Hydrogen sulfide (H2S) and nitric oxide (NO) are major gasotransmitters produced in endothelial cells (ECs), contributing to the regulation of vascular contractility and structural integrity. Their ...interaction at different levels would have a profound impact on angiogenesis. Here, we showed that H2S and NO stimulated the formation of new microvessels. Incubation of human umbilical vein endothelial cells (HUVECs‐926) with NaHS (a H2S donor) stimulated the phosphorylation of endothelial NO synthase (eNOS) and enhanced NO production. H2S had little effect on eNOS protein expression in ECs. L‐cysteine, a precursor of H2S, stimulated NO production whereas blockage of the activity of H2S‐generating enzyme, cystathionine gamma‐lyase (CSE), inhibited this action. CSE knockdown inhibited, but CSE overexpression increased, NO production as well as EC proliferation. LY294002 (Akt/PI3‐K inhibitor) or SB203580 (p38 MAPK inhibitor) abolished the effects of H2S on eNOS phosphorylation, NO production, cell proliferation and tube formation. Blockade of NO production by eNOS‐specific siRNA or nitro‐L‐arginine methyl ester (L‐NAME) reversed, but eNOS overexpression potentiated, the proliferative effect of H2S on ECs. Our results suggest that H2S stimulates the phosphorylation of eNOS through a p38 MAPK and Akt‐dependent pathway, thus increasing NO production in ECs and vascular tissues and contributing to H2S‐induced angiogenesis.
The aim of this study was to perform a systematic overview of the pharmacogenetic studies conducted in Jordan. A structured search of Medline was conducted for articles over the last decade (January ...2010-July 2020). Studies were classified by design, sample size, drug-gene combination, and the significance of the results. Thirty-two studies met the criteria for review. Most pharmacogenomic studies had a case-only design (n = 23). Only five studies included >500 participants. The total number of genetic variants in all studies was one hundred fifteen, which were found in forty genes, including dynamic (n = 27), and kinetic (n = 9) genes. The most commonly studied drugs were within the hematology and cardiology therapeutic areas and included statins, warfarin, aspirin, and clopidogrel. Most studies (n = 18) reported results with mixed p values <0.05 and >0.05. Pharmacogenomic research in Jordan is still in its infancy and is limited mainly to replication attempts. The need for standardization is imperative, especially in developing countries with scarce funding resources.
The goal of the current study was to investigate the role of exogenous and endogenous hydrogen sulfide (H₂S) on neovascularization and wound healing in vitro and in vivo. Incubation of endothelial ...cells (ECs) with H₂S enhanced their angiogenic potential, evidenced by accelerated cell growth, migration, and capillary morphogenesis on Matrigel. Treatment of chicken chorioallantoic membranes (CAMS) with H₂S increased vascular length. Exposure of ECs to H₂S resulted in increased phosphorylation of Akt, ERK, and p38. The KATP channel blocker glibenclamide or the p38 inhibitor SB203580 abolished H₂S-induced EC motility. Since glibenclamide inhibited H₂S-triggered p38 phosphorylation, we propose that KATP channels lay upstream of p38 in this process. When CAMs were treated with H₂S biosynthesis inhibitors dl-propylargylglycine or beta-cyano-L-alanine, a reduction in vessel length and branching was observed, indicating that H₂S serves as an endogenous stimulator of the angiogenic response. Stimulation of ECs with vascular endothelial growth factor (VEGF) increased H₂S release, while pharmacological inhibition of H₂S production or KATP channels or silencing of cystathionine gamma-lyase (CSE) attenuated VEGF signaling and migration of ECs. These results implicate endothelial H₂S synthesis in the pro-angiogenic action of VEGF. Aortic rings isolated from CSE knockout mice exhibited markedly reduced microvessel formation in response to VEGF when compared to wild-type littermates. Finally, in vivo, topical administration of H₂S enhanced wound healing in a rat model, while wound healing was delayed in CSE⁻/⁻ mice. We conclude that endogenous and exogenous H₂S stimulates EC-related angiogenic properties through a KATP channel/MAPK pathway.
The endothelium is a cellular monolayer that lines the inner surface of blood vessels and plays a central role in the maintenance of cardiovascular homeostasis by controlling platelet aggregation, ...vascular tone, blood fluidity and fibrinolysis, adhesion and transmigration of inflammatory cells, and angiogenesis. Endothelial dysfunctions are associated with various cardiovascular diseases, including atherosclerosis, hypertension, myocardial infarction, and cardiovascular complications of diabetes. Numerous studies have established the anti-inflammatory, anti-apoptotic, and anti-oxidant effects of hydrogen sulfide (H2S), the latest member to join the gasotransmitter family along with nitric oxide and carbon monoxide, on vascular endothelium. In addition, H2S may prime endothelial cells (ECs) toward angiogenesis and contribute to wound healing, besides to its well-known ability to relax vascular smooth muscle cells (VSMCs), and thereby reducing blood pressure. Finally, H2S may inhibit VSMC proliferation and platelet aggregation. Consistently, a deficit in H2S homeostasis is involved in the pathogenesis of atherosclerosis and of hyperglycaemic endothelial injury. Therefore, the application of H2S-releasing drugs or using gene therapy to increase endogenous H2S level may help restore endothelial function and antagonize the progression of cardiovascular diseases. The present article reviews recent studies on the role of H2S in endothelial homeostasis, under both physiological and pathological conditions, and its putative therapeutic applications.
Abstract
Background
Huge efforts are being made to control the spread and impacts of the coronavirus pandemic using vaccines. However, willingness to be vaccinated depends on factors beyond the ...availability of vaccines. The aim of this study was three-folded: to assess children’s rates of COVID-19 Vaccination as reported by parents, to explore parents’ attitudes towards children’s COVID-19 vaccination, and to examine the factors associated with parents’ hesitancy towards children’s vaccination in several countries in the Eastern Mediterranean Region (EMR).
Methods
This study utilized a cross-sectional descriptive design. A sample of 3744 parents from eight countries, namely, Iraq, Jordan, Kuwait, Lebanon, Palestine, Qatar, Saudi Arabia (KSA), and the United Arab Emirates (UAE), was conveniently approached and surveyed using Google forms from November to December 2021. The participants have responded to a 42-item questionnaire pertaining to socio-demographics, children vaccination status, knowledge about COVID-19 vaccines, and attitudes towards vaccinating children and the vaccine itself. The Statistical Package for Social Sciences (SPSS- IBM, Chicago, IL, USA) was used to analyze the data. A cross-tabulation analysis using the chi-square test was employed to assess significant differences between categorical variables and a backward Wald stepwise binary logistic regression analysis was performed to assess the independent effect of each factor after controlling for potential confounders.
Results
The prevalence of vaccinated children against COVID-19 was 32% as reported by the parents. Concerning parents’ attitudes towards vaccines safety, about one third of participants (32.5%) believe that all vaccines are not safe. In the regression analysis, children’s vaccination was significantly correlated with parents’ age, education, occupation, parents’ previous COVID-19 infection, and their vaccination status. Participants aged ≥50 years and those aged 40-50 years had an odds ratio of 17.9 (OR = 17.9, CI: 11.16-28.97) and 13.2 (OR = 13.2, CI: 8.42-20.88); respectively, for vaccinating their children compared to those aged 18-29 years. Parents who had COVID-19 vaccine were about five folds more likely to vaccinate their children compared with parents who did not receive the vaccine (OR = 4.9, CI: 3.12-7.70). The prevalence of children’s vaccination in the participating Arab countries is still not promising.
Conclusion
To encourage parents, vaccinate their children against COVID-19, Arab governments should strategize accordingly. Reassurance of the efficacy and effectiveness of the vaccine should target the general population using educational campaigns, social media, and official TV and radio channels.
A growing body of evidence suggests that hydrogen sulfide (H₂S) is a signaling molecule in mammalian cells. In the cardiovascular system, H₂S enhances vasodilation and angiogenesis. H₂S-induced ...vasodilation is hypothesized to occur through ATP-sensitive potassium channels (K(ATP)); however, we recently demonstrated that it also increases cGMP levels in tissues. Herein, we studied the involvement of cGMP-dependent protein kinase-I in H₂S-induced vasorelaxation. The effect of H₂S on vessel tone was studied in phenylephrine-contracted aortic rings with or without endothelium. cGMP levels were determined in cultured cells or isolated vessel by enzyme immunoassay. Pretreatment of aortic rings with sildenafil attenuated NaHS-induced relaxation, confirming previous findings that H₂S is a phosphodiesterase inhibitor. In addition, vascular tissue levels of cGMP in cystathionine gamma lyase knockouts were lower than those in wild-type control mice. Treatment of aortic rings with NaHS, a fast releasing H₂S donor, enhanced phosphorylation of vasodilator-stimulated phosphoprotein in a time-dependent manner, suggesting that cGMP-dependent protein kinase (PKG) is activated after exposure to H₂S. Incubation of aortic rings with a PKG-I inhibitor (DT-2) attenuated NaHS-stimulated relaxation. Interestingly, vasodilatory responses to a slowly releasing H₂S donor (GYY 4137) were unaffected by DT-2, suggesting that this donor dilates mouse aorta through PKG-independent pathways. Dilatory responses to NaHS and L-cysteine (a substrate for H₂S production) were reduced in vessels of PKG-I knockout mice (PKG-I⁻/⁻). Moreover, glibenclamide inhibited NaHS-induced vasorelaxation in vessels from wild-type animals, but not PKG-I⁻/⁻, suggesting that there is a cross-talk between K(ATP) and PKG. Our results confirm the role of cGMP in the vascular responses to NaHS and demonstrate that genetic deletion of PKG-I attenuates NaHS and L-cysteine-stimulated vasodilation.
High glucose (HG)‐induced dysfunction of vascular endothelial cells plays a crucial role in the development of diabetic vascular complications. Inhibition of cystathionine γ‐synthase/hydrogen sulfide ...(CSE/H2S) pathway is one of the causes of vascular endothelial cell injury induced by HG. Dopamine D1 receptors (DR1) are widely expressed and regulate important physiological functions in the vascular system. However, the effect of DR1 inhibition on HG‐induced vascular endothelial apoptosis by regulating the CSE/H2S pathway is unclear. Therefore, we aimed to determine if DR1 can regulate the CSE/H2S pathway and regulate the effect of DR1 on HG‐induced apoptosis in human umbilical vein endothelial cells. In this study, we found that HG treatment significantly decreased the expression of DR1 and CSE and the endogenous content of H2S; DR1 agonist SKF 38393 reversed these effects, while sodium hydrosulfide (NaHS) only increased CSE expression and the endogenous H2S production and had no effect on DR1 expression. Meanwhile, HG significantly increased the intracellular calcium concentration (Ca2+i), and SKF 38393 further increased HG‐induced Ca2+i. In addition, HG increased the lactate dehydrogenase activity, malondialdehyde and reactive oxygen species contents, apoptotic rate, the expression of cleaved caspase‐3, caspase‐9, and cytochrome c, and the activity of phosphorylated‐inhibitor of nuclear factor‐kappaBα (NF‐κBα) (p‐IκBα) and phosphorylated‐NF‐κB (p‐NF‐κB), and reduced cell viability, superoxide dismutase activity, and Bcl‐2 expressions. SKF 38393 and NaHS markedly reversed the effect of HG. The effect of SKF 38393 was similar to N‐acetyl‐
l‐cysteine (an inhibitor of oxidative stress) or pyrrolidinedithiocarbamate ammonium (an NF‐kB inhibitor). Taken together, DR1 upregulates the CSE/H2S pathway by increasing the Ca2+i, which inhibits HG‐induced apoptosis via downregulating NF‐κB/IκBα pathway in vascular endothelial cells.
Sharing and reuse biosamples can facilitate biomedical research. Little is known about researchers' perception and practice about sharing, reusing, and storing biosamples in Jordan. Therefore, the ...current study aimed to evaluate the practices of biomedical researchers in Jordan regarding biosamples management.
The study was cross-sectional and involved biomedical researchers from different parts of Jordan. A questionnaire was designed to achieve the aim of this study. The questionnaire was web-based and distributed via e-mails using Google forms.
Opinions of Jordanian biomedical researchers from different academic ranks and institutional backgrounds were measured and recorded anonymously. The majority of the sample was males (57.9%), from public universities (64.3%), and (64.6%) were from health-related fields. About 82.9% of participants stored biosamples using codes, whereas the rest used the subject's name. Sharing of biosamples was commonly practiced by 61.7% of Jordanian researchers locally, while 47.2% of the Jordanian researchers shared biosamples overseas. The reuse of biosamples in other projects was reported to be 55.4%. The majority explained the possibility of reusing and sharing biosamples in the consent form (range: 53-58%). Sharing and reusing biosamples were associated with gender, the number of publications in peer-reviewed international journals, and academic rank (P<0.05).
Sharing and reusing biosamples are common among Jordanian biomedical researchers. Therefore, ethically grounded biosamples sharing and reuse standards are essential for protecting human subjects' rights and privacy in Jordan.
The primary objective of this study was to investigate the influence of living near a thermal spring and being exposed to hydrogen sulfide (Hsub.2S) gas, which lingers in the surrounding atmosphere, ...on the redox and lipid peroxidation status of individuals with low ferritin levels. Participants in the study were divided into two groups based on their Hsub.2S exposure frequency and ferritin levels. Within Group A, individuals who did not experience occasional Hsub.2S exposure (2-3 h, 2-3 times per year) and had an average of normal ferritin levels of 87.5 ng/mL exhibited lower levels of oxidative stress and lipid peroxidation compared to those with low ferritin levels (average of 6.57 ng/mL) in the same group. Additionally, individuals with normal ferritin levels showed higher levels of thiol, Hsub.2S, and antioxidant capacity. However, it was observed that individuals with low ferritin levels had significantly lower levels of endogenous Hsub.2S and thiol and higher levels of oxidative stress and lipid peroxidation. In Group B, individuals who experienced occasional Hsub.2S exposure (2-3 h, 10-12 times per year) and had an average of normal ferritin levels of 91.65 ng/mL showed lower oxidative stress and lipid peroxidation, as well as higher thiol, Hsub.2S, and antioxidant capacity. Surprisingly, individuals in Group B with low ferritin levels (average of 6.18 ng/mL) showed increased endogenous levels of Hsub.2S, which resulted in lower oxidative stress, and lipid peroxidation. These findings suggest that inhaling environmental Hsub.2S emitted from thermal springs may serve as an adaptive and protective mechanism for individuals with low ferritin levels by enhancing antioxidant capacity and reducing oxidative stress and lipid peroxidation modification, thus mitigating the harmful effects of reactive oxygen species.
Introduction: Despite decades of research, obesity and its related medical complications remain a major health concern globally. Therefore, novel therapeutic strategies are needed to combat obesity ...and its numerous debilitating complications. Resveratrol (RES) has a potential therapeutic effect in obesity and diabetes by improving oxidative metabolism and insulin signaling. Background and Objectives: The aim of this study was to investigate the effect of RES treatment on weight loss and glucose and fatty acid metabolism. Methods: Obesity was induced in 24 mice by exposure to a high-fat diet (HFD) for 8 weeks. Mice were randomly assigned to one group of either: group 1: control, non-treated low-fat diet (LFD) for 12 weeks (n = 8), group 2: non-treated high-fat diet (HFD) for 12 weeks (n = 8), group 3: RES-treated HFD (HFD + RES) (n = 8), or group 4: RES-treated and switched to LFD (HFD-LFD + RES) (n = 8). HFD + RES mice were first fed an HFD for 8 weeks followed by 4 weeks of RES. The HFD-LFD + RES group was first fed an HFD for 8 weeks and then treated with RES and switched to an LFD for 4 weeks. Results: After 12 weeks, group 2 mice had significantly higher body weights compared to group 1 (23.71 ± 1.95 vs. 47.83 ± 2.27; p < 0.05). Group 4 had a significant decrease in body weight and improvement in glucose tolerance compared to mice in group 2 (71.3 ± 1.17 vs. 46.1 ± 1.82 and 40.9 ± 1.75, respectively; p < 0.05). Skeletal muscles expression of SIRT1, SIRT3, and PGC1α were induced in group 3 and 4 mice compared to group 2 (p < 0.01), with no changes in AMP-activated protein kinase expression levels. Furthermore, combination of RES and diet ameliorated skeletal muscle intermediate lipid accumulation and significantly improved insulin sensitivity and secretion. Conclusions: The results of this study suggest a synergistic beneficial effect of LFD and RES to lower body weight and enhance glucose and fatty acid metabolism.
PDF
