Asha Jacob

Bio: Asha Jacob is an academic researcher from Long Island Jewish Medical Center. The author has contributed to research in topics: Proinflammatory cytokine & Inflammation. The author has an hindex of 17, co-authored 25 publications receiving 1182 citations. Previous affiliations of Asha Jacob include The Feinstein Institute for Medical Research & North Shore-LIJ Health System.

Mechanism of the Anti-inflammatory Effect of Curcumin: PPAR-γ Activation

Abstract: Curcumin, the phytochemical component in turmeric, is used as a dietary spice and a topical ointment for the treatment of inflammation in India for centuries. Curcumin (diferuloylmethane) is relatively insoluble in water, but dissolves in acetone, dimethylsulphoxide, and ethanol. Commercial grade curcumin contains 10–20% curcuminoids, desmethoxycurcumin, and bisdesmethoxycurcumin and they are as effective as pure curcumin. Based on a number of clinical studies in carcinogenesis, a daily oral dose of 3.6 g curcumin has been efficacious for colorectal cancer and advocates its advancement into Phase II clinical studies. In addition to the anticancer effects, curcumin has been effective against a variety of disease conditions in both in vitro and in vivo preclinical studies. The present review highlights the importance of curcumin as an anti-inflammatory agent and suggests that the beneficial effect of curcumin is mediated by the upregulation of peroxisome proliferator-activated receptor-γ (PPAR-γ) activation.

Review: milk fat globule-EGF factor 8 expression, function and plausible signal transduction in resolving inflammation.

Abstract: Although the cloning and molecular characterization of MFG-E8 was first reported in the early 90s, breakthrough on MFG-E8 research came into light when it was explored as an outstanding factor for phagocytosis of apoptotic cells by professional macrophages in 2002. Since then numerous studies have been performed on MFG-E8 not only to demonstrate the role of phagocytic clearance of apoptotic cells, but also to focus on a wide range of aspects, even emphasizing on a direct link to innate-immune systems. In terms of its role as therapeutic potentials, our group, as well as others, has shown MFG-E8 to be an essential factor in attenuating inflammation and improving prognosis in several animal models of life threatening diseases. Considering these versatile functions of MFG-E8, several in vitro and in vivo studies were embarked on to explore the mechanistic pathways exerted by MFG-E8 during inflammation. With the relevant cumulative findings, herein we reviewed the potential roles of MFG-E8 in pathophysiological conditions by highlighting its plausible signal-transduction mechanisms.

The Parasympathetic Nervous System in the Quest for Stroke Therapeutics

Abstract: Stroke is a devastating neurovascular disease with limited therapeutic options. The pathogenesis of stroke involves complex interrelated molecular mechanisms including excitotoxicity, oxidative and nitrosative stress, cortical spreading depolarizations, inflammation, necrosis, and apoptosis. Successful development of stroke therapeutics depends on understanding these molecular mechanisms and how to counteract them to limit tissue damage during stroke. Activation of the parasympathetic nervous system (PNS) has been shown to antagonize a multiplicity of pathologic mechanisms. Elements of parasympathetic activation such as vagus nerve stimulation have already been used successfully in treating brain disorders such as epilepsy and depression. This review discusses the anatomical basis and molecular mechanisms involved in activation of the PNS, and assesses the strength of available evidence for the further development of this modality into a stroke therapy.

Pre-Treatment of Recombinant Mouse MFG-E8 Downregulates LPS-Induced TNF-α Production in Macrophages via STAT3-Mediated SOCS3 Activation

Abstract: Milk fat globule-epidermal growth factor factor 8 (MFG-E8) regulates innate immune function by modulating cellular signaling, which is less understood Herein, we aimed to investigate the direct anti-inflammatory role of MFG-E8 in macrophages by pre-treatment with recombinant murine MFG-E8 (rmMFG-E8) followed by stimulation with LPS in RAW2647 cells and in peritoneal macrophages, isolated from wild-type (WT) or MFG-E8−/− mice RAW2647 cells and mouse peritoneal macrophages treated with rmMFG-E8 significantly downregulated LPS-induced TNF-α mRNA by 25% and 24%, and protein levels by 29% and 23%, respectively (P<005) Conversely, peritoneal macrophages isolated from MFG-E8−/− mice produced 28% higher levels of TNF-α, as compared to WT mice when treated with LPS In in vivo, endotoxemia induced by intraperitoneal injection of LPS (5 mg/kg BW), at 4 h after induction, serum level of TNF-α was significantly higher in MFG-E8−/− mice (837 pg/mL) than that of WT (570 pg/mL, P<005) To elucidate the direct anti-inflammatory effect of MFG-E8, we examined STAT3 and its target gene, SOCS3 Treatment with rmMGF-E8 significantly induced pSTAT3 and SOCS3 in macrophages Similar results were observed in in vivo treatment of rmMFG-E8 in peritoneal cells and splenic tissues Pre-treatment with rmMFG-E8 significantly reduced LPS-induced NF-κB p65 contents These data clearly indicated that rmMFG-E8 upregulated SOCS3 which in turn interacted with NF-κB p65, facilitating negative regulation of TLR4 signaling for LPS-induced TNF-α production Our findings strongly suggest that MFG-E8 is a direct anti-inflammatory molecule, and that it could be developed as a therapy in attenuating inflammation and tissue injury

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

A comprehensive 1000 Genomes–based genome-wide association meta-analysis of coronary artery disease

Abstract: Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

Role of WHO.

Abstract: OVERVIEW The GRA Marketing Internship Program is offered to students who are interested in gaining valuable work experience through efforts in marketing, membership, sales, and events. Interns work directly to assist the Director of Marketing and Communications on various tasks relating to upcoming GRA events. During this internship, students will work a minimum of 10 hours a week and a maximum of 20 hours a week. Students are encouraged to earn credit for their internship, however this is a paid internship. Students interested in obtaining credit for their internship must consult their academic advisor or the intern coordinator at their academic unit.

Intensive insulin therapy for the critically ill patients with stress hyperglycemia

Abstract: Objective To observe the effect of intensive insulin therapy on the critically ill patients with stress hyperglycemia in ICU.Methods One hundred and ten critically ill patients in ICU were randomly divided into two groups,the intensive insulin therapy group(n=55) and control group(n=55).The blood glucose in the intensive insulin therapy group was controlled at 4.4 to 6.1 mmol/L,and the blood glucose in control group was controlled at 10.0 to 11.1 mmol/L.The two groups were observed and compared the days in the ICU,the numbers of patients requiring mechanical ventilation,the days of mechanical ventilation,the incidences of infection in hospital,the days of using antibiotics,Acute Physiology and Chronic Health Evaluation Ⅱ score of the last day in ICU,the morbidity of multiple organ failure,the morbidity of hypoglycemia and mortality.Results All the above indices except morbidity of hypoglycemia were significantly lower in the intensive insulin therapy group than those in control group(P0.05 or P0.01).Conclusion Intensive insulin therapy and keeping blood glucose at 4.4 to 6.1 mmol/L can improve the clinical curative effect and reduce the mortality for the critically ill patients with stress hyperglycemia,