relationship between the gut microbiome and AILDs. These insights provide a foundation for developing preventive strategies for AILDs in clinical practice.
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Affiliation(s)
- Jikang Zhang
- General Surgery Department, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yiqi Hu
- General Surgery Department, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jin Xu
- General Surgery Department, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Hua Shao
- General Surgery Department, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Qingping Zhu
- Digestive Endoscopic Treatment Center, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Hao Si
- General Surgery Department, Nanjing Pukou District Traditional Chinese Medicine Hospital, Nanjing, China
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Zeng ZX, Wu JY, Wu JY, Li YN, Fu YK, Zhang ZB, Liu DY, Li H, Ou XY, Zhuang SW, Yan ML. The TAE score predicts prognosis of unresectable HCC patients treated with TACE plus lenvatinib with PD-1 inhibitors. Hepatol Int 2024; 18:651-660. [PMID: 38040945 DOI: 10.1007/s12072-023-10613-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 10/29/2023] [Indexed: 12/03/2023]
Abstract
BACKGROUND AND AIMS Transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors (triple therapy) exhibits promising efficacy for unresectable hepatocellular carcinoma (uHCC). We aimed to evaluate the prognosis of patients with uHCC who received triple therapy and develop a prognostic scoring model to identify patients who benefit the most from triple therapy. METHODS A total of 246 patients with uHCC who received triple therapy at eight centers were included and assigned to the training and validation cohorts. Prognosis was evaluated by the Kaplan-Meier curves. The prognostic model was developed by utilizing predictors of overall survival (OS), which were identified through the Cox proportional hazards model. RESULTS In the training cohort, the 3-year OS was 52.0%, with a corresponding progression-free survival (PFS) of 30.6%. The median PFS was 13.2 months [95% confidence interval, 9.7-16.7]. Three variables (total bilirubin ≥ 17 μmol/L, alpha-fetoprotein ≥ 400 ng/mL, and extrahepatic metastasis) were predictors of poor survival and were used for developing a prognostic model (TAE score). The 2-year OS rates in the favorable (0 points), intermediate (1 point), and dismal groups (2-3 points) were 96.9%, 61.4%, and 11.4%, respectively (p < 0.001). The PFS was also stratified according to the TAE score. These findings were confirmed in an external validation cohort. CONCLUSIONS Triple therapy showed encouraging clinical outcomes, and the TAE score aids in identifying patients who would benefit the most from triple therapy.
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Affiliation(s)
- Zhen-Xin Zeng
- The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, 350001, Fujian, China
| | - Jia-Yi Wu
- The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, 350001, Fujian, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Jun-Yi Wu
- The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, 350001, Fujian, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Yi-Nan Li
- The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, 350001, Fujian, China
| | - Yang-Kai Fu
- The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, 350001, Fujian, China
| | - Zhi-Bo Zhang
- Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - De-Yi Liu
- The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, 350001, Fujian, China
| | - Han Li
- The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, 350001, Fujian, China
| | - Xiang-Ye Ou
- The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, 350001, Fujian, China
| | - Shao-Wu Zhuang
- Department of Interventional Radiology, Zhangzhou Affiliated Hospital of Fujian Medical University, Shengli Road 59, Zhangzhou, 363000, Fujian, China.
| | - Mao-Lin Yan
- The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, 350001, Fujian, China.
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian, China.
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Lin Y, Wu J, Zhuo Y, Feng B, Fang Z, Xu S, Li J, Zhao H, Wu D, Hua L, Che L. Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model. J Anim Sci Biotechnol 2024; 15:19. [PMID: 38310243 PMCID: PMC10838427 DOI: 10.1186/s40104-023-00970-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 12/04/2023] [Indexed: 02/05/2024] Open
Abstract
BACKGROUND Intrauterine growth retardation (IUGR) affects intestinal growth, morphology, and function, which leads to poor growth performance and high mortality. The present study explored whether maternal dietary methyl donor (MET) supplementation alleviates IUGR and enhances offspring's growth performance by improving intestinal growth, function, and DNA methylation of the ileum in a porcine IUGR model. METHODS Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery. After farrowing, 8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum. RESULTS The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets. Moreover, maternal MET supplementation significantly reduced the plasma concentrations of isoleucine, cysteine, urea, and total amino acids in sows and newborn piglets. It also increased lactase and sucrase activity in the jejunum of newborn piglets. MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets. DNA methylation analysis of the ileum showed that MET supplementation increased the methylation level of DNA CpG sites in the ileum of newborn piglets. Down-regulated differentially methylated genes were enriched in folic acid binding, insulin receptor signaling pathway, and endothelial cell proliferation. In contrast, up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosynthetic process. CONCLUSIONS Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets, which may be associated with better intestinal function and methylation status.
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Affiliation(s)
- Yan Lin
- Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China
| | - Jiangnan Wu
- Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China
| | - Yong Zhuo
- Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China
| | - Bin Feng
- Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China
| | - Zhengfeng Fang
- Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China
| | - Shengyu Xu
- Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China
| | - Jian Li
- Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China
| | - Hua Zhao
- Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China
| | - De Wu
- Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China
| | - Lun Hua
- Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China
| | - Lianqiang Che
- Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
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Tan GJ, Lee CH, Sun Y, Tan CH. Is non-contrast-enhanced magnetic resonance imaging cost-effective for screening of hepatocellular carcinoma? Singapore Med J 2024; 65:23-29. [PMID: 34628803 PMCID: PMC10863734 DOI: 10.11622/smedj.2021153] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 06/08/2021] [Indexed: 11/18/2022]
Abstract
INTRODUCTION Ultrasonography (US) is the current standard of care for imaging surveillance in patients at risk of hepatocellular carcinoma (HCC). Magnetic resonance imaging (MRI) has been explored as an alternative, given the higher sensitivity of MRI, although this comes at a higher cost. We performed a cost-effective analysis comparing US and dual-sequence non-contrast-enhanced MRI (NCEMRI) for HCC surveillance in the local setting. METHODS Cost-effectiveness analysis of no surveillance, US surveillance and NCEMRI surveillance was performed using Markov modelling and microsimulation. At-risk patient cohort was simulated and followed up for 40 years to estimate the patients' disease status, direct medical costs and effectiveness. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio were calculated. RESULTS Exactly 482,000 patients with an average age of 40 years were simulated and followed up for 40 years. The average total costs and QALYs for the three scenarios - no surveillance, US surveillance and NCEMRI surveillance - were SGD 1,193/7.460 QALYs, SGD 8,099/11.195 QALYs and SGD 9,720/11.366 QALYs, respectively. CONCLUSION Despite NCEMRI having a superior diagnostic accuracy, it is a less cost-effective strategy than US for HCC surveillance in the general at-risk population. Future local cost-effectiveness analyses should include stratifying surveillance methods with a variety of imaging techniques (US, NCEMRI, contrast-enhanced MRI) based on patients' risk profiles.
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Affiliation(s)
| | - Chau Hung Lee
- Department of Radiology, Tan Tock Seng Hospital, Singapore
| | - Yan Sun
- Health Services and Outcomes Research Unit, National Healthcare Group, Singapore
| | - Cher Heng Tan
- Department of Radiology, Tan Tock Seng Hospital, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
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Zhang Y, Szramowski M, Sun S, Henderson GC. Combining albumin deficiency and acute exercise reduces hepatic lipid droplet size in mice. Lipids Health Dis 2023; 22:78. [PMID: 37344835 PMCID: PMC10286408 DOI: 10.1186/s12944-023-01845-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 06/08/2023] [Indexed: 06/23/2023] Open
Abstract
Hepatic lipid droplets (LDs) are implicated in ectopic lipid accumulation. The core of LDs, triacylglycerol (TAG), is synthesized from the esterification of fatty acids to a glycerol-3-phosphate (G-3-P) backbone. Albumin transports plasma free fatty acids, and previously albumin knockout (Alb-/-) mice were shown to exhibit lower hepatic TAG levels than wildtype (WT). Exercise is a beneficial strategy to alter hepatic metabolism, but its impacts on reducing hepatic lipids are far from satisfactory. The aim of this study was to investigate the combined effect of albumin deficiency and acute exercise on hepatic LDs. Eight-week-old male Alb-/- and WT mice were divided into sedentary and exercise groups. Exercised mice performed a 30-min high-intensity exercise bout. Results showed that sedentary Alb-/- mice had smaller hepatic LDs (P < 0.0001), associated with mitochondria, while WT mice exhibited larger LDs, surrounded by glycogen granules. Following acute exercise, hepatic LDs in Alb-/- mice reduced by 40% in size, while in WT increased by 14% (P < 0.0001). The maintenance of WT hepatic LDs was associated with elevated G-3-P level (P < 0.05), potentially derived from glycogen (R = -0.32, %change in glycogen versus LD content, P < 0.05). The reduction in Alb-/- mice LDs after exercise was possibly due to their low glycogen level. In conclusion, Alb-/- mice exhibited an enhanced capacity for reducing hepatic LD size and content in response to exercise. These findings suggest that modulating albumin's functions combined with exercise could be a potential strategy to reduce ectopic lipid deposition in the liver.
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Affiliation(s)
- Yi Zhang
- Department of Nutrition Science, Purdue University, 700 Mitch Daniels Blvd., West Lafayette, IN, 47907, USA
| | - Mirandia Szramowski
- Department of Nutrition Science, Purdue University, 700 Mitch Daniels Blvd., West Lafayette, IN, 47907, USA
| | - Shuhan Sun
- Department of Nutrition Science, Purdue University, 700 Mitch Daniels Blvd., West Lafayette, IN, 47907, USA
| | - Gregory C Henderson
- Department of Nutrition Science, Purdue University, 700 Mitch Daniels Blvd., West Lafayette, IN, 47907, USA.
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Wei Y, Gao C, Wang H, Zhang Y, Gu J, Zhang X, Gong X, Hao Z. Mori fructus aqueous extracts attenuates liver injury by inhibiting ferroptosis via the Nrf2 pathway. J Anim Sci Biotechnol 2023; 14:56. [PMID: 37032323 PMCID: PMC10084661 DOI: 10.1186/s40104-023-00845-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 01/31/2023] [Indexed: 04/11/2023] Open
Abstract
BACKGROUND Liver fibrosis and hepatocellular carcinogenesis secondary to liver fibrosis are serious liver diseases with no effective treatments. Mori fructus aqueous extracts (MFAEs) have served as successful treatments for many types of liver injury including fibrosis although the molecular mechanisms are unknown at present. PURPOSE To investigate the effect of MFAEs in alleviating acute and chronic liver injury and tried to decipher the underlying mechanism. METHODS AND RESULTS Mice were divided into 5 groups (n = 8) for acute (groups: control, 0.3% CCl4, bifendate (BD), 100 and 200 mg/kg MFAEs, 7 d) and chronic (groups: control, 10% CCl4, BD, 100 and 200 mg/kg MFAEs, 4 weeks) liver injury study. Each mouse was injected intraperitoneally with 10 µL/g corn oil containing CCl4 expect the control group. HepG2 cells were used in vitro study. Eighteen communal components were identified by UPLC-LTQ-Orbitrap-MS. We utilized a mouse model for acute and chronic liver injury using CCl4 and MFAEs administration effectively blocked fibrosis and significantly inhibited inflammation in the liver. MFAEs activated the nuclear factor erythroid derived 2 like 2/heme oxygenase 1 (Nrf2/HO-1) pathway and promoted the synthesis of the antioxidants glutathione (GSH), superoxidedismutase (SOD) and glutathione peroxidase (GSH-Px) that resulted in reduced levels of CCl4-induced oxidative stress molecules including reactive oxygen species. These extracts administered to mice also inhibited ferroptosis in the liver by regulating the expression of Acyl-CoA synthetase long chain family member 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), thus reducing the occurrence of liver fibrosis. Both in vivo and in vitro tests indicated that the mechanism of MFAEs protection against liver fibrosis was linked to activation of Nrf2 signaling. These effects were blocked in vitro by the addition of a specific Nrf2 inhibitor. CONCLUSION MFAEs inhibited oxidative stress, ferroptosis and inflammation of the liver by activating Nrf2 signal pathway and provided a significant protective effect against CCl4-induced liver fibrosis.
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Affiliation(s)
- Yuanyuan Wei
- Innovation Centre of Chinese veterinary medicine, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193, China
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing, 100193, P. R. China
- National Center of Technology Innovation for Medicinal function of Food, National Food and Strategic Reserves Administration, Beijing, China
| | - Chen Gao
- Innovation Centre of Chinese veterinary medicine, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193, China
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing, 100193, P. R. China
- National Center of Technology Innovation for Medicinal function of Food, National Food and Strategic Reserves Administration, Beijing, China
| | - Huiru Wang
- Innovation Centre of Chinese veterinary medicine, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193, China
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing, 100193, P. R. China
- National Center of Technology Innovation for Medicinal function of Food, National Food and Strategic Reserves Administration, Beijing, China
| | - Yannan Zhang
- Innovation Centre of Chinese veterinary medicine, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193, China
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing, 100193, P. R. China
- National Center of Technology Innovation for Medicinal function of Food, National Food and Strategic Reserves Administration, Beijing, China
| | - Jinhua Gu
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing, 100193, P. R. China
- China Institute of Veterinary Drug Control, Beijing, 100081, China
| | - Xiuying Zhang
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing, 100193, P. R. China
- China Institute of Veterinary Drug Control, Beijing, 100081, China
| | - Xuhao Gong
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing, 100193, P. R. China
- China Institute of Veterinary Drug Control, Beijing, 100081, China
| | - Zhihui Hao
- Innovation Centre of Chinese veterinary medicine, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193, China.
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing, 100193, P. R. China.
- National Center of Technology Innovation for Medicinal function of Food, National Food and Strategic Reserves Administration, Beijing, China.
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Li H, Men D, Jia M, Wang Z, Xiao W, Xue J, Kang C. Quantitative evaluation of renal tissue changes in patients with liver cirrhosis by shear wave elastography. Abdom Radiol (NY) 2023; 48:2085-2090. [PMID: 36943422 DOI: 10.1007/s00261-023-03881-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 03/01/2023] [Accepted: 03/02/2023] [Indexed: 03/23/2023]
Abstract
PURPOSE Hepatocirrhotic nephropathy progresses rapidly and has a poor prognosis, and early detection of renal changes in patients with cirrhosis is particularly important for its prevention and treatment. The objective of this study was to evaluate the value of shear wave elastography (SWE) in the early diagnosis of hepatocirrhotic nephropathy. METHODS 206 hepatic cirrhosis patients with normal conventional renal function were enrolled and divided into Child-Pugh grade A (Group A), Child-Pugh grade B (Group B), and Child-Pugh grade C (Group C) according to the Child-Pugh grading method. Meanwhile, 60 healthy volunteers matched in age and sex were selected as the control group. The maximum Young's modulus (Emax), average Young's modulus (Emean), and minimum Young's modulus (Emin) of the left renal parenchyma were measured by SWE in all subjects. The Emax, Emean, and Emin values of the left renal parenchyma were compared between the cirrhosis and control groups. RESULTS The Emax, Emean, and Emin values of left renal parenchyma in cirrhosis group were higher than those in control group (p = 0.00, 0.00, 0.00). The Emax, Emean, and Emin values of left renal parenchyma in cirrhosis group B and group C were higher than those in control group (p = 0.00, 0.00, 0.00; p = 0.00, 0.00, 0.00), but these values in cirrhosis group A were not significantly different from control group(p = 0.48, 0.52, 0.92). Comparison of the Emax, Emean, and Emin values in left renal parenchyma of three cirrhosis groups, the values of Group B and Group C were higher than those of Group A (p = 0.00, 0.00, 0.00; p = 0.00, 0.00, 0.00), and there was no significant difference between Group B and Group C (p = 0.71, 0.18, 0.39). CONCLUSION SWE can detect renal tissue damage in patients with liver cirrhosis earlier than changes identified during routine laboratory examination by quantitatively measuring the elastic parameters of renal parenchyma and may become a new method for early diagnosis of hepatorenal syndrome.
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Affiliation(s)
- Huizhan Li
- Department of Ultrasonography, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, The Third Hospital of Shanxi Medical University, 99 Longcheng Street, Taiyuan City, 030032, Shanxi Province, China
| | - Dianxia Men
- Department of Ultrasonography, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, The Third Hospital of Shanxi Medical University, 99 Longcheng Street, Taiyuan City, 030032, Shanxi Province, China
| | - Meihong Jia
- Department of Ultrasonography, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, The Third Hospital of Shanxi Medical University, 99 Longcheng Street, Taiyuan City, 030032, Shanxi Province, China
| | - Zhifen Wang
- Department of Ultrasonography, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, The Third Hospital of Shanxi Medical University, 99 Longcheng Street, Taiyuan City, 030032, Shanxi Province, China
| | - Wenli Xiao
- Department of Ultrasonography, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, The Third Hospital of Shanxi Medical University, 99 Longcheng Street, Taiyuan City, 030032, Shanxi Province, China
| | - Jiping Xue
- Department of Ultrasonography, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, The Third Hospital of Shanxi Medical University, 99 Longcheng Street, Taiyuan City, 030032, Shanxi Province, China
| | - Chunsong Kang
- Department of Ultrasonography, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, The Third Hospital of Shanxi Medical University, 99 Longcheng Street, Taiyuan City, 030032, Shanxi Province, China.
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Liu Z, Liang S, Wei X, Du X, Zhang J. Defibrotide improved the outcome of monocrotaline induced rat hepatic sinusoidal obstruction syndrome. BMC Gastroenterol 2022; 22:525. [PMID: 36526956 PMCID: PMC9758875 DOI: 10.1186/s12876-022-02523-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 09/23/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND AND AIM Pyrrolizidine alkaloids (PA) induced hepatic sinusoidal obstruction syndrome (HSOS) occurred worldwide and the mortality rate remained high because there were no specific therapies. Defibrotide was effective for HSOS following hematopoietic stem cell transplantation. But the pathogenesis of the two types of HSOS were not equivalent. The purpose of this study was to see if defibrotide was also effective in PA induced rat HSOS. METHODS First we improved rat HSOS model by using higher dose (230 mg/kg) of monocrotaline (a kind of PA) as the dose of median lethal dose. So drug effectiveness could be assessed by survival time. Next, male SD rats were divided into 5 groups. They were control group, model group, low dose low molecular weight heparin (LMWH) treatment group, high dose LMWH treatment group and defibrotide treatment group. Rats' survival time, liver function, white blood cell count and cytokines were compared among the groups. The DeLeve score was used to assess the severity of liver pathology. RESULTS The model group exhibited typical liver pathology of HSOS, such as hepatic sinus dilation, congestion, endothelial injury of central lobular vein, coagulative necrosis of hepatocytes and fibrin deposition in the subendothelial. The pathologic characteristics indicated that the model was built up successfully. The survival rate was significantly higher in defibrotide group (81.8%) than model group (43.7%), while the survival rates were similar in the two LMWH groups (62.5% and 75%) and model group. The survival time only be prolonged by defibrotide (P=0.028) but not LMWH (P>0.05). DeLeve score was improved most in the defibrotide group than the two LMWH groups (both P<0.01). Changes in DeLeve score, liver function, plasma level of tumor necrosis factor α and plasminogen activator inhibitor-1 exhibited the same trends. CONCLUSION Defibrotide could improve the outcome of monocrotaline-induced rat HSOS indicating that defibrotide might be a better choice than LMWH in clinical practice.
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Affiliation(s)
- Zhenli Liu
- grid.24696.3f0000 0004 0369 153XThe Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, Youwai Xitoutiao Street, Fengtai District, 100069 Beijing, China
| | - Shan Liang
- grid.24696.3f0000 0004 0369 153XThe Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, Youwai Xitoutiao Street, Fengtai District, 100069 Beijing, China
| | - Xinhuan Wei
- grid.24696.3f0000 0004 0369 153XThe Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, Youwai Xitoutiao Street, Fengtai District, 100069 Beijing, China
| | - Xiaofei Du
- grid.24696.3f0000 0004 0369 153XThe Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, Youwai Xitoutiao Street, Fengtai District, 100069 Beijing, China
| | - Jing Zhang
- grid.24696.3f0000 0004 0369 153XThe Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, Youwai Xitoutiao Street, Fengtai District, 100069 Beijing, China
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Zhang W, Zhang N, Zheng S, Zhang W, Liu J, He L, Ezemaduka AN, Li G, Ning J, Xian B, Gao S. Effects of commercial beverages on the neurobehavioral motility of Caenorhabditis elegans. PeerJ 2022; 10:e13563. [PMID: 35855427 PMCID: PMC9288823 DOI: 10.7717/peerj.13563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 05/19/2022] [Indexed: 01/17/2023] Open
Abstract
To study the effects of different types of commercially available drinks/beverages on neurobehavior using the model organism C. elegans, and critically review their potential health hazards. Eighteen kinds of beverages from the supermarket were randomly selected and grouped into seven categories namely functional beverage, tea beverage, plant protein beverage, fruit juice beverage, dairy beverage, carbonated beverage and coffee beverage. The pH value, specific gravity and osmotic pressure were also examined. The L4 stage N2 worms were exposed to different concentration of tested beverages (0, 62.5, 125, 250 and 500 µL/mL) for 24 h to measure the survival rate and locomotory behavior such as head thrashing, body bending as well as pharyngeal pumping. All the 18 beverages tested did not induce any visible lethal effects in the nematodes. However, exposure to different types of tested beverages exhibited different effects on the behavioral ability of C. elegans: (1) sports functional beverage and herbal tea drink accelerated the head thrashing and body bending of nematodes when compared to the control group (P < 0.05). (2) The vibration frequency of the pharyngeal pump of nematodes was significantly accelerated after treated with three plant protein beverages (almond milk, coconut milk and milk tea) and dairy products A and B (P < 0.05), and decelerated after treatment with other tested beverages. (3) Carbonated beverage significantly inhibits the head thrashing, body bending and pharyngeal pumping vibration (P < 0.05). Our results indicate that 18 kinds of popular beverages in the market have different influence on the neurobehavior in C. elegans, which may be related to their different components or properties. Further research would be required to conduct a systematic analysis of the effect of beverages by appropriate kinds, taking into consideration other endpoints such as reproduction, lifespan and molecular stress response, etc., and to elucidate the mechanism for its potential health hazards.
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Affiliation(s)
- Wenjing Zhang
- Beijing Center for Disease Prevention and Control, Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing, China
| | - Nan Zhang
- Beijing Center for Disease Prevention and Control, Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing, China
| | - Shan Zheng
- Beijing Center for Disease Prevention and Control, Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing, China
| | - Wei Zhang
- Beijing Center for Disease Prevention and Control, Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing, China
| | - Jingjing Liu
- Beijing Center for Disease Prevention and Control, Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing, China
| | - Liwei He
- Beijing Center for Disease Prevention and Control, Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing, China
| | - Anastasia Ngozi Ezemaduka
- Key Laboratory of Wetland Ecology and Environment, Northeast institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun, China
| | - Guojun Li
- Beijing Center for Disease Prevention and Control, Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing, China,School of Public Health, Capital Medical University, Beijing, China
| | - Junyu Ning
- Beijing Center for Disease Prevention and Control, Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing, China,School of Public Health, Capital Medical University, Beijing, China
| | - Bo Xian
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Shan Gao
- Beijing Center for Disease Prevention and Control, Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing, China
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11
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Liu Y, Li D, Liu Y, Shuai P. Association Between Helicobacter Pylori Infection and Non-alcoholic Fatty Liver Disease, Hepatic Adipose Deposition and Stiffness in Southwest China. Front Med (Lausanne) 2022; 8:764472. [PMID: 35004736 PMCID: PMC8739268 DOI: 10.3389/fmed.2021.764472] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 12/02/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Both nonalcoholic fatty liver disease (NAFLD) and Helicobacter pylori (H. pylori) infection have high prevalence worldwide, and the relationship between both remains controversial. We try to investigate whether H. pylori infection is associated with NAFLD and increased liver fat deposition and stiffness in this cross-sectional study. Methods: The physical examination data of 5,665 subjects were obtained from February 2018 to June 2019 in this study. Clinical and biochemical data were collected. NAFLD was diagnosed using abdominal color Doppler ultrasonography. Liver steatosis and stiffness were understood by two parameters of transient elastography (TE): fat attenuation parameter (FAP) and liver stiffness measurement (LSM). H. pylori infection was determined using the 13C urea breath tests. Results: The total prevalence of NAFLD and H. pylori infection was 30.2 and 37.0%, respectively. In men, the prevalence of NAFLD and the levels of FAP and LSM in H. pylori-positive group were significantly higher than H. pylori-negative group (all p < 0.01), but no significant difference was found in women. In men, the infection rate of H. pylori in NAFLD group and LSM ≥ 7.4 kPa group was significantly higher than control group. Multivariate logistic regression analysis revealed that H. pylori infection was not independently associated with NAFLD and FAP ≥ 240 dB/m. However, H. pylori infection was associated with LSM ≥ 7.4 kPa in men. Conclusions: Our study suggests that H. pylori infection is not significantly associated with NAFLD and elevated liver steatosis, whereas it may be the risk factor of elevated liver stiffness in men.
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Affiliation(s)
- Ying Liu
- Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.,Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Dongyu Li
- Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.,Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Yuping Liu
- Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.,Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Ping Shuai
- Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.,Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
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12
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Guo K, Xu S, Zeng Z. "Liver-gut" axis: A target of traditional Chinese medicine for the treatment of non-alcoholic fatty liver disease. Front Endocrinol (Lausanne) 2022; 13:1050709. [PMID: 36531498 PMCID: PMC9747758 DOI: 10.3389/fendo.2022.1050709] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 10/28/2022] [Indexed: 12/05/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) occurs when fat accumulates in the liver even without excessive alcohol intake. Among the current therapeutic approaches for NAFLD, lifestyle modification with dietary changes and regular exercise is the mainstay treatment. With the rise of intestinal microecology, regulation of the "liver-gut" axis can be an effective treatment for NAFLD. This review aimed to assess the modulation of the liver-gut microbiota axis with traditional Chinese medicine (TCM) as a therapeutic approach to NAFLD and further explored its application in the newly discovered therapeutic avenues beyond NAFLD treatment.
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Xu Y, Guo W, Zhang C, Chen F, Tan HY, Li S, Wang N, Feng Y. Herbal Medicine in the Treatment of Non-Alcoholic Fatty Liver Diseases-Efficacy, Action Mechanism, and Clinical Application. Front Pharmacol 2020; 11:601. [PMID: 32477116 PMCID: PMC7235193 DOI: 10.3389/fphar.2020.00601] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 04/17/2020] [Indexed: 12/19/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease with high prevalence in the developed countries. NAFLD has been considered as one of the leading causes of cryptogenic cirrhosis and chronic liver disease. The individuals with obesity, insulin resistance and diabetes mellitus, hyperlipidaemia, and hypertension cardiovascular disease have a high risk to develop NAFLD. The related critical pathological events are associated with the development of NAFLD including insulin resistance, lipid metabolism dysfunction, oxidative stress, inflammation, apoptosis, and fibrosis. The development of NAFLD range from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic steatosis is characterized by fat accumulation, which represents the early stage of NAFLD. Then, inflammation triggered by steatosis drives early NAFLD progression into NASH. Therefore, the amelioration of steatosis and inflammation is essential for NAFLD therapy. The herbal medicine have taken great effects on the improvement of steatosis and inflammation for treating NAFLD. It has been found out that these effects involved the multiple mechanisms underlying lipid metabolism and inflammation. In this review, we pay particular attention on herbal medicine treatment and make summary about the research of herbal medicine, including herb formula, herb extract and naturals compound on NAFLD. We make details about their protective effects, the mechanism of action involved in the amelioration steatosis and inflammation for NAFLD therapy as well as the clinical application.
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Affiliation(s)
| | | | | | | | | | | | | | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
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14
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Changes in renal function indices in cirrhotic chronic hepatitis C patients treated with sofosbuvir-containing regimens. Oncotarget 2017; 8:90916-90924. [PMID: 29207613 PMCID: PMC5710894 DOI: 10.18632/oncotarget.18701] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2017] [Accepted: 06/04/2017] [Indexed: 12/15/2022] Open
Abstract
This study aimed to explore changes in hepatic and renal function indices in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAAs). Forty-three CHC patients treated with sofosbuvir (SOF)-containing regimens were enrolled. At the end of treatment, the estimated glomerular filtration rate (eGFR) level was significantly decreased and the serum creatinine (Scr) and uric acid (UA) levels were significantly increased compared with baseline levels (eGFR: 86.7 ± 20.4 vs 80.5 ± 21.3, P01 = 0.005; Scr: 83.9 ± 19.1 vs 89.6 ± 21.1, P01 < 0.001; UA: 323.7± 86.2 vs 358.5 ± 93.2, P01 < 0.001); no significant improvements were observed at 24 w post-treatment (eGFR: 86.7 ± 20.4 vs 81.4 ± 18.6, P02 = 0.013; Scr: 83.6 ± 17.9 vs 87.9 ± 18.3, P02 = 0.014; UA: 320.8 ± 76.3 vs 349.3 ± 91.0, P02 = 0.004). When the patients were grouped by liver conditions, non-cirrhotic patients and cirrhotic patients had decreased eGFR levels and increased Scr levels at the end of treatment; at 24 w post-treatment, the eGFR and Scr levels were significantly improved in non-cirrhotic patients (88.4 ± 21.7 vs 83.8 ± 18.5, P02 = 0.142; 84.4 ± 20.4 vs 87.0 ± 16.9, P02 = 0.088), while no obvious improvements were observed in cirrhotic patients (84.3 ± 18.7 vs 78.1 ± 18.6, P02 = 0.002; 83.2 ± 17.7 vs 89.2 ± 20.6, P02 = 0.006). Clinical physicians should closely monitor renal function in patients treated with SOF-containing regimens, especially in cirrhotic patients.
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15
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He LT, Ye XG, Zhou XY. Effect of switching from treatment with nucleos(t)ide analogs to pegylated interferon α-2a on virological and serological responses in chronic hepatitis B patients. World J Gastroenterol 2016; 22:10210-10218. [PMID: 28028369 PMCID: PMC5155180 DOI: 10.3748/wjg.v22.i46.10210] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 08/25/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the efficacy of switching to pegylated interferon-α-2a (PegIFNα-2a) treatment in nucleos(t)ide analog (NA)-treated chronic hepatitis B (CHB) responder patients.
METHODS A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir (ETV) for at least 48 wk and had serum hepatitis B virus (HBV)-DNA < 500 IU/mL, serum hepatitis B envelope antigen (HBeAg) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to PegIFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the PegIFNα-2a group, and 44 patients were simultaneously randomized to the ETV group.
RESULTS After 48 wk of therapy, the decrease in hepatitis B surface antigen (HBsAg) levels was greater in the PegIFNα-2a group than in the ETV group (3.1340 log10 IU/mL vs 3.6950 log10 IU/mL, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBsAg loss when switched to PegIFNα-2a (15.91% vs 0%, P = 0.018). The HBeAg serological conversion rate was higher in the PegIFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes (34.38% vs 21.88%, P = 0.232). In the PegIFNα-2a group, patients with HBsAg levels < 1500 IU/mL at baseline had higher HBeAg seroconversion and HBsAg loss rates at week 48 than those with HBsAg levels ≥ 1500 IU/mL (HBeAg seroconversion: 17.86% vs 62.5%, P = 0.007; HBsAg loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBsAg levels < 1500 IU/mL at week 24 had higher HBsAg loss rates after therapy than those with HBsAg levels ≥ 1500 IU/mL (36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBeAg seroconversion rates (47.06% vs 25.93%, P = 0.266).
CONCLUSION NA-treated CHB patients switched to sequential PegIFNα-2a achieved highly potent treatment termination safely.
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Windemuller F, Xu J, Rabinowitz SS, Hussain MM, Schwarz SM. Lipogenesis in Huh7 cells is promoted by increasing the fructose: Glucose molar ratio. World J Hepatol 2016; 8:838-843. [PMID: 27458503 PMCID: PMC4945503 DOI: 10.4254/wjh.v8.i20.838] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Revised: 03/28/2016] [Accepted: 06/14/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To determine whether hepatocyte lipogenesis, in an in vitro cell culture model, is modulated by adjusting culture media monosaccharide content and concentration. METHODS Hepatocytes (Huh7), demonstrating glucose and fructose uptake and lipid biosynthesis, were incubated in culture media containing either glucose alone (0.65-0.72 mmol/L) or isosmolar monosaccharide (0.72 mmol/L) comprising fructose:glucose (F:G) molar ratios ranging from 0.58-0.67. Following a 24-h incubation, cells were harvested and analyzed for total protein, triglyceride (TG) and cholesterol (C) content. Significant differences (P < 0.05) among groups were determined using analysis of variance followed by Dunnett's test for multiple comparisons. RESULTS After a 24 h incubation period, Huh7 cell mass and viability among all experimental groups were not different. Hepatocytes cultured with increasing concentrations of glucose alone did not demonstrate a significant change either in C or in TG content. However, when the culture media contained increasing F:G molar ratios, at a constant total monosaccharide concentration, synthesis both of C and of TG increased significantly [F:G ratio = 0.58, C/protein (μg/μg) = 0.13; F:G = 0.67, C/protein = 0.18, P < 0.01; F:G ratio = 0.58, TG/protein (μg/μg) = 0.06; F:G ratio = 0.67, TG/protein = 0.11, P < 0.01]. CONCLUSION In an in vitro hepatocyte model, glucose or fructose plus glucose support total cell mass and lipogenic activity. Increasing the fructose:glucose molar ratio (but not glucose alone) enhances triglyceride and cholesterol synthesis. These investigations demonstrate fructose promotes hepatocellular lipogenesis, and they provide evidence supporting future, in vivo studies of fructose's role in the development of hepatic steatosis and non-alcoholic fatty liver disease.
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Affiliation(s)
- Fernando Windemuller
- Fernando Windemuller, Jiliu Xu, Simon S Rabinowitz, Steven M Schwarz, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
| | - Jiliu Xu
- Fernando Windemuller, Jiliu Xu, Simon S Rabinowitz, Steven M Schwarz, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
| | - Simon S Rabinowitz
- Fernando Windemuller, Jiliu Xu, Simon S Rabinowitz, Steven M Schwarz, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
| | - M Mahmood Hussain
- Fernando Windemuller, Jiliu Xu, Simon S Rabinowitz, Steven M Schwarz, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
| | - Steven M Schwarz
- Fernando Windemuller, Jiliu Xu, Simon S Rabinowitz, Steven M Schwarz, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, State University of New York Downstate Medical Center, Brooklyn, NY 11203, United States
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Ning G, Lin CS. History and future of antiviral therapy of chronic hepatitis C. Shijie Huaren Xiaohua Zazhi 2016; 24:2117-2130. [DOI: 10.11569/wcjd.v24.i14.2117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection often leads to chronic diseases, and antiviral therapy is an important way to prevent chronic hepatitis C from progressing to end-stage liver disease. Up to now, hepatitis C antiviral therapy has successively experienced eras of interferon monotherapy, interferon and ribavirin combination therapy, and combination therapy of pegylated-interferon (PEG-IFN) and ribavirin. Now we are entering into a new era of direct-acting antiviral agents (DAAs). Just like acquired immune deficiency syndrome (AIDS) cocktails, combination therapy consists of two or more antiviral agents. DAAs will be the primary antiviral therapy for hepatitis C in the future for their better tolerance, lower drug resistance, higher sustained virological response and shorter treatment course. In this article, we review the history and future of antiviral therapy of HCV infection.
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Luo M, Guo JY, Cao WK. Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis. World J Gastroenterol 2015; 21:11815-11824. [PMID: 26557005 PMCID: PMC4631979 DOI: 10.3748/wjg.v21.i41.11815] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Revised: 06/19/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE.
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Yang SZ, Wang JT, Yu WW, Liu Q, Wu YF, Chen SG. Downregulation of KIF1B mRNA in hepatocellular carcinoma tissues correlates with poor prognosis. World J Gastroenterol 2015; 21:8418-8424. [PMID: 26217094 PMCID: PMC4507112 DOI: 10.3748/wjg.v21.i27.8418] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Accepted: 05/07/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare kinesin family member 1B (KIF1B) expression with clinicopathologic parameters and prognosis in hepatocellular carcinoma (HCC) patients.
METHODS: KIF1B protein and mRNA expression was assessed in HCC and paracarcinomatous (PC) tissues from 68 patients with HCC using Western blot and quantitative real-time reverse transcription-PCR, respectively. Student’s t-tests were used to analyze relationships between clinicopathologic parameters and KIF1B expression, the Kaplan-Meier method was used to analyze survival outcomes, and the log-rank test was used to compare survival differences between groups.
RESULTS: Mean protein and mRNA levels of KIF1B were similar between HCC and PC tissues. However, HCC tissues with vein invasions had significantly lower KIF1B protein levels compared to those without vein invasions (2.30 ± 0.82 relative units vs 2.77 ± 0.84 relative units, P < 0.05). KIF1B protein levels in HCC tissues from patients with recurrence during the follow-up period were significantly lower than those without recurrence (2.31 ± 0.92 relative units vs 2.80 ± 0.80 relative units, P < 0.05). However, KIF1B protein and mRNA expression in HCC patients was not associated with other clinicopathologic parameters. Ratios of KIF1B mRNA expression in HCC tissues to those in PC tissues were correlated with overall survival (13.5 mo vs 20.0 mo, P < 0.05) and disease-free survival (11.5 mo vs 19.5 mo, P < 0.05).
CONCLUSION: Downregulation of KIF1B in HCC tissues is associated with poor prognosis; additional clinical studies are needed to confirm whether KIF1B can serve as a prognostic marker.
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MESH Headings
- Aged
- Biomarkers, Tumor/analysis
- Biomarkers, Tumor/genetics
- Blotting, Western
- Carcinoma, Hepatocellular/enzymology
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/therapy
- Disease-Free Survival
- Down-Regulation
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Kaplan-Meier Estimate
- Kinesins/analysis
- Kinesins/genetics
- Liver Neoplasms/enzymology
- Liver Neoplasms/genetics
- Liver Neoplasms/mortality
- Liver Neoplasms/pathology
- Liver Neoplasms/therapy
- Male
- Middle Aged
- Neoplasm Invasiveness
- Neoplasm Recurrence, Local
- RNA, Messenger/genetics
- Real-Time Polymerase Chain Reaction
- Retrospective Studies
- Reverse Transcriptase Polymerase Chain Reaction
- Risk Factors
- Time Factors
- Treatment Outcome
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Niu TH, Jiang M, Xin YN, Jiang XJ, Lin ZH, Xuan SY. Lack of association between apolipoprotein C3 gene polymorphisms and risk of nonalcoholic fatty liver disease in a Chinese Han population. World J Gastroenterol 2014; 20:3655-3662. [PMID: 24707151 PMCID: PMC3974535 DOI: 10.3748/wjg.v20.i13.3655] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Revised: 10/26/2013] [Accepted: 01/02/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the association between two polymorphisms of apolipoprotein C3 (APOC3) and risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese Han population.
METHODS: Genotypes for rs2854116 and rs2854117 in APOC3 and the known rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) in 390 patients with NAFLD and 409 control subjects were determined by sequencing and polymerase chain reaction analysis. Serum lipid profiles were determined using biochemical methods, and an index of insulin resistance (IR, HOMA-IR), serum APOC3 concentrations and total antioxidant status (TAS) were also assessed.
RESULTS: No significant differences in genotype and allele frequencies of rs2854116 and rs2854117 were found between the NAFLD population and the controls (P > 0.05). The OR for the association between -455C and -482T allele carriers and the risk of NAFLD were 1.06 (95%CI: 0.72-1.57, P > 0.05) and 1.00 (95%CI: 0.68-1.48, P > 0.05), respectively. The variant carriers did not have a significantly increased risk of NAFLD or elevated clinical and biochemical parameters such as APOC3 concentrations, IR (1.42 ± 0.43 vs 1.48 ± 0.52, P > 0.05), liver enzymes and TAS (13.94 ± 2.01 vs 14.38 ± 1.92, P > 0.05) compared with the controls. Moreover, the results were similar when testing was carried out independent of the genetic variation in PNPLA3.
CONCLUSION: The two polymorphisms of the APOC3 gene are not associated with a risk of NAFLD, or with lipid profiles, IR and oxidative stress in the Chinese Han population.
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Kim YJ, Sinn DH, Gwak GY, Choi MS, Koh KC, Paik SW, Yoo BC, Lee JH. Tenofovir rescue therapy for chronic hepatitis B patients after multiple treatment failures. World J Gastroenterol 2012; 18:6996-7002. [PMID: 23322999 PMCID: PMC3531685 DOI: 10.3748/wjg.v18.i47.6996] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2012] [Revised: 05/31/2012] [Accepted: 06/08/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients after multiple failures.
METHODS: A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue (NA) treatments were included. Study subjects were treated with TDF alone (n = 13) or in combination with lamivudine (LAM, n = 12) or entecavir (ETV, n = 4) for ≥ 6 mo. Complete virologic response (CVR) was defined as an achievement of serum hepatitis B virus (HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment. Safety assessment was based on serum creatinine and phosphorus level. Eleven patients had histories of LAM and adefovir dipivoxil (ADV) treatment and 18 patients were exposed to LAM, ADV, and ETV. Twenty-seven patients (93.1%) were hepatitis B e antigen (HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL. The median treatment duration was 16 mo (range 7 to 29 mo).
RESULTS: All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it. Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV. One patient had a resistance to both ADV and ETV. The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%, respectively. Although one patient failed to achieve CVR, serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL, achieving near CVR. No patients in this study showed viral breakthrough or primary non-response during the follow-up period. The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%, 12%, and 27% at 6, 12, and 18 mo of treatment, respectively. Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations. History of prior exposure to specific antiviral agents did not make a difference to treatment outcome. Treatment efficacy of TDF was not affected by combination therapy with LAM or ETV. No patient developed renal toxicity and no cases of hypophosphatemia associated with TDF therapy were observed. There were no other adverse events related to TDF therapy observed in the study subjects.
CONCLUSION: TDF can be an effective and safe rescue therapy in CHB patients after multiple NA therapy failures.
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Aroor AR, Shukla SD. Binge ethanol intake in chronically exposed rat liver decreases LDL-receptor and increases angiotensinogen gene expression. World J Hepatol 2011; 3:250-5. [PMID: 21969878 PMCID: PMC3182283 DOI: 10.4254/wjh.v3.i9.250] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2011] [Revised: 07/06/2011] [Accepted: 08/10/2011] [Indexed: 02/06/2023] Open
Abstract
AIM To investigated the status of low-density lipoprotein (LDL)-receptor and angiotensionogen gene expression in rats treated chronically with ethanol followed by binge administration, a model that mimics the human scenario. METHODS Rats were chronically treated with ethanol in liquid diet for 4 wk followed by a single binge mode of ethanol administration (5 mg/kg body weight). Samples were processed 4 h after binge ethanol administration (chronic ethanol binge). Control rats were fed isocaloric diet. In the control for binge, ethanol was replaced by water. Expression of mRNA for angiotensinogen, c-fos and LDL-receptor, and nuclear accumulation of phospho-extracellular regulated kinases (ERK)1/2 and ERK1/2 protein were examined. RESULTS Binge ethanol administration in chronically treated rats caused increase in steatosis and necrosis. Chronic ethanol alone had negligible effect on mRNA levels of LDL-receptor, or on the levels of nuclear ERK1/2 and phospho-ERK1/2. But, chronic ethanol followed by binge caused a decrease in LDL-receptor mRNA, and also decreased the levels of ERK1/2 and phospho-ERK1/2 in the nuclear compartment. On the other hand, chronic ethanol-binge increased mRNA expression of angiotensinogen and c-fos. CONCLUSION Binge ethanol after chronic exposure, causes transcriptional dysregulation of LDL-receptor and angiotensinogen genes, both cardiovascular risk factors.
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Affiliation(s)
- Annayya R Aroor
- Annayya R Aroor, Shivendra D Shukla, Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO 65212, United States
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