Alcoholic hepatitis is the most severe and acute form of alcoholic liver disease. The mortality rate associated with alcoholic hepatitis is high, largely due to the lack of suitable pharmacological interventions. While there has been substantial research in the area, generating pharmacological interventions has been plagued by the lack of a robust mouse model both for testing and for understanding the underlying pathology. A number of major notable advances have been made in this area recently, with the goal of generating a mouse model of alcoholic hepatitis. The purpose of this article is to review recent advances in modeling alcoholic liver disease both in vitro and in vivo in the mouse, and place them in the context of the greater spectrum of alcoholic liver disease, with a focus on how we can translate current advances into a high-fidelity model of alcoholic hepatitis. In addition, we will review the basic mechanisms of alcoholic hepatitis as it is currently understood, focusing on recent advancements in diagnosis, prognosis and current pathophysiology, especially as it relates to the profound immune dysfunction present during alcoholic hepatitis.

Hepatocellular carcinoma (HCC) is a leading cause of liver-related death worldwide. Hepatitis C virus (HCV) infection is a major cause of advanced hepatic fibrosis and cirrhosis, with significantly increased risk for development of HCC. The morbidity and mortality of HCV-related HCC remains high, as rates of HCV cirrhosis continue to increase. The long-term goal of antiviral therapy for chronic HCV is to reduce complications from cirrhosis, including HCC. The advent of new direct-acting antivirals with high rates of virological clearance has revolutionized cure of HCV infection. While the development of HCC in HCV patients who achieve disease sustained virologic response is reduced, these patients remain at risk for HCC, particularly those patients with advanced fibrosis and cirrhosis. This review outlines the epidemiology of HCC in chronic HCV, various mechanisms, risk factors and pathophysiology that contribute to this disease process, screening recommendations, and the available data on the impact of new direct-acting antiviral treatment on the development on HCC.

Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality. The principal treatment is surgical resection or liver transplantation, depending on whether the patient is a suitable transplant candidate. However, in most patients with HCC the diagnosis is often late, thereby excluding the patients from definitive surgical resection. Medical treatment includes sorafenib, which is the most commonly used systemic therapy; although, it has been shown to only minimally impact patient survival by several months. Chemotherapy and radiotherapy are generally ineffective. Due to the poor prognosis of patients with HCC, newer treatments are needed with several being in development, either in pre-clinical or clinical studies. In this review article, we provide an update on the current and future medical and surgical management of HCC.

Autoimmune hepatitis has been considered as a relatively rare immunological liver disease, especially in the Asia-Pacific area. Although the diagnosis criteria and immunosuppressive treatment regimens have been established, there are still some challenges. According to the different presentations, the personalized management of patients who suffer from this disease, including those with chronic or acute severe onset, the autoantibody-negative phenotype and cirrhosis are necessarily descriptive. Each subgroup of patients should receive an individualized therapy. Here, we review the recent studies of autoimmune hepatitis, mainly focusing on the epidemiology and genetics, personalized diagnostics, individualized treatment strategies, special subgroups and outcomes. Most of the research in the literature is based on Japanese and Chinese populations.

Chylous ascites (CA) is a rare form of ascites that results from the leakage of lipid-rich lymph into the peritoneal cavity. This usually occurs due to trauma and rupture of the lymphatics or increased peritoneal lymphatic pressure secondary to obstruction. The underlying etiologies for CA have been classified as traumatic, congenital, infectious, neoplastic, postoperative, cirrhotic or cardiogenic. Since malignancy and cirrhosis account for about two-thirds of all the cases of CA in Western countries, in this article we have attempted to reclassify CA based on portal and non-portal etiologies. The diagnosis of CA is based on the distinct characteristic of the ascitic fluid which includes a milky appearance and a triglyceride level of >200 mg/dL. The management consists of identifying and treating the underlying disease process, dietary modification, and diuretics. Some studies have also supported the use of agents such as orlistat, somatostatin, octreotide and etilefrine. Paracentesis and surgical interventions in the form of transjugular intrahepatic portosystemic shunt (commonly known as TIPS), peritoneal shunt, angiography with embolization of a leaking vessel, and laparotomy remain as treatment options for cases refractory to medical management.

Melaleuca viminalis (syn. Callistemon viminalis, red bottle brush) and Melaleuca armillaris (white Bottle brush) belong to the family Myrtaceae and are reported for their traditional medicinal properties. The objective of this study was to explore and compare the chemical compositions and biological properties of these two species.

Sequential extraction and hydro-distillation methods were employed to extract essential oils for further analysis of chemical composition by gas chromatography-mass spectrometry (GC-MS). The biological potential as antioxidants was investigated for both species by assessing 1,1-diphenyl-2-picrylhydrazyl (commonly known as DPPH) scavenging activity and by use of ferric iron reducing assay. The biological potential as antibacterials was investigated by agar well diffusion assay. The in vitro cytotoxicity analysis was carried out by MTT assay.

GC-MS analysis of the essential oil of Melaleuca viminalis indicated the presence of eucalyptol as the principal chemical constituent, while that of Melaleuca armillaris indicated the presence of methyl eugenol. Comparative studies indicated that Melaleuca viminalis had higher potential for antioxidant and antibacterial activities than Melaleuca armillaris. Also, the essential oil of Melaleuca viminalis exhibited in vitro cytotoxicity against the cancer cell lines of A549 (lung; IC50 24.12 µg/mL), HCT-116 (colon; IC50 21.5 µg/mL) and T47D (breast; IC50 21.78 µg/mL), in comparison to Melaleuca armillaris for which cytotoxicity was only observed against theA549 (IC50 10.2 µg/mL) lung cancer cell line.

The present findings suggest that essential oil of Melaleuca viminalis (leaves) hold potential for future application in various medical procedures. However, the presence of methyl eugenol in Melaleuca armillaris raises concern of its being acarcinogenic compound, so further detailed toxicological studies are required to validate its therapeutic potential.

Liver resection is increasingly used for a variety of benign and malignant conditions. Despite advances in preoperative selection, surgical technique and perioperative management, posthepatectomy liver failure (PHLF) is still a leading cause of morbidity and mortality following liver resection. Given the devastating physiological consequences of PHLF and the lack of effective treatment options, identifying risk factors and preventative strategies for PHLF is paramount. In the past, a major limitation to conducting high quality research on risk factors and prevention strategies for PHLF has been the absence of a standardized definition. In this article, we describe relevant definitions for PHLF, discuss risk factors and prediction models, and review advances in liver assessment tools and PHLF prevention strategies.

The ability of plants to exert health benefits beyond antioxidant and micronutrient capacity introduces a gap in scientific understanding. The xenohormesis hypothesis aims to fill this gap, proposing that an evolutionary adaptation of enzyme and receptor pathways allow us to react to information that plants provide about the environment, offering a distinct survival advantage. The concept suggests that phytochemicals produced by plants under stress are able to activate longevity pathways in other organisms when consumed. The same pathways activated by calorie restriction, the highly conserved sirtuin enzymes and cellular homeostasis mechanisms provide an exciting perspective for treating chronic conditions related to excessive consumption. Harnessing the biological activity associated with the xenohormesis paradigm could provide a simple and achievable therapeutic alternative, although it needs to be considered within the confounding framework. The objective of this paper is to provide an update on the role of xenohormesis within nutritional medicine and to discuss the impact of modern food supply and consumption practices on evolutionary processes.

To synthesize 2-naphthylamine analogs containing azetidin-2-one (4a–g) and thiazolidin-4-one (5a–g) ring moiety, with the aim of finding new potent antimicrobial agents.

The antimicrobial activities (antibacterial and antifungal) of the newly-prepared compounds were tested in vitro against bacterial cultures (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) and fungal culture (Candida albicans) using agar plate diffusion antimicrobial bioassay. The structures of the title compounds were supported by their spectral data (IR, 1H NMR and 13C NMR).

The synthetic methodology used for the synthesis of the title compounds is shown in Scheme 1 in the paper. Among all the prepared analogs, four compounds (4a, 4e, 4g and 4f) exhibited broad spectrum activity, as compared to the standard drug (ampicillin). Another three compounds (3b, 5b and 5e) showed remarkable antifungal activity, as compared with the standard drug (amphotericin B).

The present investigation led to the synthesis and biological evaluation of naphthylamine analogs having azetidin-2-one and thiazolidin-4-one heterocyclic nucleus/moiety.

Vitamin D has been linked to brain function. To date, there have been limited studies investigating vitamin D receptor (VDR) genetic polymorphisms and cognition. The objective of this study was, therefore, to examine whether any relationships exist between VDR polymorphisms and cognitive decline in an elderly population.

Six hundred and fifty participants aged ≥ 65 years were recruited from the Central Coast, New South Wales, Australia, and were genotyped for 8 VDR polymorphisms (VDR-ApaI, VDR-BsmI, VDR-TaqI, VDR-FokI, VDR-Tru91, VDR-Cdx2, VDR-A1012G, and VDR-NIaIII). Gene variants were identified using polymerase chain reaction, followed by restriction fragment length polymorphism analysis and gel electrophoresis. Cognitive decline was measured using the mini-mental state examination (MMSE), while a self-administered food frequency questionnaire was used to estimate participants’ dietary intake of vitamin D.

Odds ratio (OR) analysis found that VDR-BsmI and VDR-TaqI polymorphic alleles were both associated with increased risk of cognitive decline (OR = 1.55 and OR = 1.49, respectively). VDR-TaqI was also found to be significantly associated with MMSE score, following adjustment for age and sex (p = 0.0005). Examination of the distribution of VDR-TaqI genotypes showed that a greater proportion of participants with the homozygous recessive tt genotype had some degree of cognitive decline (24%). As might be predicted, a significant association was also observed between age and MMSE score (p = 0.015). When examined by sex, a significant relationship was found between age and MMSE for females (p ≤ 0.0001) but no relationship was observed in males. Dietary intake of vitamin D did not influence MMSE outcomes in this cohort.

The VDR-BsmI and VDR-TaqI genetic polymorphisms are associated with cognitive decline in an elderly population.

Cases of suspected herb-induced liver injury (HILI) caused by herbal Traditional Chinese Medicines (TCMs) and of drug-induced liver injury (DILI) are commonly published in the scientific literature worldwide. As opposed to the multiplicity of botanical chemicals in herbal TCM products, which are often mixtures of several herbs, conventional Western drugs contain only a single synthetic chemical. It is therefore of interest to study how HILI by TCM and DILI compare with each other, and to what extent results from each liver injury type can be transferred to the other. China is among the few countries with a large population using synthetic Western drugs as well as herbal TCM. Therefore, China is well suited to studies of liver injury comparing drugs with TCM herbs. Despite some concordance, recent analyses of liver injury cases with verified causality, using the Roussel Uclaf Causality Assessment Method, revealed major differences in HILI caused by TCMs as compared to DILI with respect to the following features: HILI cases are less frequently observed as compared to DILI, have a smaller proportion of females and less unintentional rechallenge events, and present a higher rate of hepatocellular injury features. Since many results were obtained among Chinese residents who had access to and had used Western drugs and TCM herbs, such ethnic homogeneity supports the contention that the observed differences of HILI and DILI in the assessed population are well founded.

Locoregional therapy is playing an increasingly important role in the non-surgical management of hepatocellular carcinoma (HCC). The novel technique of non-thermal electric ablation by nanosecond pulsed electric field has been recognized as a potential locoregional methodology for indicated HCC. This manuscript explores the most recent studies to indicate its unique anti-tumor immune response. The possible immune mechanism, termed as nano-pulse stimulation, was also analyzed.