INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 2
·1593
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IF 5.6
Ji Ma,Yang Deng,Tingting Yang,Maoru Li,Jing Shang
Non-alcoholic fatty liver disease (NAFLD), defined in recent years as metabolic-associated fatty liver disease (MAFLD), is one of the most common liver diseases in the world, with no drugs on market. Esculetin (ESC) is an active compound discovered in a variety of natural products that modulates a wide range of metabolic diseases and is a potential drug for the treatment of NAFLD. In this study, we used an HCD-induced NAFLD larval zebrafish model in vivo and an FFA-induced BRL-3A hepatocyte model in vitro to evaluate the anti-NAFLD effect of ESC. Lipid lowering, anti-oxidation and anti-inflammation effects were revealed on ESC and related gene changes were observed. This study provides a reference for further study and development of ESC as a potential anti-NAFLD/MAFLD drug.Keywords:esculetin;non-alcoholic fatty liver disease;lipid-lowering;antioxidant
研究领域:
药理学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
CLINICA CHIMICA ACTA
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2022
·
IF 6.314
Jiyun Zhang,Zhizhen Lai,Rui Ding,Jinyu zhou,Zhonghao Yuan,Dan Li,Xuzhen Qin,Jiang Zhou,Zhili li
Background Altered glycosylation modulates the structure and function of disease-related proteins. The associations between serotransferrin (STF) N -glycosylation and liver diseases (LDs) have been revealed. However, how intact N -glycopeptides vary among different types of liver diseases remains unclear. Methods Intact STF N -glycopeptides from patients with chronic liver disease (CLD, n = 92), primary liver cancer (PLC, n = 123), metastatic liver cancer (MLC, n = 57), and healthy controls (HCs, n = 59) were determined using high-resolution mass spectrometry. Results Significant changes were displayed in STF glycosylation among 4 groups. The LD screening model, including Asn432 G1S/G2S, Asn432 G2S/G2S2, and Asn630 G2NS2/G2FNS2, was constructed to differentiate LDs from HCs, with a AUC of 0.92. The liver cancer (LC) diagnostic model, a combination of Asn432 G1-N/G1S-N, Asn432 G1/G2, Asn432 G2FS/G2FS2, and Asn630 G1S-N /G1S, showed good performance in discriminating LC from CLD (AUC = 0.93). Moreover, AFP-negative LC patients (93 %) were successfully predicted by the LC diagnostic model. Furthermore, the MLC triage model, composed of Asn432 G1/G2, Asn432 G3F/G3FS, Asn630 G2/G2S, Asn630 G2S2/G2NS2, and Asn630 G3FS/G3FS2, yielded an AUC of 0.98 between PLC and MLC. Conclusions STF N -glycosylation is a potential biomarker for the accurate classification of different LDs.
研究领域:
医学研究
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分子生物学
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临床诊断
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DOI
PubMed
高影响因子
AMERICAN JOURNAL OF PATHOLOGY
·
2025
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IF 3.6
Lin Xu,Yuanyuan Zhao,Yang Yang,Enbo Qi,Boao Liu,Peili Zhuang,Shiyi Song,Tingmin Chang,Zhiguo Chen,Xiaohong Kang,Xiwen Xiong
Alcohol-related liver disease (ALD), a consequence of excessive alcohol use, manifests across a broad spectrum of liver damage, ranging from steatosis to cirrhosis. DEPDC5 is a component of the GATOR1 complex, which functions as a repressor of the amino acid-sensing branch of the mTORC1 pathway. In this study, hepatocyte specific Depdc5 knockout mice (Depdc5 △Hep ) were generated and it was found that aberrant activation of mTORC1 caused by Depdc5 deletion led to exacerbated ER stress and hepatocyte ferroptosis in the livers of ethanol-fed mice. Torin-1, an ATP-competitive mTOR inhibitor, suppressed the mTORC1 activity and reversed the effects of Depdc5 deletion on ER stress and ferroptosis in ethanol-fed mouse livers. Furthermore, pharmacological relief of ER stress using TUDCA or inhibition of ferroptosis with liproxstatin-1 both alleviated the liver abnormalities induced by Depdc5 ablation in ethanol-fed mice. Additionally, the research uncovered that ER stress functions as an upstream signal of ferroptosis in the progression of ALD. These findings provide novel in vivo evidence that sustained mTORC1 activation leads to alcoholic liver injury by inducing ER stress and ferroptosis, suggesting that targeting these pathways may represent a potential therapeutic strategy for ALD.
研究领域:
医学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Microbiology
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2019
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IF 4.259
Xiao Yu,Liu Chunlan,Tang Wei,Zhang Haiwei,Chen Xulin
Chronic hepatitis B (CHB) is a global health problem caused by human hepatitis B virus (HBV). Current treatment with interferons and nucleos(t)ide analogs (NAs) can cause population tolerance and drug resistance. Therefore, new antiviral drugs, especially those targeting host factors, are urgently needed. Here, we identified Evans blue as a new HBV inhibitor by screening an FDA drug library using Huh7DhNTCP cells and confirmed the antiviral activity in primary human hepatocytes and human sodium taurocholate cotransporting polypeptide (hNTCP)-transfected porcine primary hepatocytes. Our efficacy study showed that Evans blue has an IC50 of 2 μM against HBV infection in Huh7DhNTCP cells, and no apparent toxicity at up to 1000 μM. The IC50 of Evans blue against HBV in primary human hepatocytes was approximately 5 μM. Mechanism studies revealed that Evans blue has a dual anti-HBV effect. It inhibits both the binding of viral preS1 to host cells through the host factor NTCP and the virus capsid assembly by targeting the host factor BK channel. The KD of the direct interaction between Evans blue and NTCP is 8.82E-8 M. Evans blue can suppress capsid assembly at micromolar concentrations by reducing the cytosolic calcium ion concentration. Since the antiviral effects on HBV binding and assembly are both achieved through targeting host factors, Evans blue inhibits the infection of nucleos(t)ide analog drug-resistant HBV strains in Huh7DhNTCP cells. Taken together, our results suggest that Evans blue may be a promising anti-HBV drug candidate in the classes of both entry and assembly inhibitors.
研究领域:
病毒学
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肝病学
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药物研发
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
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2023
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IF 7.2
Li Luo,Huafeng Zhang,Weiliang Chen,Ziming Zheng,Zihao He,Haoyu Wang,Kaiping Wang,Yu Zhang
Angelica sinensis polysaccharide (ASP) showed increasingly recognized hepatoprotective effects and lipid regulation. Because polysaccharides are typically degraded into fragments or short-chain fatty acids in the gut, rather than being absorbed in their intact form, it is worth pondering why ASP can regulate hepatic lipid metabolism and protect the liver from damage caused by lipid accumulation. In vivo and in vitro nonalcoholic fatty liver disease (NAFLD) models with lipid accumulation were established to investigate the effect and potential mechanisms of ASP on hepatic fat accumulation. Our results showed that ASP remodeled the composition and abundance of the gut microbiota in high-fat diet-fed mice and increased their levels of propionate (0.92 ± 0.30 × 10 7 vs. 2.13 ± 0.52 × 10 7 ) and butyrate (1.83 ± 1.31 × 10 7 vs. 6.39 ± 1.44 × 10 7 ). Sodium propionate significantly increased the expression of estrogen-related receptor α (ERRα) in liver cells (400 mM sodium propionate for 2.19-fold increase) and alleviated the progress of NAFLD in methionine–choline-deficient diet model. Taken together, our study demonstrated that ASP can regulate hepatic lipid metabolism via propionate/ERRα pathway and ultimately relieving NAFLD. Our findings demonstrate that ASP can be used as a health care product or food supplement to prevent NAFLD.
研究领域:
药理学
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肝病学
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微生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
Small
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2025
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IF 12.1
Xinxin Liu,Tao Liu,Xueli Yuan,Jing Zhang,Mengjiao Zhu,Wei Zhang,Zhenyu Chu,Wanqin Jin
Viral hepatitis is a highly infectious disease caused by various hepatitis viruses that, thus far, have no cure. In early viral invasion, a low viral load in the blood makes early detection difficult unless the symptoms are severe. Herein, a new ultrasensitive and ultrafast hepatitis virus detection strategy is proposed by constructing a dual-surface-activated nanotube that enables recognition probes to not only bind to the outer surface of the nanotube but also penetrate and lock onto its inner surface. This approach significantly enhances both the specific surface area and number of active sites, thereby improving the capture efficiency for traces of hepatitis viral DNA, such as the B type (HBV-DNA). Compared with current DNA detection methods, this approach eliminates the additional amplification steps to achieve an ultralow detection limit of 10 −18 m , advancing the available detection time as early as possible. Using human serum as a sample, this technique enables the precise and quantitative reporting of HBV-DNA within only 15 min and overcomes the interference of usual proteins and other viral DNA. This technique provides new inspiration for quick and early hepatitis diagnosis for in-hospital and non-hospital patients without bulky instruments and complex operations.
研究领域:
生物技术
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医学诊断
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
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2025
·Vol. 105
·期 4
·e70097
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IF 3.3
Wei-fang Song,Sheng-nan Li,Rui-xin Yao,Qiu-yan Jiang,Ting Shi,Dan-dan Fan,Hai-juan Zhang,Wen-hui Zhang,Rui-jun Wang
The primary objective aims to evaluate the therapeutic efficacy of echinacoside in ameliorating hepatic steatosis and exploring its role in modulating autophagic flux through AMP-activated protein kinase (AMPK) signaling, positioning it as a potential treatment for non-alcoholic fatty liver disease (NAFLD). A well-established NAFLD rat model was employed, administering varying concentrations of echinacoside. Biochemical parameters, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alongside liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), were measured to assess liver function. To elucidate the molecular mechanisms, western blot analyses were performed to assess the expressions of p-AMPK, total AMPK, and key autophagy markers LC-3 I/II and Beclin-1. Echinacoside significantly improved the lipid profile by lowering plasma TG, TC, and LDL-C levels while increasing HDL-C. It also reduced serum ALT, AST, and ALP activities, demonstrating hepatoprotective effects. Notably, echinacoside reversed the p-AMPK levels in NAFLD rats in a dose-dependent manner, with the highest dosage showing the strongest effect. This was accompanied by increased expression of LC-3 I/II and Beclin-1. Echinacoside is expected to be a therapeutic drug for NAFLD by activating AMPK activity and enhancing autophagy to improve liver function. These findings suggest its clinical potential, with autophagy modulation via the AMPK pathway as a possible therapeutic mechanism for NAFLD treatment.
研究领域:
药理学
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代谢生物学
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肝脏疾病研究
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产品关联
DOI
PubMed
高影响因子
CERAMICS INTERNATIONAL
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2020
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IF 3.83
Baoqing Han,Hairong Wang,Wanying Yang,Jiuhong Wang,Xueyong Wei
For advanced fibrosis, isoprene is a typical characteristic marker that could be used to quickly screen the population for chronic liver disease (CLD). To achieve trace detection of isoprene, different mol% Pt-decorated In 2 O 3 and pure In 2 O 3 samples were prepared with the commonly used hydrothermal method . The obtained characterization results show that the prepared Pt-decorated In 2 O 3 (1 mol%) sample had Pt nanoparticles uniformly attached to the surface of porous hierarchical In 2 O 3 nanosheets , and the specific surface area was 62.3 m 2 /g. Subsequently, these sensors based on Pt–In 2 O 3 and pure In 2 O 3 nanomaterials were prepared, and their response characteristics were studied. The results show that the response of 1 mol% Pt–In 2 O 3 to isoprene gas was significantly enhanced, and the optimal working temperature was 200 °C. The response of 1 mol% Pt–In 2 O 3 to 5 ppb and 5 ppm isoprene was approximately 3.2 times and 25.9 times that of pure In 2 O 3 , respectively. Meanwhile, the 1 mol% Pt-modified sample exhibited excellent selectivity for isoprene relative to other biomarkers (carbon monoxide, hydrogen, ethanol, and ammonia). The sensor shows good repeatability and long-term stability. Therefore, the developed 1 mol% Pt-decorated In 2 O 3 was expected to be applied as a gas-sensitive material for breath isoprene, which could be suitable for large-scale CLD rapid breath detection.
研究领域:
材料科学
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医学诊断
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传感器技术
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DOI
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Zhang Hui,Cui Xiao,Liu Wei,Xiang Zheng,Ye Ji-Feng
Introduction: Alcoholic liver disease (ALD) was the second leading cause of liver injury. Penthorum chinense Pursh (GHC) is an important Miao ethnic drug of traditional Chinese medicine for the treatment of liver disease, but the pathogenesis is not clear.Aim of the study: To analysis the intestinal microflora and metabolic pathway of GHC on ALD mice.Methods: An HPLC-QTOF-MS method was used to identified the components from GHC extract, firstly. 60 mice were divided into six groups including blank group, model group, positive group and GHC groups (0.29, 0.87 and 2.61 g/kg). ALD mice was treated with GHC for 12 days. ALT, AST, TC and TG in serum were determined, liver index and pathological analysis were achieved. 16S rRNA gene sequencing was used to detect the intestinal microbial diversity. Finally, UPLC-QTOF-MS was used to analysis the metabolic pathways.Results: 38 ingredients were identified in GHC extract. Compared with the model group, liver index of the positive group and GHC (2.61 g/kg) group was significantly reduced. Compared with the model group, contents of ALT, AST, TC and TG of GHC groups reduced in a dose-dependent manner. Intestinal microbial diversity analysis indicated that Chao1, Observed species, Pielou_e, and Shannon indexes in GHC group (2.61 g/kg) were lower than those in model group. Principal coordinate analysis indicated that the intestinal microbial composition between blank group and model group, the model group and GHC (2.61 g/kg) group changed significantly. Compared with the model group, proportion of Firmicutes decreased, and the proportion of Bacteroidetes increased significantly in GHC group, which were 50.84% and 40.15%. The more prominent bacteria in the GHC group were odoribacteraceae, turicibacter, deferribacteraceae, and the intestinal beneficial symbiotic bacteria mucispirillum. Metabolic analysis indicated that, compared with blank group, 90 metabolites in model group changed significantly, and 68 metabolites were significantly callback in GHC group.Discussion: GHC has a therapeutic effect on ALD by regulating intestinal flora imbalance and metabolic pathways including Glycine, serine and threonine metabolism, Glutathione metabolism, Arginine and proline metabolism, Alanine, aspartate and glutamate metabolism, Butanoate metabolism and primary bile acid biosynthesis.
研究领域:
药理学
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微生物学
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代谢组学
✓ 已验证
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
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2025
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IF 8.4
Wang Hao,Xia Guo-qing,Ke Ting,Chen Xi-xi,Zhen Wen-jun,Tian Yuan-yuan,Chen Shi,Zhang Cheng,Li Jun,Zhang Lei,Wu De-jun,Wang Ye-tao,He Liang,Tian Wen-fang,Wu Bao-ming
Alcohol-related liver disease (ALD) refers to a spectrum of liver diseases caused by chronic or acute excessive alcohol consumption. Excess alcohol consumption and dysregulated immunometabolism are the major contributors to the disease progression. The pathogenesis of ALD remains unclear with macrophage activity playing a key role in disease development. Kv1.3 potassium channel is essential for the regulation of macrophage function. In this study, we investigated whether Kv1.3 channels influenced the progression of ALD by modulating macrophage function. A murine model of ALD was established in male mice. We showed that Kv1.3 knockdown significantly attenuated alcohol-induced liver injury, lipid deposition, and inflammatory responses in ALD mice. Metabolomic analysis revealed that Kv1.3 knockdown significantly increased the levels of tryptamine, a tryptophan metabolite, in the liver of ALD mice. During the last 5 days of the EtOH feeding period, injection of exogenous tryptamine (1, 10, 20 mg·kg −1 ·d −1 , i.p.) notably alleviated ethanol-induced liver steatosis and inflammation in ALD mice. In LPS-challenged RAW264.7 cells, tryptamine (62.5, 125, 250 μM) dose-dependently suppressed the secretion of pro-inflammatory cytokines IL-6, IL-1β and TNF-α. RNA-seq analysis of RAW264.7 cells revealed that tryptamine treatment significantly altered Toll-like receptor and NF-κB signaling pathways. We conclude that in the ALD mice, Kv1.3 negatively regulates tryptamine levels, which inhibits macrophage activation and reduces the inflammatory responses through the TLR4/NF-κB signaling pathway. Our results offer new targets and intervention strategies for the prevention and treatment of ALD.
研究领域:
医学
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免疫学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Metabolites
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2022
·Vol. 12
·期 9
·867
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IF 5.581
Shipeng Zhou,Qiuhua Tan,Bingjian Wen,Yan Bai,Qishi Che,Hua Cao,Jiao Guo,Zhengquan Su
Alcoholic liver disease (ALD) is a primary cause of mortality and morbidity worldwide. Oxidative stress and inflammation are important pathogenic factors contributing to ALD. We investigated the protective mechanism of galacto-oligosaccharide (GOS) against ALD through their antioxidant and anti-inflammatory activities by performing in vivo and in vitro experiments. Western blot and RT‒PCR results indicated that the expression of cytochrome P450 protein 2E1 (CYP2E1) in liver tissues and L02 cells was reduced in the GOS-treated mice compared with the model group. In addition, GOS prominently reduced the expression of Kelch-like ECH-associated protein 1 (Keap1), increased the expression of the nuclear factor erythroid-2-related factor 2 (Nrf2) and haem oxygenase-1 (HO-1) proteins, and enhanced the antioxidant capacity. In addition, GOS decreased inflammation by reducing inflammatory factor levels and inhibiting the mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway. Based on these results, GOS may be a prospective functional food for the prevention and treatment of ALD.Keywords:alcoholic liver disease (ALD);antioxidant;anti-inflammatory;galacto-oligosaccharide;hepatoprotective
研究领域:
肝病学
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药理学
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营养学
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产品关联
DOI
PubMed
高影响因子
Nutrients
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2023
·Vol. 15
·期 19
·4176
·
IF 5.9
Yuxu Chen,Zhiye Zhao,Shancheng Guo,Yaxian Li,Haiaolong Yin,Lei Tian,Guiguang Cheng,Ye Li
Alcoholic liver disease (ALD), leading to the most common chronic liver diseases, is increasingly emerging as a global health problem, which is intensifying the need to develop novel treatments. Herein, our work aimed to estimate the therapeutic efficacy of red rice (Oryza sativaL.) seed coat on ALD and further uncover the underlying mechanisms. Red rice seed coat extract (RRA) was obtained with citric acid–ethanol and analyzed via a widely targeted components approach. The potential targets of RRA to ALD were predicted by bioinformatics analysis. Drunken behavior, histopathological examination, liver function, gut microbiota composition and intestinal barrier integrity were used to assess the effects of RRA (RRAH, 600 mg/kg·body weight; RRAL, 200 mg/kg·body weight) on ALD. Oxidative stress, inflammation, apoptosis associated factors and signaling pathways were measured by corresponding kits, Western blot and immunofluorescence staining. In ALD model mice, RRA treatment increased sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate (S1P) levels, improved gut microbiota composition, restored intestinal barrier, decreased lipopolysaccharide (LPS) levels in plasma and the liver, cut down Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) pathways, alleviated liver pathological injury and oxidative stress, attenuated inflammation and apoptosis and enhanced liver function. To sum up, RRA targeting SPHK2 can ameliorate ALD by repairing intestinal barrier damage and reducing liver LPS level via the TLR4/NF-κB pathway and intestinal microbiota, revealing that red rice seed coat holds potential as a functional food for the prevention and treatment of ALD.Keywords:red rice seed coat;alcoholic liver disease;SPHK2;gut microbiota;intestinal barrier
研究领域:
药理学
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胃肠病学
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微生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）