Downregulation of Talin‐1 is associated with the increased expression of miR‐182‐5p and miR‐9‐5p in coronary artery disease

BackgroundEvidence indicates that the dysregulation of extracellular matrix (ECM) components can lead to cardiovascular diseases. The Talin‐1 (TLN1) gene is a major component of the ECM, and it mediates integrin adhesion to the ECM. In this study, we aimed to determine microRNAs (miRs) that regulate the expression of TLN1 and determine expression alterations in TLN1 and its targeting miRs in coronary artery disease (CAD).MethodsData sets of CAD and normal samples of blood exosomes were downloaded, and TLN1 was chosen as one of the genes with differential expressions in an in silico analysis. Next, miR‐182‐5p and miR‐9‐5p, which have a binding site on 3´‐UTR of TLN1, were selected using bioinformatics tools. Then, the miR target site was cloned in the psiCHECK‐2 vector, and direct interaction between the miR target site and the TLN1 3′‐UTR putative target site was investigated by luciferase assay. The expression of miR‐182‐5p, miR‐9‐5p, and TLN1 in the serum samples of CAD and non‐CAD individuals was assessed via a real‐time quantitative polymerase chain reaction.ResultsOur data revealed that miR‐182‐5p directly regulated the expression of TLN1. Moreover, miR‐182‐5p and miR‐9‐5p were significantly upregulated in the CAD group. Hence, both bioinformatics and experimental analyses determined the downregulated expression of TLN1 in the CAD samples.ConclusionsOur findings demonstrated that miR‐182‐5p and miR‐9‐5p could play significant roles in TLN1 regulation and participate in CAD development by targeting TLN1. These findings introduce novel biomarkers with a potential role in CAD pathogenesis.     

Scoring systems of metabolic syndrome and prediction of cardiovascular events: A population based cohort study

Background and AimsContinuous scoring systems were developed versus traditional dichotomous approaches to define metabolic syndrome. The current study was carried out to evaluate the ability of scoring systems to predict fatal and nonfatal cardiovascular events.Materials and MethodsThe data of 5147 individuals aged 18 years or more obtained from a population‐based cohort study were analyzed. The occurrence of atherosclerotic cardiovascular disease (ASCVD) in the period of 7 years follow‐up was considered as the associated outcome. Joint Interim Statement (JIS) definition, as a traditional definition of metabolic syndrome (MetS), and two versions of MetS scoring systems, based on standardized regression weights from structural equation modeling (SEM) and simple method for quantifying metabolic syndrome (siMS) were considered as potential predictors.ResultsThe scoring systems, particularly, based on SEM, were observed to have a significant association with composite cardiovascular events (HR = 1.388 [95% CI = 1.153–1.670], p = .001 in men and HR = 1.307 [0.95% CI = 1.120–1.526] in women) in multiple Cox proportional hazard regression analyses, whereas the traditional definition of MetS did not show any significant association. While both two scoring systems showed acceptable predictive abilities for cardiovascular events in women (MetS score based on SEM: area of under curve [AUC] = 0.7438 [95% CI = 0.6195–0.7903] and siMS: AUC = 0.7207 [95% CI = 0.6676–0.7738]), the two systems were not acceptable for identifying risk in men.ConclusionUnlike the dichotomous definition of MetS, the scoring systems showed an independent association with cardiovascular events. Scoring systems, particularly those based on SEM, may be useful for the prediction of cardiovascular events in women.     

Leukotriene B4 activates T cells that inhibit B-cell proliferation in EBV-infected cord blood-derived mononuclear cell cultures

Epstein-Barr virus (EBV)-specific cellular memory is not transferred from mother to child. Therefore, EBV-induced B-cell proliferation in in vitro-infected cord blood mononuclear cell cultures is not inhibited. However, by addition of immunomodulators, polysaccharide K (PSK) or truncated thioredoxin (Trx80) that activate monocytes, EBV-specific T-cell response could be generated in such cultures. Presently, we demonstrate that leukotriene B(4) (LTB(4)) is involved in the effect of the immunomodulators. LTB(4) was detected in the medium, and T-cell activation was compromised by addition of leukotriene biosynthesis inhibitors. Moreover, we found that LTB(4) added to infected cultures, which did not receive the immunomodulators, induced functional activation of the T cells. LTB(4) activated the monocytes and acted directly on the T cells. In consequence, addition of LTB(4) inhibited the EBV-induced proliferation of B lymphocytes. Specific cytotoxicity could be generated by restimulation of the T cells. The experiments showed successive stages of T-cell activation in acquisition of their immunologic effector function. This is orchestrated by complex cellular interactions, and autocrine loops mediated by soluble factors-here interferon (IFN)-gamma, interleukin (IL)-15, IL-12, and LTB(4). Importantly, the results indicate that endogenous LTB(4) can induce T-cell activation that inhibits the EBV-induced proliferation of B lymphocytes.     

A positive deviance-based antenatal nutrition project improves birth-weight in Upper Egypt

The positive deviance approach identifies and promotes existing uncommon healthy behaviours. A positive deviance-informed antenatal project was pilot-tested in Al-Minia Governorate, Upper Egypt, during 2003-2004, after a positive deviance study in 2000 found that successful pregnancies had increased consumption of meat and vegetables, daytime rest, and antenatal care; less second-hand smoke exposure; and symptoms of no urinary tract infection. Accordingly, health facilities were upgraded in target and comparison areas to provide quality antenatal care, including treatment of urinary tract infection. Additionally, in the target villages, women at-risk of delivering low-birth-weight infants were enrolled in weekly 'IMPRESS' (improved pregnancy through education and supplementation) sessions with counselling and supplemental food. In total, 519 women (344 target, 175 comparison) were enrolled in the third or fourth month of pregnancy and were followed through delivery. Birth-weights of the target mothers increased 2.2 times more than birth-weights of the comparison mothers over baseline (mean increase: 0.58 vs 0.26 g respectively, p<0.01). Similarly, the decrease in prevalence of low birth-weight from baseline was greater in the target villages than in the comparison mothers (% of decrease: 26.9 vs 11.9 respectively, p<0.01). The target at-risk women were far more likely than their counterparts to report eating more food (54.9% vs 10.6%), more meat (57.1% vs 4.2%), more vegetables (66.9% vs 5.3%), increasing daytime rest (64.1% vs 11.7%), and avoiding second-hand smoke (91.3% vs 51.6%) during pregnancy. The cost per 100 g of improvement in birth-weight was US$ 3.98. The Government of Egypt and partners are scaling up the elements of the project.     

On the mechanism of genotoxicity of ethephon on embryonic fibroblast cells

Ethephon is one of the most widely used plant growth regulator in agriculture that its application has been increased in recent years. Many reports have raised concern over the safety of this organophosphorus compound. The aim of the current study was to assess the potential genotoxic effect of ethephon on murine embryonic fibroblast (MEF) cell line, using two genotoxicity endpoints: γH2AX expression and comet assay. γH2AX served as an early and sensitive biomarker of genotoxic damage. Oxidative stress biomarkers, including reactive oxygen species (ROS), lipid peroxidation (LPO) and total antioxidant capacity were also examined. The results showed a significant increase in cell proliferation, 24?h post-treatment with 10, 40,160?μg/ml ethephon, while at the higher concentrations cytotoxic effect was observed. The γH2AX expression and γH2AX foci count per cell were significantly increased at non-cytotoxic concentrations of ethephon, accompanied with increased DNA damage as illustrated by comet assay. LPO and ROS levels were elevated only at 160?μg/ml and higher doses. The results interestingly showed that low non-cytotoxic doses of ethephon promoted DNA damage inducing cell proliferation, raising the possibility of ethephon mutagenicity. The genotoxic effect of ethephon at low doses might not relate to oxidative damage and that increased in the level of ROS and LPO generation at higher doses could account for the cytotoxic effect of ethephon. Taken together, our study provides strong in vitro evidence on potential genotoxicity of ethephon at low doses. More precise studies are needed to clarify the mutagenic effect of chronic exposure to ethephon.     

Effect of bucladesine,pentoxifylline, and H‐89 as cyclic adenosine monophosphate analog,phosphodiesterase, and protein kinase A inhibitor on acute pain

The aim of this study was to determine the effects of cyclic adenosine monophosphate (cAMP) and its dependent pathway on thermal nociception in a mouse model of acute pain. Here, we studied the effect of H‐89 (protein kinase A inhibitor), bucladesine (Db‐cAMP) (membrane‐permeable analog of cAMP), and pentoxifylline (PTX; nonspecific phosphodiesterase (PDE) inhibitor) on pain sensation. Different doses of H‐89 (0.05, 0.1, and 0.5 mg/100 g), PTX (5, 10, and 20 mg/100 g), and Db‐cAMP (50, 100, and 300 nm /mouse) were administered intraperitoneally (I.p.) 15 min before a tail‐flick test. In combination groups, we injected the first and the second compounds 30 and 15 min before the tail‐flick test, respectively. I.p. administration of H‐89 and PTX significantly decreased the thermal‐induced pain sensation in their low applied doses. Db‐cAMP, however, decreased the pain sensation in a dose‐dependent manner. The highest applied dose of H‐89 (0.5 mg/100 g) attenuated the antinociceptive effect of Db‐cAMP in doses of 50 and 100 nm /mouse. Surprisingly, Db‐cAMP decreased the antinociceptive effect of the lowest dose of H‐89 (0.05 mg/100 g). All applied doses of PTX reduced the effect of 0.05 mg/100 g H‐89 on pain sensation; however, the highest dose of H‐89 compromised the antinociceptive effect of 20 mg/100 g dose of PTX. Co‐administration of Db‐cAMP and PTX increased the antinociceptive effect of each compound on thermal‐induced pain. In conclusion, PTX, H‐89, and Db‐cAMP affect the thermal‐induced pain by probably interacting with intracellular cAMP and cGMP signaling pathways and cyclic nucleotide‐dependent protein kinases.