Diseases, Volume 3, Issue 3 (September 2015) – 9 articles , Pages 122-220

Hepatitis B virus (HBV) infection, a cause of hepatocellular carcinoma (HCC), remains a serious global health concern. HCC development and human hepatocarcinogenesis are associated with hepatic inflammation caused by host interferons and cytokines. This article focused on the association between the HBV core protein, which is one of the HBV-encoding proteins, and cytokine production. The HBV core protein induced the production of interferons and cytokines in human hepatoma cells and in a mouse model. These factors may be responsible for persistent HBV infection and hepatocarcinogenesis. Inhibitors of programmed death (PD)-1 and HBV core and therapeutic vaccines including HBV core might be useful for the treatment of patients with chronic HBV infection. Inhibitors of HBV core, which is important for hepatic inflammation, could be helpful in preventing the progression of liver diseases in HBV-infected patients. Full article

A mosaic pattern of lung attenuation on chest computed tomography (CT) may be due to various etiologies. There is limited published data on CT results when used to evaluate pulmonary hypertension (PH). We retrospectively studied the frequency of mosaic pattern in patients with PH and the cause of the PH by diagnostic group, as well as the correlation between the mosaic pattern and the following: demographics, severity of the PH, main pulmonary artery (PA) size, PA/aorta (PA/Ao) ratio, pulmonary function tests (PFT), and ventilation perfusion scan results. Overall, 18% of the cohort had CT mosaic pattern (34/189). Mosaic pattern was present in 17/113 (15%) in Group 1 pulmonary arterial hypertension, 5/13 (28%) in Group 2 pulmonary venous hypertension and 8/50 (16%) in Group 3 PH. Conversely, Group 4 chronic thromboembolic PH was more prevalent in 4/8 (50%). Main PA size, PA/Ao ratio, and segmental perfusion defect were positively associated with mosaic pattern. In contrast, factors such as age, gender, body mass index, functional class, hemodynamic data, and PFT values were not associated with mosaic pattern. Mosaic pattern is not specific as an isolated finding for distinguishing the subtype of PH. Full article

Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possesses antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc, and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management. Full article

Metabolic syndrome is an ever-increasing health problem among the world’s population. It is a group of intertwined maladies that includes obesity, hypertriglyceridemia, hypertension, nonalcoholic fatty liver disease (NAFLD), and diabetes mellitus type II (T2D). There is a direct correlation between high triacylglycerol (triglyceride; TAG) level and severity of metabolic syndrome. Thus, controlling the synthesis of TAG will have a great impact on overall systemic lipid metabolism and thus metabolic syndrome progression. The Acyl-CoA: monoacylglycerolacyltransferase (MGAT) family has three members (MGAT1, -2, and -3) that catalyze the first step in TAG production, conversion of monoacylglycerol (MAG) to diacylglycerol (DAG). TAG is then directly synthesized from DAG by a Acyl-CoA: diacylglycerolacyltransferase (DGAT). The conversion of MAG → DAG → TAG is the major pathway for the production of TAG in the small intestine, and produces TAG to a lesser extent in the liver. Transgenic and pharmacological studies in mice have demonstrated the beneficial effects of MGAT inhibition as a therapy for treating several metabolic diseases, including obesity, insulin resistance, T2D, and NAFLD. In this review, the significance of several properties of MGAT physiology, including tissue expression pattern and its relationship to overall TAG metabolism, enzymatic biochemical properties and their effects on drug discovery, and finally what is the current knowledge about MGAT small molecule inhibitors and their efficacy will be discussed. Overall, this review highlights the therapeutic potential of inhibiting MGAT for lowering TAG synthesis and whether this avenue of drug discovery warrants further clinical investigation. Full article

Metabolomics is the study of low molecular weight molecules or metabolites produced within cells and biological systems. It involves technologies such as mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR) that can measure hundreds of thousands of unique chemical entities (UCEs). The metabolome provides one of the most accurate reflections of cellular activity at the functional level and can be leveraged to discern mechanistic information during normal and disease states. The advantages of metabolomics over other “omics” include its high sensitivity and ability to enable the analysis of relatively few metabolites compared with the number of genes and messenger RNAs (mRNAs). In clinical samples, metabolites are more stable than proteins or RNA. In fact, metabolomic profiling in basic, epidemiologic, clinical, and translational studies has revealed potential new biomarkers of disease and therapeutic outcome and has led to a novel mechanistic understanding of pathogenesis. These potential biomarkers include novel metabolites associated with cancer initiation, regression, and recurrence. Unlike genomics or even proteomics, however, the degree of metabolite complexity and heterogeneity within biological systems presents unique challenges that require specialized skills and resources to overcome. This article discusses epidemiologic studies of altered metabolite profiles in several cancers as well as challenges in the field and potential approaches to overcoming them. Full article

Over the last decades, improvement of medical and surgical therapy has increased life expectancy in Marfan patients. Consequently, the number of such patients requiring secondary interventions on the descending thoracic aorta due to new or residual dissections, and distal aneurysm formation has substantially enlarged. Surgical and endovascular procedures represent two valuable options of treatment, both associated with advantages and drawbacks. The aim of the present manuscript was to review endovascular outcomes in Marfan syndrome and to assess the potential role of Thoracic Endovascular Aortic Repair (TEVAR) in this subset of patients. Full article

Recently, new therapeutics have been developed for hepatocellular carcinoma (HCC). However, the overall survival rate of HCC patients is still unsatisfactory; one of the reasons for this is the high frequency of recurrence after radical treatment. Consequently, to improve prognosis, it will be important to develop a novel anti-tumor agent that is especially effective against HCC recurrence. For clinical application, long-term safety, together with high anti-tumor efficacy, is desirable. Recent studies have proposed menahydroquinone-4 1,4-bis-N,N-dimethylglycinate hydrochloride (MKH-DMG), a prodrug of menahydroquinone-4 (MKH), as a promising candidate for HCC treatment including the inhibition of recurrence; MKH-DMG has been shown to achieve good selective accumulation of MKH in tumor cells, resulting in satisfactory inhibition of cell proliferation in des-γ-carboxyl prothrombin (DCP)-positive and DCP-negative HCC cell lines. In a spleen-liver metastasis mouse model, MKH-DMG has been demonstrated to have anti-proliferation and anti-metastatic effects in vivo. The characteristics of MKH-DMG as a novel anti-HCC agent are presented in this review article. Full article

The gluten-free diet has long been considered the standard treatment for celiac disease. However, a significant number of patients continue to experience persistent symptoms despite following a gluten-free diet. Inadvertent gluten ingestion, fermentable carbohydrates, cross-contamination, and social or financial burdens present obstacles to maintaining a gluten-free diet. Proper diet education and follow-up by an expert Registered Dietitian (RD) is essential to ensure adequate nutrition on the gluten-free diet. Patients may experience unintended weight gain or elevated cholesterol levels after initiating the gluten-free diet due to adequate absorption and healing of the intestines. This review deals with the evolving gluten-free diet, optimal recommendations while considering the overall health of patients, and multi-factorial aspects of the permanent lifestyle change. Full article

Since the first evidence demonstrating the dramatically high incidence of H. pylori infection and the subsequent medical challenges it incurs, health management of H. pylori infection has been a high priority for health authorities worldwide. Despite a decreasing rate of infection in western countries, prevalence of H. pylori infection in developing and in some industrial countries is still very high. Whereas treatment and vaccination against H. pylori is a contemporary issue in medical communities, selective treatment and prior high-throughput screening of the subject population is a major concern of health organizations. So far, diagnostic tests are either elaborative and require relatively advanced medical care infrastructure or they do not fulfill the criteria recommended by the Maastricht IV/Florence consensus report. In this review, in light of recent scientific studies, we highlight current and possible future approaches for the diagnosis of H. pylori. We point out that novel non-invasive tests may not only cover the requirements of gold standard methods in H. pylori detection but also offer the potential for risk stratification of infection in a high throughput manner. Full article