HUWE1 cooperates with RAS activation to control leukemia cell proliferation and human hematopoietic stem cells differentiation fate

Acute myeloid leukemia (AML) is a poor prognosis hematopoietic malignance characterized by abnormal proliferation and differentiation of hematopoietic stem cells (HSCs). Although advances in treatment have greatly improved survival rates in young patients, in the elderly population, ~70% of patients present poor prognosis. A pan-cancer analysis on the TCGA cohort showed that AML has the second higher HUWE1 expression in tumor samples among all cancer types. In addition, pathway enrichment analysis pointed to RAS signaling cascade as one of the most important pathways associated to HUWE1 expression in this particular AML cohort. In silico analysis for biological processes enrichment also revealed that HUWE1 expression is correlated with 13 genes involved in myeloid differentiation. Therefore, to understand the role of HUWE1 in human hematopoietic stem and progenitor cells (HSPC) we constitutively expressed KRASG12V oncogene concomitantly to HUWE1 knockdown in stromal co-cultures. The results showed that, in the context of KRASG12V, HUWE1 significantly reduces cell cumulative growth and changes myeloid differentiation profile of HSPCs. Overall, these observations suggest that HUWE1 might contribute to leukemic cell proliferation and impact myeloid differentiation of human HSCs, thus providing new venues for RAS-driven leukemia targeted therapy approach

Towards Understanding The Hepatoprotective effect of Grape Seeds Extract on Cholesterol-Fed Rats

Abstract: In our previous studies, a phenolic-rich extract of grape seed was prepared under optimal conditions. The antioxidant activity of grape seed extract (GSE) was determined in addition to 50 determination of acute oral LD toxicity. The current work studies the protective effect of GSE on hypercholesterolemia, where, W istar rats fed a standard laboratory diet (control group-CG) or a cholesterol-rich diet (hypercholesterolemic group-HCD) and to see the effect of GSE, another group fed on cholesterol-rich diet enriched with 0.3% GSEW /W-PG) for 8 weeks. Serum lipid levels, serum antioxidant status, Liver and kidney function were analysed in addition to histopathological examination of the liver. The hypocholesterolemic effects of GSE is confirmed by lowering the serum total cholesterol (TC) by 31%, low-density lipoprotein cholesterol LDL-C by 41% and elevated the high-density lipoprotein cholesterol HDL-C by 25% compared to TC, LDL-C and HDL-C of HCD group . Furthermore, the liver function expressed as glutamic pyruvate transaminase (GPT) and Albumin serum levels, decreased significantly and reached to normal level in case of oral administration of GSE. The kidney function showed no adverse effect in all groups. In addition, the antioxidant status serum level was increased as compared to those of rats fed only on cholesterol-rich diet. Histological examination of liver sections confirmed the serum analysis where GSE had a protective effect on animals fed on HCD, the liver of these animals showed mild affection in the form of microvesicular vacuolation of hepatocytes in the peripheral zone of the hepatic lobule (<50%) in comparison to the fatty change observed as microvesicular and macrovesicular vacuolation in >50% and <70% of the liver sections in HCD group. T hese results suggested that the GSE has a hypocholesterolemic effect which might be due to its ability to lower serum TC and LDL-C levels as well as slowing the lipid peroxidation process by enhancing antioxidant enzyme activity

Kepercayaan pelajar terhadap konsep ubudiyyah dalam pengurusan halal / Mahfuzah Mohammed Zabidi … [et al.]

Pengurusan halal adalah satu bidang kritikal yang perlu diberikan perhatian serius demi merealisasikan Malaysia sebagai salah sebuah hab halal dunia. Bidang ini bertujuan memastikan kesucian dan sifat “patuh syariah” bagi sesuatu produk atau perkhidmatan terus terpelihara. Graduan bidang pengurusan halal diharapkan berperanan secara langsung dalam memenuhi keperluan badan pensijilan halal. Pelajar bidang ini perlu dipersiapkan dengan kefahaman mengenai konsep halal secara bersepadu dengan nilai ubudiyyah yang mendasari akidah, syariah dan tasawuf dalam Islam. Hal ini bagi memastikan mereka dapat memberi kefahaman yang jelas kepada masyarakat, khususnya kepada penggiat industri bahawa halal bukan sekadar pada label atau logo semata-mata. Kajian ini bertujuan meneroka kepercayaan pelajar Diploma Pengurusan Halal, Akademi Pengajian Islam Kontemporari (ACIS) Universiti Teknologi MARA mengenai konsep ubudiyyah dan kesepaduannya dalam pengurusan halal. Kajian ini menggunakan pendekatan kualitatif menerusi temubual kumpulan fokus berpandukan protokol separa berstruktur. Data temubual dianalisis secara separa transkrip. Temubual mendapati bahawa pelajar lebih banyak menghubungkan konsep ubudiyyah dalam pengurusan halal dengan aspek syariat berbanding aspek akidah dan tasawuf. Oleh itu, kesepaduan ilmu antara kursus-kursus akademik yang ditawarkan oleh fakulti, sama ada dalam pengajian ilmu Islam mahupun pengajian ilmu moden yang berteraskan nilai ubudiyyah dalam bidang pengurusan halal dilihat perlu diperkemaskan bagi mendepani isu halal secara lebih holistik. Natijahnya, kesepaduan ilmu ini akhirnya berupaya menzahirkan Islam sebagai agama rahmat untuk sekalian alam

Regulation of pro-inflammatory and pro-fibrotic factors by CCN2/CTGF in H9c2 cardiomyocytes

Connective tissue growth factor (CTGF), also known as CCN2, is implicated in fibrosis through both extracellular matrix (ECM) induction and inhibition of ECM degradation. The role of CTGF in inflammation in cardiomyocytes is unknown. In some mesenchymal cell systems, CTGF mediates effects through TGF-β or tyrosine kinase cell surface receptor, TrkA, signalling. In this study, cellular mechanisms by which CTGF regulates pathways involved in fibrosis and inflammation were explored. Murine H9c2 cardiomyocytes were treated with recombinant human (rh)CTGF and ECM formation gene expression: fibronectin, collagen type -I and -III and ECM degradation genes: TIMP-1, TIMP-2 and PAI-1 were found to be induced. CTGF treatment also increased pro-inflammatory cytokines TNF-α, IL-6, MCP-1 and IL-8. CTGF upregulated TGF-β1 mRNA and rapidly induced phosphorylation of TrkA. The CTGF-induced pro-fibrotic and pro-inflammatory effects were blocked by anti-TGF-β neutralizing antibody and Alk 5 inhibitor (SB431542). A specific blocker of TrkA activation, k252a, also abrogated CTGF-induced effects on fibrosis and gene expresison of MCP-1 and IL-8, but not TNF-α or IL-6. Collectively, this data implicates CTGF in effects on pro-fibrotic genes and pro-inflammatory genes via TGF-β pathway signalling and partly through TrkA

Crustose Coralline Algae and a Cnidarian Neuropeptide Trigger Larval Settlement in Two Coral Reef Sponges

In sessile marine invertebrates, larval settlement is fundamental to population maintenance and persistence. Cues contributing to the settlement choices and metamorphosis of larvae have important implications for the success of individuals and populations, but cues mediating larval settlement for many marine invertebrates are largely unknown. This study assessed larval settlement in two common Great Barrier Reef sponges, Coscinoderma matthewsi and Rhopaloeides odorabile, to cues that enhance settlement and metamorphosis in various species of scleractinian coral larvae. Methanol extracts of the crustose coralline algae (CCA), Porolithon onkodes, corresponding to a range of concentrations, were used to determine the settlement responses of sponge larvae. Cnidarian neuropeptides (GLW-amide neuropeptides) were also tested as a settlement cue. Settlement in both sponge species was approximately two-fold higher in response to live chips of CCA and optimum concentrations of CCA extract compared to 0.2 µm filtered sea water controls. Metamorphosis also increased when larvae were exposed to GLW-amide neuropeptides; R. odorabile mean metamorphosis reached 42.0±5.8% compared to 16.0±2.4% in seawater controls and in C. matthewsi mean metamorphosis reached 68.3±5.4% compared to 36.7±3.3% in seawater controls. These results demonstrate the contributing role chemosensory communication plays in the ability of sponge larvae to identify suitable habitat for successful recruitment. It also raises the possibility that larvae from distinct phyla may share signal transduction pathways involved in metamorphosis

Mutations with epigenetic effects in myeloproliferative neoplasms and recent progress in treatment: Proceedings from the 5th International Post-ASH Symposium

Immediately following the 2010 annual American Society of Hematology (ASH) meeting, the 5th International Post-ASH Symposium on Chronic Myelogenous Leukemia and BCR-ABL1-Negative Myeloproliferative Neoplasms (MPNs) took place on 7–8 December 2010 in Orlando, Florida, USA. During this meeting, the most recent advances in laboratory research and clinical practice, including those that were presented at the 2010 ASH meeting, were discussed among recognized authorities in the field. The current paper summarizes the proceedings of this meeting in BCR-ABL1-negative MPN. We provide a detailed overview of new mutations with putative epigenetic effects (TET oncogene family member 2 (TET2), additional sex comb-like 1 (ASXL1), isocitrate dehydrogenase (IDH) and enhancer of zeste homolog 2 (EZH2)) and an update on treatment with Janus kinase (JAK) inhibitors, pomalidomide, everolimus, interferon-α, midostaurin and cladribine. In addition, the new ‘Dynamic International Prognostic Scoring System (DIPSS)-plus' prognostic model for primary myelofibrosis (PMF) and the clinical relevance of distinguishing essential thrombocythemia from prefibrotic PMF are discussed