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AstragalosideⅣplays a role in reducing radiation-induced liver inflammation in mice by inhibiting thioredoxin-interacting protein/nod-like receptor protein 3 signaling pathway

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Journal of Traditional Chinese Medicine 2023年第1期43卷 87-94页

作者： DING Yanping DONG Xiaoqing MA Yifan CHEN Lili ZHOU Jie LI Xinyan SHAO Baoping College of Life Science Northwest Normal UniversityLanzhou 730000China College of Life Science Lanzhou UniversityLanzhou 730000China

OBJECTIVE:To investigate the efficacy of Astragaloside IV(AS-IV)on radiation-induced liver inflammation in mice.METHODS:The mice were divided into normal group,dimethyl sulfoxide solvent group,irradiation group(IR),irradiation+AS-IV(20 mg/kg)group(IR+AS-20)and irradiation+AS-IV(40 mg/kg)group(IR+AS-40).One month after intraperitoneal injection of AS-IV,the mice were irradiated with 8Gry Co60γ,the blood was collected for biochemical analysis,and the liver was collected for hematoxylin-eosin staining,immunofluorescence and electron microscopic observation,oxidative stress,and Western blot analysis.RESULTS:The AS-IV treatment significantly ameliorated the pathological morphology of liver and reduced the alanine aminotransferase and aspertate aminotransferase levels in serum induced by radiation;AS-IV treatment also significantly reduced the expression of inflammatory factors tumor necrosis factor alpha and interleukin 6 and antagonized malonaldehyde content and superoxide dismutase activity in liver caused by radiation;in addition,AS-IV treatment can significantly inhibited the positive expression of thioredoxin-interacting protein(TXNIP)and nod-like receptor protein 3(NLRP3)inflammasome in liver tissue after radiation;The expression of TXNIP,NLRP3 inflammasome,apoptosisassociated speck-like protein containing a CARD,cysteinyl aspartate-specific proteinase 1 and interleukin 1beta in the AS-IV prevention group decreased significantly compared to the radiation group.CONCLUSIONS:These findings suggested that Co60γradiation can cause structural and functional damage to the liver,which may be related to the NLRP3 mediated inflammatory pathway;AS-IV may play a protective role by inhibiting the TXNIP/NLRP3 inflammasome signaling pathway in the radiation-induced liver injury model.

关键词： radiation,ionizing astragalosideⅣ liver inflammation NLR family,pyrin domain-containing 3 protein thioredoxin-interacting protein

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liver Stiffness Measurement can Predict liver inflammation in Chronic Hepatitis B Patients with Normal Alanine Transaminase

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 817-826页

作者： Ling-Ling Huang Xue-Ping Yu Qing-Fa Ruan Yan-Xue Lin Huan Li Wen Jin Rui-Feng Liu Yan-Lan Liang Yu-Rui Liu Yue-Yong Zhu Jia-Ji Jiang Ri-Cheng Mao Da-Wu Zeng Department of Hepatology Hepatology Research InstituteThe First Affiliated hospitalFujian Medical UniversityFuzhouFujianChina Department of Infectious Diseases The First Hospital of Quanzhou Affiliated to Fujian Medical UniversityQuanzhouFujianChina Hepatology Center Xiamen Hospital of Traditional Chinese MedicineXiamenFujianChina Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency ResponseNational Medical Center for Infectious DiseasesHuashan HospitalFudan UniversityShanghaiChina Hepatology Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouFujianChina Hepatology Fujian Medical University Xiamen Humanity HospitalXiamenFujianChina

Background and Aims:To determine whether liver stiffness measurement(LSM)indicates liver inflammation in chronic hepatitis B(CHB)with different upper limits of normal(ULNs)for alanine aminotransferase(ALT).Methods:We grouped 439 CHB patients using different ULNs for ALT:cohort I,≤40 U/L(439 subjects);cohort II,≤35/25 U/L(males/females;330 subjects);and cohort III,≤30/19 U/L(males/females;231 subjects).Furthermore,84 and 96 CHB patients with normal ALT(≤40 U/L)formed the external and prospective validation groups,respectively We evaluated the correlation between LSM and biopsy-confirmed liver inflammation,and determined diagnostic accuracy using area under the curve(AUC).A noninvasive LSM-based model was developed using multivariate logistic regression.Results:Fibrosis-adjusted LSM values significantly increased with increasing inflammation.The AUCs of LSM in cohorts I,II,and III were 0.799,0.796,and 0.814,respectively,for significant inflammation(A≥2)and 0.779,0.767,and 0.770,respectively,for severe inflammation(A=3).Cutoff LSM values in all cohorts for A≥2and A=3 were 6.3 and 7.5 kPa,respectively.Internal,external,and prospective validations showed high diagnostic accuracy of LSM for A≥2 and A=3,and no significant differences in AUCs among the four groups.LSM and globulin independently predicted A≥2.The AUC of an LSM-globulin model for A≥2 exceeded those of globulin,ALT,and AST,but was similar to that of LSM.Conclusions:LSM predicted liver inflammation and guided the indication of antiviral therapy for CHB in patients with normal ALT.

关键词： Hepatitis B virus liver inflammation Fibrosis liver stiffness measurement Alanine aminotransferase

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Negative Correlation of Serum Hepatitis B Surface Antigen and Hepatitis B e Antigen Levels with the Severity of liver inflammation in Treatment-naive Patients with Chronic Hepatitis B Virus Infection

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Chinese Medical Journal 2017年第22期130卷 2697-2702页

作者： Lu Zhang Ming-Hui Li Wei-Hua Cao Tian-Lin Qi Yao Lu Shu-Ling Wu Hong-Xiao Hao Ge Shen Ru-Yu Liu Lei-Ping Hu Min Chang Wen-Hao Hua Shu-Jing Song Gang Wan Yao Xie liver Diseases Center Beijing Ditan Hospital Capital Medical University Beijing 100015 China Clinical Test Center Beijing Ditan Hospital Capital Medical University Beijing 100015 China

Background： Estimating the grades of liver inflammation is critical in the determination ofantiviral therapy in patients chronically infected with hepatitis B virus （HBV）. The aim of this study was to investigate the correlation ofserum levels of hepatitis B surface antigen （HBsAg） and hepatitis B e antigen （HBeAg） with the liver inflammation grades in treatment-naTve patients with chronic HBV infection. Methods： We retrospectively enrolled 584 treatment-na＇l＇ve HBeAg-positive patients who underwent liver biopsy in Ditan Hospital from January 2008 to January 2016. Based on the severity of liver inflammation, the patients were divided into minimal, mild, and moderate groups. SPSS software was used lbr statistical analysis of all relevant data. Results： The liver histological examinations showed that 324, 194, and 66 patients had minimal, mild, and moderate liver inflammation, respectively. The median age of the three groups was 30, 33, and 38 years, respectively （X2 =26.00, P 〈 0.001 ）. The median HBsAg levels in minimal, mild, and moderate inflammation groups were 4.40, 4.16, and 3.67 log U/ml, respectively, and the median HBeAg levels in the three groups were 3.12, 2.99, and 1.86 log sample/cutoff. respectively; both antigens tended to decrease as the grade of inflammation increased （X2 = 99.68 and X2 =99.23, respectively; both P 〈 0.001 ）. The cutoff values of receiver operating characteristic curve in the age, HBsAg and HBeAg levels were 36 years, 4.31 log U/ml, and 2.86 Iog S/CO, respectively, 1 to distinguish minimal grade and other grades of treatment-naTve HBeAg-positive patients with chronic HBV infection. Conclusions： Serum HBsAg and HBeAg quantitation might gradually decrease with aggravated liver inflammation and the corresponding cutoff values rnight help us to distinguish rninimal grades and other grades and detect those who do not need antiviral therapy in treatment-naive HBeAg-positive patients with chronic HBV infection.

关键词： Chronic Hepatitis B Virus Infection Hepatitis B e Antigen Hepatitis B Surface Antigen liver inflammation

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Combined deficiency of SLAMF8 and SLAMF9 prevents endotoxin-induced liver inflammation by downregulating TLR4 expression on macrophages

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Cellular & Molecular Immunology 2020年第2期17卷 153-162页

作者： Xiaokang Zeng Guangao Liu Wanwen Peng Junming He Chenxu Cai Wei Xiong Shasha Chen Meixiang Yang Zhongjun Dong The First Affiliated Hospital Biomedical Translational Research InstituteGuangdong Province Key Laboratory of Molecular Immunology and Antibody EngineeringJinan UniversityGuangzhouChina Institute for Immunology and School of Medicine Beijing Key Lab for Immunological Research on Chronic DiseasesTsinghua University100086 BeijingChina

Classical signaling lymphocyte activating molecule(SLAM)family receptors are abundant within many types of immune cells,whereas the nonclassical SLAM family receptors SLAMF8 and SLAMF9,which uniquely lack cytoplasmic signaling motifs,are highly expressed by myeloid cells.Due to the potential redundancy,whether these two receptors regulate macrophage function remains largely unknown.Here,we show that SLAMF8 and SLAMF9 co-regulate macrophage-mediated liver inflammation.To overcome the redundancy,we generated mice that simultaneously lacked SLAMF8 and SLAMF9 using CRISPR-Cas9 technology.Although macrophage differentiation was not altered by the combined deficiency of SLAMF8 and SLAMF9,the loss of these two receptors significantly protected against lipopolysaccharide(LPS)-induced liver injury.SLAMF8 and SLAMF9 double-deficient mice had a prolonged survival rate and less infiltration of inflammatory cells.The depletion of macrophages using clodronate liposomes abolished the effects of SLAMF8 and SLAMF9 deficiencies on LPS-induced liver injury,which demonstrates that these receptors are required for macrophage activation following LPS challenge.Moreover,the deficiency of SLAMF8 and SLAMF9 suppressed the secretion of inflammatory cytokines by downregulating the expression of Toll-like receptor-4(TLR4),a receptor that specifically binds LPS,which led to decreased mitogen-activated protein kinases(MAPK)signaling activation.Notably,combined injections of truncated extracellular SLAMF8 and SLAMF9 proteins significantly alleviated LPS-induced liver injury.Thus,our findings provide insights into the role of SLAMF8 and SLAMF9 in endotoxin-induced liver injury and suggest that SLAMF8 and SLAMF9 are potential therapeutic targets for acute hepatic injury.

关键词： Nonclassical SLAM family receptors liver inflammation Macrophage TLR4 MAPK

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Effect of liver inflammation on accuracy of FibroScan device in assessing liver fibrosis stage in patients with chronic hepatitis B virus infection

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World Journal of Gastroenterology 2021年第7期27卷 641-653页

作者： Ling-Ling Huang Xue-Ping Yu Ju-Lan Li Hui-Ming Lin Na-Ling Kang Jia-Ji Jiang Yue-Yong Zhu Yu-Rui Liu Da-Wu Zeng Department of Hepatology Hepatology Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhou 350005Fujian ProvinceChina Department of Infectious Diseases The First Hospital of Quanzhou Affiliated to Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Fujian Key Laboratory of Precision Medicine for Cancer Fujian Key Laboratory of Laboratory MedicineThe First Affiliated HospitalFujian Medical UniversityFuzhou 350005Fujian ProvinceChina

BACKGROUND Transient elastography(FibroScan)is a new and non-invasive test,which has been widely recommended by the guidelines of chronic hepatitis B virus(HBV)management for assessing hepatic fibrosis staging.However,some confounders may affect the diagnostic accuracy of the FibroScan device in fibrosis staging.AIM To evaluate the diagnostic value of the FibroScan device and the effect of hepatic inflammation on the accuracy of FibroScan in assessing the stage of liver fibrosis in patients with HBV infection.METHODS The data of 416 patients with chronic HBV infection who accepted FibroScan,liver biopsy,clinical,and biological examination were collected from two hospitals retrospectively.Receiver operating characteristic(ROC)curves were used to analyze the diagnostic performance of FibroScan for assessing the stage of liver fibrosis.Any discordance in fibrosis staging by FibroScan and pathological scores was statistically analyzed.Logistic regression and ROC analyses were used to analyze the accuracy of FibroScan in assessing the stage of fibrosis in patients with different degrees of liver inflammation.A non-invasive model was constructed to predict the risk of misdiagnosis of fibrosis stage using FibroScan.RESULTS In the overall cohort,the optimal diagnostic values of liver stiffness measurement(LSM)using FibroScan for significant fibrosis(≥F2),severe fibrosis(≥F3),and cirrhosis(F4)were 7.3 kPa[area under the curve(AUC)=0.863],9.7 kPa(AUC=0.911),and 11.3 kPa(AUC=0.918),respectively.The rate of misdiagnosis of fibrosis stage using FibroScan was 34.1%(142/416 patients).The group of patients who showed discordance between fibrosis staging using FibroScan and pathological scores had significantly higher alanine aminotransferase and aspartate aminotransferase levels,and a higher proportion of moderate to severe hepatic inflammation,compared with the group of patients who showed concordance in fibrosis staging between the two methods.liver inflammation activity over 2(OR=3.53)was an independent risk factor for misdia

关键词： liver stiffness measurement Fibrosis stage liver inflammation Hepatitis B virus FibroScan Predictive model

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inflammation and fibrosis in chronic liver diseases including nonalcoholic fatty liver disease and hepatitis C

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World Journal of Gastroenterology 2020年第2期26卷 109-133页

作者： Sudeep Tanwar Freya Rhodes Ankur Srivastava Paul M Trembling William M Rosenberg UCL Institute for liver and Digestive Health Division of MedicineUniversity College LondonRoyal Free CampusHampsteadLondon NW32PF United Kingdom Department of Gastroenterology Whipps Cross University HospitalBarts Health NHS TrustLeytonstoneLondon E111NRUnited Kingdom

At present chronic liver disease(CLD),the third commonest cause of premature death in the United Kingdom is detected late,when interventions are ineffective,resulting in considerable morbidity and mortality.Injury to the liver,the largest solid organ in the body,leads to a cascade of inflammatory events.Chronic inflammation leads to the activation of hepatic stellate cells that undergo transdifferentiation to become myofibroblasts,the main extra-cellular matrix producing cells in the liver;over time increased extra-cellular matrix production results in the formation of liver fibrosis.Although fibrogenesis may be viewed as having evolved as a“wound healing”process that preserves tissue integrity,sustained chronic fibrosis can become pathogenic culminating in CLD,cirrhosis and its associated complications.As the reference standard for detecting liver fibrosis,liver biopsy,is invasive and has an associated morbidity,the diagnostic assessment of CLD by non-invasive testing is attractive.Accordingly,in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice.Due to differing disease prevalence and treatment efficacy,disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection.To facilitate this,a review of the pathogenesis of both conditions is also conducted.Finally,the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed,including the current use of antifibrotic therapy.

关键词： liver inflammation Fibrosis Cirrhosis Non-alcoholic fatty liver disease Chronic hepatitis C Chronic liver disease Anti-fibrotic Biomarker

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High rumen degradable starch diet induced blood bile acids profile changes and hepatic inflammatory response in dairy goats

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Animal Nutrition 2023年第3期14卷 121-129页

作者： Lixin Zheng Jing Shen Xiaoying Han Chunjia Jin Xiaodong Chen Junhu Yao College of Animal Science and Technology Northwest A&F UniversityYanglingChina Newhope Dairy Co. LtdChengduChina

The objective of this study was to reveal the effect of rumen degradable starch(RDS)on bile acid metabolism and liver transcription in dairy goats using metabolomics and transcriptomics.Eighteen Guanzhong dairy goats of a similar weight and production level(body weight=45.8±1.54 kg,milk yield=1.75±0.08 kg,and second parity)were randomly assigned to 3 treatment groups where they were fed a low RDS(LRDS,RDS=20.52%DM)diet,medium RDS(MRDS,RDS=22.15%DM)diet,or high RDS(HRDS,RDS=24.88%DM)diet,respectively.The goats were fed with the experimental diets for 5weeks.On the last day of the experiment,all goats were anesthetized,and peripheral blood and liver tissue samples were collected.The peripheral blood samples were used in metabolomic analysis and white blood cell(WBC)count,whereas the liver tissue samples were used in transcriptomic analysis.Based on the metabolomics results,the relative abundances of primary bile acids in the peripheral blood were significantly reduced in the group that was fed the HRDS diet(Pinflammation in the HRDS group.Transcriptomic analysis showed that 4 genes related to bile acid secretion(genes:MDR1,RXRa,AE2,SULT2A1)were significantly downregulated in the HRDS group.In addition,genes related to the immune response were upregulated in the HRDS group,suggesting the HRDS diet induced a hepatic inflammatory response mediated by lipopolysaccharides(LPS)(gene:LBP),activated the Toll-like receptor 4 binding(genes:S100A8,S100A9)and the NF-kappa B signaling pathway(genes:LOC106503980,LOC108638497,CD40,LOC102180880,LOC102170970,LOC102175177,LBP,LOC102168903,LOC102185461,LY96 and CXCL8),triggered inflammation and complement responses(genes:C1QB,C1QC,and CFD).The HRDS diet induced a hepatic inflammatory response may be mediated by activating the Toll-like receptor 4 binding and NF-kappa B signaling pathway after free LPS entered the liver.The changes of bile

关键词： Rumen-degradable starch Bile acid metabolism liver inflammation Dairy goat

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Busulfan and cyclosphamide induce liver inflammation through NLRP3 activation in mice after hematopoietic stem cell transplantation

Busulfan and cyclosphamide induce liver inflammation through...

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第十一届全国免疫学学术大会

作者： Zeng Lingyu Li Wen Li Mingfeng Ding Lan Wu Yulu Qiao Jianlin Xu Kailin Department of Hematology the Affiliated Hospital of Xuzhou Medical University

关键词： liver inflammation NLRP3 inflammasome busulfan cyclosphamide hematopoietic stem cell transplanta

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Gama-aminobutyric acid(GABA)alleviates hepatic inflammation via GABA receptors/TLR4/NF-kB pathways in growing-finishing pigs generated by super-multiparous sows

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Animal Nutrition 2022年第2期9卷 280-290页

作者： Shumin Zhang Jinbiao Zhao Jinhua Hu Hengxun He Yihan Wei Linbao Ji Xi Ma State Key Laboratory of Animal Nutrition College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China

The offspring of super-multiparous sows face problems such as decreased growth performance,poor meat quality and even diseases in animal husbandry.Gama-aminobutyric acid(GABA)has long been known to promote growth and suppress inflammation,but little is known about the mechanisms.A total of 72 growing-finishing pigs from the 8th generation were randomly allotted to 2 groups with 6 replicates per treatment to receive a cornesoybean basal diet or the basal diet supplemented 20 mg/kg GABA for 60 d.After the animal-trial period,samples of serum and liver were collected for further analysis.Additionally,a lipopolysaccharide(LPS)-induced inflammatory model using HepG2 cells was established to explore the role of GABA on regulating hepatic inflammation.The results indicated that inflammatory cell infiltration occurs in the liver of progeny of super-multiparous sows,and dietary supplementation with GABA influenced liver morphology,increased activities of antioxidant enzymes and decreased the expression abundance of pro-inflammatory cytokines,including tumor necrosis factor-α(TNFα)and interleukin(IL)-1β,in the liver of growing-finishing pigs(Pliver injury may affect the growth performance of growing-finishing pigs by changing hepatic mitochondrial metabolism,the expression of pro-inflammatory cytokines and TLR4/NF-kB pathway and that GABA supplementation has a restorative effect by acting on GABARs.

关键词： Gama-aminobutyric acid Growing-finishing pig liver inflammation Lipopolysaccharide NF-kB

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Busulfan and cyclosphamide induce liver inflammation through NLRP3 activation in mice after hematopoietic stem cell transplantation

Busulfan and cyclosphamide induce liver inflammation through...

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第十二届全国免疫学学术大会

作者： Zeng Lingyu Ju Wen Zhao Pingping Liu Lu Jiang Yan Qiao Jianlin Xu Kailin the Affiliated Hospital of Xuzhou Medical University

Aims:To evaluate the role of NLRP3 inflammasome on BU/CY-induced liver inflammation in mice after HSCT.Methods:HSCT mice model was established through infusion of 5 x 106 bone marrow mononuclear cells after conditioned with BU/CY.On day 7,14,21 and 28 after HSCT,mice were sacrificed for analysis of liver inflammation,cytokine secretion,NLRP3 expression and caspase-1 activation as well as release of ATP and high-mobility group protein B1(HMGB1).Furthermore,NLRP3 selective inhibitor(BAY 11-7082) was administrated into mice after HSCT to evaluate its effects on liver inflammation.Results:Severe liver inflammation and damage with elevated secretion of IL-1β and IL-18 were found in mice after HSCT.Meanwhile,elevated expressions of NLRP3 and caspase-1 activation in liver were found.In addition,increased release of ATP and HMGBl were observed.Selective inhibition of NLRP3 decreased caspase-1 activation and secretion of IL-1β and IL-18.Furthermore,NLRP3 inhibition also reduced infiltration of macrophages and neutrophils and improved liver function.Conclusions:NLRP3 was involved in BU/CY-induced liver inflammation after HSCT and selectively inhibited it ameliorated liver inflammation and improved liver function,suggesting targeting NLRP3 might be a new approach in the prophylaxis of liver inflammation after HSCT.

关键词： liver inflammation NLRP3 inflammasome busulfan cyclosphamide hematopoietic stem cell transplanta

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