Mesenchymal Stem Cells for Cardiac Regeneration: Translation to Bedside Reality

Cardiovascular disease (CVD) is the leading cause of death worldwide. According to the World Health Organization (WHO), an estimate of 17.3 million people died from CVDs in 2008 and by 2030, the number of deaths is estimated to reach almost 23.6 million. Despite the development of a variety of treatment options, heart failure management has failed to inhibit myocardial scar formation and replace the lost cardiomyocyte mass with new functional contractile cells. This shortage is complicated by the limited ability of the heart for self-regeneration. Accordingly, novel management approaches have been introduced into the field of cardiovascular research, leading to the evolution of gene- and cell-based therapies. Stem cell-based therapy (aka, cardiomyoplasty) is a rapidly growing alternative for regenerating the damaged myocardium and attenuating ischemic heart disease. However, the optimal cell type to achieve this goal has not been established yet, even after a decade of cardiovascular stem cell research. Mesenchymal stem cells (MSCs) in particular have been extensively investigated as a potential therapeutic approach for cardiac regeneration, due to their distinctive characteristics. In this paper, we focus on the therapeutic applications of MSCs and their transition from the experimental benchside to the clinical bedside

Effectiveness of Educational and Vaccination Interventions in Preventing Monkeypox: Case of Low- and Middle-Income Countries (LMICs)

Preventing the spread of Monkeypox in endemic countries in low-resource settings is important to address the prevalence of this disease and avoid outbreaks in other regions, mostly in the Central African countries and Northern Europe. The concepts covered in this area are educational and vaccination interventions to prevent Monkeypox transmission as a vital public health priority. The aim of this dissertation is to review evidence about the effectiveness of educational and vaccination interventions in low- and-middle-income countries (LMICs) and to examine factors affecting successful implementation of these interventions. A critical review of current literature enabled to evaluate the preventative interventions and factors affecting their implementation to address Monkeypox incidence. The range of evidence included comprised nine studies, eight of which provided evidence from LMICs, while one study was from a high-resource economy, namely the United States. This paper on a high-resource setting was included to assist in establishing factors that have enabled the effective implementation of an intervention in this context to promote public health and suggest ways in which low-income settings could manage implementation challenges. LMICs have differing abilities to handle the factors that affect the successful implementation of intervention efforts. The educational intervention activities increase the ability to identify and address suspected and confirmed Monkeypox cases, while vaccination intervention approaches reduce vulnerability to Monkeypox virus exposure among community members and health care workers. A major finding revealed is that vaccination interventions increased the safety levels among the health care workers infected by Monkeypox virus over a period of four years, with an incidence of 17.4 cases per 10,000 people compared to a range of 0.6-1.8% by year. Corrective and concentrated intervention efforts by the government, health workers, and community members through relaying information and providing follow-up programs is an opportunity to cushion against vulnerability to Monkeypox in low-and-middle-income countries

Erratum: Correction to: Prevention by Regular Exercise of Acute Sleep Deprivation-Induced Impairment of Late Phase LTP and Related Signaling Molecules in the Dentate Gyrus (Molecular neurobiology (2016) 53 5 (2900-2910))

The original version of this article unfortunately does not include the second affiliating institution of Dr. Munder A. Zagaar. Department of Pharmacy Pracce and Clinical Health Sciences, Texas Southern University, Houston, TX 77004 should have been included on the paper

Orientin, a Bio-Flavonoid from <i>Trigonella hamosa</i> L., Regulates COX-2/PGE-2 in A549 Cell Lines via miR-26b and miR-146a

Cancer is a severe health condition and considered one of the major healthcare issues and is in need of innovative strategy for a cure. The current study aimed to investigate the chemical profile of Trigonella hamosa L. and a potential molecular approach to explain its regulation in cancer progression through an inflammatory mediator (COX-2) in A549 non-small lung cancer cell lines via in silico, mechanistic and molecular aspects. T. hamosa was extracted and then subjected to a CCK-8 cell viability assay in different cancer cell lines including MDA-MB-231, A549 and HCT-116. Total extract was subjected to several chromatographic techniques to yield orientin (OT); the structure was elucidated by inspection of NMR spectroscopic data. To achieve anticancer effects of OT, a cell viability assay using a CCK-8 kit, immunoprecipitation by Western blot, cell migration using a wound healing assay, cell invasion using a Matrigel-Transwell assay, apoptosis by AO/EB dual staining, flow cytometric analysis and DAPI staining, a silenced COX-2 model to determine PGE-2 production and real-time PCR and Western blot of BCL-2, CYP-1A1, iNOS and COX-2 markers were carried out. The results demonstrated that OT decreased the cell proliferation and controlled cell migration and invasive properties. OT destabilized the COX-2 mRNA and downregulated its expression in A549 cell lines. Virtual binding showed interaction (binding energy −10.43) between OT and COX-2 protein compared to the selective COX-2 inhibitor celecoxib (CLX) (binding energy −9.4). The OT-CLX combination showed a superior anticancer effect. The synergistic effect of OT-CLX combination was noticed in controlling the migration and invasion of A549 cell lines. OT-CLX downregulated the expression of BCL-2, iNOS and COX-2 and activated the proapoptotic gene CYP-1A1. OT mitigated the COX-2 expression via upregulation of miR-26b and miR-146a. Interestingly, COX-2-silenced transfected A549 cells exhibited reduced expression of miR-26b and miR-146a. The findings confirmed the direct interaction of OT with COX-2 protein. PGE-2 expression was quantified in both naïve and COX-2-silenced A549 cells. OT downregulated the release of PGE-2 in both tested conditions. These results confirmed the regulatory effect of OT on A549 cell growth in a COX-2-dependent manner. OT activated apoptosis via activation of CYP-1A1 expression in an independent manner. These results revealed that the OT-CLX combination could serve as a potential synergistic treatment for effective inflammatory-mediated anticancer strategies

Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats

To investigate mechanisms by which thymoquinone (TQ) can prevent methotrexate- (MTX-) induced hepatorenal toxicity, TQ (10 mg/kg) was administered orally for 10 days. In independent rat groups, MTX hepatorenal toxicity was induced via 20 mg/kg i.p. at the end of day 3 of experiment, with or without TQ. MTX caused deterioration in kidney and liver function, namely, blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase. MTX also caused distortion in renal and hepatic histology, with significant oxidative stress, manifested by decrease in reduced glutathione and catalase, as well as increase in malondialdehyde levels. In addition, MTX caused nitrosative stress manifested by increased nitric oxide, with upregulation of inducible nitric oxide synthase. Furthermore, MTX caused hepatorenal inflammatory effects as shown by increased tumor necrosis factor-α, besides upregulation of necrosis factor-κB and cyclooxygenase-2 expressions. MTX also caused apoptotic effect, as it upregulated caspase 3 in liver and kidney. Using TQ concurrently with MTX restored kidney and liver functions, as well as their normal histology. TQ also reversed oxidative and nitrosative stress, as well as inflammatory and apoptotic signs caused by MTX alone. Thus, TQ may be beneficial adjuvant that confers hepatorenal protection to MTX toxicity via antioxidant, antinitrosative, anti-inflammatory, and antiapoptotic mechanisms

Aqueous suspension of anise "Pimpinella an/sum" protects rats against chemically induced gastric ulcers

AIM: To substantiate the claims of Unani and Arabian traditional medicine practitioners on the gastroprotective potential effect of a popular spice anise, "Pimpinella anisum L." on experimentally-induced gastric ulceration and secretion in rats. METHODS: Acute gastric ulceration in rats was produced by various noxious chemicals including 80% ethanol, 0.2 mol/L NaOH, 25% NaCI and indomethacin. Anti-secretory studies were undertaken using pylorusligated Shay rat technique. Levels of gastric non-protein sulfhydryls (NP-SH) and wall mucus were estimated and gastric tissue was also examined histologically. Anise aqueous suspension was used in two doses (250 and 500 mg/kg body weight) in all experiments. RESULTS: Anise significantly inhibited gastric mucosal damage induced by necrotizing agents and indomethacin. The anti-ulcer effect was further confirmed histologically. In pylorus-ligated Shay rats, anise suspension signiQtantly reduced the basal gastric acid secretion, acidity and completely inhibited the rumenal ulceration. On the other hand, the suspension significantly replenished ethanol-induced depleted levels of gastric mucosal NP-SH and gastric wall mucus concentration. CONCLUSION: Anise aqueous suspension possesses signiQtant cytoprotective and anti-ulcer activities against experimentally-induced gastric lesions. The anti-ulcer effect of anise is possibly prostaglandin-mediated and/or seizures and epilepsy . The phytotherapeutic applications of anise are based on its digestive, carminative, diuretic and expectorating action'151. It has been recently reported that the essential oil of anise is highly effective as both larvicidal and ovicidal agents'161. The principal constituents of anise are volatile oil, coumarins, fatty acids, Davonoid glycosides, proteins and carbohydrates. Among others, anise oil contains anethole and caryophyllene'17'. Since we have not come across a scientiDc report on potential gastroprotective claims of anise aqueous suspension, the present study was carried out to assess its effect on chemically induced gastric ulcers in rats