Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination?

© The Author(s) 2016. Alcohol consumption is the principal factor in the pathogenesis of chronic liver diseases. Alcoholic liver disease (ALD) is defined by histological lesions on the liver that can range from simple hepatic steatosis to more advanced stages such as alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and liver failure. As one of the oldest forms of liver injury known to humans, ALD is still a leading cause of liver-related morbidity and mortality and the burden is exerting on medical systems with hospitalization and management costs rising constantly worldwide. Although the biological mechanisms, including increasing of acetaldehyde, oxidative stress with induction of cytochrome p450 2E1, inflammatory cytokine release, abnormal lipid metabolism and induction of hepatocyte apoptosis, by which chronic alcohol consumption triggers serious complex progression of ALD is well established, there is no universally accepted therapy to prevent or reverse. In this article, we have briefly reviewed the pathogenesis of ALD and the molecular targets for development of novel therapies. This review is focused on current therapeutic strategies for ALD, including lifestyle modification with nutrition supplements, available pharmacological drugs and new agents that are under development, liver transplantation, application of complementary medicines, and their combination. The relevant molecular mechanisms of each conventional medication and natural agent have been reviewed according to current available knowledge in the literature. We also summarized efficacy vs safety on conventional and herbal medicines which are specifically used for the prevention and treatment of ALD. Through a system review, this article highlighted that the combination of pharmaceutical drugs with naturally occurring agents may offer an optimal management for ALD and its complications. It is worthwhile to conduct large-scale, multiple centre clinical trials to further prove the safety and benefits for the integrative therapy on ALD

Optimization of admixture and three-layer particleboard made from oil palm empty fruit bunch and rubberwood clones

Empty fruit bunch (EFB) is a biomass that is widely available and has the potential to be used as industrial raw material especially in wood-based industries. This study focuses on producing a particleboard by incorporating EFB with two different rubberwood clones: Prang Besar (PB) 260 and RRIM 2002, respectively. PB 260 is a commercially planted clone and wood from matured (>25 year-old) trees are used by wood-based panel manufacturers. RRIM 2002 is a new clone planted at the Malaysian Rubber Board (MRB) research trial plots and consists of only 4-year-old trees. Two types of particleboards (admixture and three-layer) with different ratios were produced. The Japanese Industrial Standard (JIS-5908 2003 particleboard) was used to evaluate mechanical and dimensional stability properties of the particleboards. From the study, it was found that admixture particleboards showed superior properties compared to three-layer particleboards. Layering EFB and rubberwood significantly decreased board performance for all properties (except internal bonding). The optimum ratios of EFB and both rubberwood clones are found to be 1:1 (50% EFB: 50% rubberwood). Meanwhile, increasing the rubberwood clones ratio to 70% lowered board performance especially for EFB (30%):RRIM 2002 clone (70%) boards which showed the lowest values for all properties for both admixture and three-layer board

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

Cytoskeletal dynamics during cell behaviours ranging from endocytosis and exocytosis to cell division and movement is controlled by a complex network of signalling pathways, the full details of which are as yet unresolved. Here we show that SILAC-based proteomic methods can be used to characterize the rapid chemoattractant-induced dynamic changes in the actin–myosin cytoskeleton and regulatory elements on a proteome-wide scale with a second to minute timescale resolution. This approach provides novel insights in the ensemble kinetics of key cytoskeletal constituents and association of known and novel identified binding proteins. We validate the proteomic data by detailed microscopy-based analysis of in vivo translocation dynamics for key signalling factors. This rapid large-scale proteomic approach may be applied to other situations where highly dynamic changes in complex cellular compartments are expected to play a key role

Spectrum of PEX1 and PEX6 variants in Heimler syndrome

Heimler syndrome (HS) consists of recessively inherited sensorineural hearing loss, amelogenesis imperfecta (AI) and nail abnormalities, with or without visual defects. Recently HS was shown to result from hypomorphic mutations in PEX1 or PEX6, both previously implicated in Zellweger Syndrome Spectrum Disorders (ZSSD). ZSSD are a group of conditions consisting of craniofacial and neurological abnormalities, sensory defects and multi-organ dysfunction. The finding of HS-causing mutations in PEX1 and PEX6 shows that HS represents the mild end of the ZSSD spectrum, though these conditions were previously thought to be distinct nosological entities. Here, we present six further HS families, five with PEX6 variants and one with PEX1 variants, and show the patterns of Pex1, Pex14 and Pex6 immunoreactivity in the mouse retina. While Ratbi et al. found more HS-causing mutations in PEX1 than in PEX6, as is the case for ZSSD, in this cohort PEX6 variants predominate, suggesting both genes play a significant role in HS. The PEX6 variant c.1802G>A, p.(R601Q), reported previously in compound heterozygous state in one HS and three ZSSD cases, was found in compound heterozygous state in three HS families. Haplotype analysis suggests a common founder variant. All families segregated at least one missense variant, consistent with the hypothesis that HS results from genotypes including milder hypomorphic alleles. The clinical overlap of HS with the more common Usher syndrome and lack of peroxisomal abnormalities on plasma screening suggest that HS may be under-diagnosed. Recognition of AI is key to the accurate diagnosis of HS

Multifrequency Strategies for the Identification of Gamma-Ray Sources

More than half the sources in the Third EGRET (3EG) catalog have no firmly established counterparts at other wavelengths and are unidentified. Some of these unidentified sources have remained a mystery since the first surveys of the gamma-ray sky with the COS-B satellite. The unidentified sources generally have large error circles, and finding counterparts has often been a challenging job. A multiwavelength approach, using X-ray, optical, and radio data, is often needed to understand the nature of these sources. This chapter reviews the technique of identification of EGRET sources using multiwavelength studies of the gamma-ray fields.Comment: 35 pages, 22 figures. Chapter prepared for the book "Cosmic Gamma-ray Sources", edited by K.S. Cheng and G.E. Romero, to be published by Kluwer Academic Press, 2004. For complete article and higher resolution figures, go to: http://www.astro.columbia.edu/~muk/mukherjee_multiwave.pd

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains

The ISWI family of ATP-dependent chromatin remodelers represses transcription by changing nucleosome positioning. The interactions with extranucleosomal DNA and the requirement of a minimal length of extranucleosomal DNA by ISWI mediate the spacing of nucleosomes. ISW2 from Saccharomyces cerevisiae, a member of the ISWI family, has a conserved domain called SLIDE (SANT-like ISWI domain), whose binding to extranucleosomal DNA ~19 bp from the edge of nucleosomes is required for efficiently pushing DNA into nucleosomes and maintaining the unidirectional movement of nucleosomes, as reported here. Loss of SLIDE binding does not perturb ATPase domain binding to the SHL2 site of nucleosomes or its initial movement of DNA inside of nucleosomes. ISW2 has therefore two distinct roles in mobilizing nucleosomes, with the ATPase domain translocating and moving DNA inside nucleosomes, and the SLIDE domain facilitating the entry of linker DNA into nucleosomes

Assessment of HIF-1α expression and release following endothelial injury in-vitro and in-vivo

Background: Endothelial injury is an early and enduring feature of cardiovascular disease. Inflammation and hypoxia may be responsible for this, and are often associated with the up-regulation of several transcriptional factors that include Hypoxia Inducible Factor-1 (HIF-1). Although it has been reported that HIF-1α is detectable in plasma, it is known to be unstable. Our aim was to optimize an assay for HIF-1α to be applied to in vitro and in vivo applications, and to use this assay to assess the release kinetics of HIF-1 following endothelial injury. Methods: An ELISA for the measurement of HIF in cell-culture medium and plasma was optimized, and the assay used to determine the best conditions for sample collection and storage. The results of the ELISA were validated using Western blotting and immunohistochemistry (IHC). In vitro, a standardized injury was produced in a monolayer of rat aortic endothelial cells (RAECs) and intracellular HIF-1α was measured at intervals over 24 hours. In vivo, a rat angioplasty model was used. The right carotid artery was injured using a 2F Fogarty balloon catheter. HIF-1α was measured in the plasma and in the arterial tissue (0, 1, 2, 3 and 5 days post injury). Results: The HIF-1α ELISA had a limit of detection of 2.7 pg/ mL and was linear up to 1000 pg/ mL. Between and within-assay coefficient of variation values were less than 15%. HIF-1α was unstable in cell lysates and plasma, and it was necessary to add a protease inhibitor immediately after collection, and to store samples at -800C prior to analysis. The dynamics of HIF-1α release were different for the in vitro and in vivo models. In vitro, HIF-1α reached maximum concentrations approximately 2h post injury, whereas peak values in plasma and tissues occurred approximately 2 days post injury, in the balloon injury model. Conclusion: HIF-1α can be measured in plasma, but this requires careful sample collection and storage. The carotid artery balloon injury model is associated with the transient release of HIF-1α into the circulation that probably reflects the hypoxia induced in the artery wall

Transcriptional Analysis of Murine Macrophages Infected with Different Toxoplasma Strains Identifies Novel Regulation of Host Signaling Pathways

Most isolates of Toxoplasma from Europe and North America fall into one of three genetically distinct clonal lineages, the type I, II and III lineages. However, in South America these strains are rarely isolated and instead a great variety of other strains are found. T. gondii strains differ widely in a number of phenotypes in mice, such as virulence, persistence, oral infectivity, migratory capacity, induction of cytokine expression and modulation of host gene expression. The outcome of toxoplasmosis in patients is also variable and we hypothesize that, besides host and environmental factors, the genotype of the parasite strain plays a major role. The molecular basis for these differences in pathogenesis, especially in strains other than the clonal lineages, remains largely unexplored. Macrophages play an essential role in the early immune response against T. gondii and are also the cell type preferentially infected in vivo. To determine if non-canonical Toxoplasma strains have unique interactions with the host cell, we infected murine macrophages with 29 different Toxoplasma strains, representing global diversity, and used RNA-sequencing to determine host and parasite transcriptomes. We identified large differences between strains in the expression level of known parasite effectors and large chromosomal structural variation in some strains. We also identified novel strain-specifically regulated host pathways, including the regulation of the type I interferon response by some atypical strains. IFNβ production by infected cells was associated with parasite killing, independent of interferon gamma activation, and dependent on endosomal Toll-like receptors in macrophages and the cytoplasmic receptor retinoic acid-inducible gene 1 (RIG-I) in fibroblasts.National Institutes of Health (U.S.) (R01-AI080621)New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (Developmental Grant AIO57159)Pew Charitable Trusts (Biomedical Scholars Program)Robert A. Swanson Career Development awardThe Knights Templar Eye Foundation, Inc.Pre-Doctoral Grant in the Biological Sciences (5-T32-GM007287-33)Cleo and Paul Schimmel Foundatio

Perceptions, Attitude, Responses, Knowledge and Emotional Well-being (PARKE) of COVID-19 among students at Newcastle University Medicine Malaysia (NUMed)

\ua9 2021, International Society of Global Health. All rights reserved. Background: Adherence to preventative measures designed to mitigate transmission of COVID-19 depends on individual’s understanding and perception of COVID-19. The objective of this study was to assess the knowledge, perceptions, behavioural adaptation and psychological well-being related to COVID-19 among students attending Newcastle University Medicine Malaysia. Methods: A cross-sectional study was conducted using convenience sampling of students. The self-administered online questionnaire was sent via email in Google forms format between 18 April and 30 April 2020. The questionnaire focused on sociodemographic, perception, attitude and behavioural responses, knowledge and sources of information and anxiety level. Results 326 university students with mean age of 21.8 (S.D 2.3) participated in this study. More females (n =236) took part in the study than males (n= 90). Most students (80%) believed that they knew how to protect themselves. More than two-thirds (68%) of students strongly agreed that COVID-19 was a serious public health issue. Most students (>90%) practised the recommended measures, except for avoid touching of eyes, nose and mouth with unwashed hands (82%). Wearing a facemask was positively associated with behavioural uptake in university students. Conclusions: This study showed a good attitude, behavioural responses, knowledge level and emotional responses among NUMed students towards COVID-19