HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

Recent advances in the diagnosis of drug-induced liver injury

Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes.In addition,DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease.Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems.This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

Bibliometric study of sepsis-associated liver injury from 2000 to 2023

BACKGROUND Sepsis-associated liver injury(SLI)is a severe and prevalent complication of sepsis.AIM To explore the literature on SLI via a bibliometric approach.METHODS Reviews and articles correlated with SLI published from January 1,2000 to October 28,2023 were searched from the Web of Science Core Collection.Then,the searched data were analyzed using VOSviewer,CiteSpace,and R language.RESULTS There were 787 publications involved in this paper,comprising 745 articles and 42 reviews.China,the United States,and Germany are the primary publication sources in this area.Studies related to SLI primarily focused on mechanisms of pathogenesis,as evidenced by analyzing keywords,references,and the counting of original research.These studies mainly involved tumor necrosis factor alpha,inflammation,oxidative stress,and nuclear factor-kappa B.CONCLUSION There is significant growth in the research on SLI.Current investigations primarily involve basic experiments that aimed at uncovering pathogenic mechanisms.According to the analyzed literature,the identified pathogenic mechanisms and potential therapeutic targets serve as the foundation for translating findings from basic research to clinical applications.

Insights into skullcap herb-induced liver injury

This editorial addresses the growing concern of herb-induced liver injury(HILI),focusing on a unique case of Skullcap-induced HILI report.This editorial underscore the significant mortality rate linked to Skullcap-induced HILI,emphasizing the importance of vigilant monitoring and intervention.As herbal supplement usage rises,collaboration among clinicians and researchers is crucial to comprehend and address the complexities of HILI,particularly those involving Skullcap.

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.

Sepsis-associated liver injury:Mechanisms and potential therapeutic targets

In this editorial,we examined a recent article in the World Journal of Gastroenterology that focused on sepsis-associated liver injury(SLI)and its treatment.SLI is a serious complication of sepsis,primarily caused by microcirculatory disturbances,the gut-liver axis,and inflammatory responses.Specific treatment recommendations for SLI are lacking.The gut-liver axis represents a potential therapeutic target,with metformin showing promise in modulating the gut microbiome and enhancing intestinal barrier function.Although immunomodulatory therapies are being explored,anti-tumor necrosis factor agents and interleukin-1 receptor antagonists have not demonstrated significant clinical benefits.Statins may reduce liver inflammation and prevent injury in sepsis,but their clinical application is limited.Reduced D-related human leucocyte antigen expression on monocytes and lymphocytes suggests immune suppression in patients,indicating that corticosteroids could reverse clinical deterioration in severe infections and address adrenal cortical insufficiency.Current large-scale studies on glucocorticoid therapy for sepsis have yielded mixed results,likely due to inadequate assessment of the immune status of the host.Future research should prioritize the development of personalized immunotherapy tailored to patients’immune profiles,focusing on identifying novel indicators of immune status and advancing immunomodulatory targets and therapeutics for septic patients.

Severe liver injury and clinical characteristics of occupational exposure to 2-amino-5-chloro-N,3-dimethylbenzamide: A case series

Background:The 2-amino-5-chloro-N,3-dimethylbenzamide is a key intermediate in the synthesis of pesticides and pharmaceuticals.However,no literature currently exists on 2-amino-5-chloro-N,3-dimethylbenzamide poisoning in humans.This study aimed to reveal the health hazard of this chemical for humans and summarize the clinical characteristics of patients with occupational 2-amino-5-chloro-N,3-dimethylbenzamide poisoning.Methods:This observational study included four patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning from June 2022 to July 2022.The entire course of the incidents was described in detail.Blood 2-amino-5-chloro-N,3-dimethylbenzamide concentrations were detected by a mass spectrometer.Hema-toxylin and eosin staining was performed to assess liver injury,and immunofluorescence was used to evaluate hepatic mitophagy.Results:The 2-amino-5-chloro-N,3-dimethylbenzamide powder(99%purity)entered the human body mainly via the skin and respiratory tract due to poor personal protective measures.The typical course of 2-amino-5-chloro-N,3-dimethylbenzamide poisoning was divided into latency,rash,fever,organic dam-age,and recovery phases in accordance with the clinical evolution.Rash and fever may be the important premonitory symptoms for further organ injuries.The chemical was detected in the blood of all patients and caused multiple organ injuries,predominantly liver injury,including kidney,myocardium,and micro-circulation.Three patients recovered smoothly after comprehensive treatments,including artificial liver therapy,continuous renal replacement therapy,glucocorticoids,and other symptomatic and supportive treatments.One patient survived by liver transplantation.The postoperative pathological findings of the removed liver showed acute liver failure,and immunofluorescence staining confirmed the abundance of mitophagy in residual hepatocytes.Conclusions:This study is the first to elaborate the clinical characteristics of patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning.The chemical enters the body through the respiratory tract and skin during industrial production.The 2-amino-5-chloro-N,3-dimethylbenzamide poisoning causes multiple-organ dysfunction with a predominance of liver injury.Liver transplantation may be an effective option for patients with severe liver failure.The mechanisms of liver injury induced by 2-amino-5-chloro-N,3-dimethylbenzamide might involve abnormal mitochondrial function and mitophagy.

Diagnostic value of tissue plasminogen activator-inhibitor complex in sepsis-induced liver injury:A single-center retrospective casecontrol study

BACKGROUND Sepsis often causes severe liver injury and leads to poor patient outcomes.Early detection of sepsis-induced liver injury(SILI)and early treatment are key to improving outcomes.AIM To investigate the clinical characteristics of SILI patients and analyze the associated risk factors,to identify potential sensitive biomarkers.METHODS Retrospective analysis of clinical data from 546 patients with sepsis treated in the intensive care unit of the 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force between May 2018 and December 2022.The patients were divided into the sepsis group(n=373)and SILI group(n=173)based on the presence of acute liver injury within 2 hours of admission.We used the random forest algorithm to analyze risk factors and assessed potential diagnostic markers of SILI using the area under the receiver operating characteristic curve,Kaplan-Meier survival curves,subgroup analysis and correlation analysis.RESULTS Compared with the sepsis group,tissue plasminogen activator-inhibitor complex(t-PAIC)levels in serum were significantly higher in the SILI group(P<0.05).Random forest results showed that t-PAIC was an independent risk factor for SILI,with an area under the receiver operating characteristic curve of 0.862(95%confidence interval:0.832-0.892).Based on the optimal cut-off value of 11.9 ng/mL,patients at or above this threshold had significantly higher levels of lactate and Acute Physiology and Chronic Health Evaluation II score.The survival rate of these patients was also significantly worse(hazard ratio=2.2,95%confidence interval:1.584-3.119,P<0.001).Spearman’s correlation coefficients were 0.42 between t-PAIC and lactate,and 0.41 between t-PAIC and aspartate transaminase.Subgroup analysis showed significant differences in t-PAIC levels between patients with different severity of liver dysfunction.CONCLUSION T-PAIC can serve as a diagnostic indicator for SILI,with its elevation correlated with the severity of SILI.

Spectrum of COVID-19 induced liver injury:A review report

The coronavirus disease 2019(COVID-19)pandemic has caused changes in the global health system,causing significant setbacks in healthcare systems worldwide.This pandemic has also shown resilience,flexibility,and creativity in reacting to the tragedy.The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection targets most of the respiratory tract,resulting in a severe sickness called acute respiratory distress syndrome that may be fatal in some individuals.Although the lung is the primary organ targeted by COVID-19 viruses,the clinical aspect of the disease is varied and ranges from asymptomatic to respiratory failure.However,due to an unorganized immune response and several affected mechanisms,the liver may also experience liver cell injury,ischemic liver dysfunction,and drug-induced liver injury,which can result in respiratory failure because of the immune system’s disordered response and other compromised processes that can end in multisystem organ failure.Patients with liver cirrhosis or those who have impaired immune systems may be more likely than other groups to experience worse results from the SARS-CoV-2 infection.We thus intend to examine the pathogenesis,current therapy,and consequences of liver damage concerning COVID-19.

Complement activation targeted inhibitor C2-FH ameliorates acetaminophen-induced liver injury in mice

BACKGROUND Complement activation is recognized as an important factor in the progression of liver damage caused by acetaminophen(APAP).However,the role of the complement inhibitor C2-FH in APAP-induced liver injury remains unclear.AIM To explore C2-FH in protecting against APAP-induced liver injury by inhibiting complement activation.METHODS A model of APAP-induced liver injury was used to study the protective effect of C2-FH on liver injury.C2-FH was administered through intraperitoneal injection 30 minutes after APAP treatment.We detected the effects of C2-FH on liver function,inflammatory response and complement activation.Additionally,RNA-sequencing(RNA-Seq)analysis was conducted to understand the mechanism through which C2-FH provides protection against APAP-induced liver injury.RESULTS C2-FH inhibited the increase in serum alanine aminotransferase activity,aspartate aminotransferase activity and lactate dehydrogenase,and reduced liver tissue necrosis caused by APAP.Moreover,it attenuated the inflammatory response and inhibited complement activation in APAP-induced liver injury.RNA-Seq analysis provided additional explanations for the protective role of C2-FH against APAP-induced liver injury.CONCLUSION C2-FH attenuates APAP-induced liver injury by inhibiting complement activation.

Effects of Yigan Capsule on the expression of HMGB1,RAGE and NF-κB protein in rats with drug-induced liver injury

Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI.

Wedelolactone attenuates sepsis-associated acute liver injury by regulating the macrophage M1/M2 polarization balance through the PI3K/AKT/NF-κB signalling pathway

Background:Liver injury caused by sepsis seriously impairs the normal physiology of the liver.Wedelactone(WED)has an obvious anti-inflammatory effect against liver damage caused by various factors.Nevertheless,further research is needed to determine if WED might mitigate acute liver damage linked to sepsis by influencing macrophage polarization.Methods:We first assessed the effect of WED on lipopolysaccharides-triggered liver injury by biochemistry assay and tissue staining.Inflammatory factors were assessed using the ELISA kits.The expression of Cluster of Differentiation 86(CD86)and Cluster of Differentiation 206(CD206)was measured by immunofluorescence assay.The protein levels of inducible nitric oxide sythase(iNOS),Arginase 1(Arg-1),phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT),PI3K phosphorylation(p-PI3K),AKT phosphorylation(p-AKT),inhibitor of kappa B kinase(IKK),inhibitor of kappa B(IκB),and nuclear factor kappa-B(NF-κB)p65 were quantified by western blot analysis.Results:WED decreased the level of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)and malondialdehyde,and increased the activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-PX).Moreover,WED exerted effective anti-inflammatory effects by decreasing the level of Tumor necrosis factor-α(TNF-α)and Interleukin 6(IL-6)and increasing the level of Interleukin 10(IL-10)in serum and cells.WED not only decreased CD86 and iNOS expression but also increased CD206 and Arg-1 expression.WED also downregulated the increased expression of PI3K,AKT,p-PI3K,p-AKT,IKK,and NF-κB p65 induced by lipopolysaccharides,while up-regulated the decreased expression of IκB.Besides,LY294002 with WED decreased the expression of protein PI3K,AKT,p-PI3K,p-AKT,IKK and NF-κB p65,and raised the expression of IκBα.Conclusion:Wedelolactone could attenuate sepsis-associated acute liver injury,and its mechanism may be associated with balancing pro-inflammatory and anti-inflammatory by the regulation of M1/M2 macrophage polarization via the PI3K/AKT/NF-κB signaling pathway.

Role of albumin-bilirubin score in non-malignant liver disease

The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver injury.The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models.It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators.An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation events.This article presents a review of the application of ALBI scores in various non-malignant liver diseases.

Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury

BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances.However,its contribution to the progression of liver damage remains unclear.AIM To determine the role and mechanism of UGT1A1 in liver damage progression.METHODS We investigated the relationship between UGT1A1 expression and liver injury through clinical research.Additionally,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study.RESULTS Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis.This suggests that low UGT1A1 levels may be associated with the progression of liver damage.In mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be increased.In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ACLF.UGT1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid metabolism.CONCLUSION UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver injury.UGT1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.

The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

Albumin-bilirubin score in non-malignant liver and other diseases

The albumin-bilirubin(ALBI)score is derived from albumin and bilirubin levels.Currently,the ALBI score is widely used in various clinical settings.A recent article in the World Journal of Gastroenterology summarized the application of the ALBI score in various non-malignant liver diseases.The ALBI score has a predictive power that is superior or non-inferior to established numerous measures.This may be related to its contiguity,sensitivity,and inclusion of albumin.While we recognize the good results of the ALBI score in a number of diseases,the ALBI score also has limitations.Variation studies for population characteristics and other factors should be performed to validate the performance of ALBI.Further modifications or optimization of ALBI scores should be taken into account.

COVID-19 and liver injury: An ongoing challenge

The new coronavirus severe acute respiratory syndrome coronavirus 2(SARSCoV-2)was identified in December 2019,in Wuhan,China.The virus was rapidly spread worldwide,causing coronavirus disease 2019(COVID-19)pandemic.Although COVID-19 is presented,usually,with typical respiratory symptoms(i.e.,dyspnea,cough)and fever,extrapulmonary manifestations are also encountered.Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and,even,acute liver failure.The pathogenesis of liver damage is not clearly defined;multiple mechanisms contribute to liver disorder,including direct cytopathic viral effect,cytokine storm and immune-mediated hepatitis,hypoxic injury,and druginduced liver toxicity.Patients with underlying chronic liver disease(i.e.,cirrhosis,non-alcoholic fatty liver disease,alcohol-related liver disease,hepatocellular carcinoma,etc.)may have greater risk to develop both severe COVID-19 and further liver deterioration,and,as a consequence,certain issues should be considered during disease management.The aim of this review is to present the prevalence,clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection.Moreover,we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.