Effect of Cistanches Herba Phenylethanoid Glycosides on Intestinal Mucosal Barrier and Gut Microbiota in ALD Mice / 中国实验方剂学杂志

ObjectiveTo discuss the effects of Cistanches Herba phenylethanoid glycosides （CHPhGs） on the intestinal mucosal barrier and gut microbiota in alcoholic liver disease （ALD） mice were discussed. MethodThe 36 C57BL/6N female mice were randomly divided normal group， normal group of CHPhGs， model group， and low， medium， and high-dose groups （175， 350， 700 mg·kg-1） of CHPhGs， with six mice in each group. The ALD mouse model was built using Lieber-Decarli alcohol liquid feed. The normal group and low， medium， and high-dose groups of CHPhGs were given CHPhGs by gavage daily. Serum aspartate aminotransferase aminotransferase （ALT）， alanine aminotransferase （AST）， triglycerides （TG）， and total cholesterol （TC） levels were detected by an automatic biochemical analyzer. Serum tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， lipopolysaccharide （LPS）， lipopolysaccharide-binding protein （LBP）， D-lactic acid （D-LA）， diamine oxidase （DAO）， and LBP of liver were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of TG and TC in the liver were detected by colorimetry. Liver tissue was treated by oil red O and hematoxylin-eosin （HE） staining. The microstructure of jejunum epithelial cells was observed by electron microscope. Jejunum and colon were treated by HE staining and alcian blue-periodate-scheff (AB-PAS) staining staining， and mucin 2 （Muc2） was treated by immunohistochemistry. The intestinal contents of the normal group， normal group of CHPhGs， model group， and high-dose group of CHPhGs were collected and sequenced. ResultThe ALD model was established successfully. Compared with the normal group， the levels of serum ALT， AST， and TG， as well as the levels of liver TG and TC in the model group were significantly increased （P<0.05）. Histopathology showed that compared with the normal group， the liver cells in the model group showed obvious steatosis. Compared with the model group， the levels of serum TG and liver TG and TC in the low， medium， and high-dose groups of CHPhGs decreased significantly （P<0.05）. The serum ALT， AST， TNF-α， IL-1β， LPS， and LBP in the high-dose group of CHPhGs were also significantly decreased （P<0.05）. The number of liver cells with steatosis in the high-dose group of CHPhGs was significantly reduced， and the microvilli structure of jejunum epithelial cells was basically intact. The expression of Muc2 was reduced in the colon， and the gut microbiota of the high-dose group of CHPhGs changed significantly （P<0.05）. Compared with the normal group， the Allobaculum was significantly up-regulated in the model group （P<0.05）. Compared with the model group， the abundance of Akkermansia in the high-dose group of CHPhGs was significantly increased （P<0.01）. The abundance of Akkermansia was negatively correlated with that of Allobaculum （r=-0.701， P<0.01）. ConclusionCHPhGs can reduce the intestinal barrier injury caused by ALD， which may play a protective role by regulating the abundance and structure of Akkermansia and Allobaculum and affecting the homeostasis of intestinal mucus.

Randomized Clinical Trial of an Ayurvedic Formulation, BV-7310 in Alcoholic Liver Disease

Alcoholic liver disease (ALD) is caused by excessive intake of alcohol for many years. The incidence is as high as 25% in the United States, India and several other countries. The disease spectrum varies from fatty liver in initial stages, to hepatitis and finally cirrhosis. Untreated ALD can be fatal. Yet the options for prescription drugs are limited, and not easily available or affordable to the masses worldwide. BV-7310 contains herbal extracts of Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa and Andrographis paniculata. The individual plants are known hepatoprotective agents in Ayurveda. The objective of this study was to investigate the safety and efficacy of BV-7310, a proprietary combination standardized formulation, in subjects with ALD. A multi-centric, double-blind, placebo-controlled, randomized study of 61 subjects was conducted for a period of 12 weeks. Subjects on BV-7310 showed improvement in clinical features of ALD as compared to placebo, including reduction and normalization of transaminases. BV-7310 also reduced bilirubin levels to normal, showing improvement in the detoxifying and excretory capabilities of the liver. No significant adverse events were seen in the treatment group. Based on the data shown, BV-7310 shows promise as a safe and effective hepatoprotective in patients of ALD.

Amelioration of ethanol-induced oxidative stress and alcoholic liver disease by in vivo RNAi targeting Cyp2e1

Alcoholic liver disease (ALD) results from continuous and heavy alcohol consumption. The current treatment strategy for ALD is based on alcohol withdrawal coupled with antioxidant drug intervention, which is a long process with poor efficacy and low patient compliance. Alcohol-induced CYP2E1 upregulation has been demonstrated as a key regulator of ALD, but CYP2E1 knockdown in humans was impractical, and pharmacological inhibition of CYP2E1 by a clinically relevant approach for treating ALD was not shown. In this study, we developed a RNAi therapeutics delivered by lipid nanoparticle, and treated mice fed on Lieber-DeCarli ethanol liquid diet weekly for up to 12 weeks. This RNAi-based inhibition of Cyp2e1 expression reduced reactive oxygen species and oxidative stress in mouse livers, and contributed to improved ALD symptoms in mice. The liver fat accumulation, hepatocyte inflammation, and fibrosis were reduced in ALD models. Therefore, this study suggested the feasibility of RNAi targeting to CYP2E1 as a potential therapeutic tool to the development of ALD.

Puerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8 / 中国天然药物

Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1β, compared with silymarin (Sil, 100 mg·kg-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.

Melatonin alleviates alcoholic liver disease via EGFR-BRG1-TERT axis regulation

Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT. MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models (optimal doses of 10 μmol/L and 5 mg/kg, respectively), including lowered liver steatosis, cell death, and inflammation. RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase (TERT) was a key downstream effector of MLT. Biophysical assay found that epidermal growth factor receptor (EGFR) on the hepatocyte surface was a direct binding and regulating target of MLT. Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection, partly through the regulation of nuclear brahma-related gene-1 (BRG1). Long-term administration (90 days) of MLT in healthy mice did not cause evident adverse effect. In conclusion, MLT is an efficacious and safe agent for ALD alleviation. Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis. MLT might be used as a complimentary agent for alcoholics.

Methyl ferulic acid ameliorates ethanol-induced L02 cell steatosis through microRNA-378b-mediated CaMKK2-AMPK pathway / 中国中药杂志

Alcoholic liver disease(ALD), with its increasing morbidity and mortality, has seriously and extensively affected the health of people worldwide. Methyl ferulic acid(MFA) has been proven to significantly inhibit alcohol-induced lipid production in L02 cells through the AMP-activated protein kinase(AMPK) pathway, but its in-depth mechanism remains unclear. This study aimed to further clarify the mechanism of MFA in improving lipid accumulation in L02 cells through the microRNA-378b(miR-378b)-mediated calcium/calmodulin-dependent protein kinase kinase 2(CaMKK2)-AMPK signaling pathway based on existing researches. L02 cells were induced by 100 mmol·L~(-1) ethanol for 48 h to establish the model of ALD in vitro, and 100, 50, and 25 μmol·L~(-1) concentration of MFA was treated. MiR-378b plasmids(containing the overexpression plasmid-miR-378b mimics, silence plasmid-miR-378b inhibitor, and their respective negative control-miR-378b NCs) were transfected into L02 cells by electroporation to up-regulate or down-regulate the levels of miR-378b in L02 cells. The levels of total cholesterol(TC) and triglyceride(TG) in cells were detected by commercial diagnostic kits and automatic biochemical analyzers. The expression levels of miR-378b in L02 cells were detected by real-time quantitative polymerase chain reaction(qRT-PCR). CaMKK2 mRNA levels were detected by PCR, and protein expressions of related factors involved in lipid synthesis, decomposition, and transport in lipid metabolism were detected by Western blot. The results displayed that ethanol significantly increased TG and TC levels in L02 cells, while MFA decreased TG and TC levels. Ethanol up-regulated the miR-378b level, while MFA effectively inhibited the miR-378b level. The overexpression of miR-378b led to lipid accumulation in ethanol-induced L02 cells, while the silence of miR-378b improved the lipid deposition induced by ethanol. MFA activated the CaMKK2-AMPK signaling pathway by lowering miR-378b, thus improving lipid synthesis, decomposition, and transport, which improved lipid deposition in L02 cells. This study shows that MFA improves lipid deposition in L02 cells by regulating the CaMKK2-AMPK pathway through miR-378b.

Caracterización clínico-epidemiológica de los pacientes sometidos a trasplante hepático por cirrosis alcohólica en el Hospital Pablo Tobón Uribe de Medellín entre 2004 y 2015 / Clinical-epidemiological characterization of patients undergoing liver transplantation for alcoholic cirrhosis at the Pablo Tobón Uribe Hospital in Medellín between 2004 and 2015

Introducción. El alcohol ha sido asociado con más de 60 enfermedades diferentes y es el tercer factor de riesgo más común relacionado con muerte y discapacidad en el mundo. La enfermedad alcohólica hepática (EAH) es la causa más común de enfermedad hepática terminal (EHT) en los países occidentales. El objetivo de este estudio fue caracterizar la población adulta sometida a trasplante ortotópico hepático (TOH) indicado por EHT secundaria a EAH, en el Hospital Pablo Tobón Uribe (HPTU) de Medellín entre 2004 y 2015. Metodología. Estudio observacional retrospectivo. Se revisaron las historias clínicas electrónicas de todos los pacientes trasplantados en el HPTU entre los años 2004 y 2015, sometidos a TOH indicado por EHT secundaria a EAH. Se registraron las características demográficas, comorbilidades médicas y psiquiátricas, complicaciones tempranas y tardías, recaída en el consumo de alcohol posterior al TOH, supervivencia y causa de la muerte. Resultados. Se encontraron 59 pacientes trasplantados por cirrosis de origen alcohólico. El 91,5 % fueron de sexo masculino, el 82,6 % (38/46) tuvo un período abstinencia previo al TOH mayor o igual a 6 meses, y solamente el 10,2 % (6/59) de los pacientes estuvieron vinculados a un programa de adicciones. Se encontró comorbilidad psiquiátrica en el 30 % (18/59) con predomino de depresión. Se identificó recaída pesada en el consumo de alcohol postrasplante en 6 pacientes, este subgrupo se caracterizó por una alta mortalidad (66 %), pobre adherencia a la terapia inmunosupresora y alta frecuencia de depresión (83 %). En general, la cohorte tuvo una supervivencia a 5 y 10 años de 60,8 % y 28,1 %, respectivamente. Conclusiones. Las características epidemiológicas de la población son compartidas con reportes previos en relación al predominio de sexo masculino y adultos en la sexta década de la vida. La recaída en el consumo pesado de alcohol no es la regla, sin embargo, se encuentra asociada con abandono del tratamiento inmunosupresor y muerte. En comparación con reportes de otros países, nuestras tasas de complicaciones y mortalidad a 5 años son superiores.

Introduction. Alcohol has been associated with more than 60 different diseases and is the third most common risk factor related to death and disability throughout the world. Alcoholic liver disease is the most common cause of end-stage liver disease in Western countries. The main objective of this study was to characterize adult patients with orthotopic liver transplant due to alcoholic cirrhosis at the Pablo Tobón Uribe Hospital in Medellín between 2004 to 2015. Methodology. Observational retrospective study. We reviewed clinical records of all patients with orthotopic liver transplant due to alcoholic cirrhosis at the HPTU between 2004 and 2015, and retrieved demographic data, comorbidities, complications, consumption relapse and survival. Results. We analyzed 59 patients, 91.5% were male, 82.6% had an abstinence period previous to liver transplant equal or greater to six months, 10.2% were part of an addiction program, and 30% had psychiatric morbidities, mainly depression. We identified 6 patients with heavy alcoholic relapse after transplantation, this subgroup was characterized by a high mortality (66%), poor adherence to immunosuppressive therapy and high rates of depression (83%). In general, this cohort had a 5- and 10-year survival of 60.8% and 20.1%, respectively. Conclusions. The epidemiological characteristics of the population are shared with previous reports regarding the predominance of males and adults in the sixth decade of life. Relapse into heavy alcohol consumption is not the rule, however, it is associated with discontinuation of immunosuppressive treatment and death. In comparison with other reports, we have higher complications and mortality rates at 5 five years.

Recaída en el consumo de alcohol después del trasplante de hígado por hepatopatía alcohólica / Alcohol relapse after liver transplantation for alcoholic liver disease

Introducción. La enfermedad hepática inducida por uso de alcohol se ha considerado una enferme-dad autoinfligida que limitaba el acceso al trasplante. Actualmente es una de las principales indicacio-nes de trasplante hepático en Colombia y el mundo, con excelente sobrevida. Metodología. Estudio descriptivo observacional donde se realizó una caracterización de los pacientes con trasplante hepá-tico por hepatopatía alcohólica en una institución de cuarto nivel, que incluyó un estudio cualitativo de la recaída en el consumo de alcohol postrasplante. Resultados. De 87 pacientes de una cohorte inicial de 96 pacientes trasplantados entre 2003 y 2021, se describieron características sociodemo-gráficas, comorbilidades previas y adquiridas posterior al trasplante, supervivencia del paciente y del injerto, y factores de riesgo asociados al consumo de alcohol. Adicionalmente, a 65 pacientes se les pudo realizar una entrevista estructurada para evaluar la recaída en el consumo de alcohol, 41,53 % volvieron a consumir alcohol; 23,07 % en patrón de riesgo de recaída y 18,46 % en patrón de slip (desliz). El antecedente de hepatitis alcohólica tuvo un RR de 3,273 (1,464­7,314) y p=0,007 para recaída en el consumo de alcohol, y la comorbilidad psiquiátrica un RR de 2,395 (1,002­5,722) y p=0,047. Finalmente, haber presentado al menos una recaída postrasplante tuvo un RR de 5,556 (1,499­20,588) con p=0,005 para rechazo del injerto. Conclusiones. La recaída en el consumo de alcohol fue frecuente, la hepatitis alcohólica previa y la comorbilidad psiquiátrica son factores de riesgo asociados. La recaída se asoció a rechazo del injerto sin afectar la sobrevida del paciente.

Introduction. Alcohol-induced liver disease has been considered a self-inflicted disease that limited access to transplantation. It is currently one of the main indications for liver transplantation in Colom-bia and the world, with excellent survival. Methodology. Observational descriptive study where a characterization of liver transplant patients due to alcoholic liver disease was carried out in a fourth level institution, which included a qualitative study of relapse in post-transplant alcohol consumption. Results. Of 87 patients from an initial cohort of 96 transplant patients between 2003 and 2021, sociodemographic characteristics, previous and acquired post-transplant comorbidities, patient and graft survival, and risk factors associated with alcohol consumption were described. Additionally, 65 patients were able to undergo a structured interview to assess relapse in alcohol consumption, 41.53% returned to alcohol consumption; 23.07% in risk relapse pattern, and 18.46% in slip pattern. The history of alcoholic hepatitis had a RR of 3.273 (1.464-7.314) and a p=0.007 for relapse in alcohol consumption, and psychiatric comorbidity a RR of 2.395 (1.002-5.722) and a p=0.047. Finally, having presented at least one post-transplant relapse had a RR of 5.556 (1.499-20.588) with ap=0.005 for graft rejection. Conclusions. Relapse in alcohol consumption was fre-quent, previous alcoholic hepatitis and psychiatric comorbidity were associated risk factors. Relapse was associated with graft rejection without affecting patient survival.

Knowledge of alcohol consumers towards alcoholic liver disease in Afikpo, Ebonyi, Nigeria A community-based cross-sectional study

Background: Daily alcohol consumption above recommended limits is an important cause of Alcoholic Lher Disease. Hence, this study aimed to assess the knowledge of Alcoholic Liver Disease among alcohol consumers and screenfor alcohol misuse, dependence, and disorder. Methods: A community-based cross-sectional survey using simple random sampling technique was conducted on residents ofÅfikpo age 15 and above who consume alcohol using a structured questionnaire to obtain information on alcoholic use disorder and alcohol dependence. The sample size Itas determined Il'ith the aid of a Raosoft sample size calculator. Data obtained was entered into an excel spreadsheetfor data cleaning. The frequency, percentages and mean and Standard deviation was also obtained. Data was exported into IBM SPSS to determine the relationship behre.en knou:ledge of Alcoholic Liver Disease and demographic variables using One-way ANOL4 and Chi-Square Il'here appropriate at P-value <0.05 and 5% significance level. Results: The total number of study participants was 435 with a response rate of 97%. Out of which had a good knowledge of Alcoholic Liver Disease. Adults above the age of 60 had a mean audit score of 12.808 Il'hile male respondents had a mean audit score of 11.395. Adolescents had a mean CAGE test score of 1.89 while adults above 60 scored 2.48. Hou•ever, participants with no education had the highest mean CAGE score of2.27. The males had good knowledge ofAlcoholic Liver Disease. (P 0.006). Conclusion: The residents ofÅfikpo community have a good knowledge ofAlcoholic Lher Disease though there is alcohol use disorder, alcohol misuse and dependence amongst residents in the community. Gender is the only demographic characteristics that influenced the knowledge ofAlcoholic Liver Disease

Research advances on the role of epigenetic modifications in the long-term progression of alcoholic liver disease / 药学学报

There are more than 60 million alcoholic liver disease (ALD) patients in China, which has become a public health problem that cannot be ignored. Moreover, the social problem of "alcohol culture" is still hardly to solve, so that safe and effective prevention and treatment for ALD are in urgent need clinically. Previous studies on ALD have focused on the direct damaging effects of alcohol and its toxic metabolites, while recent studies have shown that the pathogenesis of ALD also include alcohol metabolic reprogramming and endogenous metabolites disorder. Although the endogenous metabolites have no direct toxicity, its long-term effect should not be ignored. These endogenous metabolites could change epigenetic modifications, cause widespread and persistent abnormal gene expression and signal pathway activation abnormally to promote metabolic reprogramming and stamp it as "metabolic memory", which manifest pathological changes and promote ALD, especially liver fibrosis/cirrhosis and liver cancer. Based on this, the article reviews the important epigenetic modifications caused by related metabolites in ALD and their associated effects. The role of traditional Chinese medicine (TCM) and its active ingredients in regulating epigenetics was also analyzed. The results suggest that regulation of epigenetics and alteration of "metabolic memory" may be a novel mechanism of TCM in the prevention and treatment of ALD.

Glycated hemoglobin and fructosamine level in complicated and non-complicated chronic alcoholic liver disease

Background: Chronic alcohol ingestion is one of the major causes of liver disease. Uncontrolled glucose concentration in chronic alcoholic liver disease will have poor prognosis. Hence, the study is undertaken to see markers of chronic glucose control, that is, serum fructosamine and glycated hemoglobin and their usefulness to show the severity of chronic alcoholic liver disease. Aim and Objectives: The study is conducted to check that between glycated hemoglobin and fructosamine which is better to check glycemic control and severity/prognosis of chronic alcoholic liver disease. Materials and Methods: 60 cases of chronic alcoholic liver disease patients of age group 20–70 years of both sexes with 30 age- and sex-matched healthy controls were taken. Cases were divided into non-complicated and complicated groups. Glycated hemoglobin was estimated by immunoturbidimetry method, serum fructosamine level was estimated by colorimetry using nitro blue tetrazolium, SGOT was estimated by method by IFCC and serum total protein was estimated by biuret method. Results: The mean concentration of HbA1c and serum total protein was decreased in both groups of cases compared to controls. The mean concentrations of serum fructosamine and SGOT were increased in both groups of cases. There was no significant difference in the mean value of serum total protein in non-complicated cases with controls. There was no significant difference in the mean value of HbA1c between non-complicated and complicated cases. SGOT was considered for correlation, it was found out that it had significant negative correlation with serum total protein, significant positive correlation with serum fructosamine, and no correlation with HbA1c. Significant negative correlation was found between serum total protein and serum fructosamine. Conclusion: This study shows that serum fructosamine is a better marker to monitor chronic glucose control and severity of chronic alcoholic liver disease compared to HbA1c.

A rare case of thrombocytosis presentation in patient alcoholic liver disease with portal hypertension gastropathy: a stepwise evaluation

Thrombocytosis is rarely found in patient with chronic liver disease (CLD). The possibility of reactive thrombocytosis could be due to sustained process such as iron deficiency anemia (IDA) because of occult bleeding. Occult bleeding can happen in CLD patient because of portal hypertension gastropathy (PHG) as complication of portal hypertension. A carefully evaluation of anemia can lead to underlying cause of disease, even in limited of supportive evaluationand some other confounding presentation that is thrombocytosis.We report a case of 54 years-old male patient with severe anemia. He had same symptom previously and got transfusion. Peripheral blood smear showed microcytic hypochromic anemia, anisocytosis, and poikilocytosis even pencil cells (pencil cells or cigar cells) with thrombocytosis. No symptom of acute inflammation setting and no clear blood loss was founded. As patient admitted to smoking and heavy alcohol consumption in the past, Ultrasound was performed for screening of underlying disease that cause occult bleeding. Ultrasound of the liver showed generally increased echogenicity suggestive of liver cirrhosis, splenomegaly and minimal ascites. Thus, our patient clinically be suggestive of CLD with portal hypertension that cause PHG.

Adulto con hematoma medular epidural espontáneo

RESUMEN El hematoma espinal es una entidad clínica poco frecuente. Se necesita de una alta sospecha clínica para su diagnóstico precoz y tratamiento oportuno. Habitualmente se presenta en forma de deterioro neurológico súbito debida a la compresión medular mecánica producida por sangre en el canal medular. Presentamos el caso de un paciente de sexo masculino de 53 años, consumidor de bebidas alcohólicas (ron paraguayo) en forma diaria que presenta un deterioro neurológico brusco comprometiendo miembros superiores e inferiores. Con la resonancia magnética se llega al diagnóstico de hematoma epidural a nivel de C4-C5 y mielopatía compresiva de los segmentos adyacentes.

ABSTRACT The spinal hematoma spinal is a infrequent clinical entity. A high clinical suspicion is needed for early diagnosis and timely treatment. It usually presents as a sudden neurological deterioration due to mechanical spinal cord compression caused by blood in the spinal canal. We present the case of a 53-year-old male patient, a daily consumer of alcoholic beverages (Paraguayan rum) who presented sudden neurological deterioration compromising upper and lower limbs. Magnetic resonance imaging leads to a diagnosis of epidural hematoma at the C4-C5 level and compressive myelopathy of the adjacent segments.

A Comparative Study on Outcome of Amoebic Liver Abscess in Patients With and Without Alcoholic Liver Disease

Background: Amoebic liver abscesses (ALA) in the presence of Alcoholic liver disease (ALD) constitutes a high-risk group of patients who are prone to complications and may need more aggressive treatment. This study was aimed at evaluating disease course and outcomes in patients of ALA with ALD, in comparison to those without ALD. Material & Methods: This prospective observational study was conducted on 60 consecutive patients of ALA without ALD (Group-I) and 60 consecutive patients of ALA with ALD (Group II). Result: The patients ALA with ALD were older (47.2 ±13.3 years) than those without ALD (34.1±14 years). Mean size of the abscess cavity was significantly larger in patients with ALD (391.2± 208.7 cc in Group I and 594.3 ± 297.9 cc in Group II). In Group I, conservative management was most common (43.3%); while in Group II pigtail catheter insertion was the most frequently used modality of treatment (45%). Complications like empyema (6.6%), acute on chronic liver failure (8.3%) and impending liver failure (23.3%) manifesting as ascites and oedema were seen only in patients in Group II and they also had longer hospital stay. (4.87 days in Group I vs 8.37 in Group II). Conclusion: Patients of ALA with ALD have a more aggressive course of disease and should be managed with a lower threshold for abscess drainage.

Advances in the establishment of rodent model of alcoholic liver disease / 中国热带医学

@#Abstract:Alcoholic liver disease (ALD) is one of the most common liver diseases in the world. Long-term alcoholism causes a series of pathological changes in the liver, which eventually leads to the occurrence of liver diseases with an increasing incidence. At present, significant progress has been made in the pathogenesis and pathological development of alcoholic liver disease, but the relevant mechanism of ALD has not been thoroughly studied. It is necessary to improve the existing animal model or establish a new, more comprehensive animal ALD model to simulate human ALD. Experimental animal models of ALD, especially rodents, are often used to simulate human ALD, and the ideal rodent ALD model can effectively simulate all aspects of alcohol in human liver. But so far, the commonly used animal models all have certain defects, and there is no complete animal model that can simulate human ALD. This paper reviewed the pathogenesis of ALD, related methods and influencing factors of ALD model, and provided a theoretical basis for relevant researchers to establish the ALD rodent model. 

Research advances in glucose and lipid metabolism disorders in different types of chronic liver diseases / 临床肝胆病杂志

The liver is an important metabolic organ in the body. Studies have shown that chronic liver disease is closely associated with glucose and lipid metabolism disorders, and different types of liver diseases often show different characteristics of glucose and lipid metabolism. This article reviews the epidemiological characteristics, disease severity, pathogenesis, and treatment methods of glucose and lipid metabolism disorders in different types of chronic liver diseases, so as to improve the awareness among clinicians.

Extracts of Poria cocos polysaccharides improves alcoholic liver disease in mice via CYP2E1 and NF-κB inflammatory pathways / 中国中药杂志

The present study investigated the effect of extract of Poria cocos polysaccharides(PCP) on cytochrome P450 2 E1(CYP2 E1) and nuclear factor κB(NF-κB) inflammatory signaling pathways in alcoholic liver disease(ALD) mice and explored its protective effect and mechanism. Sixty male C57 BL/6 N mice of SPF grade were randomly divided into a control group, a model group, a positive drug group(bifendate, 200 mg·kg~(-1)), and high-(200 mg·kg~(-1)) and low-dose(50 mg·kg~(-1)) PCP groups. Gao-binge mo-del was induced and the mice in each group were treated correspondingly. Liver morphological and pathological changes were observed and organ index was calculated. Serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected. Malondialdehyde(MDA) and superoxide dismutase(SOD) in liver tissues were detected by assay kits. The levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The activation of macrophages was observed by immunofluorescence staining and protein expression of CYP2 E1, Toll-like receptor 4(TLR4), NF-κB p65, and phosphorylated NF-κB p65(p-NF-κB p65) were analyzed by Western blot. The ALD model was properly induced. Compared with the model group, the PCP groups significantly improved the pathological injury of liver tissues. Immunofluorescence staining revealed that compared with the model group, the groups with drug intervention showed decreased macrophages in liver tissues. Additionally, the PCP groups showed reduced ALT, AST, MDA, IL-6, and TNF-α(P<0.05), and potentiated activity of SOD(P<0.01). PCP extract has the protective effect against alcoholic liver injury in mice, and the underlying mechanism may be related to the regulation of the expression of CYP2 E1 and inhibition of TLR4/NF-κB inflammatory signaling pathway to reduce oxidative stress and inflammatory injury, thereby inhibiting the development of ALD.

Protective effects of the total glycosides of Cistanche deserticola Y. C. Ma in alcoholic liver injury in mice / 药学学报

Modern pharmacological studies have shown that Cistanche deserticola (C. deserticola) has a protective effect on the liver, but its active fraction and mechanism are not clear. In order to identify the effective fraction of C. deserticola Y. C. Ma, an acute alcoholic liver injury model in mice was established with 56-proof Erguotou and different fractional extracts of C. deserticola Y. C. Ma (total glycosides, polysaccharides, and oligosaccharides) were administered. After 14 days of oral administration, liver pathology and lipid deposition were measured and the expression of nuclear factor E2-related factor (Nrf-2), kelch-like ECH-associated protein-1 (Keap-1), and plasmalemma vesicle-associated protein-1 (PV1) were measured by immunofluorescence. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), endotoxin (ET), diamine oxidase (DAO), and D-lactic acid (D-LA) in serum, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) in liver were measured by ELISA. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Peking University Health Science Center. The results show that the total glycosides of C. deserticola Y. C. Ma (400 mg·kg-1) could decrease liver pathology, decrease serum endotoxin, diamine oxidase, and D-lactic acid, and reduce hepatic lipid deposition. Total glycosides also promoted Nrf-2 transfer into the nucleus and decreased the expression of Keap-1 and PV1. In summary, the total glycosides of C. deserticola Y. C. Ma had a protective effect in acute alcoholic liver injury and the mechanism may be related to the activation of the Nrf-2/Keap-1 pathway, improvement of intestinal wall integrity, and inhibition of the transport of harmful substances into the liver.

The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment

A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2 (ALDH2). The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported. Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types. Furthermore, the ALDH2∗2 polymorphism (rs671) is the most common single nucleotide polymorphism (SNP) in Asia. Epidemiological studies associate ALDH2∗2 with tumorigenesis and progression. This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence, progression, and treatment of tumors in various types of cancer. Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy.

The Role of Interleukin-6 in Alcoholic Liver Disease / 中国生物化学与分子生物学报

Alcoholic liver disease (ALD) is a chronic liver disease in which the internal liver tissues are inflammation damaged caused by long-term excessive drinking. Direct or indirect induction of hepatic inflammatory response by ethanol and its derivatives in the metabolic process may be an important mechanism of ALD, but the underlying cellular and molecular mechanisms of this process are still unclear. Recent study found that interleukin-6 (IL-6) response to ethanol mediated inflammation of the liver cells with dual role. It is involved in an inflammatory process that drives alcohol damage, activate cell apoptosis signaling pathways to stimulate macrophage and lymphocyte acute reactive protein synthesis aggravate the inflammatory response, and can lead to liver cell regeneration, increase anti-inflammatory cytokine levels play anti-inflammatory function to improve the degree of liver injury, and exercise stress can cause muscle source sex IL-6 temporary increased significantly, change the liver oxidation-inflammatory state. Then the body is kept in the adaptive state of long-term anti-inflammation to prevent the inflammatory damage of liver cells. Based on deepening the understanding of ALD inflammation pathological mechanism at the same time, the review on alcoholic liver cell inflammation related factor change and the IL-6 regulation pathway, considering the clinical use of IL-6 joint inflammatory factor pathway of targeted therapy is expected to be a novel therapy, the feasibility for laboratory screening of inflammatory related ALD drug intervention, for the prevention of alcoholic liver disease and treatment to provide new targets and train of thought.