Acetaminophen overdose-induced acute liver injury can be alleviated by static magnetic field

Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine(NAC);however,its efficacy is limited in cases of advanced liver injury or when administered at a late stage.In the current study,we discovered that treatment with a moderate intensity static magnetic field(SMF)notably reduced the mortality rate in mice subjected to high-dose APAP from 40%to 0%,proving effective at both the initial liver injury stage and the subsequent recovery stage.During the early phase of liver injury,SMF markedly reduced APAPinduced oxidative stress,free radicals,and liver damage,resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione(GSH).During the later stage of liver recovery,application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation.Moreover,the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery,even 24 h post overdose,when the effectiveness of NAC alone substantially declines.Overall,this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose.Of note,this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP,and potentially other toxic overdoses.

Scavenger receptor A-mediated nanoparticles target M1 macrophages for acute liver injury

Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was limited due to its high hydrophobicity.Palmitic acid-modified serum albumin(PSA)is not only an effective carrier for hydrophobic drugs,but also has a superb targeting effect via scavenger receptor-A(SR-A)on the M1 macrophages,which are potential therapeutic targets for ALI.Compared with the common macrophage-targeted delivery systems,PSA enables site-specific drug delivery to reduce off-target toxicity.Herein,we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI.In vitro,compared with human serum albumin encapsulated SchB nanoparticles(SchB-HSA NPs),the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide(LPS)stimulated Raw264.7(LAR)cells,and LAR cells took up PSA NPs 8.79 times more than HSA NPs.As expected,the PSA NPs also accumulated more in the liver.Moreover,SchB-PSA NPs dramatically reduced the activation of NF-κB signaling,and significantly relieved inflammatory response and hepatic necrosis.Notably,the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%.Hence,SchB-PSA NPs are promising to treat ALI.

Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.

Mori fructus aqueous extracts attenuates liver injury by inhibiting ferroptosis via the Nrf2 pathway

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 ps:contro=8)for acute(groups:control,0.3%CCl_(4),bifendate(BD),100 and 200 mg/kg MFAEs,7 d)and chronic(groul,10%CCl_(4),BD,100 and 200 mg/kg MFAEs,4 weeks)liver injury study.Each mouse was injected intraperitoneally with 10μL/g corn oil containing CCl_(4)expect the control group.HepG2 cells were used in vitro study.Eighteen communal components were identified by UPLC-LTQOrbitrap-MS.We utilized a mouse model for acute and chronic liver injury using CCl_(4)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 CCl_(4)-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 CCl_(4)-induced liver fibrosis.

Protective Effect of Procyanidin B2 on Acute Liver Injury Induced by Aflatoxin B1 in Rats

Objective This study aimed to explore the protective effect of procyanidin B2(PCB2)on acute liver injury induced by aflatoxin B1(AFB1)in rats.Methods Forty Sprague Dawley rats were randomly divided into control,AFB1,AFB1+PCB2,and PCB2 groups.The latter two groups were administrated PCB2 intragastrically(30 mg/kg body weight)for 7 d,whereas the control and AFB1 groups were given the same dose of double distilled water intragastrically.On the sixth day of treatment,the AFB1 and AFB1+PCB2 groups were intraperitoneally injected with AFB1(2 mg/kg).The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide(DMSO).On the eighth day,all rats were euthanized:serum and liver tissue were isolated for further examination.Hepatic histological features were assessed by hematoxylin and eosin-stained sections.Weight,organ coefficient(liver,spleen,and kidney),liver function(serum alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total bilirubin,and direct bilirubin),oxidative index(catalase,glutathione,superoxide dismutase,malondialdehyde,and 8-hydroxy-2′-deoxyguanosine),inflammation factor[hepatic interleukin-6(IL-6)m RNA expression and serum IL-6],and bcl-2/bax ratio were measured.Results AFB1 significantly caused hepatic histopathological damage,abnormal liver function,oxidative stress,inflammation,and bcl-2/bax ratio reduction compared with DMSO-treated controls.Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB1.Conclusion Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB1.

Effects of a combination of Japanese Raisin Tree Seed and Flower of Lobed Kudzuvine against acute alcohol-induced liver injury in mice

Objective:The Flower of Lobed Kudzuvine[Pueraria lobata(Willd.)Ohwi;Gehua in Chinese;GH]and Japanese Raisin Tree Seed(Hovenia dulcis Thunnb.;Zhijuzi in Chinese;ZJZ)are herbs that have been used in China for the treatment of alcohol intoxication and liver diseases.We aimed to evaluate the hepatoprotective potential of a combination of these in mice with acute alcohol-induced liver injury,and to elucidate the mechanisms involved.Methods:Male ICR mice were randomly allocated to six groups:a control group,an alcohol-administered group,and groups that were administered alcohol and one of silibinin,the GH,the ZJZ or a GH-ZJZ combination(at a ratio of 2:1).Animals were orally administered 56%alcohol(Er Guo-tou white spirit,0.12 mL/10 g/d)for 10 days and at the end of this period,hepatic biochemical indicators,antioxidant parameters,alcohol metabolic enzymes,and histopathologic changes were evaluated.Moreover,the expression of the signaling molecules KEAP1,NRF2,and AQP9 were measured by qRT-PCR and western blotting.Results:Compared with the model group,GH-ZJZ(2:1)had lower serum ALT(12.15±0.39,P紏.003),AST(104.07±1.03,P紏.001),and ALP(148.09±2.55,P紏.010)activities,and lower TC(1.97±0.05,P紏.001)and TG(1.54±0.07,P?.002)concentrations.GH-ZJZ(2:1)also significantly increased the hepatic activities of SOD and GSH(4.24±0.25 and 1.57±0.06,respectively;both P<.01),reduced the ROS and MDA concentrations(97.50±3.00 and 2.39±0.19,respectively;both P<.01),and upregulated Nrf2 expression(P<.01).GH-ZJZ(2:1)significantly reduced the expression of KEAP1 and AQP9 in the liver,compared with alcohol-administered mice(P<.01).Importantly,the GH-ZJZ combination caused a more marked improvement in acute liver injury than GH or ZJZ alone.Conclusion:We have demonstrated protective effects of GH-ZJZ(2:1)against acute alcohol-induced hepatic injury,and shown that these effects may be associated with improvements in lipid and alcohol metabolism,antioxidant capacity,and lipid peroxidation.

Risk Factors for Acute Kidney Injury after Orthotopic Liver Transplantation:A Single-center Data Analysis

Acute kidney injury（AKI） is a common complication following orthotopic liver transplantation（OLT） and is associated with increased morbidity and mortality. The aim of the current study was to determine the risk factors for AKI in patients undergoing OLT. A total of 103 patients who received OLT between January 2015 and May 2016 in Tongji Hospital, China, were retrospectively analyzed. Their demographic characteristics and perioperative parameters were collected, and AKI was diagnosed using 2012 Kidney Disease： Improving Global Outcomes（KDIGO） staging criteria. It was found that the incidence of AKI was 40.8% in this cohort and AKI was significantly associated with body mass index, urine volume, operation duration（especially 〉 480 min）, and the postoperative use of vasopressors. It was concluded that relative low urine output, long operation duration, and the postoperative use of vasopressors are risk factors for AKI following OLT.

Effects of Salmonella infection on hepatic damage following acute liver injury in rats

BACKGROUND： Acute liver injury is a common clinical disorder associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The purpose of this study was to address this unanswered question using a rat model. METHODS： Oral supplementation with Salmonella enterica serovar enteritidis（S. enteritidis） was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver injury.RESULTS： The levels of liver damage and endotoxin were significantly increased in the Salmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury（P〈0.01）; The peyer＇s patch CD3＋ T cell counts were increased significantly when the Salmonella infection with severe injury group was compared with the normal group（P〈0.05）. S. enteritidis pretreatment enhanced intestinal barrier impairment and bacterial translocation.CONCLUSIONS： Oral S. enteritidis administration exacerbates acute liver injury, especially when injury was severe.Major factors of the exacerbation include inflammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.

Protection Effect of Qiwei Jingganling on Carbon Tetrachloride-induced Acute Liver Injury in Mice

[Objectives] The aim was to study the protection effect of Qiwei Jingganling on carbon tetrachloride-induced acute liver injury in mice and its mechanism of action. [Methods]Total 60 mice were randomly and evenly divided into 6 groups,normal group,model group,silymarin group( 150 mg/kg),high-dose Qiwei Jingganling group( 8 g/kg,crude drug),middle-dose Qiwei Jingganling group( 4 g/kg,crude drug) and low-dose Qiwei Jingganling group( 2 g/kg,crude drug). The mice were administered orally once a day according to the amount of10 m L/kg,and 10-day continuous administration was carried out. After 2 h of the last administration,0. 12% CCl4 peanut oil solution( 10 m L/kg) was injected intraperitoneally to all the mice except those in the normal group to establish acute liver injury model. After 16 h,the blood of the mice was collected from the eyeballs,and their liver tissues were collected. The levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),superoxide dismutase( SOD),malondialdehyde( MDA) and glutathione peroxidase( GSH-Px) in the sera were determined by biochemical methods,and the contents of tumor necrosis factor-α( TNF-α),interleukin-1β( IL-1β) and interleukin-6( IL-6) in the liver tissues were determined with enzyme-linked immunosorbent assays( ELISA). [Results]Qiwei Jingganling significantly reduced the activities or content of ALT,AST and MDA in serum of mice with liver injury( P < 0. 05,P < 0. 01),increased the activities of SPD and GSH-Px( P < 0. 05,P < 0. 01) and down-regulated the expression levels of IL-1β,IL-6 and TNF-α in liver tissue( P < 0. 05,P < 0. 01).[Conclusions]Qiwei Jingganling has a good protection effect on CCl4-induced acute liver injury in mice,which may be related to the inhibition of oxidative stress and inhibition of inflammatory responses.

Protective Effect and Mechanism of Polysaccharides from Cordyceps cicadae on Acute Liver Injury Induced by D-GlaN in Mice

[Objectives]To observe the protective effect of Cordyceps cicadae polysaccharides on acute liver injury induced by D-galactosamine( D-GlaN) in mice,and to explore its mechanism. [Methods] Seventy-five male Kunming mice were randomly and evenly divided into 5 groups according to the digital table method: normal group( CK)( injected intraperitoneally with saline solution),model group( injected intraperitoneally with D-GlaN),low-dose C. cicadae polysaccharides group( administered with 0. 5 g/kg of C. cicadae polysaccharides solution by gavage),middle-dose C. cicadae polysaccharides group( administered with 1. 0 g/kg of C. cicadae polysaccharides solution by gavage) and high-dose C. cicadae polysaccharides group( administered with 2. 0 g/kg of C. cicadae polysaccharides solution by gavage). After 12 d of administration,the liver histopathological score,liver homogenate indexes( superoxide dismutase,SOD; malondialdehyde,MDA; glutathione peroxidase,GSH-Px; nitric oxide,NO) and serum markers( aspartate transaminase,AST; alanine transaminase,ALT; alkaline phosphatase,ALP; cholinesterase,CHE) of mice in each group were detected. The expression levels of nuclear factor-κB( NF-κB) and tumor necrosis factor-α( TNF-α) in liver tissues were detected by immunohistochemistry. [Results]The liver histopathological score and the MDA,NO,AST,ALT,ALP,NF-κB and TNF-α levels were significantly higher( P < 0. 05) and the SOD,GSH-Px and CHE levels were significantly lower( P <0. 05) in the model group compared with the normal group. Compared with those in the model group,the liver tissue histopathological scores in the low-,middle-and high-dose C. cicadae polysaccharides groups were all significantly reduced( P < 0. 05). With the increase of treatment dose,the liver tissue histopathological scores showed a significant decrease( P < 0. 05). Compared with the model group,the levels of MDA,NO,AST,ALT,ALP,NF-κB and TNF-α were significantly lower( P < 0. 05),and the levels of SOD,GSH-Px and CHE were significantly higher( P < 0. 05) in the low-,middle-and high-dose C. cicadae polysaccharides groups. With the increase of treatment dose,the levels of MDA,NO,AST,ALT,ALP,NF-κB and TNF-α declined significantly( P < 0. 05),while the levels of SOD,GSH-Px and CHE rose significantly( P < 0. 05). [Conclusions] C. cicadae polysaccharides have a significant protective effect on D-GlaN-induced acute liver injury in mice in a dose-dependent manner,and the mechanism may be related to the inhibition of NF-κB inflammatory signaling pathway.

Protective Effects of Flavonoids from Pteridium aquilinum on CCl_(4)-induced Acute Liver Injury in Mice

[Objectives]To explore the protective effects of flavonoids from Pteridium aquilinum(PAFL)on carbon tetracholoride(CCl_(4))-induced acute liver injury in mice and its potential mechanism.[Methods]All mice were randomly divided into four groups(n=10 in each),normal group,CCl_(4)group,CCl_(4)+PAFL groups[treated with PAFL(50 or 200 mg/kg)].Animal treatment was continued for 7 consecutive days.The blood was collected after injection of CCl_(4)for 24 h,and the liver tissue was removed from the mice and stored at-80℃.[Results]The PAFL(50 and 200 mg/kg)significantly inhibited the increase of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels in serum caused by CCl_(4)treatment.PAFL administration not only increased the activity of antioxidant enzymes superoxide dismutase(SOD),Glutathione(GSH)and catalase(CAT)in mice,but also reduced the level of malondialdehyde(MDA).Meanwhile,PAFL administration decreased the expression of nuclear factor-kappa B(NF-κB)and Cyclooxygenase-2(COX-2)proteins and inhibited the release of pro-inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin 6(IL-6).In addition,PAFL(200 mg/kg)treatment down-regulated extracellular regulated protein kinases(ERK)and c-Jun N-terminal kinase(JNK)protein levels in liver tissue.[Conclusions]These findings clearly indicate that the protective effects of PAFL on CCl_(4)-induced acute liver injury is related to its antioxidant and anti-inflammatory activity,which may be mediated by NF-κB and MAPKs signaling pathways.

Study on Protection Mechanism of Viscum coloratum (Kom.) Nakai f. lutescens kitag Fruit Polysaccharides on Mice with Acute Alcoholic Liver Injury

This study was conducted to investigate the protective mechanism of V. coloratum fruit polysaccharides（ VCFP） on mice with acute alcoholic liver injury. Acute liver injury model was built by one-time alcohol gavage. The mice were randomly divided into VCFP-treated groups（ low-,medium-,and highdose）,alcohol model group and normal control group at the same time. VCFP-treated groups were administrated polysaccharide intragastrically continuously for4 weeks; and the alcohol model group and normal control group were administrated intragastrically the same amount of normal saline. The general situation and liver tissue morphological structure changes were observed. The results showed that the levels of ALT,AST,TC,TG,MDA contents,and CAT and GSH-Px activity of mice in the model group increased significantly（ P 〈 0. 01）,while the activity of SOD and weight and liver index decreased significantly（ P 〈 0. 01） compared with the normal control group. After 4 weeks of gavage,VCFP could significantly improve weight,liver index and SOD activity,and significantly reduce ALT,AST,TC and TG levels,MDA content and CAT and GSH-Px activity. These results suggest that VCFP can improve antioxidant enzyme activity,remove oxygen free radical and reduce membrane lipid peroxidation reaction,thereby protecting liver cells.

Elaborately engineering of lipid nanoparticle for targeting delivery of siRNA and suppressing acute liver injury

Small interfering RNA(siRNA)-based gene silencing has been considered as a potential therapy modality against inflammatory diseases.Nevertheless,the effective delivery of siRNA to desired destination still remains challenging due to poor stability,high molecular weight and negative charge.Currently,ionizable lipid nanoparticle(LNP)has been extensively used as vector for effective delivery of siRNA.Herein,we report a mannose-modified LNP(M-MC_(3) LNP@TNFα)loading tumor necrosis factorα(TNFα)siRNA for targeting liver macrophages,achieving effectively inhibit acute liver injury.The M-MC_(3) LNP@TNFαnot only increases the internalization of LNP by macrophages,but also enhances the gene silencing efficiency of TNFαin vitro.Additionally,the M-MC_(3) LNP@TNFαexhibits higher accumulation in liver of healthy mice than that of MC_(3) LNP@TNFα(un-modified LNP)owing to the targeting effect of mannose.As expected,the M-MC_(3) LNP@TNFαsignificantly suppresses the expression of TNFαand ameliorates liver damage in acute liver injury model.Such a LNP targeting siRNA delivery holds great potential for the treatment of diseases associated with liver in the future.

Definition and classification of acute-on-chronic liver diseases

Patients with chronic liver diseases(CLDs)develop acute liver injury and/or acute decompensation under the attack of various precipitants and present with significantly elevated alanine aminotransferase and/or total bilirubin levels,liver failure,or acute decompensation of liver cirrhosis,which is called acute-on-CLD(AoCLD).AoCLD accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases.AoCLD is complicated by various clinical types,the severity of the disease,and may pose a high risk of death.To date,the definition of AoCLD is still vague,and a consensus concept of the clinical classification is lacking.This review aimed to define the concept and clinical types of AoCLD based on related studies and the literature.

Acute hepatitis of unknown etiology in an adult female:A case report

BACKGROUND Acute liver injury(ALI)refers to inflammation of the hepatic parenchyma without hepatic encephalopathy that lasts less than 6 mo.When the etiology is unknown,Acute Hepatitis of Unknown Origin(AHUO)can present as a diagnostic and treatment challenge.AHUO in the adult population is unusual and poorly documented.It has an incidence between 11%and 75%.Currently,no treatment guidelines exist.With no identified cause,treatment is often blind,and the wrong treatment plan may have unintended consequences.CASE SUMMARY We present the case of a 58-year-old woman who presented to the emergency room for elevated liver function tests(LFTs).Her symptoms started 10 d prior to admission and included nausea,vomiting,jaundice,decreased appetite,weight loss of 10 lbs,and dark urine.She denied drinking alcohol or taking any hepatotoxic agents,including acetaminophen,statins,vitamins,or supplements.She was admitted to the hospital,and an etiologic work-up was carried out.Her initial bloodwork revealed elevated liver enzymes(alanine aminotransferase 2500 U/L,aspartate aminotransferase 3159 U/L,and alkaline phosphatase 714 U/L)and elevated total bilirubin of 6.4 mg/dL.She tested negative for common infectious etiologies such as hepatotropic viruses A,B,C,and E.Further infective work-up revealed negative serology for cytomegalovirus,Epstein-Barr virus,herpes simplex virus 1&2,and human immunodeficiency virus.Her autoanti-body test results were negative,including anti-smooth muscle antibody,anti-mitochondrial antibody,and anti-liver kidney microsome 1 antibody.Magnetic resonance cholangiopancreatography ruled out biliary causes of elevated LFTs,and her core liver biopsy proved inconclusive.Over the course of her hospital stay,the patient's LFTs improved with supportive care and without steroids.CONCLUSION Idiopathic hepatitis makes treatment challenging.It can leave patients feeling confused and unfulfilled.Thus,educating the patient thoroughly for shared decision-making and management becomes essential.

Lycium barbarum polysaccharides ameliorate canine acute liver injury by reducing oxidative stress,protecting mitochondrial function,and regulating metabolic pathways

The development of acute liver injury can result in liver cirrhosis,liver failure,and even liver cancer,yet there is currently no effective therapy for it.The purpose of this study was to investigate the protective effect and therapeutic mechanism of Lycium barbarum polysaccharides(LBPs)on acute liver injury induced by carbon tetrachloride(CCl_(4)).To create a model of acute liver injury,experimental canines received an intraperitoneal injection of 1 mL/kg of CCl_(4)solution.The experimental canines in the therapy group were then fed LBPs(20 mg/kg).CCl_(4)-induced liver structural damage,excessive fibrosis,and reduced mitochondrial density were all improved by LBPs,according to microstructure data.By suppressing Kelch-like epichlorohydrin(ECH)-associated protein 1(Keap1),promoting the production of sequestosome 1(SQSTM1)/p62,nuclear factor erythroid 2-related factor 2(Nrf2),and phaseⅡdetoxification genes and proteins downstream of Nrf2,and restoring the activity of anti-oxidant enzymes like catalase(CAT),LBPs can restore and increase the antioxidant capacity of liver.To lessen mitochondrial damage,LBPs can also enhance mitochondrial respiration,raise tissue adenosine triphosphate(ATP)levels,and reactivate the respiratory chain complexes I–V.According to serum metabolomics,the therapeutic impact of LBPs on acute liver damage is accomplished mostly by controlling the pathways to lipid metabolism.9-Hydroxyoctadecadienoic acid(9-HODE),lysophosphatidylcholine(Lyso PC/LPC),and phosphatidylethanolamine(PE)may be potential indicators of acute liver injury.This study confirmed that LBPs,an effective hepatoprotective drug,may cure acute liver injury by lowering oxidative stress,repairing mitochondrial damage,and regulating metabolic pathways.

Portulaca oleracea alleviates CCl4-induced acute liver injury by regulating hepatic S100A8 and S100A9

Objective: Acute liver injury(ALF) is a potential factor of many serious hepatopathies. Carbon tetrachloride(CCl4) is a possible environmental toxicant that can induce ALF. Portulaca oleracea(PO) is one of the most popular edible herbs and has several biological activities such as antioxidant, antimicrobial, antiinflammatory effects. We explored the significance of PO in regulating inflammatory function in animal models and cultured hepatocytes during liver damage caused by CCl4.Methods: The effect of PO on ALF was evaluated by CCl4-induced mice models in vivo. Hepatic levels of transaminase activities and inflammatory factors were examined. The gene and protein expression of S100A8 and S100A9 were measured by RT-PCR and Western blot analysis. Meanwhile, the efficacy of PO was certified by HepG2 cells in vitro. The transaminase activities, inflammatory factors, and the protein expression of S100A8 and S100A9 were also detected.Results: Animal tests showed that pretreatment with PO reduced the liver pathological tissue damage and the serum levels of ALT, AST, ALT and LDH, as well as reducing the pro-inflammatory cytokines(IL-1β, IL-6, TNF-a) secretion in CCl4-induced liver injury mice. Simultaneously, Hep G2 cells pretreated with PO exhibited a significant decrease in the activities of ALT and AST. Moreover, PO resulted in a significant downregulation of the pro-inflammatory markers S100A8, S100A9 gene and protein expression on CCl4induced acute liver injury was demonstrated entirely in vivo and vitro experiments.Conclusion: PO may down-regulate S100A8 and S100A9 and inhibit pro-inflammatory cytokines’ release,indicating a potential clinical effect for controlling the disease.

MALAT1-mediated EZH2 Recruitment to the GFER Promoter Region Curbs Normal Hepatocyte Proliferation in Acute Liver Injury

Background and Aims:The goal of this study was to investigate the mechanism by which the long noncoding RNA MALAT1 inhibited hepatocyte proliferation in acute liver injury(ALI).Methods:Lipopolysaccharide(LPS)was used to induce an ALI cellular model in HL7702 cells,in which lentivirus vectors containing MALAT1/EZH2/GFER overexpression or knockdown were introduced.A series of experiments were performed to determine their roles in liver injury,oxidative stress injury,and cell biological processes.The interaction of MALAT1 with EZH2 and enrichment of EZH2 and H3K27me3 in the GFER promoter region were identified.Rats were treated with MALAT1 knockdown or GFER overexpression before LPS induction to verify the results derived from the in vitro assay.Results:MALAT1 levels were elevated and GFER levels were reduced in ALI patients and the LPS-induced cell model.MALAT1 knockdown or GFER overexpression suppressed cell apoptosis and oxidative stress injury induced cell proliferation,and reduced ALI.Functionally,MALAT1 interacted directly with EZH2 and increased the enrichment of EZH2 and H3K27me3 in the GFER promoter region to reduce GFER expression.Moreover,MALAT1/EZH2/GFER was activated the AMPK/mTOR signaling pathway.Conclusion:Our study highlighted the inhibitory role of reduced MALAT1 in ALI through the modulation of EZH2-mediated GFER.

Rationally designed meso-benzimidazole-pyronin with emission wavelength beyond 700 nm enabling in vivo visualization of acute-liver-injury-induced peroxynitrite

Fluorescent dyes with fluorescence emission above 700 nm are favorable for bio-imaging due to the higher tissue transparency and lower background fluorescence. In this study, we present a mesobenzimidazole-pyronin platform(Si BMs) with fluorescence emission maxima above 700 nm, which possess good cell permeability, photostability, and lysosomal localization. The great photophysical properties of the Si BMs encouraged us to further exploit their application toward bio-imaging. We synthesized the reduced ‘dihydro’ derivative HSi BM3 for sensing ONOO^(-), with high selectivity and sensitivity and a fast fluorescence “off-on” response(within 2 s). Then, we confirmed the potential of HSi BM3 for visualizing exogenous and endogenous ONOO-in cells and mice. More importantly, HSi BM3 was successfully employed for visualizing acute-liver-injury-induced peroxynitrite.

COVID-19 pandemic:Its impact on liver disease and liver transplantation

Severe pulmonary disease caused by the novel coronavirus[severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)],has devastated many countries around the world.It has overwhelmed the medical system.The priorities of many institutions have changed to manage critically ill corona virus infectious disease-2019(COVID-19)patients,which affected the working style of many departments.Hepatologists and transplant surgeons look after a very sensitive patient group.Patients with liver disease need special attention and continuous follow-up.Similarly,transplant candidates also need special care.Healthcare professionals in the field of hepatology face the overwhelming task of taking care of COVID-19 patients with hepatic complications,liver disease or transplant patients who are SARS-CoV-2 positive,and the patients on routine surveillance who do not have COVID-19.This review will evaluate COVID-19 from the perspective of its effect on the liver and its possible effects on patients with liver disease.Furthermore,the level of care for liver transplant recipients during the pandemic will be discussed.