PHYTOMEDICINE
·
2024
·
IF 6.7
Weiqi Cui,Qianwen Cao,Luyao Liu,Xuecui Yin,Xiaohan Wang,Yang Zhao,Yanhong Wang,Bo Wei,Xia Xu,Youcai Tang
Background The hepatotoxicity induced by acetaminophen (APAP), a commonly used antipyretic, analgesic and anti-inflammatory drug in clinical practice, has received accumulated attention. Artemisia argyi essential oil (AAEO), a volatile oil component extracted from traditional Chinese medicine Artemisia argyi H.Lév. & Vaniot, has great hepatoprotective effects. However, the potential role of AAEO in APAP-induced hepatotoxicity has not been characterized. The present study aimed to investigate the effects of AAEO on hepatic metabolic changes in mice exposed to APAP. Methods In this study, 300.00 mg/kg acetaminophen was used to establish liver injury model in C57BL/6 J mice. Hepatoprotective effect of AAEO on APAP-induced hepatotoxicity in mice was investigated by detecting liver function enzymes and histopathological examination. Secondly, UPLC-MS/MS was used to analyze the to analyze the small molecule metabolites and metabolic pathways induced by AAEO treatment; In addition, the effect of AAEO on APAP-induced oxidative stress and inflammation were evaluated by detecting the levels of glutathione peroxidase 4, malondialdehyde, reactive oxygen species and inflammatory factors. Finally, the active components of AAEO were preliminarily screened by cellular assays. The hepatoprotective effect of AAEO against APAP-induced hepatotoxicity was examined through the Western blotting, after the CYP2E1 gene was knocked down in AML12 cells by siRNA transfection. Results Compared with the APAP group, AAEO could reduce the abnormal increase in the levels of liver function enzymes caused by APAP. AAEO could enhance the antioxidant capacity by down-regulating the biosynthesis pathway of unsaturated fatty acids and promoting the activity of antioxidant enzymes SOD and CAT in liver tissue induced by APAP. Our study revealed that AAEO promoted GSH synthesis and covalently combined to form APAP-GSH conjugates to reduce the accumulation of APAP in liver tissue. In addition, the chemical constituents in AAEO were analyzed by GC–MS/MS, and it was determined to identify that dihydro-beta-ionone and (-)-verbenone in AAEO might have a significant protective effect on hepatocyte survival after APAP exposure. Further studies on the hepatoprotective mechanism of AAEO indicated that it might reduce the production of toxic metabolites by regulating CYP2E1 levels. Conclusion AAEO exerted hepatoprotective effects on acetaminophen-induced hepatotoxicity in mice via regulating the activity of CYP2E1 and regulating the γ-glutamyl cycle pathway.
研究领域:
药理学
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肝病学
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毒理学
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代谢组学
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中药学
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2025
·
IF 7.3
Peng Zhang,Guanghua Lu,Leibo Zhang,Zhenhua Yan,Min Wang
Microplastics (MPs) can accumulate and enrich antibiotics in aquatic environments, with their interactions exacerbating threats to aquatic organisms and complicating hepatotoxicity. Therefore, this study aimed to elucidate the effects of single or combined exposure to polyethylene MPs and ciprofloxacin (CIP) on hepatic injury in crucian carp, and to reveal the potential gut-liver axis toxicity mechanisms. The results showed that MPs enhanced the bioaccumulation of CIP, which increased with increasing MPs concentration. Co-exposure induced extensive eosinophilic necrosis and localised hepatocyte clustering in hepatocytes, alongside severe vacuolization and lymphocytic infiltration in intestinal cells. Glutamate aminotransferase and alanine aminotransferase activities, and total antioxidant capacity levels in the liver were significantly elevated, whilst glutamyltransferase activities were suppressed by the co-exposure. High-concentration MPs in combination with CIP significantly enriched the pathways of amino acid metabolism, glycerophospholipid metabolism, and primary bile acid biosynthesis in the liver. Moreover, co-exposure markedly suppressed the abundance of Cetobacterium while promoting that of Gemmobacter and Bosea . The imbalances in Bacteroides and pathogens ( Aeromonas and Bose ) are closely associated with related products in primary bile acid biosynthesis and glycerophospholipid metabolism pathways. These findings underscore that exposure to MPs and CIP induces hepatitis and reveal the pivotal role of the indirect gut-liver axis in elucidating the potential mechanisms underlying hepatotoxicity induced by co-exposure, thereby furnishing critical evidence for the holistic assessment of health hazards posed by these pollutants.
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PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Jiabin Zhang,Xiaodie Chen,Yurong Chai,Yuanyuan Jin,Fenfang Li,Chenya Zhuo,Yanteng Xu,Haixia Wang,Enguo Ju,Yeh-Hsing Lao,Xi Xie,Mingqiang Li,Yu Tao
Acute liver failure (ALF) is a highly lethal condition characterized by massive tissue necrosis, excessive oxidative stress, and serious inflammatory storms, necessitating prompt medical intervention. Although hepatocyte-like cells (HLCs) derived from mesenchymal stromal/stem cells (MSCs) offer a promising alternative cell source for hepatocyte therapy, their low in-vivo integration and differentiation efficiency may compromise the eventual therapeutic efficacy. To this end, MSCs are bioengineered into multicellular spheroids in the present study. The proteomic analyses and experimental results reveal that extracellular vesicles (EVs) derived from these MSC spheroids (SpEV) contain abundant highly expressed bioactive proteins and can be efficiently endocytosed by recipient cells, resulting in enhanced pro-angiogenic and antioxidative effects. In addition, MSC spheroids exhibit superior hepatic cell differentiation compared to an equivalent number of dissociated single MSCs, particularly when being co-cultured with hexagonally patterned endothelial cells in a liver lobule-like arrangement. Following orthotopic implantation in the mouse model, the enhanced paracrine effects of SpEV, combined with an immunoregulatory decellularized extracellular matrix hydrogel carrier and functional artificial liver lobules (ALL), synergically contribute to the effective amelioration of ALF, highlighting the substantial potential for clinical translation.
研究领域:
再生医学
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肝脏疾病
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生物工程
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细胞治疗
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2024
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IF 5.7
Hang Gong,Ganping Cai,Yong Li,Ning Jiang,Chunyan Chen,Feng Chen,Changqun Cai
Background Viral epidemics have long endangered human health and had dramatic impacts on environment and society. The currently known viruses and the rapid emergence of previously unknown viruses lead to an urgent need for effective virus detection strategies. It is important to develop methods that can detect multiple related viruses simultaneously in order to improve detection efficiency and to avoid treatment delays due to misdiagnoses. However, an important practical problem for viruses simultaneously detection is mutual interference between the targets, which is caused by a certain degree of signal superposition. Results A portable ratio-based triple-emission molecular imprinting fluorescence sensor was constructed to detect hepatitis A virus (HAV) and hepatitis B virus (HBV) simultaneously, which eliminated background interference and mutual interference between the two targets, and improved detection accuracy. In this sensor, a layer containing blue fluorescent carbon quantum dots (B-CDs) coated with silicon was used as a constant luminescent core to permit ratiometric detection of signals, this layer also affords visual analysis due to its constant blue color. As signal sources to employ yellow-green and red quantum dots, HAV- and HBV-specific molecularly imprinted polymers (MIPs) were prepared by imprinting virus onto the core containing the B-CDs. Under the optimized detection conditions, the simply physically mixing HAV-MIPs and HBV-MIPs in a specific ratio, which leads to non-interfering fluorescence signals and the simultaneous detection of the two target viruses via the rich color visualization under ultraviolet light. Significance This strategy provides a simple and low-cost (0.26 ¥/sensor) method for the simultaneous detection of two hepatitis viruses, and provides an avenue for the development of portable methods for the simultaneous detection of similar highly infectious viruses. This self-service sensor also has the potential to be used by patients themselves, reducing pressures on medical staff and decreasing risks of cross-infection.
研究领域:
病毒学
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医学检测
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纳米材料科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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IF 7.7
Zixuan Tang,Mingli Zhong,Houkang Cao,Yongwang Wang,Guoqiang Guan,Gang Wang,Jianzhao Wu,Fei Han,Ya Gao,Kefeng Zhang
Dicliptera chinensis (L.) Juss., is an herb known for its anti-inflammatory and anti-oxidant properties. In the previous studies, the chemical composition of the polysaccharide from Dicliptera chinensis (L.) Juss. (DCP) has been characterized as consisting of DCP 1 and DCP 2 , of which DCP 2 has hepatoprotective effects. The study examined the hepatoprotective potential of DCP 2 against alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver disease (CLD). In this study, RNA sequencing identified key research pathways involving bile acid metabolism, oxidative stress, and inflammation. Furthermore, qRT-PCR and Western blot analyses were conducted to further characterize these pathways. Additionally, the study included in vitro experiments with HepG2 cells to further investigate the effects of DCP 2 on bile acid metabolism. In summary, the protective effect of DCP 2 on the liver was reflected in alleviating the inflammatory response and oxidative stress, regulating the metabolism of bile acids, and mitigating liver damage caused by bile acids. This study further elucidated the hepatoprotective effects of DCP 2 by examining its ability to counteract ANIT-induced CLD, suggesting that DCP 2 is a promising biomacromolecule for hepatoprotection.
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
Materials Today Bio
·
2025
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IF 10.2
Yue Wang,Chen Wei,Xiaoyu Zhao,Fantao Lin,Shijie Liu,Jingkun Bai
Chemotherapy is crucial for treating intermediate and advanced hepatocellular carcinoma (HCC). However, anthracycline agents such as doxorubicin (DOX) are often expelled from tumor cells by P-glycoprotein (P-gp), which decreases the intracellular drug levels and leads to treatment failure. Activated hepatic stellate cells (aHSCs) are critical in liver fibrosis and HCC progression and facilitate liver cancer development. Importantly, liver fibrosis progression is closely linked to the expression of cyclooxygenase-2 (COX-2). Here, we developed a pH-responsive peptide drug delivery system, Pep loaded with DOX and CXB (DC/Pep), which targets HCC by transporting the COX-2 inhibitor celecoxib (CXB) alongside the conventional chemotherapeutic drug DOX. DC/Pep targeted HCC cells and transitioned from spherical particles to high aspect ratio aggregates in a mildly acidic environment, effectively delaying chemotherapeutic agent efflux from the tumor. DC/Pep effectively inhibited hepatic stellate cell activation and reduced collagen fiber synthesis, thereby preventing the development of liver fibrosis. Consequently, the proliferation of ectopic and orthotopic HCC tumors was effectively inhibited, leading to an enhanced antitumor effect. This study is important for designing novel drug delivery systems using peptide amphiphiles for the treatment of intermediate and advanced HCC.
研究领域:
肿瘤学
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药剂学
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分子生物学
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DOI
PubMed
高影响因子
Heliyon
·
2023
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IF 4
Jinlin Xu,Yuehui Jin,Chengwu Song,Guangya Chen,Qiaoyu Li,Hao Yuan,Sha Wei,Min Yang,Sen Li,Shuna Jin
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide and had no approved pharmacological treatments. Diwuyanggan prescription (DWYG) is a traditional Chinese medicine preparation composed of 5 kinds of herbs, which has been used for treating chronic liver diseases in clinic. Whereas, the synergistic mechanism of this prescription for anti-NAFLD remains unclear. In this study, we aimed to demonstrate the synergetic effect of DWYG by using the disassembled prescriptions and untargeted metabolomics research strategies. The therapeutic effects of the whole prescription of DWYG and the individual herb were divided into six groups according to the strategy of disassembled prescriptions, including DWYG, Artemisia capillaris Thunb. (AC), Curcuma longa L. (CL), Schisandra chinensis Baill. (SC), Rehmannia glutinosa Libosch. (RG) and Glycyrrhiza uralensis Fisch. (GU) groups. The high fat diets-induced NAFLD mice model was constructed to evaluate the efficacy effects of DWYG. An untargeted metabolomics based on the UPLC-QTOF-MS/MS approach was carried out to make clear the synergetic effect on the regulation of metabolites dissecting the united mechanisms. Experimental results on animals revealed that the anti-NAFLD effect of DWYG prescription was better than the individual herb group in reducing liver lipid deposition and restoring the abnormality of lipidemia. In addition, further metabolomics analysis indicated that 23 differential metabolites associated with the progression of NAFLD were identified and 19 of them could be improved by DWYG. Compared with five single herbs, DWYG showed the most extensive regulatory effects on metabolites and their related pathways, which were related to lipid and amino acid metabolisms. Besides, each individual herb in DWYG was found to show different degrees of regulatory effects on NAFLD and metabolic pathways. SC and CL possessed the highest relationship in the regulation of NAFLD. Altogether, these results provided an insight into the synergetic mechanisms of DWYG from the metabolic perspective, and also supported a scientific basis for the rationality of clinical use of this prescription.
研究领域:
药理学
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代谢组学
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中医药
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肝病学
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DOI
高影响因子
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
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2024
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IF 3.7
Shenglu Liu,Haoxian Gou,Hui Wei,Shengdeng Chen,Shijie Zhuo,Ming Luo,Shu Qin,Mengyu Zhang,Jiatong Chen,Zhiwei Huang,Xianming Xia,Xiaoli Yang,Kai He
Background and Aim The impact of cholecystectomy, which blocks the cholecystohepatic shunt pathway (CHSP), on the prognosis of patients with hepatocellular carcinoma (HCC) is unclear. Hepatic secondary bile acids (BAs) inhibit natural killer T (NKT) cell-mediated immunity against HCC, and the regulation of homeostasis of hepatic secondary BAs is controlled by the CHSP. However, the influence of CHSP on NKT cell-mediated immunity against HCC remains unclear. Methods The clinical data of hospitalized patients undergoing HCC resection were collected. Meanwhile, an in situ HCC mouse model was established, and the CHSP was augmented using oleanolic acid (OA). Results After 1:1 propensity score matching, Cox regression analysis revealed that cholecystectomy was an independent risk factor for HCC recurrence after hepatectomy ( P = 0.027, hazard ratio: 1.599, 95% confidence interval: 1.055–2.422). Experimentally, when OA enhanced CHSP, a significant decrease was observed in the accumulation of secondary BAs in the livers of mice. Additionally, a significant increase was observed in the levels of C-X-C ligand 16 and interferon γ in the serum and tumor tissues. Further, the percentage of C-X-C receptor 6 (+) NKT cells in the tumor tissues increased significantly, and the growth of liver tumors was inhibited. Conclusions This clinical study revealed that cholecystectomy promoted the recurrence after radical hepatectomy in patients with HCC. Preserving the normal-functioning gallbladder as much as possible during surgery may be beneficial to the patient's prognosis. Further investigation into the mechanism revealed that CHSP enhanced NKT cell-mediated immunity against HCC by reducing the hepatic accumulation of secondary BAs.
研究领域:
胃肠病学
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肝病学
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免疫学
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肿瘤学
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DOI
PubMed
高影响因子
Nanoscience and Nanotechnology Letters
·
2017
·Vol. 9
·期 10
·1453-1462
·
IF 1.889
Wu Yulong,Zhou Feng,Jiang Haitao,Wang Zhengjiong,Hua Chun,Wang Renlei
Two novel polysaccharides fractions were isolated from Cordyceps militaris substrate polysaccharides (CMSP) by DEAE-52 cellulose and Sephadex G-100 column chromatography, and named as CMSP-1 and CMSP-2. The CMSP-1 was a heteropolysaccharide mainly composed of sorbin, D-mannose,
D-glucose, galactose, arabinose, with the molar ratios of 1.00:6.32:10.23:2.86:1.02, and the molecular weight of CMSP-1 was 10715.2 Da. The CMSP-1 was used to investigate the protective effect on acute ethanolic hepatotoxicity (AAH) in male mice. The results indicated that oral administration
of CMSP-1 could significantly decrease the liver index, and increase body weight in mice with AAH. CMSP-1 could also significantly increase the levels of SOD, GSH and GSH-PX, and decrease the levels of ALT, AST, TG, VLDL and MDA in AAH model mice. Moreover, Histopathological examination of
liver showed that CMSP-1 could significantly alleviate the symptoms of liver injury caused by ethanol, such as swelling of hepatocytes, loose cytoplasm and lipid changes. Therefore, CMSP-1 has obvious protective effect on AAH model mice, and has a good prospect in functional foods or natural
medicine.
研究领域:
药理学
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肝病学
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营养保健品
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DOI
高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 10
·1-15
·
IF 8.1
Zhao Rong,Guo Zizhen,Lu Kaikai,Chen Qian,Riaz Farooq,Zhou Yimeng,Yang Luyun,Cheng Xiaona,Wu Litao,Cheng Kexin,Feng Lina,Liu Sitong,Wu Xiaodan,Zheng Minghua,Yin Chunyan,Li Dongmin
Nonalcoholic steatohepatitis (NASH) is a prevalent chronic disease, yet its exact mechanisms and effective treatments remain elusive. Nuclear receptor subfamily 5 group A member 2 (NR5A2), a transcription factor closely associated with cholesterol metabolism in the liver, has been hindered from comprehensive investigation due to the lethality of NR5A2 loss in cell lines and animal models. To elucidate the role of NR5A2 in NASH, we generated hepatocyte-specific knockout mice for Nr5a2 (Nr5a2 HKO ) and examined their liver morphology across different age groups under a regular diet. Furthermore, we established cell lines expressing haploid levels of NR5A2 and subsequently reintroduced various isoforms of NR5A2. In the liver of Nr5a2 HKO mice, inflammation and fibrosis spontaneously emerged from an early age, independent of lipid accumulation. Pyroptosis occurred in NR5A2-deficient cell lines, and different isoforms of NR5A2 reversed this form of cell death. Our findings unveiled that inhibition of NR5A2 triggers pyroptosis, a proinflammatory mode of cell death primarily mediated by the activation of the NF-κB pathway induced by reactive oxygen species (ROS). As a transcriptionally regulated molecule of NR5A2, aldehyde dehydrogenase 1 family member B1 (ALDH1B1) participates in pyroptosis through modulation of ROS level. In conclusion, the diverse isoforms of NR5A2 exert hepatoprotective effects against NASH by maintaining a finely tuned balance of ROS, which is contingent upon the activity of ALDH1B1.
研究领域:
肝病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2025
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IF 3.8
Yang Qian,Zhang Yong,Zhang He,Yang Zi,Feng Yanruyu,Ye Bengui,Gong Puyang,Qian Guangsheng,Li Dapeng
Sexual dimorphism plays a critical role in disease pathophysiology, but the subtlety and complexity of these differences, along with a lack of precise comparative methods, hinder the advancement of precision medicine and drug development. This limitation is particularly evident in metabolic dysfunction–associated steatotic liver disease (MASLD), where sex-specific molecular mechanisms remain insufficiently understood. To address this gap, we employed an advanced integrative N-glycoproteomics and proteomics approach to systematically analyze sex-biased molecular signatures in primary mouse hepatocytes (PMHs) under healthy and MASLD conditions. Our analysis identified 280 sex-biased proteins and 39 sex-biased N-glycosites, and KEGG enrichment revealed that female-biased molecules were primarily involved in lipid metabolism, while male-biased molecules were associated with inflammation and cytoskeletal remodeling. A combined dataset of 302 sex-biased molecules was further analyzed using protein–protein interaction (PPI) analysis and Rc value calculations, resulting in the identification of 21 hub proteins and 2 hub N-glycosites as MASLD-associated sex-biased signatures. Notably, MASLD amplified proteomic sex differences while attenuating them in N-glycosylation. Western blot validation of key signatures, including female-biased MVK and male-biased LGALS3, highlighted distinct molecular adaptations between the sexes in MASLD progression. Our study introduced an advanced analytical framework for high-resolution comparative molecular profiling by integrating N-glycoproteomics with proteomics, providing valuable insights into sex-biased molecular signatures, enhancing preclinical model development, and advancing sex-specific therapeutic strategies in MASLD research and broader biological systems. Graphical
研究领域:
生物化学
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分子生物学
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医学
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DOI
PubMed
高影响因子
SENSORS
·
2020
·Vol. 20
·期 17
·4912
·
IF 3.275
Xuexue Xu,Rongbin Nie,Jingwen Huang,Li Yang
Optical fiber based immunosensors are very attractive for biomarker detection. In order to improve the sensor response, we propose a promising strategy which combines porous-layer modification of the fiber surface and streptavidin-biotin-peroxidase nano-complex signal amplification in chemiluminescent detection. Two hepatitis B antigens, hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), are used as the targets for analysis using the proposed sensor. Comparing to immunoassays using normal optical fiber sensors, the response of the present sensor is enhanced by a factor of 4.8 and 6.7 for detection of HBsAg and HBeAg, respectively. The limit-of-quantitation of the proposed method is as low as 0.3 fg/mL (0.01 fg/mL) with a wide linear response range of 3 fg/mL–150 ng/mL (0.1 fg/mL–160 ng/mL) for sensing HBsAg (HBeAg). Quantitative determination of HBsAg and HBeAg in human serum samples is performed, showing the applicability of the proposed method for biomarker detection.Keywords:optical fiber immunosensor;surface modification;signal amplification;hepatitis B surface antigen;hepatitis B e antigen
研究领域:
生物医学工程
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分析化学
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医学诊断
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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）