Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid

Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate;however,the molecular mechanisms underpinning its pathogenesis are not well elucidated.Here,a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus(SGIV),focusing on the roles of key metabolites.Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver.Furthermore,SGIV significantly reduced the contents of lipid droplets,triglycerides,cholesterol,and lipoproteins.Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways,with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid(ALA),consistent with disturbed lipid homeostasis in the liver.Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide,carbohydrate,amino acid,and lipid metabolism,supporting the conclusion that SGIV infection induced liver metabolic reprogramming.Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade.Of note,integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid(LA)metabolites,and the accumulation of L-glutamic acid(GA),accompanied by alterations in immune,inflammation,and cell death-related genes.Further experimental data showed that ALA,but not GA,suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host.Collectively,these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases.

Curcumin delivery nanoparticles based on Maillard reaction of Haematococcus pluvialis protein/galactose for alleviating acute alcoholic liver damage

The aim of this study is to investigate the feasibility of Maillard reaction products of Haematococcus pluvialis protein and galactose(HPP-GAL)for improving the bioactivities of curcumin(CUR)for alleviating alcoholic liver damage.CUR was embedded into HPP-GAL nanoparticles by the self-assembly of hydrogen bonding and hydrophobic interaction with the particle size around 200 nm.HPP-GAL enhanced the encapsulation efficiency and loading amount of CUR with the value of(89.21±0.33)%and(0.500±0.004)%,respectively.The stabilities of CUR under strong acid,salt ion stability and ultraviolet irradiation conditions were improved by the encapsulation.HPP-GAL-CUR nanoparticles exhibited excellent concentration-dependent in vitro antioxidant activities including DPPH and ABTS scavenging rates,and better protective effect on CUR against gastric acid environment as well as longer release of CUR in simulated intestinal fluid.In addition,the HPPGAL-CUR delivery system possessed liver targeting property due to the existence of GAL,which could effectively alleviate the alcohol-induced liver damage and the inflammation indexes by inhibiting the oxidative stress.Therefore,HPP-GAL-CUR nanoparticles might be a potential candidate system for the prevention of alcoholic liver damage in the future.

Protective Effect of Ascorbate-Lysine on Carbon Tetrachloride and Alcohol-Induced Liver Injury in Mice

As an essential amino acid, lysine boosts protein synthesis (Nestor et al1997). Yao et al demonstrated that, lysine also exerts protective effect against the isch-emiclesion of brain. Meanwhile, vitamin C is a natural antioxidant, which has undisputable protectiveaction against free radical damages. In order to ascertain whether their combination could affordbetter effect, we have investigated the prophylactic effect of the couplant ascorbate-lysine inliver injuries.

Coexistence of hyperlipidemia and acute cerebral ischemia/reperfusion induces severe liver damage in a rat model

AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver damage,which was confirmed by liver histology.In addition,HL combined with I/R also caused significantly increased hepatocyte apoptosis,as evidenced by increased TUNEL-positive cells(6.20 ± 0.29 vs 1.5 ± 0.22,4.47 ± 0.45 or 1.97 ± 0.47,P < 0.01),elevated expression of caspase-3 and lower expression of bcl-2.Furthermore,when compared to HL or I/R alone,HL plus I/R enhanced serum TNF-,IL-1,liver mitochondrial MDA and Ca 2+ levels,suppressed SOD and GSH-Px in liver mitochondria,and markedly up-regulated the activity(11.76 ± 2.36 vs 4.77 ± 2.31 or 3.11 ± 1.35,P < 0.01) and expression(3.24 ± 0.38 vs 1.98 ± 0.88 or 1.72 ± 0.58,P < 0.01) of CYP2E1 in liver.CONCLUSION:The coexistence of HL and acute cerebral I/R induces severe liver damage,suggesting that cerebral ischemic stroke would exaggerate the damage of liver caused by HL.This effect is possibly due to en-hanced CYP2E1 induction which further promotes oxidative damage,inflammation and hepatocyte apoptosis.

Effects of extract from Ginkgo biloba on carbon tetrachloride-induced liver injury in rats

AIM： To study the effects of extract from Ginkgo biloba （EGb） containing 22% flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats induced by carbon tetrachloride （CCh）. METHODS： All rats were randomly divided into control group, CCl4-treated group, colchicine-treated group and EGb-protected group. Chronic liver injury was induced in experimental groups by subcutaneous injection of CCh and fed with chows premixed with 79.5% corn powder, 20% lard and 0.5% cholesterol （v/v）. EGb-protected group was treated with EGb （0.5 g/kg body weight per day） for 7 wk. At the end of wk 8, all the rats were killed. Liver function, liver fibrosis, oxidative stress and expression of transforming growth factor β1 （TGF-β1） a-smooth muscle actin （α-SMA） and type I collagens in liver were determined. In addition, pathology changes of liver tissue were observed under light microscope. RESULTS： The levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and albumin （AIb） in EGb-protected group were notably improved as compared with the CCL4-treated group （P 〈 0.01）. The contents of serum hyaluronic acid （HA）, type III procollagen （PCⅢ）, type IV collagen （CIV） and the expression of hepatic tissue TGF-β1, α-SMA and type I collagen in EGb-protected group were significantly lower than those in CCL4-treated groups （P 〈 0.05, P 〈 0.01）. The degrees of liver fibrosis in EGb-protected groups were lower than those in CCL4-treated groups （6.58 ±1.25 vs 9.52 ± 2.06, P 〈 0.05）. Compared to the CCL4-treated group, the levels of plasma glutathoine peroxidase （Se-GSH-Px）, superoxide dismutase （SOD） and malondialdehyde （MDA） were strikingly improved also in EGb-protected group （P 〈 0.05, P 〈 0.01）. CONCLUSION： EGb resists oxidative stress and thereby reduces chronic liver injury and liver fibrosis in rats with liver injury induced by CCl4.

Extrahepatic collaterals and liver damage in embolotherapy for ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery

AIM: To evaluate the effects of extrahepatic collaterals to the liver on liver damage and patient outcome after embolotherapy for the ruptured hepatic artery pseudoa- neurysm following hepatobiliary pancreatic surgery. METHODS: We reviewed 9 patients who underwent transcatheter arterial embolization (TAE) for the ruptured hepatic artery pseudoaneurysm following major hepato- biliary pancreatic surgery between June 1992 and April 2006. We paid special attention to the extrahepatic arte- rial collaterals to the liver which may affect post-TAE liver damage and patient outcome. RESULTS: The underlying diseases were all malignan- cies, and the surgical procedures included hepatopancre- atoduodenectomy in 2 patients, hepatic resection with removal of the bile duct in 5, and pancreaticoduodenec- tomy in 2. A total of 11 pseudoaneurysm developed: 4 in the common hepatic artery, 4 in the proper hepatic artery, and 3 in the right hepatic artery. Successful he- mostasis was accomplished with the initial TAE in all patients, except for 1. Extrahepatic arterial pathways to the liver, including the right inferior phrenic artery, the jejunal branches, and the aberrant left hepatic artery, were identified in 8 of the 9 patients after the completion of TAE. The development of collaterals depended on the extent of liver mobilization during the hepatic resection, the postoperative period, the presence or absence of an aberrant left hepatic artery, and the concomitant arte- rial stenosis adjacent to the pseudoaneurysm. The liver tolerated TAE without significant consequences when at least one of the collaterals from the inferior phrenic ar-tery or the aberrant left hepatic artery was present. One patient, however, with no extrahepatic collaterals died of liver failure due to total liver necrosis 9 d after TAE. CONCLUSION: When TAE is performed on ruptured hepatic artery pseudoaneurysm, reduced collateral path- ways to the liver created by the primary surgical proce- dure and a short postoperative interval may lead to an unfavorable outcome.

Antioxidant and hepatoprotective effects of Hypsizygus ulmarius polysaccharide on alcoholic liver injury in rats

Hypsizygus ulmarius polysaccharide(HUP)is a water-soluble polysaccharide obtained by hot water extraction,followed by precipitation and deproteinization.The characteristics of HUP,antioxidant activity and liver protection against alcohol-induced liver damage were studied.Structural characteristics indicate that the HUP is a pyran-type polysaccharide with a molecular weight of 2076 Da.In antioxidant scavenging assay,HUP showed moderate DMPD radical scavenging activity,cupric ion reducing antioxidant capacity and inhibitory effect against lipid peroxidation in a dose-dependent manner.Regarding in vivo hepatoprotective activity,compared with the ethanol induction group,pre-treatment of low and high doses of HUP signifi cantly reduced the behaviours of serum enzymes,lowered the levels of hepatic oxidative stress markers,restored the levels of biochemical constituents,enhanced the levels of liver and serum enzymatic antioxidants and non-enzymatic antioxidants,and improved the serum lipid levels of alcohol-intoxicated rats.The hepatoprotective effect of HUP was comparable to positive control silymarin.Besides,HUP pre-treatment signifi cantly normalized the histopathological changes induced by ethanol.The results indicate that HUP could be used as a functional food and may protect the biological system from oxidative stress through its antioxidant activity,thus having a signifi cant protective effect on acute alcoholic liver injury.

Mesona chinensis Benth polysaccharides alleviates liver injury by beneficial regulation of gut microbiota in cyclophosphamide-induced mice

There are a number of health benefits of Mesona chinensis Benth polysaccharide(MP),but little is known about its hepatoprotective effect and effect on gut microbiota composition in mice with liver damage induced by cyclophosphamide(CTX).This study indicated that MP supplementation effectively inhibited the production of serum aspartate aminotransferase(AST)and alanine aminotransferase(ALT),enhanced liver antioxidant capacity and repaired liver damage in mice caused by CTX.The release of inflammatory cytokines in liver and the concentration of lipopolysaccharide(LPS)in serum were decreased,and the level of short chain fatty acids(SCFAs)in colon was increased after MP administration.Those effects may be correlated with the regulation of the gut microbiota.Importantly,MP restrained liver inflammatory responses induced by CTX may via increasing the SCFAs-producing bacteria family Ruminococcaceae and reduced LPS-producing bacteria genus Bacteroides.In short,the prevention of CTX-induced liver injury by supplementing MP is achieved at least in part by regulating the community structure of the gut microbiota,and MP is expected to be a potential prebiotic to treat and prevent liver diseases.

Therapeutic effect of natural melanin from edible fungus Auricularia auricula on alcohol-induced liver damage in vitro and in vivo

This study explored the therapeutic effects of Auricularia auricula melanin(AAM)on alcoholic liver damage in vitro and in vivo.Human normal liver L02 cells were pre-treated with ethanol and then treated with AAM to explore the therapeutic effect of AAM on ethanol-induced hepatocyte injury.The results show that AAM signifi cantly elevated the cell viability,ameliorated the cell morphology,reduced the ROS and increased the GSH/GSSG of ethanol-pretreated L02 cells.Then,mice were administered with ethanol to induce acute alcoholic liver damage,and administered with AAM to further study the therapeutic effect of AAM on alcoholic liver damage in mice.As a result,AAM reduced the levels of ALT,AST,TG,and MDA,increased the levels of ADH,SOD,and CAT in liver damage mice.The therapeutic effect of AAM may be related to inhibition of CYP2E1 expression and activation of Nrf2 and its downstream antioxidase.The research enriched the bioactivity of AAM and provided some ideas for the development of melanin-related health foods.

Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl_4-induced chronic liver damage in rats

AIM： To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan （GB34） on CCl4-induced chronic liver damage in rats. METHODS： Rats were injected intraperitoneally with CCh （1 mL/kg） and treated with manual acupuncture using reinforcing manipulation techniques at left GB34 （Yanglingquan） 3 times a week for 10 wk. A nonacupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index, biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted. RESULTS： Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes. CONCLUSION： Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCh-intoxicated rats.

Efficacy of MK615 for the treatment of patients with liver disorders

AIM： To investigate the hepatoprotective effect of MK615, a Japanese apricot extract, in an animal model, and its clinical therapeutic effect. METHODS： Wistar rats were administered physiologi- cal saline （4 mL/kg） or MK615 solution （4 mL/kg） for 7 d. On the sixth d, acute hepatic injury was induced by administering a single intraperitoneal injection （ip） of D-galactosamine hydrochloride （D-GaIN） （600 mg/kg）. Plasma levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined, and liver tissues were used for histopathological analy- sis. Fifty-eight patients with liver disorders [hepatitis C （n = 40）, non-alcoholic fatty liver disease （n = 15）, and autoimmune liver disease （n = 3）] were orally admin- istered commercially available Misatol ME-containing MK615 （13 g/d） daily for 12 wk. Blood and urine were sampled immediately before and 6 wk, 12 wk, and 16 wk after the start of intake to measure various bio- chemical parameters. The percentage change in ALT and AST levels after 12 wk from the pre-intake baseline served as a primary endpoint. RESULTS： D-GaIN effectively induced acute hepatic injury in the rats. At 48 h after the ip injection of D-GaIN, the plasma levels of ALT （475.6 ：t： 191.5 IU/L vs 225.3 ＋ 194.2 IU/L, P 〈 0.05） and AST （1253.9：1：223.4 IU/L vs 621.9 ＋ 478.2 IU/L, P 〈 0.05） in the MK615 group were significantly lower than the control group. Scattered single cell necrosis, loss of hepatocytes, and extensive inflammatory cell infiltration were observed in hepatic tissue samples collected from the control group. However, these findings were less pronounced in the group receiving MK615. At the end of the clinical study, serum ALT and AST levels were significantly de- creased compared with pre-intake baseline levels from 103.5 ：l： 58.8 IU/L to 71.8 ＋ 39.3 IU/L （P 〈 0.05） and from 93.5 ：E 55.6 IU/L to 65.5 ＋ 34.8 IU/L （P 〈 0.05）, respectively. A reduction of 〉~ 30% from the pre-study baseline ALT level was observed in 26 （45%） of the 58 patients, while 25 （43%） patients exhibited similar AST level reductions. The chronic hepatitis C group exhibit- ed significant ALT and AST level reductions from 93.4：1： 51.1 IU/L to 64.6 ＋ 35.1 IU/L （P 〈 0.05） and from 94.2 ＋ 55.5 IU/L to 67.2：1：35.6 IU/L （P 〈 0.05）, respective- ly. A reduction of 〉~ 30% from the pre-study baseline ALT level was observed in 20 （50%） of the 40 patients.ALT levels in both the combined ursodeoxycholic acid （UDCA） treatment and the UDCA uncombined groups were significantly lower after Misatol ME administration. MK615 protected hepatocytes from D-GaiN-induced cytotoxicity in rats. Misatol ME decreased elevated ALT and AST levels in patients with liver disorders. CONCLUSION： These results suggest that MK615 and Misatol ME are promising hepatoprotective agents for patients with liver disorders.

Cyclosporin A protects Balb/c mice from liver damage induced by superantigen SEB and D-GaIN

AIM To investigate the pathogenic effect ofSEB and D-GalN on liver and the protection ofcyclosporin A, the relationship between hepaticapoptosis and necrosis and the possiblemechanism of acute hepatic necrosis.METHODS After staphylococcal enterotoxin B(SEB ) mixed with D--galactosamine (D-GaiN )were injected intraperitoneally into Balb/c miceand those previously treated with cyclosporin A,blood samples were collected and livers wereisolated at 2, 6, 12 and 24 h. Patterns othepatocellular death were studiedmorphologically and biochemically, circulatingcytokines (TNF-a, IFN--y ) and mice mortalitywithin 24h was assessed.RESU’LTS The SEB could induce the typicalapoptotic changes of hepatocytes, the D-GaiNcould induce hepatocytes apoptosis anddegeneration at the same time, and the micehaving received the SEB + D-GaiN injectionsdeveloped apoptosis at 2 and 6 h, but after 12 hhepatocytes were characterized by severein jury, whereas all the examinations in thecyclosporin A treated mice were normal.CONCLUSION Hepatic cell apoptosis might berelated to necrosis, and massive hepatocyteapoptosis is likely the initiating step of acutehepatic necrosis in mice. The effects induced bySEB and D--GaiN on hepatocytes might bemediated by T cells, and could be prevented bycyclosporin A.

Insight into the liver dysfunction in COVID-19 patients: Molecular mechanisms and possible therapeutic strategies

As of June 2022,more than 530 million people worldwide have become ill with coronavirus disease 2019(COVID-19).Although COVID-19 is most commonly associated with respiratory distress(severe acute respiratory syndrome),metaanalysis have indicated that liver dysfunction also occurs in patients with severe symptoms.Current studies revealed distinctive patterning in the receptors on the hepatic cells that helps in viral invasion through the expression of angiotensinconverting enzyme receptors.It has also been reported that in some patients with COVID-19,therapeutic strategies,including repurposed drugs(mitifovir,lopinavir/ritonavir,tocilizumab,etc.)triggered liver injury and cholestatic toxicity.Several proven indicators support cytokine storm-induced hepatic damage.Because there are 1.5 billion patients with chronic liver disease worldwide,it becomes imperative to critically evaluate the molecular mechanisms concerning hepatotropism of COVID-19 and identify new potential therapeutics.This review also designated a comprehensive outlook of comorbidities and the impact of lifestyle and genetics in managing patients with COVID-19.

Reabsorption of iron into acutely damaged rat liver:A role for ferritins

AIM To studied iron metabolism in liver, spleen, and serum after acute liver-damage, in relation to surrogate markers for liver-damage and repair.METHODS Rats received intraperitoneal injection of the hepatotoxin thioacetamide(TAA), and were sacrificed regularly between 1 and 96 h thereafter. Serum levels of transaminases and iron were measured using conventional laboratory assays. Liver tissue was used for conventional histology, immunohistology, and iron staining. The expression of acute-phase cytokines, ferritin light chain(FTL), and ferritin heavy chain(FTH)was investigated in the liver by q RT-PCR. Western blotting was used to investigate FTL and FTH in liver tissue and serum. Liver and spleen tissue was also used to determine iron concentrations.RESULTS After a short initial decrease, iron serum concentrations increased in parallel with serum transaminase(aspartate aminotransferase and alanine aminotransferase) levels, which reached a maximum at 48 h, and decreased thereafter. Similarly, after 48 h a significant increase in FTL, and after 72 h in FTH was detected in serum. While earliest morphological signs of inflammation in liver were visible after 6 h, increased expression of the two acute-phase cytokines IFN-γ(1 h) and IL-1β(3 h) was detectable earlier, with maximum values after 12-24 h. Iron concentrations in liver tissue increased steadily between 1 h and 48 h, and remained high at 96 h. In contrast, spleen iron concentrations remained unchanged until 48 h, and increased mildly thereafter(96 h). Although tissue iron staining was negative, hepatic FTL and FTH protein levels were strongly elevated. Our results reveal effects on hepatic iron concentrations after direct liver injury by TAA. The increase of liver iron concentrations may be due to the uptake of a significant proportion of the metal by healthy hepatocytes, and only to a minor extent by macrophages, as spleen iron concentrations do not increase in parallel. The temporary increase of iron, FTH and transaminases in serum is obviously due to their release by damaged hepatocytes.CONCLUSION Increased liver iron levels may be the consequence of hepatocyte damage. Iron released into serum by damaged hepatocytes is obviously transported back and stored via ferritins.

Protective Effect of Dimethyl-4,4'-Dimethoxy-5,6,5',6'-Dimethylene Dioxybiphenyl-2,2'-Dicarboxylate (DDB) against Carcinogen-Induced Rat Liver Nuclear DNA Damage

The protective effect of DDB against carcinogen-induced DNA damage was examined in the present investigation. Preincubation of rat liver nuclei with DDB (1 mmol.L-1) resulted in 60% inhibition of binding of 3H-benzo (a) pyrene to nuclear DNA. Unscheduled DNA synthesis (UDS) induced by aflatoxin BI (10^(-7) mol.L-1) in freshly isolated rat hepatocytes was also inhibited by DDB (10^(-6)-10^(-3)mol.L-1). Oral administration of DDB at 200 mg.kg-1 once daily for 3 d induced a significant increase of liver cytosol glutathione-S-transferase and microsomal UDPG-transferase activity in mice. These results indicate that DDB is able to directly or indirectly antagonize certain carcinogen-induced DNA damages.

Effect of Buzhong Yiqi Decoction (补中益气汤) on Murine Liver Damage Induced by Food Allergy

Objective: To investigate the effect of Buzhong Yiqi decoction (补中益气汤, BZYQD) on liver damage induced by food allergy in mice. Methods: Nc/Jic strain mice with high levels of serum IgE were sensitized by ovalbumin (OVA), and then divided into two groups and respectively treated with BZYQD (treated group) or normal saline (model group). Samples of serum, liver tissues and small intestine were collected two weeks later, and another group of non-sensitized mice was set as the normal group. The levels of serum alanine aminotransferase (ALT) were measured with spectrophotometry. The liver tissue and small intestine were stained with hematoxylin and eosin (HE) for pathologic analysis. The liver samples were also subjected to analysis of CD4-T helper cell and cytokine (interleukin-4, IL-4, interleukin-6, IL-6) expression with immunohistochemical (avidin-biotin complex, ABC) method. Results: Serum ALT levels decreased and obvious pathologic improvements were seen in the mice treated with BZYQD. And compared with the model mice, the number of positive cells of IL-4, IL-6 and CD4 cell decreased significantly in those treated with BZYQD. Conclusion: BZYQD can effectively decrease the production of cytokines associated with allergic reaction in the liver of mice thus effective in treating liver damage caused by food allergy.

Liver dysfunction as a cytokine storm manifestation and prognostic factor for severe COVID-19

patients with or without preexisting liver disorders,posing a significant complication and mortality risk.During coronavirus disease 2019(COVID-19),abnormal liver function is typically observed.However,liver injury may occur because of the treatment as well.Ischemia,cytokine storm,and hypoxia were identified as the three major factors contributing to liver damage during COVID-19.Indeed,raised liver enzymes during hospitalizations may be attributed to medications used,as well as sepsis and shock.As a result,the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14%to 53%.Aminotransferases and bilirubin are found most often elevated.Usually,increased gamma-glutamyltransferase,alkaline phosphatase,and decreased serum albumin levels are demonstrated.Additionally,although there is no specific treatment for COVID-19,many of the drugs used to treat the infection are hepatotoxic.In this mini-review,we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm.Furthermore,data show that liver injury can be an independent predictor of severe COVID-19,the need for hospitalization,and death.

Role of immune dysfunction in drug induced liver injury

Drug-induced liver injury(DILI)is one of the leading causes of liver failure and withdrawal of drugs from the market.A poor understanding of the precipitating event aetiology and mechanisms of disease progression has rendered the prediction and subsequent treatment intractable.Recent literature suggests that some drugs can alter the liver’s repair systems resulting in injury.The pathophysiology of DILI is complex,and immune dysfunction plays an important role in determining the course and severity of the disease.Immune dysfunction is influenced by the host response to drug toxicity.A deeper understanding of these processes may be beneficial in the management of DILI and aid in drug development.This review provides a structured framework presenting DILI in three progressive stages that summarize the interplay between drugs and the host defence networks.

Molecular mechanism of Solanum Nigrum Linn in alcoholic liver damage based on network pharmacology and molecular docking

Solanum Nigrum Linn,the purpose of this study was to characterize the chemical components of the extract of Solanum Nigrum Linn by LC-MS/MS,and to identify 29 compounds by positive and negative total ion flow maps.The potential mechanism of action of Solanum Nigrum Linn in treating alcoholic liver injury was investigated by means of network pharmacology and molecular docking.A total of 288 component target genes and 1010 disease target genes were obtained,and 98 intersection targets and 7 core targets were obtained after the intersection of the two genes.GO analysis and KEGG analysis respectively obtained 20 signaling pathways such as anti-inflammation and anti-apoptosis.The results of molecular docking showed that the blood components could successfully dock with the target proteins of the disease such as GAPDH,IL6,SRC,EGFR and ESR1.This study provided a scientific basis for the development and application of Solanum Nigrum Linn.

Correlation of serum arylesterase activity on phenylacetate estimated by the integrated method to common classical biochemical indexes of liver damage

The correlation of serum arylesterase(PON1) activity on phenylacetate determined by an integrated method to clas-sical biochemical indexes of liver damage was investigated for the use of PON1 activity to evaluate liver damage.PON1 reaction curve as absorbance at 270 nm for 0.20 mmol/L phenylacetate hydrolysis was analyzed by the integrated method to determine maximal PON1 reaction rate.Classical biochemical indexes of liver damage were determined routinely.The 95% confidence threshold of PON1 activity in sera from healthy individuals was 2.12 mkat/L [(4.73±1.31) mkat/L,n=105].PON1 activity in clinical sera was closely correlated to serum albumin,total protein and the ratio of albumin to globulins,but was weakly correlated to both direct and total bilirubin in serum.There were no correlations of PON1 activity to γ-glutamyltransferase,alkaline phos-phatase,alanine aminotransferase and aspartate aminotransferase.Among 127 clinical sera with PON1 activity>2.12 mkat/L,there were 92% healthy individuals examined by albumin,90% healthy individuals examined by total protein,88% healthy individuals examined by total bilirubin,86% healthy individuals examined by direct bilirubin and 64% healthy individuals examined by the ratio of albumin to globulins,respectively.In each group of healthy individuals judged by classical biochemical indexes of close correlation to PON1 activity,percentage of healthy individuals examined by PON1 activity was always >80%.These results suggested PON1 activity on phenylacetate estimated by the integrated method was also suitable for the evaluation of liver damage.