Various Types Of Liver Disease Research Articles

Advances in the study of the mechanism of action of miR‑22 in liver lesions (Review).

Globally, nearly 2 million deaths annually are attributed to the development of liver diseases, with liver cancer and cirrhosis being particularly prominent, which makes liver disease a significant global health concern. Cirrhosis is closely linked to the evolution of hepatitis, hepatic fibrosis and fatty liver. However, most liver diseases have an insidious onset, are challenging to treat and the prognosis and efficacy of current therapies are unsatisfactory, which can result in irreversible functional damage to the liver. Therefore, there is an urgent need to explore the molecular mechanisms underlying liver disease and identify new biomarkers and therapeutic targets. In previous years, microRNAs (miRs), a class of short non-coding RNAs comprising 17-25 nucleotides, have attracted attention for their roles in various types of liver diseases. Among them, miR-22 serves a unique role in mediating multiple pathway mechanisms and epigenetic modifications and can act both as an inhibitor of liver cancer and a metabolic blocker. Given its close association with the liver, several studies have reported that the differential expression of miR-22 regulates the metabolic process of liver cancer and is involved in the evolution of hepatic fibrosis and steatohepatitis, making it a potential target for early diagnosis and treatment. The present manuscript aimed to comprehensively review the key role of miR-22 in the evolution of liver diseases and offer valuable references and guidance for subsequent studies by identifying its specific mechanism of action and future development prospects.

Alteration of liver function tests in various liver diseases

Background: The burden of liver diseases in India has witnessed a significant rise, spurred by factors such as viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, and a spectrum of metabolic and genetic disorders. Liver function tests (LFTs) serve as invaluable tools in the hands of clinicians, offering insights into the dynamic interplay between hepatic health and various disease processes. This study aims to provide a detailed exploration of the alterations in LFTs associated with various liver diseases prevalent in India. Aim and Objectives: (i) To Identify the various types of Liver diseases; (ii) To evaluate the various liver function tests in various liver diseases. Materials and Methods: The study involved the collection of samples from 100 liver disease patients who seek medical care at C. U. Shah Medical College and Hospital. Informed consent was obtained from all participants and the study protocol was approved by the institutional ethics committee. Results: Our study shows that the prevalence of cirrhosis of liver was 25% among study participants. Majority of liver disease were prevalent in male whereas, mostly affected age group was 51–60 years. Bilirubin was altered in cirrhosis of liver (88%), obstructive jaundice (100%), alcoholic liver disease (80%), viral hepatitis (75%), and in other liver disease (85%). Conclusion: Altered LFT is a useful tool to reach the Etiology of Liver disease. Alterations in liver enzymes as well as HbsAg reactivity are specific tests for cirrhosis of liver and viral hepatitis.

Effects of Sedi Herba (Sedum sarmentosum) on attenuating cholestasis by the activation of the farnesoid x receptor (FXR)-mediated signaling

Sedum sarmentosum (Sedi Herba) has traditionally been used to treat jaundice and various types of liver disease. This study aimed to clarify the anti-cholestatic efficacy and the mechanism of S. sarmentosum ethyl acetate extract (SDEAE), as well as to screen the potential compounds with FXR activation. SDEAE effectively ameliorated ANIT-induced cholestasis in rats, as evidenced by the ameliorative histopathology of the liver and the significant decrease in biochemical markers (ALT, AST, ALP, GGT, TBIL, DBIL and TBA). The analysis of bile acid profile by LC–MS indicated that SDEAE decreased the toxic bile acid levels (TCA, TMCA and CA). Western blotting indicated that SDEAE activated FXR-associated pathway, thereby upregulating FXR, SHP, BSEP and UGT2B4 expression, and downregulating CYP7A1 and NTCP expression. Twenty-three compounds (7 nor-sesquiterpenoids, 13 flavonoids, 1 lignin, 1 sterol and 1 anthraquinone) were isolated and identified from SDEAE by comparing NMR data with the literature. The HPLC profiles of SDEAE and isolated compounds were also compared. High-content analysis showed that eight compounds (6, 7, 8, 11, 12, 13, 14 and 23) could activate FXR and compound 8 exhibited the most potent activity (p < 0.01). Molecular docking suggested that the main binding modes between these active compounds and FXR were hydrogen bonding and van der Waals forces, and compound 8 had the highest docking score 6.34. The activation of compound 8 on FXR-mediated signaling was validated in L02 cells. After siRNA down-regulation of FXR, compound 8 significantly elevated FXR, SHP, BSEP and UGT2B4 expression, and reduced CYP7A1 and NTCP expression.

Targeted bile acid profiles reveal the liver injury amelioration of Da-Chai-Hu decoction against ANIT- and BDL-induced cholestasis.

Multiple types of liver diseases, particularly cholestatic liver diseases (CSLDs) and biliary diseases, can disturb bile acid (BA) secretion; however, BA accumulation is currently seen as an important incentive of various types of liver diseases’ progression. Da-Chai-Hu decoction (DCHD) has long been used for treating cholestatic liver diseases; however, the exact mechanisms remain unclear. Currently, our study indicates that the liver damage and cholestasis status of the α-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis and bile duct ligation (BDL)-induced extrahepatic cholestasis, following DCHD treatment, were improved; the changes of BA metabolism post-DCHD treatment were investigated by targeted metabolomics profiling by UPLC-MS/MS. DCHD treatment severely downregulated serum biochemical levels and relieved inflammation and the corresponding pathological changes including necrosis, inflammatory infiltration, ductular proliferation, and periductal fibrosis in liver tissue. The experimental results suggested that DCHD treatment altered the size, composition, and distribution of the BAs pool, led the BAs pool of the serum and liver to sharply shrink, especially TCA and TMCA, and enhanced BA secretion into the gallbladder and the excretion of BAs by the urinary and fecal pathway; the levels of BAs synthesized by the alternative pathway were increased in the liver, and the conjugation of BAs and the pathway of BA synthesis were actually affected. In conclusion, DCHD ameliorated ANIT- and BDL-induced cholestatic liver injury by reversing the disorder of BAs profile.

Germline Mutations in CIDEB and Protection against Liver Disease

BackgroundExome sequencing in hundreds of thousands of persons may enable the identification of rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for the discovery of new therapeutic targets.MethodsWe performed a multistage exome sequencing and genetic association analysis to identify genes in which rare protein-coding variants were associated with liver phenotypes. We conducted in vitro experiments to further characterize associations.ResultsThe multistage analysis involved 542,904 persons with available data on liver aminotransferase levels, 24,944 patients with various types of liver disease, and 490,636 controls without liver disease. We found that rare coding variants in APOB, ABCB4, SLC30A10, and TM6SF2 were associated with increased aminotransferase levels and an increased risk of liver disease. We also found that variants in CIDEB, which encodes a structural protein found in hepatic lipid droplets, had a protective effect. The burden of rare predicted loss-of-function variants plus missense variants in CIDEB (combined carrier frequency, 0.7%) was associated with decreased alanine aminotransferase levels (beta per allele, −1.24 U per liter; 95% confidence interval [CI], −1.66 to −0.83; P=4.8×10−9) and with 33% lower odds of liver disease of any cause (odds ratio per allele, 0.67; 95% CI, 0.57 to 0.79; P=9.9×10−7). Rare coding variants in CIDEB were associated with a decreased risk of liver disease across different underlying causes and different degrees of severity, including cirrhosis of any cause (odds ratio per allele, 0.50; 95% CI, 0.36 to 0.70). Among 3599 patients who had undergone bariatric surgery, rare coding variants in CIDEB were associated with a decreased nonalcoholic fatty liver disease activity score (beta per allele in score units, −0.98; 95% CI, −1.54 to −0.41 [scores range from 0 to 8, with higher scores indicating more severe disease]). In human hepatoma cell lines challenged with oleate, CIDEB small interfering RNA knockdown prevented the buildup of large lipid droplets.ConclusionsRare germline mutations in CIDEB conferred substantial protection from liver disease. (Funded by Regeneron Pharmaceuticals.)

Potential role of noninvasive biomarkers during liver fibrosis.

Various types of liver disease exist, such as hepatitis and alcoholic liver disease. These liver diseases can result in scarring of liver tissue, cirrhosis, and finally liver failure. During liver fibrosis, there is an excess and disorganized accumulation of extracellular matrix (ECM) components which cause the loss of normal liver cell functions. For patients with chronic liver disease, fibrosis prediction is an essential part of the assessment and management. To diagnose liver fibrosis, several invasive and noninvasive markers have been proposed. However, the adoption of invasive markers remains limited due to their inherent characteristics and poor patient acceptance rate. In contrast, noninvasive markers can expedite the clinical decision through informed judgment about disease stage and prognosis. These noninvasive markers are classified into two types: Imaging techniques and serum biomarkers. However, the diagnostic values of biomarkers associated with liver fibrosis have also been analyzed. For example, the serum levels of ECM proteins can react to either matrix accumulation or degradation. During virus-host interactions, several regulatory steps take place to control gene expression, such as the change in cellular microRNA expression profiles. MicroRNAs are a class of non-coding RNAs (18-20 long nucleotides) that function by post-transcriptional regulation of gene expression. Although various noninvasive markers have been suggested in recent years, certain limitations have restricted their clinical applications. Understanding the potential of non-invasive biomarkers as a therapeutic option to treat liver fibrosis is still in progress.

Effects of Afsantin Plant on Liver Diseases From the Perspective of Three Books of Traditional Iranian Medicine (Kitab Al-Hawi, Qanon, and Zakhirah-i Khwarazm Shahi)

Objective: Recent studies have shown the positive effectiveness of Afsantin plant in treatment of liver diseases. Therefore, it may be possible to find new ways in treatment of liver diseases by examining how to use this plant based on the Traditional Iranian Medicine (TIM) Methods: In this qualitative study, by referring to specialized libraries of TIM books in Iran and using various online resources, the terminology of Afsantin plant was first studied based on TIM. After knowing the different names of this plant, they were searched in various medical books, especially the three famous TIM books of Kitab Al-Hawi, Qanun and Zakhirah-i Khwarazm Shahi. Then, different medical prescriptions related to Afsantin were extracted from these books and different applications of this plant in diseases, especially liver diseases, were recorded and coded in Excel software. Then, articles that reported the medicinal applications of Afsantin plant in treatment of liver diseases were searched in online databases such as PubMed, Google Scholar, MagIran, Irandoc, IranMedex . The collected data were finally analyzed and compared with the data obtained from the TIM books. Results: Ancient Iranian physicians had described various types of liver disease in their works. The Afsantin plant been used alone or in combination with other substances in three books (Kitab Al-Hawi, Qanon, and Zakhirah-i Khwarazm Shahi) in 179 prescriptions for treatment of different diseases mostly for liver inflammation (23%), jaundice (20%), ascites (19%), and liver disease (18%). The most common form of administration of this plant was oral form (80%) followed by topical form (20%). In combined forms of use, lavender (30.2%), lemongrass (24.6%), anise (17.3%), Chinese rhubarb (17.3%), rose (16.2%), saffron (15.1%), Maghsoul (14.5%) champignon (14%), and Agrimonia eupatoria extract (14%) had been mostly used along with Afsantin to enhance the therapeutic effect of Afsantin or eliminate its negative effects on the body. The examination of modern medicine articles also revealed the sufficient knowledge of the authors of these books about liver diseases. The results of comparison showed that primary liver diseases such as hepatitis and alcoholic and non-alcoholic liver diseases were in the same category as primary diseases and initiators of liver diseases, i.e. bad mazaj, and ascites was equivalent to cirrhosis plus ascites. Conclusion: Considering the frequent use of Afsantin by famous TIM physicians and the consistency of their findings with modern medicine in terms of treating liver diseases, it seems that if the effect of this plant on liver diseases based on TIM be studied more widely and the results of this study be evaluated by the standards of modern medicine, new solutions can be achieved in the treatment of liver diseases.

Fluorescent sensing of free bilirubin at nanomolar level using a Langmuir-Blodgett film of glucuronic acid-functionalized gold nanoclusters.

Serum bilirubin is an important indicator to assess liver function and diagnose various types of liver diseases. The level of serum bilirubin is also negatively correlated with the risk of cardiovascular disease and cancer. We had fabricated a fluorescent film sensor aiming at free bilirubin detection at the nanomolar level. Gold nanoclusters capped by human serum albumin (HSA-AuNCs) were utilized as a fluorescent platform for bilirubin biorecognition. HSA-AuNCs were functionalized with glucuronic acid to increase the binding sites for bilirubin. An ultrathin film of glucuronic acid-functionalized gold nanoclusters was obtained by the Langmuir-Blodgett (LB) technique. When exposed to bilirubin, the interaction between free bilirubin and the functionalized AuNCs resulted in fluorescent quenching of the film. Good linearity could be achieved for the quenching efficiency versus the logarithm of free bilirubin concentration over a concentration range of 1.00nM~5.00μM. The limit of detection (LOD) was calculated to be (2.70 ± 0.14) × 10-1nM (S/N = 3). The film sensor presents a good anti-interference capability towards common substances coexisting with bilirubin in serum. Satisfactory results achieved in the tests of real serum samples indicate that the LB film sensor can be used for bilirubin determination in nanomolar concentration.

Label-free quantitative proteomic analysis of serum extracellular vesicles differentiating patients of alcoholic and nonalcoholic fatty liver diseases

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are typically asymptomatic and slow-progressing but potentially fatal diseases that are common causes of liver cirrhosis and related complications. Exosomes are nano-sized extracellular vesicles that have been linked to various intercellular communication processes and can carry biological materials reflecting the state and severity of disease. In this study, shotgun proteomic analysis of the protein expression profiles of extracellular vesicles, including exosomes and microvesicles, enriched from human serum samples of 24 patients diagnosed with various fatty liver diseases was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS) followed by protein identification and label-free quantification using the MaxQuant platform. A total of 329 proteins, including 190 previously reported exosome-specific proteins, were identified from four types of liver disease, where significant differences in protein expression were found in apolipoproteins, immunoglobulins, and other previously reported markers of liver disease. Principal component analysis of 61 proteins identified from MaxQuant analysis of the LC-MS/MS data provided a confident differentiation between ALD and NAFLD. SignificanceThe current investigation revealed the difference among various types of liver disease using LC-MS/MS of exosomes enriched from human serum samples of 24 patients where the most significantly up-regulation proteins were alpha-2-macroglobulin for alcoholic hepatitis and apolipoprotein C3 for nonalcoholic fatty liver disease.

Metabolic mechanism of Prunella vulgaris in treatment of ethanol-induced oxidative stress in rats based on metabonomics

Prunella vulgaris(PV) is an edible and traditional medicinal herb which has a wide range application in fighting inflammation and oxidative stress, and protecting liver. Now it has been used to treat various types of liver diseases and has significant clinical efficacy. This study aims to investigate the effects of PV on ethanol-induced oxidative stress injury in rats and its metabolic mechanism. The rats were divided into control group, model group, PV group, and VC group. The liver protection of PV was identified by measuring pharmacological indexes such as antioxidant and anti-inflammatory activity. The metabolic mechanism of long-term ethanol exposure and the metabolic regulation mechanism of PV treatment were studied by LS-MS metabonomics. The pharmacological investigation indicated that ethanol could significantly decrease the contents of SOD, GSH-Px, CAT and other antioxidant enzymes in liver and increase the content of MDA. At the same time, PV could significantly reduce the contents of inflammatory factors(TNF-α, IL-6 and IL-1β) and liver function markers(ALT, AST, ALP) in serum. What's more, long-term ethanol exposure could significantly cause liver injury, while PV could protect liver. Metabolomics based on multiple statistical analyses showed that long-term ethanol exposure could cause significant metabolic disorder, and fatty acids, phospholipids, carnitines and sterols were the main biomarkers. Meanwhile, pathway analysis and enrichment analysis showed that the β oxidation of branched fatty acids was the main influencing pathway. Also, PV could improve metabolic disorder of liver injury induced by ethanol, and amino acids, fatty acids, and phospholi-pids were the main biomarkers in PV treatment. Metabolic pathway analysis showed that PV mainly regulated metabolic disorder of ethanol-induced liver injury through phenylalanine, tyrosine and tryptophan biosynthetic pathways. This study could provide a new perspective on the hepatoprotective effect of natural medicines, such as PV.

Fibrinolysis in Patients with Liver Disease.

Patients with liver disease acquire complex changes in their hemostatic system. Historically, these patients were considered to have a bleeding tendency related, in part, to a hyperfibrinolytic state. However, studies using more modern fibrinolysis tests have questioned the presence of a hyperfibrinolytic state in patients with liver disease and its association with bleeding risk. It may be that the sickest patients with liver disease do have fibrinolytic abnormalities. However, the debate on the fibrinolytic state of patients with (decompensated) cirrhosis or critically ill liver disease is complicated by the fact that hypo- and hyperfibrinolysis have been poorly defined. This could, in part, be explained by the lack of reliable tests that assess a patient's fibrinolytic status. Moreover, large clinical studies on the relationship between bleeding and fibrinolysis in patients with liver disease are scarce. Here, we provide an overview of the current knowledge on fibrinolysis in various types of liver diseases and possible implications as a target for therapeutic strategies in liver disease. As antifibrinolytic therapy has been shown to be safe and effective during liver transplantation, it could potentially be of use in patients with (either laboratory-established or suspected) hyperfibrinolysis-related bleeding.

Neutrophil-Induced Liver Injury and Interactions Between Neutrophils and Liver Sinusoidal Endothelial Cells.

Neutrophils are the most abundant type of leukocytes with diverse functions in immune defense including production of reactive oxygen species, bacteriocidal proteins, neutrophil extracellular traps, and pro-inflammatory mediators. However, aberrant accumulation of neutrophils in host tissues and excessive release of bacteriocidal compounds can lead to unexpected injury to host organs. Neutrophil-mediated liver injury has been reported in various types of liver diseases including liver ischemia/reperfusion injury, nonalcoholic fatty liver disease, endotoxin-induced liver injury, alcoholic liver disease, and drug-induced liver injury. Yet the mechanisms of neutrophil-induced hepatotoxicity in different liver diseases are complicated. Current knowledge of these mechanisms are summarized in this review. In addition, a substantial body of evidence has emerged showing that liver sinusoidal endothelial cells (LSECs) participate in several key steps of neutrophil-mediated liver injury including neutrophil recruitment, adhesion, transmigration, and activation. This review also highlights the current understanding of the interactions between LSECs and neutrophils in liver injury. The future challenge is to explore new targets for selectively interfering neutrophil-induced liver injury without impairing host defense function against microbial infection. Further understanding the role of LSECs in neutrophil-induced hepatotoxicity would aid in developing more selective therapeutic approaches for liver disease.

Long non-coding RNAs in liver diseases: Focusing on nonalcoholic fatty liver disease, alcohol-related liver disease, and cholestatic liver disease.

Long non-coding RNAs (lncRNAs), a class of transcribed RNA molecules with the lengths exceeding 200 nucleotides, are not translated into protein. They can modulate protein-coding genes by controlling transcriptional and posttranscriptional processes. The dysregulation of lncRNAs has been related to various pathological disorders. In this review, we summarized the current knowledge of lncRNAs and their implications in the pathogenesis of three common liver diseases: nonalcoholic fatty liver disease, alcohol-related liver disease, and cholestatic liver disease. Future studies to further define the role of lncRNAs and their mechanisms in various types of liver diseases should be explored. An improved understanding from these studies will provide us a useful perspective leading to mechanism-based intervention by targeting specific lncRNAs for the treatment of liver diseases.

Biomarkers to Assess Liver Function in Various Types of Liver Diseases

Background: It is estimated that liver diseases are among the top ten killer diseases in India, causing deaths every year. Besides, there are those who suffered from chronic liver problems needing recurrent hospitalization and prolonged medical attention, which leaves them physically, mentally, emotionally and financially devastated. Methodology: The study included (n=80) various liver disease patients admitted to the General Medicine department and controls (n=20) subjects were having normal health within the age group of 30-55 years. Serum levels of bilirubin, Aspartate Transaminase, Alanine Amino Transferase, Alkaline Phosphatase and Gamma Glutamyl Transferase parameters were studied among the subjects suffering from cirrhosis, alcoholic liver disease, viral hepatitis, obstructive jaundice type of liver diseases. Result: The results of this study showed that the increase in serum levels of Bilirubin, AST, ALT, ALP and GGT in various types of liver diseases i.e Obstructive jaundice, Cirrhosis of the liver, Viral hepatitis, Alcoholic Liver disease when compared with controls. Conclusion: Biochemistry laboratory investigations i.e. Liver Function Test (LFT) are a simple, easy measure of tools which can early diagnose the various types of liver diseases.&#x0D; Keywords: Liver diseases; Liver Bio-markers; Liver Function Test.

A Gold Nanoclusters Film Supported on Polydopamine for Fluorescent Sensing of Free Bilirubin.

Serum bilirubin is an important biomarker for the diagnosis of various types of liver diseases and blood disorders. A polydopamine/gold nanoclusters composite film was fabricated for the fluorescent sensing of free bilirubin. Bovine serum albumin (BSA)-stabilized gold nanoclusters (AuNCs) were used as probes for biorecognition. The polydopamine film was utilized as an adhesion layer for immobilization of AuNCs. When the composite film was exposed to free bilirubin, due to the complex that was formed between BSA and free bilirubin, the fluorescence intensity of the composite film was gradually weakened as the bilirubin concentration increased. The fluorescence quenching ratio (F0/F) was linearly proportional to free bilirubin over the concentration range of 0.8~50 μmol/L with a limit of detection of 0.61 ± 0.12 μmol/L (S/N = 3). The response was quick, the film was recyclable, and common ingredients in human serum did not interfere with the detection of free bilirubin.

Engineering molecularly mobile polyrotaxane surfaces with heparin-binding EGF-like growth factors for improving hepatocyte functions.

Hepatocytes in vitro may be useful for treating various types of liver diseases, but these cells immediately lose their functions. Here, we designed sulfonated-polyrotaxane (PRX) surfaces with immobilized heparin binding-epidermal growth factor-like growth factors (HB-EGFs) for improving hepatic functions. Sulfonated-PRX triblock copolymers, composed of sulfopropyl ether-modified α-cyclodextrins (α-CDs) threaded onto a poly(ethylene glycol) (PEG) chain as a PRX segment and poly(benzyl methacrylate) at both terminals of the PEG as anchoring segments, were coated onto polystyrene surfaces by a drop cast method. The sulfonated-PRX surfaces with a small number of threading α-CDs induced cytoplasmic localization of yes-associated proteins in HepG2 cells. Moreover, immobilization of HB-EGFs onto the sulfonated-PRX surfaces with a small number of threading α-CDs promoted hepatic functions, including albumin secretion and gene expression. These results suggest that the combination of modulating the mobility of PRXs and immobilizing growth factors is effective for improving hepatic functions. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1080-1085, 2019.

Accuracy of real-time shear wave elastography in the assessment of normal liver tissue in the guinea pig (cavia porcellus).

Shear wave elastography is a novel technique enabling real-time measurement of the elasticity of liver tissue. The color map is superimposed on the classic ultrasound image of the assessed tissue, which enables a precise evaluation of the stiffness of the liver tissue. The aim of the study was to assess the stiffness of normal liver tissue in the guinea pig using shear wave elastography. The study was carried out on 36 guinea pigs using the SuperSonic Imagine Aixplorer scanner, and a 1 to 6 MH convex SC6-1 transducer. An ultrasound guided Try-Cut liver core needle biopsy was carried out in all the studied animals and the collected samples were examined to exclude pathological lesions. The mean liver tissue stiffness ranged from 0.89 to 5.40 kPa. We found that shear wave elastography is an easy, non-invasive technique that can be used to assess the stiffness of liver tissue. The obtained results can be used in future studies to assess the types and changes of liver tissue in the course of various types of liver disease.

Nuclear magnetic resonance metabolomics and human liver diseases: The principles and evidence associated with protein and carbohydrate metabolism.

During the last decade, metabolomics has become widely used in the field of human diseases. Numerous studies have demonstrated that this is a powerful technique for improving the understanding, diagnosis and management of various types of liver disease, such as acute and chronic liver diseases, and liver transplantation. Nuclear magnetic resonance (NMR) spectroscopy is one of the two most commonly applied methods for metabolomics. The aim of the present review was to investigate the results from recent key publications focusing on aspects of protein and carbohydrate metabolism. The review includes existing procedures, which are currently used for NMR data acquisition and statistical analysis. In addition, notable results obtained by these studies on protein and carbohydrate metabolism concerning human liver diseases are presented.

Protective effect and mechanism of ginsenoside Rg1 on carbon tetrachloride‑induced acute liver injury.

Liver injury is a common pathological state in various types of liver disease; severe or persistent liver damage is the basis of hepatic failure. Ginsenoside Rg1 (Rg1), one of the primary active ingredients of ginseng, has been reported to reduce concanalin A‑induced hepatitis and protect against lipopolysaccharide‑ and galactosamine‑induced liver injury. However, the underlying protective mechanism of Rg1 in acute liver injury remains unclear. In the present study, a carbon tetrachloride (CCl4)‑induced acute liver injury model was established, and the protective effect of Rg1 on CCl4‑induced acute liver injury was demonstrated in cell culture and animal experimental systems. Further investigation of the mechanisms demonstrated that pretreatment with Rg1 reduced elevated levels of alanine aminotransferase and aspartate aminotransferase, enhanced the antioxidant activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) content. Experiments invitro demonstrated that Rg1 decreased p65 expression and inhibited nuclear factor (NF)‑κB activity. In addition to the effect of Rg1, an NF‑κB inhibitor promoted cell survival, enhanced SOD activity and reduced MDA level. It was observed through invivo experiments that pretreatment with Rg1 inhibited NF‑κB expression and activity in Kupffer cells and reduced the serum levels of tumor necrosis factor‑α and interleukin‑6. In conclusion, the results of the present study indicated that pretreatment with Rg1 may rescue CCl4‑induced acute liver injury invivo and invitro through inhibition of NF‑κB activity, to restore the anti‑oxidative defense system and down‑regulate pro‑inflammatory signaling pathways. The present observations provide a theoretical foundation for the clinical application of Rg1 therapy in acute liver injury.

The relationship between transcription factor NF-E2-related factor 2 and liver diseases

The liver is the most exuberant organs of human metabolism, susceptible to oxidative stress injury.More and more studies in recent years show that various types of liver diseases such as hepatitis, liver fibrosis, liver cirrhosis, liver cancer and so on are closely related with oxidative stress injury.The transcription factor NF-E2-related factor 2(Nrf2) is an important transcription factor regulating oxidative stress reaction.It combines with the antioxidant response element antioxidant response elements(ARE), then activates target gene transcription, and increases the resi-stance of cell to oxidative stress.Kelch-like ECH-associated protein 1-Nrf2-ARE pathway plays an important role in the pathogenesis of liver diseases. Key words: Nuclear transcription factor NF-E2-related factor 2; Oxidative stress; Liver