Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopath...Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.展开更多
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 ...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.展开更多
In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the inte...In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.展开更多
Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment ...Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes.This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of Gastroenterology.We summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current research.We also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis.Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application.展开更多
BACKGROUND Hepatic epithelioid angiomyolipoma(HEA)has a low incidence and both clinical manifestations and imaging lack specificity.Thus,it is easy to misdiagnose HEA as other tumors of the liver,especially in the pre...BACKGROUND Hepatic epithelioid angiomyolipoma(HEA)has a low incidence and both clinical manifestations and imaging lack specificity.Thus,it is easy to misdiagnose HEA as other tumors of the liver,especially in the presence of liver diseases such as hepatitis cirrhosis.This article reviewed the diagnosis and treatment of a patient with HEA and alcoholic cirrhosis,and analyzed the literature,in order to improve the understanding of this disease.CASE SUMMARY A 67-year-old male patient with a history of alcoholic cirrhosis was admitted due to the discovery of a space-occupying lesion in the liver.Based on the patient’s history,laboratory examinations,and imaging examinations,a malignant liver tumor was considered and laparoscopic partial hepatectomy was performed.Postoperative pathology showed HEA.During outpatient follow-up,the patient showed no sign of recurrence.CONCLUSION HEA is difficult to make a definite diagnosis before surgery.HEA has the poten-tial for malignant degeneration.If conditions permit,surgical treatment is recom-mended.展开更多
Alcoholic liver injury is a liver disease caused by excessive alcohol consumption,which can lead to chronic liver disease death.Solanum Nigrum Linn taste bitter,cold,has the effect of clearing heat and detoxification,...Alcoholic liver injury is a liver disease caused by excessive alcohol consumption,which can lead to chronic liver disease death.Solanum Nigrum Linn taste bitter,cold,has the effect of clearing heat and detoxification,promoting blood and detumescence.Solanum Nigrum Linn fruit contains a variety of antioxidant enzymes,can remove the body produced by aerobic metabolism harmful substances.In this paper,a model of alcohol-induced liver injury in C57BL/6 mice was established to evaluate the protective effect of Solanum Nigrum Linn green fruit(SNGF)ethanolic extract on alcohol-induced liver injury.H&E staining and oil red O(ORO)staining showed that hepatic lobules were clearly demarcated,vacuoles were significantly reduced and lipid droplets were reduced in SNGF ethanolic extract treatment group.Serum levels of TC,TG,LDH,TBA,AKP,ALT and AST were decreased in the SNGF ethanolic extract treatment group,and SNGF ethanolic extract could clear reactive oxygen species(ROS)in time.MDA content was signifi cantly decreased after SNGF ethanolic extract treatment,while superoxide dismutase(SOD)and GSH-Px contents were increased after SNGF ethanolic extract treatment.These results suggest that SNGF ethanolic extract has a protective effect on alcohol-induced liver injury.展开更多
BACKGROUND Alcoholic liver disease(ALD)remains one of the major indications for liver transplantation in the United States and continues to place a burden on the national healthcare system.There is evidence of increas...BACKGROUND Alcoholic liver disease(ALD)remains one of the major indications for liver transplantation in the United States and continues to place a burden on the national healthcare system.There is evidence of increased alcohol consumption during the coronavirus disease 2019(COVID-19)pandemic,and the effect of this on the already burdened health systems remains unknown.AIM To assess the trends for ALD admissions during the COVID-19 pandemic,and compare it to a similar pre-pandemic period.METHODS This retrospective study analyzed all admissions at a tertiary health care system,which includes four regional hospitals.ALD admissions were identified by querying a multi-hospital health system’s electronic database using ICD-10 codes.ALD admissions were compared for two one-year periods;pre-COVID-19 from April 2019 to March 2020,and during-COVID-19 from April 2020 to March 2021.Data were analyzed using a Poisson regression model and admission rates were compared using the annual quarterly average for the two time periods,with stratification by age and gender.Percent increase or decrease in admissions from the Poisson regression model were reported as incident rate ratios.RESULTS One thousand three hundred and seventy-eight admissions for ALD were included.80.7%were Caucasian,and 34.3%were female.An increase in the number of admissions for ALD during the COVID-19 pandemic was detected.Among women,a sharp rise(33%)was noted in those below the age of 50 years,and an increase of 22%in those above 50 years.Among men,an increase of 24%was seen for those below 50 years,and a 24%decrease in those above 50 years.CONCLUSION The COVID-19 pandemic has had widespread implications,and an increase in ALD admissions is just one of them.However,given that women are often prone to rapid progression of ALD,this finding has important preventive health implications.展开更多
Substance use disorder has a damaging effect on the family members of alcoholics and drug users.On the other hand,the reactions and behaviours of family members may negatively influence a person with substance use dis...Substance use disorder has a damaging effect on the family members of alcoholics and drug users.On the other hand,the reactions and behaviours of family members may negatively influence a person with substance use disorder.The behaviours of significant others of a person with substance use disorder that contribute to the maintenance of substance use disorder are called enabling.This study aimed to explore enabling behaviours of wives of persons with substance use disorder in Chapter 8 of Alcoholic Anonymous’Big Book by utilising qualitative content analysis.Alcoholics Anonymous(AA)is one of the most commonly used programs for recovery from alcoholism.The current study sought to help mental health professionals get a better understanding of the views and premises of the AA program in reference to enabling behaviours of wives by conducting a qualitative content analysis of the AA Big Book.The study also discusses the healthy behaviours suggested by the authors of the Big Book and the comprehensiveness of the text for the readers.展开更多
Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic ...Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.展开更多
As a result of the obesity epidemic,Nonalcoholic fatty liver disease(NAFLD)and its complications have increased among millions of people.Consequently,a group of experts recommended changing the term NAFLD to an inclus...As a result of the obesity epidemic,Nonalcoholic fatty liver disease(NAFLD)and its complications have increased among millions of people.Consequently,a group of experts recommended changing the term NAFLD to an inclusive terminology more reflective of the underlying pathogenesis;metabolic-associated fatty liver disease(MAFLD).This new term of MAFLD has its own disease epidemiology and clinical outcomes prompting efforts in studying its differences from NAFLD.This article discusses the rationale behind the nomenclature change,the main differences,and its clinical implications.展开更多
Heavy alcohol consumption results in alcoholic liver disease(ALD)with inadequate therapeutic options.Here,we first report the potential beneficial effects of ginsenoside Rk2(Rk2),a rare dehydroprotopanaxadiol saponin ...Heavy alcohol consumption results in alcoholic liver disease(ALD)with inadequate therapeutic options.Here,we first report the potential beneficial effects of ginsenoside Rk2(Rk2),a rare dehydroprotopanaxadiol saponin isolated from streamed ginseng,against alcoholic liver injury in mice.Chronic-plus-single-binge ethanol feeding caused severe liver injury,as manifested by significantly elevated serum aminotransferase levels,hepatic histological changes,increased lipid accumulation,oxidative stress,and inflammation in the liver.These deleterious effects were alleviated by the treatment with Rk2(5 and 30 mg/kg).Acting as an nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)inhibitor,Rk2 ameliorates alcohol-induced liver inflammation by inhibiting NLRP3 inflammasome signaling in the liver.Meanwhile,the treatment with Rk2 alleviated the alcohol-induced intestinal barrier dysfunction via enhancing NLRP6 inflammasome in the intestine.Our findings indicate that Rk2 is a promising agent for the prevention and treatment of ALD and other NLPR3-driven diseases.展开更多
BACKGROUND Portal hypertension(PHT)in patients with alcoholic cirrhosis causes a range of clinical symptoms,including gastroesophageal varices and ascites.The hepatic venous pressure gradient(HVPG),which is easier to ...BACKGROUND Portal hypertension(PHT)in patients with alcoholic cirrhosis causes a range of clinical symptoms,including gastroesophageal varices and ascites.The hepatic venous pressure gradient(HVPG),which is easier to measure,has replaced the portal venous pressure gradient(PPG)as the gold standard for diagnosing PHT in clinical practice.Therefore,attention should be paid to the correlation between HVPG and PPG.METHODS Between January 2017 and June 2020,134 patients with alcoholic cirrhosis and PHT who met the inclusion criteria underwent various pressure measurements during transjugular intrahepatic portosystemic shunt procedures.Correlations were assessed using Pearson’s correlation coefficient to estimate the correlation coefficient(r)and determination coefficient(R^(2)).Bland-Altman plots were constructed to further analyze the agreement between the measurements.Disagreements were analyzed using paired t tests,and P values<0.05 were considered statistically significant.RESULTS In this study,the correlation coefficient(r)and determination coefficient(R2)between HVPG and PPG were 0.201 and 0.040,respectively(P=0.020).In the 108 patients with no collateral branch,the average wedged hepatic venous pressure was lower than the average portal venous pressure(30.65±8.17 vs.33.25±6.60 mmHg,P=0.002).Hepatic collaterals were identified in 26 cases with balloon occlusion hepatic venography(19.4%),while the average PPG was significantly higher than the average HVPG(25.94±7.42 mmHg vs 9.86±7.44 mmHg;P<0.001).The differences between HVPG and PPG<5 mmHg in the collateral vs no collateral branch groups were three cases(11.54%)and 44 cases(40.74%),respectively.CONCLUSION In most patients,HVPG cannot accurately represent PPG.The formation of hepatic collaterals is a vital reason for the strong underestimation of HVPG.展开更多
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...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.展开更多
[Objectives]This study was conducted to explore the optimization of ultrasonic-assisted organic solvent extraction of pomegranate peel polyphenols(PPPs),and to study the protective effect of PPPs on acute alcoholic li...[Objectives]This study was conducted to explore the optimization of ultrasonic-assisted organic solvent extraction of pomegranate peel polyphenols(PPPs),and to study the protective effect of PPPs on acute alcoholic liver injury in mice.[Methods]The optimal extraction conditions of PPPs were determined by single factor and orthogonal experiments,and an acute alcoholic liver injury model in mice was established.Bifendate was used as the positive control group to investigate the protective effect of low,medium and high doses of PPPs on acute alcoholic liver injury.[Results]The optimum extraction process parameters were followed as 60%ethanol concentration,solid-liquid ratio of 1:40(w/v),extraction temperature of 50℃,and extraction time of 1.5 h,and the yield was 1.42%.The results of animal experiments showed that PPPs could effectively reduce the degree of alcoholic liver injury in mice,reduce the levels of serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST),and reduce the inflammation and necrosis of liver tissue in mice.Meanwhile,the total polyphenols from pomegranate peel also significantly reduced the expression levels of malondialdehyde(MDA),tumor necrosis factor(TNF-α)and interleukin-6(IL-6)in mice,and increased the levels of superoxide dismutase(SOD)and reduced glutathione(GSH)in liver tissue of mice,indicating its antioxidant and anti-inflammatory effects,further illustrating its protective effect on alcoholic liver injury.[Conclusions]PPPs could reduce the expression levels of TNF-α,IL-6 and MDA in mice,and increase the expression levels of SOD and GSH to achieve the protective effect on acute alcoholic liver injury in mice.This study will provide new ideas for the development of new anti-alcoholic liver injury drug resources.展开更多
Alcoholic liver disease(ALD)is the most common liver disease in the Western world.For many reasons,it isunderestimated and underdiagnosed.An early diagnosis is absolutely essential since it(1)helps to identify patient...Alcoholic liver disease(ALD)is the most common liver disease in the Western world.For many reasons,it isunderestimated and underdiagnosed.An early diagnosis is absolutely essential since it(1)helps to identify patients at genetic risk for ALD;(2)can trigger efficient abstinence namely in non-addicted patients;and(3)initiate screening programs to prevent life-threateningcomplications such as bleeding from varices,spontaneous bacterial peritonitis or hepatocellular cancer.The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis(AH).The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on acombination of laboratory,clinical and imaging findings.It is not widely conceived that conventional screeningtools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca.40%of manifest alcoholic liver cirrhosis.Non-invasive methods such as transient elastography(Fibroscan),acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholiccirrhosis.Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca.95%of patients.The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels.Other non-invasive methods such as controlled attenuation parameter,serum levels of M30 or M65,susceptometry or breath tests are under current evaluation to assess the degree of steatosis,apoptosis and iron overload in these patients.Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH.展开更多
The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most florid presentation of alcoholic liver disease, co...The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most florid presentation of alcoholic liver disease, continues to have high morbidity and mortality, with significant financial and healthcare burden with limited treatment options. Steroids remain the current standard of care in severe alcoholic hepatitis in carefully selected patients. No specific treatments are available for those patients who are steroid ineligible, intolerant or unresponsive. Liver transplant has shown good short-term outcome; however, feasibility, ethical and economic concerns remain. Modification of gut microbiota composition and their products, such as lipopolysaccharide, nutritional interventions, immune modulation, increasing steroid sensitivity, genetic polymorphism and epigenetic modification of alcohol induced liver damage, augmenting hepatic regeneration using GCSF are potential therapeutic avenues in steroid non-responsive/ineligible patients. With better understanding of the pathophysiology, using “Omics” platforms, newer options for patients with alcoholic hepatitis are expected soon.展开更多
Non-alcoholic fatty liver disease(NAFLD)is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome(MetS).Because alcohol consumption in NAFLD patients is common,there is a significa...Non-alcoholic fatty liver disease(NAFLD)is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome(MetS).Because alcohol consumption in NAFLD patients is common,there is a significant overlap in the pathogenesis of NAFLD and alcoholic liver disease(ALD).Indeed,MetS also significantly contributes to liver injury in ALD patients.This“syndrome of metabolic and alcoholic steatohepatitis”(SMASH)is thus expected to be a more prevalent presentation in liver patients,as the obesity epidemic continues.Several pre-clinical experimental models that couple alcohol consumption with NAFLDinducing diet or genetic obesity have been developed to better understand the pathogenic mechanisms of SMASH.These models indicate that concomitant MetS and alcohol contribute to lipid dysregulation,oxidative stress,and the induction of innate immune response.There are significant limitations in the applicability of these models to human disease,such as the ability to induce advanced liver injury or replicate patterns in human food/alcohol consumption.Thus,there remains a need to develop models that accurately replicate patterns of obesogenic diet and alcohol consumption in SMASH patients.展开更多
AIM: To investigate the protein expression of phosphatase and tensin homolog (PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease.METHODS: PTEN protein expression was assessed by i...AIM: To investigate the protein expression of phosphatase and tensin homolog (PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease.METHODS: PTEN protein expression was assessed by immunohistochemistry in formalin-fixed, paraffin-embedded liver sections of patients with non-alcoholic fatty liver disease (NAFLD) (n = 44) or alcoholic liver disease (ALD) (n = 25). Liver resections obtained from 3 healthy subjects candidate for partial liver donation served as controls. Histological evaluations were performed by two experienced pathologists, and diagnoses established based on international criteria. The intensity of the PTEN staining in nuclei was compared between steatotic and non-steatotic areas of each liver fragment analyzed. For each liver specimen, the antibody-stained sections were examined and scored blindly by three independent observers, who were unaware of the patients’ clinical history.RESULTS: In healthy individuals, PTEN immunostaining was intense in both the cytoplasm and nuclei of all hepatocytes. However, PTEN was strongly downregulated in both the nucleus and the cytoplasm of hepatocytes from steatotic areas in patients with NAFLD, independently of the disease stage. In contrast, no changes in PTEN protein expression were observed in patients with ALD, regardless of the presence of steatosis or the stage of the disease. The degree of PTEN downregulation in hepatocytes of patients with NAFLD correlated with the percentage of steatosis (r = 0.3061, P = 0.0459) and the BMI (r = 0.4268, P = 0.0043). Hovewer, in patients with ALD, PTEN expression was not correlated with the percentage of steatosis with or without obesity as a confounding factor (P = 0.5574). Finally, PTEN expression level in steatotic areas of ALD patients was significantly different from that seen in steatotic areas of NAFLD patients (P < 0.0001).CONCLUSION: PTEN protein expression is downregulated early in NAFLD, but not in ALD. PTEN immunohistochemical detection could help in the differential diagnosis of NAFLD and ALD.展开更多
The severity of alcoholic hepatitis(AH) which may coexist with cirrhosis varies greatly, from asymptomatic forms which are detected in alcoholic patients without any sign of liver disease, except laboratory abnormalit...The severity of alcoholic hepatitis(AH) which may coexist with cirrhosis varies greatly, from asymptomatic forms which are detected in alcoholic patients without any sign of liver disease, except laboratory abnormalities, to severe forms characterised by deep jaundice, ascites, hepatic encephalopathy and low prothrombin index. In hospitalized patients the mortality could be as high as 75%. The elevated number of therapeutic proposals reported for more than forty years reveals the lack of efficacy of a particular modality. Even in the most favorable trials, the survival is already very poor and in some cases related to the development of renal failure or hepatorenal syndrome. There are some motivating reports concerning albumin dialysis as a support treatment in patients with severe AH, either alone or in combination with other pharmacological therapies. The favorable effects of albumin dialysis in patients with severe AH suggest that the procedure used alone or in combination with other therapies may have a role in this clinical condition. This will be particularly relevant to offer an alternative therapy in these patients, thus being a potential bridge to recovery or to be listed for liver transplantation.展开更多
The aggregation behavior of the mixture of cetyltrimethylammonium chloride(CTAC), a cationic surfactant, and moxifloxacin hydrochloride(MFH), a fourth-generation fluoroquinolone antibiotic drug, has been studied using...The aggregation behavior of the mixture of cetyltrimethylammonium chloride(CTAC), a cationic surfactant, and moxifloxacin hydrochloride(MFH), a fourth-generation fluoroquinolone antibiotic drug, has been studied using the conductivity technique in aqueous and alcoholic(EtOH, 1-PrOH, and 2-BuOH)media. The study was performed at several temperatures between 298.15 and 323.15 K at 5 K intervals.The assembly has been characterized by evaluating the micellar parameters, such as the critical micelle concentration(CMC) and the counter ion binding(β), of the CTAC + MFH mixture. The values of the CMC for the assembly of the CTAC + MFH mixture were reliant on the composition of alcohols in the mixed solvents and the temperature. The CMC values of the CTAC + MFH mixture increased with increasing temperature;that is, assembly was delayed by increased temperature. The micellization of the CTAC + MFH mixed system was delayed in alcoholic media. The observed-ΔG0mvalues for the association of the CTAC + MFH mixed system demonstrated a spontaneous aggregation process under all study conditions.Based on the-ΔH^(0)_(m) and +ΔS^(0)_(m) values, the association of the CTAC + MFH mixture is exothermic and the interaction forces acting between the CTAC and MFH species are hydrophobic, ion–dipole, and electrostatic interactions. The transfer properties and enthalpy–entropy compensation were also assessed and described comprehensively.展开更多
基金The current project is funded by Shandong Provincial Natural Science Foundation,China(ZR2020MH370)Major Science and Technology Innovation in Shandong Province(2017CXGC1307)Ji’nan Science and Technology Project(201303055)。
文摘Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.
基金supported by the National Key Research and Development Program of China(2022YFF1100205)the National Natural Science Foundation of China(31972105)the National Science Fund for Distinguished Young Scholars of China(31925031).
文摘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.
文摘In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.
文摘Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes.This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of Gastroenterology.We summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current research.We also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis.Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application.
基金Supported by Natural Science Foundation of Zhejiang Province,No.LY19H030004and The Lishui City Key Research and Ddevelopment Project,No.2022ZDYF08。
文摘BACKGROUND Hepatic epithelioid angiomyolipoma(HEA)has a low incidence and both clinical manifestations and imaging lack specificity.Thus,it is easy to misdiagnose HEA as other tumors of the liver,especially in the presence of liver diseases such as hepatitis cirrhosis.This article reviewed the diagnosis and treatment of a patient with HEA and alcoholic cirrhosis,and analyzed the literature,in order to improve the understanding of this disease.CASE SUMMARY A 67-year-old male patient with a history of alcoholic cirrhosis was admitted due to the discovery of a space-occupying lesion in the liver.Based on the patient’s history,laboratory examinations,and imaging examinations,a malignant liver tumor was considered and laparoscopic partial hepatectomy was performed.Postoperative pathology showed HEA.During outpatient follow-up,the patient showed no sign of recurrence.CONCLUSION HEA is difficult to make a definite diagnosis before surgery.HEA has the poten-tial for malignant degeneration.If conditions permit,surgical treatment is recom-mended.
文摘Alcoholic liver injury is a liver disease caused by excessive alcohol consumption,which can lead to chronic liver disease death.Solanum Nigrum Linn taste bitter,cold,has the effect of clearing heat and detoxification,promoting blood and detumescence.Solanum Nigrum Linn fruit contains a variety of antioxidant enzymes,can remove the body produced by aerobic metabolism harmful substances.In this paper,a model of alcohol-induced liver injury in C57BL/6 mice was established to evaluate the protective effect of Solanum Nigrum Linn green fruit(SNGF)ethanolic extract on alcohol-induced liver injury.H&E staining and oil red O(ORO)staining showed that hepatic lobules were clearly demarcated,vacuoles were significantly reduced and lipid droplets were reduced in SNGF ethanolic extract treatment group.Serum levels of TC,TG,LDH,TBA,AKP,ALT and AST were decreased in the SNGF ethanolic extract treatment group,and SNGF ethanolic extract could clear reactive oxygen species(ROS)in time.MDA content was signifi cantly decreased after SNGF ethanolic extract treatment,while superoxide dismutase(SOD)and GSH-Px contents were increased after SNGF ethanolic extract treatment.These results suggest that SNGF ethanolic extract has a protective effect on alcohol-induced liver injury.
文摘BACKGROUND Alcoholic liver disease(ALD)remains one of the major indications for liver transplantation in the United States and continues to place a burden on the national healthcare system.There is evidence of increased alcohol consumption during the coronavirus disease 2019(COVID-19)pandemic,and the effect of this on the already burdened health systems remains unknown.AIM To assess the trends for ALD admissions during the COVID-19 pandemic,and compare it to a similar pre-pandemic period.METHODS This retrospective study analyzed all admissions at a tertiary health care system,which includes four regional hospitals.ALD admissions were identified by querying a multi-hospital health system’s electronic database using ICD-10 codes.ALD admissions were compared for two one-year periods;pre-COVID-19 from April 2019 to March 2020,and during-COVID-19 from April 2020 to March 2021.Data were analyzed using a Poisson regression model and admission rates were compared using the annual quarterly average for the two time periods,with stratification by age and gender.Percent increase or decrease in admissions from the Poisson regression model were reported as incident rate ratios.RESULTS One thousand three hundred and seventy-eight admissions for ALD were included.80.7%were Caucasian,and 34.3%were female.An increase in the number of admissions for ALD during the COVID-19 pandemic was detected.Among women,a sharp rise(33%)was noted in those below the age of 50 years,and an increase of 22%in those above 50 years.Among men,an increase of 24%was seen for those below 50 years,and a 24%decrease in those above 50 years.CONCLUSION The COVID-19 pandemic has had widespread implications,and an increase in ALD admissions is just one of them.However,given that women are often prone to rapid progression of ALD,this finding has important preventive health implications.
文摘Substance use disorder has a damaging effect on the family members of alcoholics and drug users.On the other hand,the reactions and behaviours of family members may negatively influence a person with substance use disorder.The behaviours of significant others of a person with substance use disorder that contribute to the maintenance of substance use disorder are called enabling.This study aimed to explore enabling behaviours of wives of persons with substance use disorder in Chapter 8 of Alcoholic Anonymous’Big Book by utilising qualitative content analysis.Alcoholics Anonymous(AA)is one of the most commonly used programs for recovery from alcoholism.The current study sought to help mental health professionals get a better understanding of the views and premises of the AA program in reference to enabling behaviours of wives by conducting a qualitative content analysis of the AA Big Book.The study also discusses the healthy behaviours suggested by the authors of the Big Book and the comprehensiveness of the text for the readers.
文摘Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.
文摘As a result of the obesity epidemic,Nonalcoholic fatty liver disease(NAFLD)and its complications have increased among millions of people.Consequently,a group of experts recommended changing the term NAFLD to an inclusive terminology more reflective of the underlying pathogenesis;metabolic-associated fatty liver disease(MAFLD).This new term of MAFLD has its own disease epidemiology and clinical outcomes prompting efforts in studying its differences from NAFLD.This article discusses the rationale behind the nomenclature change,the main differences,and its clinical implications.
基金supported by grants from the Research Committee of the University of Macao(Grant No.:MYRG2022-00020-ICMS)the Science and Technology Development Fund,Macao SAR,China(File No.:0074/2021/AFJ and 0052/2022/A1).
文摘Heavy alcohol consumption results in alcoholic liver disease(ALD)with inadequate therapeutic options.Here,we first report the potential beneficial effects of ginsenoside Rk2(Rk2),a rare dehydroprotopanaxadiol saponin isolated from streamed ginseng,against alcoholic liver injury in mice.Chronic-plus-single-binge ethanol feeding caused severe liver injury,as manifested by significantly elevated serum aminotransferase levels,hepatic histological changes,increased lipid accumulation,oxidative stress,and inflammation in the liver.These deleterious effects were alleviated by the treatment with Rk2(5 and 30 mg/kg).Acting as an nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)inhibitor,Rk2 ameliorates alcohol-induced liver inflammation by inhibiting NLRP3 inflammasome signaling in the liver.Meanwhile,the treatment with Rk2 alleviated the alcohol-induced intestinal barrier dysfunction via enhancing NLRP6 inflammasome in the intestine.Our findings indicate that Rk2 is a promising agent for the prevention and treatment of ALD and other NLPR3-driven diseases.
文摘BACKGROUND Portal hypertension(PHT)in patients with alcoholic cirrhosis causes a range of clinical symptoms,including gastroesophageal varices and ascites.The hepatic venous pressure gradient(HVPG),which is easier to measure,has replaced the portal venous pressure gradient(PPG)as the gold standard for diagnosing PHT in clinical practice.Therefore,attention should be paid to the correlation between HVPG and PPG.METHODS Between January 2017 and June 2020,134 patients with alcoholic cirrhosis and PHT who met the inclusion criteria underwent various pressure measurements during transjugular intrahepatic portosystemic shunt procedures.Correlations were assessed using Pearson’s correlation coefficient to estimate the correlation coefficient(r)and determination coefficient(R^(2)).Bland-Altman plots were constructed to further analyze the agreement between the measurements.Disagreements were analyzed using paired t tests,and P values<0.05 were considered statistically significant.RESULTS In this study,the correlation coefficient(r)and determination coefficient(R2)between HVPG and PPG were 0.201 and 0.040,respectively(P=0.020).In the 108 patients with no collateral branch,the average wedged hepatic venous pressure was lower than the average portal venous pressure(30.65±8.17 vs.33.25±6.60 mmHg,P=0.002).Hepatic collaterals were identified in 26 cases with balloon occlusion hepatic venography(19.4%),while the average PPG was significantly higher than the average HVPG(25.94±7.42 mmHg vs 9.86±7.44 mmHg;P<0.001).The differences between HVPG and PPG<5 mmHg in the collateral vs no collateral branch groups were three cases(11.54%)and 44 cases(40.74%),respectively.CONCLUSION In most patients,HVPG cannot accurately represent PPG.The formation of hepatic collaterals is a vital reason for the strong underestimation of HVPG.
文摘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.
基金Supported by Provincial Key College Students Innovation and Entrepreneurship Training Program Project (202211834033).
文摘[Objectives]This study was conducted to explore the optimization of ultrasonic-assisted organic solvent extraction of pomegranate peel polyphenols(PPPs),and to study the protective effect of PPPs on acute alcoholic liver injury in mice.[Methods]The optimal extraction conditions of PPPs were determined by single factor and orthogonal experiments,and an acute alcoholic liver injury model in mice was established.Bifendate was used as the positive control group to investigate the protective effect of low,medium and high doses of PPPs on acute alcoholic liver injury.[Results]The optimum extraction process parameters were followed as 60%ethanol concentration,solid-liquid ratio of 1:40(w/v),extraction temperature of 50℃,and extraction time of 1.5 h,and the yield was 1.42%.The results of animal experiments showed that PPPs could effectively reduce the degree of alcoholic liver injury in mice,reduce the levels of serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST),and reduce the inflammation and necrosis of liver tissue in mice.Meanwhile,the total polyphenols from pomegranate peel also significantly reduced the expression levels of malondialdehyde(MDA),tumor necrosis factor(TNF-α)and interleukin-6(IL-6)in mice,and increased the levels of superoxide dismutase(SOD)and reduced glutathione(GSH)in liver tissue of mice,indicating its antioxidant and anti-inflammatory effects,further illustrating its protective effect on alcoholic liver injury.[Conclusions]PPPs could reduce the expression levels of TNF-α,IL-6 and MDA in mice,and increase the expression levels of SOD and GSH to achieve the protective effect on acute alcoholic liver injury in mice.This study will provide new ideas for the development of new anti-alcoholic liver injury drug resources.
文摘Alcoholic liver disease(ALD)is the most common liver disease in the Western world.For many reasons,it isunderestimated and underdiagnosed.An early diagnosis is absolutely essential since it(1)helps to identify patients at genetic risk for ALD;(2)can trigger efficient abstinence namely in non-addicted patients;and(3)initiate screening programs to prevent life-threateningcomplications such as bleeding from varices,spontaneous bacterial peritonitis or hepatocellular cancer.The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis(AH).The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on acombination of laboratory,clinical and imaging findings.It is not widely conceived that conventional screeningtools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca.40%of manifest alcoholic liver cirrhosis.Non-invasive methods such as transient elastography(Fibroscan),acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholiccirrhosis.Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca.95%of patients.The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels.Other non-invasive methods such as controlled attenuation parameter,serum levels of M30 or M65,susceptometry or breath tests are under current evaluation to assess the degree of steatosis,apoptosis and iron overload in these patients.Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH.
文摘The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most florid presentation of alcoholic liver disease, continues to have high morbidity and mortality, with significant financial and healthcare burden with limited treatment options. Steroids remain the current standard of care in severe alcoholic hepatitis in carefully selected patients. No specific treatments are available for those patients who are steroid ineligible, intolerant or unresponsive. Liver transplant has shown good short-term outcome; however, feasibility, ethical and economic concerns remain. Modification of gut microbiota composition and their products, such as lipopolysaccharide, nutritional interventions, immune modulation, increasing steroid sensitivity, genetic polymorphism and epigenetic modification of alcohol induced liver damage, augmenting hepatic regeneration using GCSF are potential therapeutic avenues in steroid non-responsive/ineligible patients. With better understanding of the pathophysiology, using “Omics” platforms, newer options for patients with alcoholic hepatitis are expected soon.
文摘Non-alcoholic fatty liver disease(NAFLD)is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome(MetS).Because alcohol consumption in NAFLD patients is common,there is a significant overlap in the pathogenesis of NAFLD and alcoholic liver disease(ALD).Indeed,MetS also significantly contributes to liver injury in ALD patients.This“syndrome of metabolic and alcoholic steatohepatitis”(SMASH)is thus expected to be a more prevalent presentation in liver patients,as the obesity epidemic continues.Several pre-clinical experimental models that couple alcohol consumption with NAFLDinducing diet or genetic obesity have been developed to better understand the pathogenic mechanisms of SMASH.These models indicate that concomitant MetS and alcohol contribute to lipid dysregulation,oxidative stress,and the induction of innate immune response.There are significant limitations in the applicability of these models to human disease,such as the ability to induce advanced liver injury or replicate patterns in human food/alcohol consumption.Thus,there remains a need to develop models that accurately replicate patterns of obesogenic diet and alcohol consumption in SMASH patients.
基金Supported by the Swiss National Science Foundation,No.314730-146991(to Negro F)the Swiss National Science Foundation,No.310030-152618 and No.CRSII3-160717(to Foti M)
文摘AIM: To investigate the protein expression of phosphatase and tensin homolog (PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease.METHODS: PTEN protein expression was assessed by immunohistochemistry in formalin-fixed, paraffin-embedded liver sections of patients with non-alcoholic fatty liver disease (NAFLD) (n = 44) or alcoholic liver disease (ALD) (n = 25). Liver resections obtained from 3 healthy subjects candidate for partial liver donation served as controls. Histological evaluations were performed by two experienced pathologists, and diagnoses established based on international criteria. The intensity of the PTEN staining in nuclei was compared between steatotic and non-steatotic areas of each liver fragment analyzed. For each liver specimen, the antibody-stained sections were examined and scored blindly by three independent observers, who were unaware of the patients’ clinical history.RESULTS: In healthy individuals, PTEN immunostaining was intense in both the cytoplasm and nuclei of all hepatocytes. However, PTEN was strongly downregulated in both the nucleus and the cytoplasm of hepatocytes from steatotic areas in patients with NAFLD, independently of the disease stage. In contrast, no changes in PTEN protein expression were observed in patients with ALD, regardless of the presence of steatosis or the stage of the disease. The degree of PTEN downregulation in hepatocytes of patients with NAFLD correlated with the percentage of steatosis (r = 0.3061, P = 0.0459) and the BMI (r = 0.4268, P = 0.0043). Hovewer, in patients with ALD, PTEN expression was not correlated with the percentage of steatosis with or without obesity as a confounding factor (P = 0.5574). Finally, PTEN expression level in steatotic areas of ALD patients was significantly different from that seen in steatotic areas of NAFLD patients (P < 0.0001).CONCLUSION: PTEN protein expression is downregulated early in NAFLD, but not in ALD. PTEN immunohistochemical detection could help in the differential diagnosis of NAFLD and ALD.
文摘The severity of alcoholic hepatitis(AH) which may coexist with cirrhosis varies greatly, from asymptomatic forms which are detected in alcoholic patients without any sign of liver disease, except laboratory abnormalities, to severe forms characterised by deep jaundice, ascites, hepatic encephalopathy and low prothrombin index. In hospitalized patients the mortality could be as high as 75%. The elevated number of therapeutic proposals reported for more than forty years reveals the lack of efficacy of a particular modality. Even in the most favorable trials, the survival is already very poor and in some cases related to the development of renal failure or hepatorenal syndrome. There are some motivating reports concerning albumin dialysis as a support treatment in patients with severe AH, either alone or in combination with other pharmacological therapies. The favorable effects of albumin dialysis in patients with severe AH suggest that the procedure used alone or in combination with other therapies may have a role in this clinical condition. This will be particularly relevant to offer an alternative therapy in these patients, thus being a potential bridge to recovery or to be listed for liver transplantation.
基金funded by Institutional Fund Projects (IFPIP:515-961-1443)technical and financial support provided by the Ministry of Education and King Abdulaziz University, DSR, Jeddah, Saudi Arabia。
文摘The aggregation behavior of the mixture of cetyltrimethylammonium chloride(CTAC), a cationic surfactant, and moxifloxacin hydrochloride(MFH), a fourth-generation fluoroquinolone antibiotic drug, has been studied using the conductivity technique in aqueous and alcoholic(EtOH, 1-PrOH, and 2-BuOH)media. The study was performed at several temperatures between 298.15 and 323.15 K at 5 K intervals.The assembly has been characterized by evaluating the micellar parameters, such as the critical micelle concentration(CMC) and the counter ion binding(β), of the CTAC + MFH mixture. The values of the CMC for the assembly of the CTAC + MFH mixture were reliant on the composition of alcohols in the mixed solvents and the temperature. The CMC values of the CTAC + MFH mixture increased with increasing temperature;that is, assembly was delayed by increased temperature. The micellization of the CTAC + MFH mixed system was delayed in alcoholic media. The observed-ΔG0mvalues for the association of the CTAC + MFH mixed system demonstrated a spontaneous aggregation process under all study conditions.Based on the-ΔH^(0)_(m) and +ΔS^(0)_(m) values, the association of the CTAC + MFH mixture is exothermic and the interaction forces acting between the CTAC and MFH species are hydrophobic, ion–dipole, and electrostatic interactions. The transfer properties and enthalpy–entropy compensation were also assessed and described comprehensively.
