Effects of Mesenchymal Stem Cell Transplantation in Combination with Heparin on Acute Myocardial Infarction in a Rabbit Model

Background and Aim: Background: Stem cell transplantation, combined with some bioactive substances, has revealed promising outcomes in treating cardiac tissue damage caused by myocardial infarction (MI). In the present study, we evaluated the beneficial consequence of mesenchymal stem cells (MSCs) transplantation combined with heparin on heart damage within infarcted rabbits. Methods: Twenty-eight male New Zealand white rabbits were randomly distributed into four groups: control, MI, MI+ MSCs, and MI+MSCs+ heparin. Functional parameters of the left ventricle through echocardiography, lesion area through Macro trichrome evaluation, and angiogenesis through Masson's trichrome staining were compared between groups. Results: Ejection fraction and fractional shortening were improved in MI +MSCs and MI+ MSCs + heparin group compared to the MI group (P<0.05). The lesion area was significantly reduced, and angiogenesis was markedly increased in MI +MSC + heparin treated animals compared to MI and MI +MSCs groups.  Conclusion: Although MSCs injection to infarcted area restored normal heart function, we concluded that in the infarcted region of animals, MSCs injection combined with exogenous heparin could have more effects on the left ventricle functional parameters, cardiac lesions, and new vessel formation. *Corresponding Author: Roya Khosh Ravesh; Email: [email protected] Please cite this article as: Hajigol S, Moradi Gardeshi T, Safizadeh F, Khosh Ravesh R, Abbasi M. Effects of Mesenchymal Stem Cell Transplantation in Combination with Heparin on Acute Myocardial Infarction in a Rabbit Model. Arch Med Lab Sci. 2021;7:1-9 (e19). https://doi.org/10.22037/amls.v7.3493

Complications of male circumcision in Iran: A systematic review and weighted averaged analysis

Male circumcision (MC) is a minimal procedure to remove penile foreskin and is one of the oldest and most frequent surgical procedures in Iran, where the majority of the population identify themselves as Muslim. Despite numerous health benefits, MC is an issue of debate among pediatricians, urologists, and other medical professionals. Much of the debate stems from the lack of national guidelines and the incidence of minor or serious clinical complications. This study performed a systematic review on the current literature on male circumcision in Iran and summarized the major clinical complications reported by the studies

An Overview of Research in the Field of Human Papilloma Virus (HPV) in Iran: a Systematic Review

Introduction: Human Papilloma Virus (HPV) has many different epidemiological, social and political aspects. The aim of this study was to determine the research priorities according to the necessary aspects of HPV in Iran. Methods: The national and international databases were searched to obtain the published articles regarding HPV in Iran. All Epidemiologic studies were included in this review to assess research priorities. Results: Of 148 studies involving 14,661 participants, the most studies were conducted in Tehran (44.75%) province. Measuring prevalence of HPV (n=63, 42.5%), diagnosis of HPV by molecular techniques (n=52, 35.1%), Knowledge, Attitude and Practice studies (KAP) (n=13, 8.7%), vaccine efficacy (n=8, 5.4%), cost and cost effectiveness analysis (n=4, 2.7%), co-infection of HPV and sexually transmitted diseases (n=5, 3.3%) were the frequent aims of the included studies. Sixty percent (n=57) of the studies were conducted in clinical patients including patients with cervical cancer (n=30, 52.6%), patients with prostate cancer/Benign Prostate Hyperplasia (n=6, 10.5%), and patients with Esophageal carcinoma (n=5, 8.7%).  Conclusion: According to our results, the high-risk groups such as female sex workers, injecting drug users and prisoners are in priority for research in the field of HPV. Despite ample epidemiologic studies on prevalence and association of HPV with specific cancers, evidence towards effectiveness and cost-benefits of HPV vaccination is required to prevent the infection and its complicated clinical consequences

Testosterone Level and Coronary Artery Disease in Iranian Men; a Systematic Review

Coronary artery disease (CAD) is among the most common cardiovascular diseases (CVDs), caused by the formation of plaques of lipids, calcium, and inflammatory cells. In Iran, CAD is responsible for about 50% of all deaths per year. There is also a probability of the role of androgens deficiency in CAD in men. We aimed to systematically review all the related original studies to achieve an overall insight into the associations of testosterone and CAD in Iranian men.  MedLine, Web of Science, Scopus, and Google scholar databases were searched from inception to January 2021. All types of studies on Iranian men older than 40 years of age, reporting results of comparing testosterone in normal individuals and those with CAD were included. The main findings of the articles were compared to achieve an overall statement. Ultimately, six studies were included. Most (66.7%) had directly stated that lower levels of testosterone are associated with CAD or the level of testosterone is lower in patients with proven CAD. Among them, in 3 (50%) studies, the mean age of the participants had no significant difference between patients with CAD and the normal group. It is clear that low testosterone level is associated with increased risk of cardiovascular events but it is not definitely determined whether it is independent of age in Iranian men.  Further well-designed studies are needed to clearly exclude all confounding variables including age and show the net effect of testosterone on CAD

The prevalence of current water pipe use among Iranian male population: a systematic review and meta-analysis

Introduction: Waterpipe as a traditional method of tobacco consumption is a public health challenge. Considering the growing trend of waterpipe (hookah) use in Iran, this systematic review aimed to measure the pooled prevalence of waterpipe current use among Iranian men. Materials and Methods: The present systematic review was conducted on the published cross-sectional studies during 2009-2019 aiming at estimating the prevalence of waterpipe current use among Iranian men. Current use of waterpipe was defined as using waterpipe within the preceding 30 days. Random Effect model was used to estimate the pooled prevalence by STATA v.14. Results: Ten cross-sectional epidemiologic studies with a total sample size of of 6,263 were included in the meta-analysis. The pooled prevalence of waterpipe current use among Iranian men was estimated at 25% (95% Confidence Interval: 30-20%).  Conclusions: There are a variety of definitions for current use of waterpipe across studies. The results of this study suggest a high prevalence of current use of waterpipe among Iranian men during 2009-2019. Increased use of waterpipe in communities should be considered as a public health concern and a matter of priority by health policymakers. Preventive programs should take into account the acceptability and appealing nature of waterpipe among Iranian population and consider them as important modifiable factors

Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin/nuclear factor of activated T-cells signaling

Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Recent evidence indicates that maternal endothelial dysfunction in preeclampsia results from increased soluble Fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein. Factors responsible for excessive production of sFlt-1 in preeclampsia have not been identified. We tested the hypothesis that angiotensin II type 1 (AT1) receptor activating autoantibodies, which occur in women with preeclampsia, contribute to increased production of sFlt-1. IgG from women with preeclampsia stimulates the synthesis and secretion of sFlt-1 via AT1 receptor activation in pregnant mice, human placental villous explants, and human trophoblast cells. Using FK506 or short-interfering RNA targeted to the calcineurin catalytic subunit mRNA, we determined that calcineurin/nuclear factor of activated T-cells signaling functions downstream of the AT1 receptor to induce sFlt-1 synthesis and secretion by AT1-receptor activating autoantibodies. AT1-receptor activating autoantibody–induced sFlt-1 secretion resulted in inhibition of endothelial cell migration and capillary tube formation in vitro. Overall, our studies demonstrate that an autoantibody from women with preeclampsia induces sFlt-1 production via angiotensin receptor activation and downstream calcineurin/nuclear factor of activated T-cells signaling. These autoantibodies represent potentially important targets for diagnosis and therapeutic intervention

Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling.

Priapism, abnormally prolonged penile erection in the absence of sexual excitation, is associated with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. It is common among males with sickle cell disease (SCD), and SCD transgenic mice are an accepted model of the disorder. Current strategies to manage priapism suffer from a poor fundamental understanding of the molecular mechanisms underlying the disorder. Here we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected priapic activity. ADA enzyme therapy successfully corrected the priapic activity both in vivo and in vitro, suggesting that it was dependent on elevated adenosine levels. Further genetic and pharmacologic evidence demonstrated that A2B adenosine receptor-mediated (A2BR-mediated) cAMP and cGMP induction was required for elevated adenosine-induced prolonged penile erection. Finally, priapic activity in SCD transgenic mice was also caused by elevated adenosine levels and A2BR activation. Thus, we have shown that excessive adenosine accumulation in the penis contributes to priapism through increased A2BR signaling in both Ada -/- and SCD transgenic mice. These findings provide insight regarding the molecular basis of priapism and suggest that strategies to either reduce adenosine or block A2BR activation may prove beneficial in the treatment of this disorder

Neuronally released vasoactive intestinal polypeptide alters atrial electrophysiological properties and may promote atrial fibrillation

BACKGROUND: Vagal hyperactivity promotes atrial fibrillation (AF), which has been almost exclusively attributed to acetylcholine. Vasoactive intestinal polypeptide (VIP) and acetylcholine are neurotransmitters co-released during vagal stimulation. Exogenous VIP has been shown to promote AF by shortening action potential duration (APD), increasing APD spatial heterogeneity, and causing intra-atrial conduction block. OBJECTIVE: The purpose of this study was to investigate the effects of neuronally released VIP on atrial electrophysiologic properties during vagal stimulation. METHODS: We used a specific VIP antagonist (H9935) to uncover the effects of endogenous VIP released during vagal stimulation in canine hearts. RESULTS: H9935 significantly attenuated (1) the vagally induced shortening of atrial effective refractory period and widening of atrial vulnerability window during stimulation of cervical vagosympathetic trunks (VCNS) and (2) vagal effects on APD during stimulation through fat-pad ganglion plexus (VGPS). Atropine completely abolished these vagal effects during VCNS and VGPS. In contrast, VGPS-induced slowing of local conduction velocity was completely abolished by either VIP antagonist or atropine. In pacing-induced AF during VGPS, maximal dominant frequencies and their spatial gradients were reduced significantly by H9935 and, more pronouncedly, by atropine. Furthermore, VIP release in the atria during vagal stimulation was inhibited by atropine, which may account for the concealment of VIP effects with muscarinic blockade. CONCLUSION: Neuronally released VIP contributes to vagal effects on atrial electrophysiologic properties and affects the pathophysiology of vagally induced AF. Neuronal release of VIP in the atria is inhibited by muscarinic blockade, a novel mechanism by which VIP effects are concealed by atropine during vagal stimulation

Targeted Expression of Cre Recombinase Provokes Placental-Specific DNA Recombination in Transgenic Mice

Background: Inadequate placental development is associated with a high incidence of early embryonic lethality and serious pregnancy disorders in both humans and mice. However, the lack of well-defined trophoblast-specific gene regulatory elements has hampered investigations regarding the role of specific genes in placental development and fetal growth. Principal Findings: By random assembly of placental enhancers from two previously characterized genes, trophoblast specific protein a (Tpbpa) and adenosine deaminase (Ada), we identified a chimeric Tpbpa/Ada enhancer that when combined with the basal Ada promoter provided the highest luciferase activity in cultured human trophoblast cells, in comparison with non-trophoblast cell lines. We used this chimeric enhancer arrangement to drive the expression of a Cre recombinase transgene in the placentas of transgenic mice. Cre transgene expression occurred throughout the placenta but not in maternal organs examined or in the fetus. Significance: In conclusion, we have provided both in vitro and in vivo evidence for a novel genetic system to achieve placental transgene expression by the use of a chimeric Tpbpa/Ada enhancer driven transgene. The availability of thi

Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950.Background Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950