Bioactive Compounds Formulated in Phytosomes Administered as Complementary Therapy for Metabolic Disorders.

Metabolic disorders (MDs), including dyslipidemia, non-alcoholic fatty liver disease, diabetes mellitus, obesity and cardiovascular diseases are a significant threat to human health, despite the many therapies developed for their treatment. Different classes of bioactive compounds, such as polyphenols, flavonoids, alkaloids, and triterpenes have shown therapeutic potential in ameliorating various disorders. Most of these compounds present low bioavailability when administered orally, being rapidly metabolized in the digestive tract and liver which makes their metabolites less effective. Moreover, some of the bioactive compounds cannot fully exert their beneficial properties due to the low solubility and complex chemical structure which impede the passive diffusion through the intestinal cell membranes. To overcome these limitations, an innovative delivery system of phytosomes was developed. This review aims to highlight the scientific evidence proving the enhanced therapeutic benefits of the bioactive compounds formulated in phytosomes compared to the free compounds. The existing knowledge concerning the phytosomes' preparation, their characterization and bioavailability as well as the commercially available phytosomes with therapeutic potential to alleviate MDs are concisely depicted. This review brings arguments to encourage the use of phytosome formulation to diminish risk factors inducing MDs, or to treat the already installed diseases as complementary therapy to allopathic medication.

Protective effects of hepatic diseases by bioactive phytochemicals in Fusarium oxysporum - A review.

Lately, liver diseases were categorized as one of the most prevalent health problems globally as it causes a severe threat to mankind all over the world due to the wide range of occurrence. There are multiple factors causing hepatic disorders, such as alcohol, virus, poisons, adverse effects of drugs, poor diet, inherited conditions and obesity. Liver diseases have various types including alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune hepatitis, liver cancer, hepatocellular carcinoma, liver fibrosis and hepatic inflammation. Therefore, it is imperative to find effective and efficacious agents in managing liver diseases. Fusarium oxysporum, an endophytic fungus and containing many bioactive compounds, could be served as a forked medication for enormous number and types of maladies. It was characterized by producing biochemical compounds which had rare pharmacological properties as it may be found in a limit number of other medicinal plants. The majority of the past researches related to Fusarium oxysporum recited the fungal negative field either on the pathogenic effects of the fungus on economical crops or on the fungal chemical components to know how to resist it. The present review will highlight on the bright side of Fusarium oxysporum and introduce the functional activities of its chemical compounds for treating its target diseases. The key point of illustrated studies in this article is displaying wide range of detected bioactive compounds isolated from Fusarium oxysporum and in other illustrated studies it was elucidated the therapeutical and pharmacological potency of these biologically active compounds (isolated from medicinal plants sources) against different types of liver diseases including non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and others. It was demonstrated that F. oxysporum contains unique types of isoflavones, flavonoids, phenols and another active chemical compounds, and these compounds showed recently a fabulous clinical contribution in the therapy of liver injury diseases, which opens new and unprecedented way for evaluating the maintaining efficacy of Fusarium oxysporum bioactive compounds in dealing with hepatic complications and its remedy impacting on liver diseases and injured hepatocytes through recommending implement a practical study.

Role of Cardiac Biomarkers in Hepatic Disorders: A Literature Review.

Various studies have reported the association between cardiac markers and hepatic disorders. The main objective of this review article was to elucidate the significance of important cardiac indicators such as ischemia-modified albumin, cardiac troponin, cardiac natriuretic peptides, creatine kinase, creatine kinase-MB, lactate dehydrogenase, heart-type fatty acid-binding protein, osteopontin, soluble suppression of tumorigenicity 2, C-reactive protein, and lipoprotein(a) in the development of hepatic disorders. In addition, it highlighted recent notable discoveries and accomplishments in this field and identified areas requiring further investigation, ongoing discussions, and potential avenues for future research. Early identification and control of these cardiac markers might be helpful to control the prevalence of hepatic disorders associated with cardiovascular diseases.

Hepatic ß-arrestins: potential roles in liver health and disease.

Β-arrestins are intracellular scaffolding proteins that have multifaceted roles in different types of disorders. In this review article, we gave a summary about the discovery, characterization and classification of these proteins and their intracellular functions. Moreover, this review article focused on the hepatic expression of ß-arrestins and their hepatocellular distribution and function in each liver cell type. Also, we showed that ß-arrestins are key regulators of distinct types of hepatic disorders. On the other hand, we addressed some important points that have never been studied before regarding the role of ß-arrestins in certain types of hepatic disorders which needs more research efforts to cover.

The body mass index increases the genetic risk scores' ability to predict risk of hepatic damage in European adolescents: The HELENA study.

BACKGROUND: Hepatic disorders are often complex and multifactorial, modulated by genetic and environmental determinants. During the last years, the hepatic disease has been progressively established from early stages in life. The use of genetic risk scores (GRS) to predict the genetic susceptibility to a particular phenotype among youth has gained interest in recent years. Moreover, the alanine aminotransferase (ALT) blood biomarker is often considered as hepatic screening tool, in combination with imaging techniques. The aim of the present study was to develop an ALT-specific GRS to help in the evaluation of hepatic damage risk in European adolescents. METHODS: A total of 972 adolescents (51.3% females), aged 12.5-17.5 years, from the Healthy Lifestyle in Europe by Nutrition in Adolescence study were included in the analyses. The sample incorporated adolescents in all body mass index (BMI) categories and was divided considering healthy/unhealthy ALT levels, using sex-specific cut-off points. From 1212 a priori ALT-related single nucleotide polymorphisms (SNPs) extracted from candidate gene selection, a first screening of 234 SNPs univariately associated was established, selecting seven significant SNPs (p < .05) in the multivariate model. An unweighted GRS (uGRS) was developed by summing the number of reference alleles, and a weighted GRS (wGRS), by multiplying each allele to its estimated coefficient. RESULTS: The uGRS and wGRS were significantly associated with ALT (p < .001). The area under curve was obtained integrating BMI as clinical factor, improving the predictive ability for uGRS (.7039) and wGRS (.7035), using 10-fold internal cross-validation. CONCLUSIONS: Considering BMI status, both GRSs could contribute as complementary tools to help in the early diagnosis of hepatic damage risk in European adolescents.

Availability, Functionality, and Safety as well as Quality Control of Hepatocytes as Seeding Cells in Liver Regenerative Medicine: State of the Art and Challenges.

Hepatic disease is one of the most common causes of death worldwide and has become a global health problem. Liver transplantation is the only effective treatment strategy for patients with hepatic function failure, but the insufficient number of donated healthy livers is the main obstacle limiting this process. To alleviate the demand for donor's livers, alternative approaches are being actively explored using liver tissue engineering principles. Liver tissue engineering consists of three elements, including seeding cells, extracellular matrix, and bioreactors. Among them, seeding cell is the most key factor. In this regard, hepatocyte-based tissue engineering can overcome the above shortages for tissue repair and regeneration in hepatic disorders. Primary human hepatocytes in liver regenerative medicine are the most preferred seeding cells, although limited access to a sufficient number of functional hepatocytes are a major issue due to the difficulties in long-term function maintenance of hepatocyte as well as the lack of availability of healthy donors. Hepatocyte-like cells (HLCs), derived from various stem cells, including non-liver-derived stem cells and liver-derived stem cells, as well as trans-differentiation of other cell types, may provide adequate cell sources and could replace primary human hepatocytes as seeding cells. However, it is still a great difficulty that HLCs generated by stem cell differentiation meet the quality required for clinical therapy. Furthermore, none of the standardized protocols to generate high-quality HLCs is available. Whether primary hepatocytes or HLCs are from various sources, preventing the functional deterioration of hepatocytes or generating fully functional hepatocytes is also a big challenge, respectively. In addition, the adoptions of three-dimensional co-culture systems and some small-molecule compounds contribute to maintaining the hepatic functionality of primary hepatocytes and enhancing the liver-specific functions of HLCs. In short, hepatocyte-based liver regenerative medicine is an attractive alternative strategy for liver diseases, notwithstanding some challenges still exist from bench to bedside. This review summarizes the current status, issues, and challenges in availability, functionality, and safety, as well as quality control of seeding hepatocytes with regard to liver tissue engineering in regenerative medicine for the treatment of liver disorders.

The impact of branched-chain amino acid supplementation on measures of glucose homeostasis in individuals with hepatic disorders: A systematic review of clinical studies.

BACKGROUND: Branched chain amino acid (BCAA) supplementation may influence glucose metabolism in individuals with an impaired glyceamic profile. This systematic review investigated the effects of isolated BCAA supplementation on measures of glucose homeostasis in individuals with hepatic disorders. METHODS: We searched PubMed, Web of Science, Cochrane Library and Scopus for published clinical trials that investigated the effects of isolated BCAA supplementation on measures of glucose homeostasis, including serum glucose and insulin, glycated haemoglobin (HbA1c) levels and homeostatic model assessment for insulin resistance (HOMA-IR) scores. RESULTS: Eleven trials met the inclusion criteria. Only one study revealed a decrease in serum glucose from BCAA supplementation compared to three studies that showed increases. Five studies demonstrated no significant changes in serum glucose, and two studies displayed no changes in HbA1c following BCAA supplementation. Serum levels of insulin were decreased in three studies, remained unchanged in one, and increased in the remaining three studies. BCAA supplementation reduced HOMA-IR scores in two studies, increased HOMA-IR scores in another two, or resulted in no changes in two other studies. CONCLUSIONS: BCAA supplementation in isolation had no effect on overall glucose homeostasis in individuals with hepatic disorders, although some improvements on serum insulin levels and HOMA-IR scores were observed. Overall, there is little evidence to support the utilisation of BCAA supplementation as a potential nutritional strategy for improving measures of glucose homeostasis in individuals with hepatic disorders.

Plant-Derived Lactobacillus paracasei IJH-SONE68 Improves the Gut Microbiota Associated with Hepatic Disorders: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

Our previous clinical study has shown that the exopolysaccharide (EPS) produced by a plant-derived lactic acid bacterium, Lactobacillus paracasei IJH-SONE68, improves chronic allergy status in humans. In addition, an inhibition of visceral fat accumulation was observed following the intake of EPS during animal experimentation. In the present study, we have further evaluated the health-promoting effects of a spray-dried powder of pineapple juice that is fermented with the IJH-SONE68 strain. This was conducted in a double-blind, randomized, placebo-controlled, parallel-group clinical trial at Hiroshima University from May 2019 to July 2021. Eighty healthy volunteers at range of ages 23-70, with a body mass index between 25 and 29.99, were enrolled. After the 12 weeks of the experimental period were complete, although the average visceral fat area in both groups similarly decreased, there was no significant difference in the content of visceral fat area or in the obesity-related physical parameters in both groups. Further, we found that the serum liver function indices (AST and ALT) in the test group decreased within a statistically determined trend (p = 0.054). The fecal microflora analysis revealed, in the test group, a statistically significant increase in the relative abundance changes within Anaerostipes, which has been reported to help suppress hepatic inflammation.

Cell therapy in congenital inherited hepatic disorders.

Congenital inherited hepatic disorders (CIHDs) are a set of diverse and heterogeneous group of genetic disorders leading to a defect in an enzyme or transporter. Most of these disorders are currently treated by liver transplantation as standard of care. Improved surgical techniques and post-operative care has led to a wider availability and success of liver transplantation program worldwide. However liver transplantation has its own limitations due to invasive surgery and lifelong use of immunosuppressive agents. Our experience from auxiliary liver transplantation (where right or the left lobe of the patient liver is replaced with a healthy liver donor) demonstrated successful treatment of the underlying defect of noncirrhotic metabolic disorder suggesting that whole liver replacement may not be necessary to achieve a change in phenotype. Large number of animal studies in human models of CIHD have shown success of hepatocyte transplantation leading to its human use. This review addresses the current state of human hepatocyte transplantation in the management of CIHDs with bottlenecks to its wider application and future perspectives.

Medicinal plants used against hepatic disorders in Bangladesh: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver disease is a major cause of illness and death worldwide which accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1 million due to viral hepatitis and hepatocellular carcinoma. That's why it is seeking the researchers' attention to find out the effective treatment strategies. Phytochemicals from natural resources are the main leads for the development of noble hepatoprotective drugs. The majority of the natural sources whose active compounds are currently employed actually have an ethnomedical use. Ethnopharmacological research is essential for the development of these bioactive compounds. These studies not only provide scientific evidence on medicinal plants utilized for particular therapeutic purposes, but they also ensure cultural heritage preservation. Plenty of experimental studies have been well-documented that the ethnomedicinal plants are of therapeutics' interest for the advanced pharmacological intervention in terms of hepatic disorders. AIM OF THE STUDY: This study summarizes the processes of hepatotoxicity induced by various toxins and explores identified hepatoprotective plants and their phytoconstituents, which can guide the extraction of novel phytochemical constituents from plants to treat liver injury. This review aimed to summarize the hepatoprotective activity of Bangladeshi medicinal plants where the bioactive compounds may be leads for the drug discovery in future. MATERIALS AND METHODS: Literature searches in electronic databases, such as Web of Science, Science Direct, SpringerLink, PubMed, Google Scholar, Semantic Scholar, Scopus, BanglaJOL, and so on, were performed using the keywords 'Bangladesh', 'ethnomedicinal plants', 'Hepatoprotective agents' as for primary searches, and secondary search terms were used as follows, either alone or in combination: traditional medicine, medicinal plants, folk medicine, liver, hepatitis, therapeutic uses, and anti-inflammatory. Besides, several books, including the book entitled "Medicinal plants of Bangladesh: chemical constituents and uses" authored by Abdul Ghani, were carefully considered, which contained pharmacological properties and phytoconstituents of many medicinal plants growing and traditionally available in Bangladesh. Among them, the most promising plant species with their latest therapeutic effects against hepatic disorders were deeply considered in this review. RESULTS: The results of this study revealed that in most cases, therapy using plant extracts stabilized altered hepatic biochemical markers induced by hepatotoxins. Initially, we investigated 32 plant species for hepatoprotective activity, however after extensive literature searching; we observed that 20 plants offer good pharmacological evidence of hepatoprotective function. Consequently, most bioactive compounds derived from the herbs including berberine, thymoquinone, andrographolide, ursolic acid, luteolin, naringenin, genistein, quercetin, troxerutin, morin, epigallocatechin-3-gallate, chlorogenic acid, emodin, curcumin, resveratrol, capsaicin, ellagic acid, etc. are appeared to be effective against hepatic disorders. CONCLUSIONS: Flavonoids, phenolic acids, monoterpenoids, diterpenoids, triterpenoids, alkaloids, chromenes, capsaicinoids, curcuminoids, and anthraquinones are among the phytoconstituents were appraised to have hepatoprotective activities. All the actions displayed by these ethnomedicinal plants could make them serve as leads in the formulation of drugs with higher efficacy to treat hepatic disorders.

Modifying influence of polyphenols on hematotoxicity, cardiotoxicity, and hepatotoxicity induced by liquefied petroleum gas in rats.

OBJECTIVE: This study was designed to investigate the effects of liquefied petroleum gas (LPG) on hematotoxic, cardiotoxic, and hepatotoxic indices and the modifying influence of selected polyphenols. METHODS: Adult male Wistar rats were exposed to1000 ppm LPG for 10 min at 12-h interval for 30 days with or without cotreatment with 50 mg/kg rutin, quercetin, tannic acid, or gallic acid followed by hematological, biochemical, and histopathological evaluations in animal tissues. RESULTS: Exposure to LPG induced hematotoxicity, cardiotoxicity, and hepatotoxicity. This is reflected in alterations to levels or activities of blood parameters (hemoglobin, packed cell volume, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin, and platelets), enzymatic and nonenzymatic oxidative stress markers, nitrite, lactate dehydrogenase, creatine kinase-MB, transaminases, γ-glutamyl transpeptidase, bilirubin, and plasma albumin. LPG exposure also caused dyslipidemia and histoarchitectural changes. Treatment with the selected polyphenols effectively attenuated LPG-induced toxicity in rat tissues. CONCLUSION: The results indicate that continuous exposure to LPG could lead to blood-, heart-, and liver-related diseases and dietary polyphenols could provide benefits in diseases associated with LPG inhalation toxicity.

Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders.

Intestinal barrier dysfunction and dysbiosis contribute to development of diseases in liver and other organs. Physical, immunologic, and microbiologic (bacterial, fungal, archaeal, viral, and protozoal) features of the intestine separate its nearly 100 trillion microbes from the rest of the human body. Failure of any aspect of this barrier can result in translocation of microbes into the blood and sustained inflammatory response that promote liver injury, fibrosis, cirrhosis, and oncogenic transformation. Alterations in intestinal microbial populations or their functions can also affect health. We review the mechanisms that regulate intestinal permeability and how changes in the intestinal microbiome contribute to development of acute and chronic liver diseases. We discuss individual components of the intestinal barrier and how these are disrupted during development of different liver diseases. Learning more about these processes will increase our understanding of the interactions among the liver, intestine, and its flora.

Effect of Rosa canina Distilled Water on Tamoxifen-treated Male Wistar Rats.

BACKGROUND AND OBJECTIVE: In spite of therapeutic effect of tamoxifen on the breast cancer, it has some side effects on the liver including non-alcoholic fatty liver disease. In this study the effects of Rosa canina distilled water on the tamoxifen-induced fatty liver and oxidative stress status in male rats were investigated. MATERIALS AND METHODS: Twenty four adult male Wistar rats were randomly divided into 4 groups of 6: 1st group: Untreated control rats (C), 2nd group (T): The rats received tamoxifen, 3rd group (T+R): Rats received tamoxifen and Rosa canina distilled water and 4th group (R): Rats received only Rosa canina distilled water. Tamoxifen at 1 mg kg-1/day was injected subcutaneously for 7 days and the rats received orally Rosa canina distilled water at 1 mL/rat/daily for 14 days. At the end of the study, animals were studied for serum biochemical parameters (glucose, lipid profile, BUN, creatinine, uric acid, urea, ALT, AST, ALP, total protein, bilirubin, oxidative stress indices, sperm analysis and histology of the liver. The data were analyzed with SPSS software version 20 and expressed as Mean±SD. RESULTS: Rosa canina distilled water improved liver enzyme and renal function indices which disturbed due to tamoxifen treatment. While tamoxifen enhanced lipid peroxidation, Rosa canina distilled water reduced it. In addition, tamoxifen reduced the mobility, morphology and viability of sperms, but the Rosa canina distilled water enhanced the sperm parameters. Histological results also confirmed the adverse effect of tamoxifen and the favorable impact of the Rosa canina distilled water on the liver structures of animals. CONCLUSION: Rosa canina distilled water could modulate tamoxifen-induced fatty liver as well as improving the sperm parameters.

The therapeutic potential of induced hepatocyte-like cells generated by direct reprogramming on hepatic fibrosis.

BACKGROUND: Until now, there is no effective anti-fibrotic therapy available for liver cirrhosis. Stem cell therapies have been studied for the treatment of hepatic fibrosis. However, the use of embryonic stem cells or induced pluripotent stem cells (iPSC) has limitations such as ethical concern or malignancy potential. Induced hepatocyte-like cells (iHEPs) generated by direct reprogramming technology may overcome these limitations. METHODS: In this study, we generated iHEPs by direct reprogramming from mouse embryonic fibroblast (MEF) either using specific transcription factors such as c-Myc and Klf-4 (type A), or adding small molecules to HNF1α (type B). RESULTS: We investigated the effect of iHEPs on acute liver injury and chronic hepatic fibrosis animal models induced by CCl4 intra-peritoneal injection in BALB/C nude mice. In acute liver injury model, serum AST/ALT levels peaked at 24 h after CCl4 injection. Intra-splenic transplantation of iHEPs significantly attenuated CCl4-induced acute liver injury. GFP-labeled iHEPs (type A) migrated to the liver after intra-splenic transplantation that was confirmed by Western blotting and immunofluorescence staining. We found that GFP and albumin were co-localized in migrated iHEPs in the liver suggesting migrated iHEPs were functional. In chronic hepatic fibrosis mice experiment, transplantation of either type A or type B iHEPs significantly attenuated liver fibrosis induced by CCl4 injection for 10 weeks. CONCLUSIONS: Our study suggests that iHEPs may be used as a novel therapeutic strategy for the treatment of hepatic fibrosis.

α4ß7 integrin inhibitors: a patent review.

INTRODUCTION: The α4ß7 integrin is heterodimeric cell surface receptors expressed on most leukocytes. Mucosal addressing cell adhesion molecule 1(MAdCAM-1) is an exclusive ligand for α4ß7 integrin. Areas covered: This article will highlight the progress that has been made in the discovery and development of α4ß7 integrin inhibitors, and their use in the treatment of inflammatory bowel diseases, multiple sclerosis, asthma, hepatic disorders, human immunodeficiency virus, allergic conjunctivitis and type 1 diabetes. Expert opinion: α4ß7 integrin inhibitors have attracted much interest for their clinical implication. Natalizumab and Vedolizumab are monoclonal antibodies (mAbs) successfully utilized clinically. Natalizumab is a mAbs of α4-subunit blocking both α4ß1 and α4ß7 integrin. Vedolizumab selectively targets the α4ß7 integrin. Several mAbs are still in the process of research and development. Among these mAbs, etrolizumab selectively against the ß7-subunit and AMG-181 specifically against the α4ß7 integrin are the most promising anti-α4ß7 integrin antibodies. Despite the unclear development stage of TR-14035 and R411, several low molecular compounds show bright future of further development, such as AJM300 and CDP323. In addition, results from laboratory data show that peptide inhibitors, such as peptide X, are effective α4ß7 integrin inhibitors.

Prevalence of CYP2C19 Genetic Polymorphism among Normal People and Patients with Hepatic Diseases.

BACKGROUND: Patients with hepatic diseases are treated with numerous drugs metabolized by cytochrome P450. OBJECTIVE: To evaluate the frequencies of CYP2C19 variant alleles (*2, *3, and *17), genotypes, and phenotypes, and the relationship between the frequency of these alleles and the underlying hepatic diseases among patients with advanced liver diseases who were candidates for liver transplantation. METHODS: The Study was conducted on 120 patients suffering from various hepatic disorders, candidates for liver transplantation, and 52 healthy volunteers. DNA was extracted from blood samples and analyzed by TaqMan SNP genotyping assay. The CYP2C19 genotypes were classified into poor, extensive, intermediate, and ultra-rapid metabolizer phenotypes. RESULTS: Viral hepatitis was the most common cause of liver disease among studied patients. The frequencies of CYP2C19 alleles *1, *17, and *2 were 66.7% (160/240), 20.8% (50/240) and 12.5% (30/240), respectively. Allele CYP2C19*3 was not found in the studied population. The most prevalent genotypes were CYP2C19 *1/*1 (47.5%) and *1/*17 (24.2%). The predicted CYP2C19 phenotypes were extensive metabolizer (47.5%), heterozygote extensive metabolizer (45.9%), ultra-rapid metabolizer (5%), and poor metabolizer (1.6%). There was no significant difference between the frequencies of CYP2C19 genotypes between healthy people and patients. The distribution of CYP2C19 genotype frequencies was not significantly associated with the underlying disease conditions (p=0.472). CONCLUSION: The distribution of CYP2C19 genotype frequencies in Iranian healthy people and patients with various hepatic diseases was not significantly different. This may allow the physicians to predict a tailoring dose regimens based on the individual's metabolic capacity, decrease the risk of harmful side effects of the drugs, and optimize the treatment.

Lin28 and let-7: roles and regulation in liver diseases.

The diagnosis and treatment of liver disease remain a major health concern worldwide because of the diverse etiologies of this disease. For this reason, new therapeutic targets are greatly needed to halt the progression of this damaging disease. Upon initiation of liver injury by viral infection, autoimmune disease or toxin, and/or hepatitis, chronic disease may develop, which can progress to cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma, liver failure, or death. The Lin28/lethal-7 (let-7) molecular switch has emerged as a central regulator of multiorgan injuries and cancer development. Lin28 is a stem cell marker vital to initiation or maintenance of a stem cell phenotype. Lin28 has not been extensively studied in the liver, despite its ability to induce tissue regeneration via reprogramming of oxidative enzymes in other tissues and its involvement with numerous upstream regulators and downstream targets in liver disease. Theoretically, overexpression of Lin28 in certain forms of liver disease could be a potential treatment that aids in liver regeneration. Alternatively, Lin28 has been implicated numerous times in the progression of diverse cancer types and is associated with increased severity of disease. In this case, Lin28 could be a potential inhibitory target to prevent malignant transformation in the liver. This review seeks to characterize the role of Lin28 in liver disease.

Curcumin and Liver Disease: from Chemistry to Medicine.

Curcumin, the natural yellow-colored active principle, also called turmeric yellow, extracted from the perennial herb Curcuma longa L., has potent biological and pharmacological properties such as antioxidant, anti-inflammatory, antifungal, antibacterial, anti-ischemic, antitumor, and anticancer actions. The molecular mechanism of the hepatoprotective action of curcumin is due to its antioxidant properties and inhibitory activity against nuclear factor (NF)-κB that regulates different proinflammatory and profibrotic cytokines. Overall, scientific reports demonstrate that curcumin has high therapeutic ability for treating hepatic disorders. Here is a systematic discussion of the hepatoprotective activity of curcumin and its possible mechanisms of actions.

Postmarketing surveillance of rabeprazole in upper gastrointestinal peptic lesions in Japanese patients with coexisting hepatic disorders.

BACKGROUND: Many Japanese patients with hepatic disorders confirmed on diagnostic imaging and coexisting upper gastrointestinal (GI) peptic lesions receive treatment with proton pump inhibitors. Some pharmacotherapies used to treat peptic ulcers have been associated with adverse drug reactions (ADRs), including elevated liver enzyme levels. OBJECTIVE: The aim of this study was to determine the tolerability and effectiveness of rabeprazole sodium in treating peptic lesions in patients with coexisting hepatic disorders. METHODS: This open-label, practice-based, postmarketing surveillance investigation was conducted at 15 centers across Japan. Male and female patients aged ≥18 years with peptic lesions confirmed on upper GI endoscopy and with underlying hepatic disease were enrolled. Patients were randomly assigned to receive rabeprazole 10 or 20 mg PO (tablet) QD after a meal for up to 8 weeks. Tolerability was assessed using monitoring of the incidence of ADRs determined by direct patient questioning, spontaneous reporting, and laboratory assessment. All patients who received at least 1 dose of study drug were included in the tolerability assessment. Effectiveness was assessed at baseline and study end using the rates of achievement of improvement on endoscopy, relief of subjective/objective symptoms (rates of improvement in epigastric pain and heartburn), and global improvement. The effectiveness analysis included all patients with complete data before and after treatment. Subanalyses were conducted to determine the effectiveness of drug by identification of the proportion of patients with coexisting hepatic disorders (cirrhosis, chronic hepatitis, and other hepatic diseases [eg, alcoholic hepatitis, fatty liver]) and by peptic lesion (gastric ulcer, duodenal ulcer, stomal ulcer, and reflux esophagitis) who achieved improvement. RESULTS: A total of 114 patients were enrolled; 108 patients were included in the tolerability analysis (81 men, 27 women; mean age, 59.9 years; 10-mg dose, 90 patients; 20-mg dose, 18 patients) and 98 patients were included in the analysis of effectiveness. Twenty-one ADRs occurred in 11 (10.2%) patients. Serious ADRs occurred in 2 patients (elevated bilirubin level and hepatic encephalopathy, 1 patient each). Administration of rabeprazole was discontinued in 5 patients due to the occurrence of the following ADRs: constipation (1 patient); epigastric pain (1); dyslalia, disorientation, tremor, sleep disorder, and hepatic encephalopathy (1); diarrhea (1); and elevated alkaline phosphatase and y-glutamyl transpeptidase levels (1). On endoscopy, the proportion of patients achieving improvement with either dose was 30/33 (90.9%). The relief rates assessed using subjective symptoms were 47/55 (85.5%) and 47/56 (83.9%) for epigastric pain and heartburn, respectively. The proportion of patients achieving global improvement with either dose was 80/98 (81.6%) patients (49/62 [79.0%] for cirrhosis, 11/16 [68.8%] for chronic hepatitis, and 20/20 [100.0%] for other hepatic diseases [alcoholic hepatitis, fatty liver]). CONCLUSION: In this study in Japanese patients with hepatic disorders, rabeprazole was well tolerated and appeared effective for the treatment of upper GI peptic lesions.