Sphingosine-1-phosphate (S1P) is a pleiotropic sphingolipid derived by the phosphorylation of sphingosine either by sphingosine kinase 1 (SPHK1) or SPHK2. Importantly, S1P acts through five different types of G-protein coupled S1P receptors (S1PRs) in immune cells to elicit inflammation and other immunological processes by enhancing the production of various cytokines, chemokines, and growth factors. The airway inflammation in asthma and other respiratory diseases is augmented by the activation of immune cells and the induction of T-helper cell type 2 (Th2)-associated cytokines and chemokines. Therefore, studying the S1P mediated signaling in airway inflammation is crucial to formulate effective treatment and management strategies for asthma and other respiratory diseases. The central aim of this study is to characterize the molecular targets induced through the S1P/S1PR axis and dissect the therapeutic importance of this key axis in asthma, airway inflammation, and other related respiratory diseases. To achieve this, we have adopted both high throughput next-generation knowledge discovery platforms such as SwissTargetPrediction, WebGestalt, Open Targets Platform, and Ingenuity Pathway Analysis (Qiagen, United States) to delineate the molecular targets of S1P and further validated the upstream regulators of S1P signaling using cutting edge multiple analyte profiling (xMAP) technology (Luminex Corporation, United States) to define the importance of S1P signaling in asthma and other respiratory diseases in humans.
IL-4Rα gene (I50V) and STAT6 gene (G2964) polymorphisms may play a role in development of eczema; however, the IL-4 gene polymorphism (C-590T) had no relationship with susceptibility to the disease among Saudi children.
Long non-coding RNAs (lncRNAs) are implicated in various cellular and
pathological processes. Two lncRNAs, myocardial infarction-associated transcript
(MIAT) and metastasis-associated lung adenocarcinoma
transcript 1 (MALAT1), may be involved in the pathogenesis of
coronary artery disease (CAD). Here, we aimed to determine the relative
circulating levels of MIAT and MALAT1 in 110
stable CAD patients and 117 controls and to correlate their levels with the
clinical and laboratory data. Peripheral blood expression levels were quantified
by Real-Time qPCR. The median MIAT expression level in CAD
patients was significantly 12-fold higher than controls
(p<0.001). Otherwise, the median MALAT1
expression level was comparable in patient and control groups. Both lncRNAs
showed significantly higher relative expression levels in patients with positive
history of previous cardiac ischemic events, and MIAT showed
significantly higher expression in diabetic CAD patients. The area under the
curve of MIAT (0.888 ± 0.02 with sensitivity 95.5% and
specificity 72.7%), was significantly larger than that of
MALAT1 (0.601 ± 0.04 with sensitivity 50% and specificity
63.6%) for detecting the presence of significant CAD. The current findings
suggest that lncRNA MIAT could have a diagnostic significance
in CAD patients. MALAT1 levels, however, are not sufficiently
reliable to have much clinical use in our cases.
BackgroundThe prevalence of obesity and vitamin D deficiency in Saudi Arabia has increased recently. Decreased physical activity might play a role in obesity. Previous studies showed an association between low vitamin D level and its receptor polymorphism with obesity development.ObjectiveTo determine association of low vitamin D level and its receptor polymorphism with obesity in Saudi men.MethodsThis case control study was carried out from March 2016 through March 2017. Three hundred Saudi male students (from applied medical sciences in Taif University, Taif, Saudi Arabia) were classified according to BMI into lean, overweight and obese groups. For each individual, blood glucose, cholesterol, HDL-C, LDL-C, insulin and 25-(OH) vitamin D were measured. In addition, Apal, BsmI and TaqI genotypes were performed for each individual from March 2016 through March 2017, through computer-based search of the following databases: PubMed, Web of Science (Thomson ReutersTM). The references of the original literature and the related articles were also searched, for potential complementary studies. Data were analyzed by SPSS version 16, using Spearman’s rho and ANOVA tests.ResultsThere was significant negative association between 25-(OH) vitamin D level and obesity (p<0.01). Genotyping study showed that both bb of BsmI and tt of TaqI genotypes were higher in the obese group compared with lean group (p<0.05). Moreover, bb genotype has higher BMI and HOMA-IR than both BB and Bb; and tt genotype also has higher BMI and HOMA-IR than TT and Tt genotypes (p<0.05).ConclusionLow vitamin D level and VDR BsmI and Taq1 genotypes may be a risk factor of obesity.
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