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Type 2 diabetes (T2D) is associated with chronic inflammation as a critical factor for muscle atrophy and disease progression. Although the combination of aerobic and resistance training leads to more significant improvements in health-related indices for T2D patients, the interference effect in concurrent training can decrease positive adaptations. The purpose of this study was to investigate the physiological adaptations in performing high-intensity interval training (HIIT) and resistance training on the same day vs. different days in T2D patients. Twenty-four non-athletic 45-65-year-old women with T2D participated in an 8-week intervention. They were randomly divided into three groups: same days (SD), different days (DD), and treatment as usual (control). SD group had resistance training followed by HIIT on Saturday, Monday, and Wednesday. In contrast, the DD group had the same volume of resistance training on Saturday, Monday, and Wednesday and HIIT on Sunday, Tuesday, and Thursday, with Friday as a resting day. Blood samples were collected 24 h before the first and 48 h after the last session in each group to measure glucose, insulin, glycosylated hemoglobin, IGF1, IL1β, CRP, lipid profile, miR-146a, and miR-29b. Three subjects dropped out during the study, and 21 participants (SD = 7, DD = 6, Control = 8) completed the 8-week intervention. MiR-146a changed significantly (P = 0.006) in both SD and DD groups compared to the control group. IGF1 (P = 0.001) and fat-free mass (P = 0.001) changed significantly in SD and DD groups compared to the control group, and also DD led to more significant increases in IGF1 and fat-free mass in comparison with SD. MiR-29 (P = 0.001) changed significantly in the DD group compared to the control group. The reduction of IL-1β, fat mass and insulin resistance was significant in SD and DD compared to the control group; DD showed more potent effects than the SD group on the fat mass (P = 0.001) and insulin resistance (P = 0.001). This study demonstrated that a combination of HIIT and resistance training could be practical for improving health-related outcomes in T2D. Our study indicated for the first time that training strength and HIIT on separate days appeared to be more effective to combat muscle atrophy and insulin resistance.

To assess in vitro and in vivo tracking of iron oxide labeled stem cells transfected by lipofectamine using magnetic resonance imaging (MRI), rat dental pulp stem cells (DPSCs) were characterized, labeled with iron oxide nanoparticles, and then transfected with lipofectamine to facilitate the internalization of these nanoparticles. Cell proliferation, viability, differentiation, and apoptosis were investigated. Prussian blue staining and MRI were used to trace transfected labeled cells. DPSCs were a morphologically spindle shape, adherent to culture plates, and positive for adipogenic and osteogenic inductions. They expressed CD73 and CD90 markers and lacked CD34 and CD45. Iron oxide labeling and transfection with lipofectamine in DPSCs had no toxic impact on viability, proliferation, and differentiation, and did not induce any apoptosis. In vitro and in vivo internalization of iron oxide nanoparticles within DPSCs were confirmed by Prussian blue staining and MRI tracking. Prussian blue staining and MRI tracking in the absence of any toxic effects on cell viability, proliferation, differentiation, and apoptosis were safe and accurate to track DPSCs labeled with iron oxide and transfected with lipofectamine. MRI can be a useful imaging modality when treatment outcome is targeted.

ObjectivesThis study aims to assess the prevalence of hypertension (HTN), and determine the relationship between HTN and anthropometric indices including fat distribution, body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) in Shiraz Heart Study.SettingIn this cross-sectional study, subjects were enrolled in 25 clinics in Shiraz. I.R. Iran between 2019 and 2021.ParticipantsA total number of 7225 individuals were selected, aged between 40 and 70 years of whom 52.3% were female. Among the people living in Shiraz, individuals living far from clinics, cases of mental or physical disabilitiy and documented cardiovascular diseases were excluded.Primary and secondary outcome measuresPrimary outcome: The association of body composition, WHR, WHtR and BMI with HTN.Secondary outcome: The sensitivity and specificity of the WHtR for the prediction of HTN.ResultsHTN prevalence was 19.3%. Obesity prevalence was estimated to be 28.5%. WHR and lean body mass showed a significant association with HTN (pConclusionHTN had a meaningful association with all the noted anthropometric indices. WHtR performed well as a predictor of HTN.

Background/Aims: Ulcerative colitis (UC), along with Crohn’s disease, is one of the main types of inflammatory bowel disease (IBD). On the other hand, deregulated autophagy is involved in many chronic diseases, including IBD. In this study, we aimed to investigate the role of Atg5 and microRNA-181a (miR-181a) in the pathophysiology of UC. Methods: Colon biopsy, stool, and blood samples of 6 men and 9 women were confirmed for UC. Also, 13 men and 17 women were selected as healthy control (HC). Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to measure the Atg-5 content of the colon biopsies. Besides, the serum and stool levels of Atg5 were measured using ELISA. Moreover, the total RNA of blood cells was extracted and evaluated for the expression of miR-181a. Results: We found 1.2 ng/mL versus 0.46 ng/mL, 0.34 ng/mL versus 0.24 ng/mL, and 0.082 ng/mL versus 0.062 ng/mL of Atg5 in stool, intestinal tissue, and serum of UC and HCs, respec tively. There was no significant difference in the expression of miR-181a in the blood samples of UC and HCs. Immunohisto chemistry showed high positivity without any significant difference between the 2 groups in the quantitative analysis. Conclu sions: The significant difference observed between the stool Atg5 content of the HCs and UC patients may provide new insight into using this protein as a diagnostic biomarker, however, considering the small size of our studied population further studies are needed. (Intest Res 2020;18:421-429)

Background: Animals can play an important role in preparing tissues for human through the development of xenotransplantation protocols. The most common problem with liver transplantation like any other organ transplantation is organ supply shortage. Objective: To evaluate the in utero xenotransplantation of mouse bone marrow-derived stromal/stem cells (BMSCs) to the liver of rat fetus to produce mouse liver tissue. Materials and Methods: BMSCs were isolated and confirmed from enhanced green fluorescent protein (eGFP)-genetic labeled mice. Using a microinjection protocol, mice BMSCs were injected into the liver of rat fetuses in utero on day 14 of pregnancy. After birth, livers were collected and the presence of mice eGFP-positive cells in rat livers was evaluated through polymerase chain reaction. Results: The eGFP mRNA was detected in the liver of injected infant rats. BMSCs of adult mice were capable to remain functional probably as hepatocyte-like cells in liver of infant rats after in utero xenotransplantation. Conclusion: BMSCs have the potential for intrauterine xenotransplantation for the treatment of liver dysfunction before birth. This method can also be used for xenoproduction of liver tissue for transplantation. Key words: Xenotransplantation, Liver, Bone marrow, Stromal/stem cell, Murine.

The recent COronaVIrus Disease (COVID)-19 pandemic has placed an unprecedented burden on the drug development opportunity to prevent the onset of multi-organ failure.Emerging experimental reports have highlighted the beneficial effects of mesenchymal stem cell (MSC) administration against COVID-19. MSCs and their derived exosomes may attenuate SARS-CoV-2-induced inflammatory response through managing the immune cell function and cytokine expression. Although these are promising results, the exposure of MSCs to chemical compounds with pharmacological activities may further improve their homing, survival, and paracrine machinery.Nicorandil (N-[2-hydroxyethyl]-nicotinamide nitrate), an established adenosine triphosphate-sensitive potassium channel opener, is recently hypothesized to modulate inflammation as well as cell injury and death in COVID-19-affected lungs through inhibiting reactive oxygen species levels and apoptosis. Since it also exerts protective effects against hypoxia-induced MSC apoptosis, we assumed that transplanted MSCs combined to long-term nicorandil administration may survive longer in a severely inflamed microenvironment and have more beneficial effects in the treatment of SARS-CoV-2 infection than MSCs alone.

Drug resistance is the main culprit of failure in cancer therapy that may lead to cancer relapse. This resistance mostly originates from rare, but impactful presence of cancer stem cells (CSCs). Ability to self-renewal and differentiation into heterogeneous cancer cells, and harboring morphologically and phenotypically distinct cells are prominent features of CSCs. Also, CSCs substantially contribute to metastatic dissemination. They possess several mechanisms that help them to survive even after exposure to chemotherapy drugs. Although chemotherapy is able to destroy the bulk of tumor cells, CSCs are left almost intact, and make tumor entity resistant to treatment. Eradication of a tumor mass needs complete removal of tumor cells as well as CSCs. Therefore, it is important to elucidate key features underlying drug resistance raised by CSCs in order to apply effective treatment strategies. However, the challenging point that threatens safety and specificity of chemotherapy is the common characteristics between CSCs and normal peers such as signaling pathways and markers. In the present study, we tried to present a comprehensive appraisal on CSCs, mechanisms of their drug resistance, and recent therapeutic methods targeting this type of noxious cells.

There are heterogeneous data regarding the impact of diabetes mellitus (DM) and hypertension (HTN) on clinical outcomes after percutaneous coronary intervention (PCI). This study explored the effect of history of DM (hDM) and HTN (hHTN), separately and in combination with each other, on major adverse cardiac events (MACE) in short‐, mid‐, and long‐term intervals after PCI. Between 2000 and 2017, 1799 patients who had PCI were registered. They were categorized in four different groups: hDM, hHTN, hDM + hHTN, and no hDMQuery no hHTN. Incidence of myocardial infarction, revascularization, and coronary death totally considered as MACE was sought in short‐ (

Background: Heart failure is a life-threatening event that could lead to sudden cardiac death. It is primarily prevented by the use of implantable cardioverter defibrillators. Applying this therapy is mainly determined by left ventricular ejection fraction. However, this criterion results in considerable pitfalls. Improving the discrimination strategies in order to select eligible patients can help avoid unnecessary insertions. Objectives: This study aimed to compare global longitudinal myocardial strain and left ventricular ejection fraction in predicting sustained ventricular tachyarrhythmia in heart failure patients. Methods: This study was performed on 70 ischemic or dilated cardiomyopathic patients randomly selected from Imam Reza clinic. Patients with left ventricular ejection fraction ≤ 40% who had undergone implantable cardioverter defibrillator implantation were recruited into the research. Left ventricular ejection fraction and global longitudinal strain were measured by 3D echocardiography. Independent sample t-test was used for analysis and statistical significance was set at < 0.05. Results: The data were expressed as mean ± SD. The study subjects in the ischemic and dilated cardiomyopathic groups were categorized according to the occurrence of ventricular tachyarrhythmia. The results showed a significant difference between arrhythmic and non-arrhythmic cases only in the ischemic group regarding the amount of left ventricular ejection fraction. Meanwhile, a significant difference was observed between arrhythmic subjects and their counterparts in both ischemic and dilated cardiomyopathic groups concerning global longitudinal strain parameters. Conclusion: Global longitudinal strain could be considered as a valuable predictor of ventricular tachyarrhythmia occurrence beside left ventricular ejection fraction. This helps selection of appropriate patients for implantable cardioverter defibrillator therapy.

Purpose Ulcerative colitis (UC) is a lifelong disease with unclear etiology and increasing prevalence worldwide. Autophagy has been reported to play roles in the pathogenesis and progression of UC. Here, we aimed to analyze the expression of autophagy related protein 10 (ATG10) and its regulator, micro‐RNA (miR) 519a, in UC patients. Methods The level of ATG10 in the serum, stool, and colon biopsies from 15 UC patients and 30 non‐UC healthy individuals (HC) group was measured by ELISA. Also, the blood level of miR‐519a was investigated by quantitative real‐time PCR. Results We found 13.63 ng/ml versus 0.99 ng/ml, 11.01 ng/ml versus 1.11 ng/ml and 6.41 ng/ml versus 3.21 ng/ml of ATG10 in the stool, colon tissue, and serum of UC and HC, respectively. There was no significant difference in the expression of miR‐519a in the blood samples of UC and HC. Conclusions ATG10 might be a potential non‐invasive diagnostic biomarker for UC.

Background: Patients presenting with chest pain (CP) at the emergency departments are challenging cases for the physicians to make valid decisions with regard to acute coronary syndrome, which needs urgent medical intervention while the majority of the admitted patients are free from serious cardiac problems. The present study was done to investigate the potential of Heart Risk Score in detecting the existence and severity of coronary artery disease in CP patients based on Syntax score.Methods: Among CP patients who were admitted at the emergency department, 100 participants were selected. Heart Risk Score was calculated for each participant on admission. Two independent cardiologists also calculated the Syntax score after angiography was done for each patient. Statistical analysis was performed to assess the correlation between Heart Risk Score and Syntax score.Results: The median age of participants was 58.42±12.42 with the majority (65%) being male. The mean Heart Risk Score of the patients was 5.76±1.56 (min=3, max=9) and the mean Syntax score was 14.82±11.42(min=0, max=44.5). Pearson correlation coefficient was 0.493 (P22).Conclusion: We found that there is a positive and significant correlation between Heart Risk Score and Syntax score which underlines the importance of using Heart Risk Score in emergency departments to reduce unnecessary invasive interventions in patients presenting with chest pain.

Background. Erectile dysfunction (ED) has been become an important health challenge in recent years affecting the quality of life significantly. In addition to imposed social problems, it may warn the existence of cardiovascular diseases especially that of ischemic heart disease (IHD). We aimed to investigate the association between ED and coronary artery disease (CAD) in a population of patients with stable angina based on angiographic findings. Methods. In this cross-sectional study, among patients who are diagnosed with stable angina referring for coronary angiography (excluding those with acute coronary syndrome), 200 patients were selected. They were divided equally into two groups of case and control. The former were positively CAD patients and the latter were normal peers, with respect to angiographic results. International index of erectile function (IIEF) questionnaire was used in order to evaluate erectile function during recent four weeks. Statistical analyses of the t-test and logistic regression were performed. The significance level was considered as a P value less than 5%. Results. The age range of the patients was 40–65 years old. The case group was significantly older ( P = 0.001 ). There was a remarkable relation between the low score from IIEF (ED) and existence of CAD. Also, the severity of ED was in a close relationship with severity of CAD. In addition, dyslipidemia in terms of high LDL and low HDL was associated with both ED and severity of CAD. Conclusion. Other than CAD, ED could be considered as one of the manifestations of atherosclerosis. Accordingly, the IIEF questionnaire is a useful tool to early diagnosis of CAD. Also, IIEF-derived scores estimate CAD severity. We suggest subjects with low score of IIEF examine their cardiovascular health with special attention to possible existence of IHD.

The coronavirus disease (COVID-19) pandemic is a global health priority. Given that cardiovascular diseases (CVD) are the leading cause of morbidity around the world and that several trials have reported severe cardiovascular damage in patients infected with SARS-CoV-2, a substantial number of COVID-19 patients with underlying cardiovascular diseases need to continue their medications in order to improve myocardial contractility and to prevent the onset of major adverse cardiovascular events (MACEs), including heart failure. Some of the current life-saving medications may actually simultaneously expose patients to a higher risk of severe COVID-19. Angiotensin-converting enzyme 2 (ACE2), a key counter regulator of the renin-angiotensin system (RAS), is the main entry gate of SARS-CoV-2 into human host cells and an established drug target to prevent heart failure. In fact, ACE inhibitors, angiotensin II receptor blockers, and mineralocorticoid antagonists may augment ACE2 levels to protect organs from angiotensin II overload. Elevated ACE2 expression on the host cell surface might facilitate viral entrance, at the same time sudden nonadherence to these medications triggers MACEs. Hence, safety issues in the use of RAS inhibitors in COVID-19 patients with cardiac dysfunction remain an unsolved dilemma and need paramount attention. Although ACE2 generally plays an adaptive role in both healthy subjects and patients with systolic and/or diastolic dysfunction, we conducted a literature appraisal on its maladaptive role. Understanding the exact role of ACE2 in COVID-19 patients at risk of heart failure is needed to safely manage RAS inhibitors in frail and non-frail critically ill patients.

While existing remedies failed to fully address the consequences of heart failure, stem cell therapy has been introduced as a promising approach. The present review is a comprehensive appraisal of the impacts of using mesenchymal stem cells (MSCs) in clinical trials mainly conducted on ischemic cardiomyopathy. The benefits of MSC therapy for dysfunctional myocardium are likely attributed to numerous secreted paracrine factors and immunomodulatory effects. The positive outcomes associated with MSC therapy are scar size reduction, reverse remodeling, and angiogenesis. Also, a decreasing in the level of chronic inflammatory markers of heart failure progression like TNF-α is observed. The intense inflammatory reaction in the injured myocardial micro-environment predicts a poor response of scar tissue to MSC therapy. Subsequently, the interval delay between myocardial injury and MSC therapy is not yet determined. The optimal requested dose of cells ranges between 100 to 150 million cells. Allogenic MSCs have different advantages compared to autogenic cells and intra-myocardial injection is the preferred delivery route. The safety and efficacy of MSCs-based therapy have been confirmed in numerous studies, however several undefined parameters like route of administration, optimal timing, source of stem cells, and necessary dose are limiting the routine use of MSCs therapeutic approach in clinical practice. Lastly, pre-conditioning of MSCs and using of exosomes mediated MSCs or genetically modified MSCs may improve the overall therapeutic effect. Future prospective studies establishing a constant procedure for MSCs transplantation are required in order to apply MSC therapy in our daily clinical practice and subsequently improving the overall prognosis of ischemic heart failure patients.

Skeletal disorders are among the leading debilitating factors affecting millions of people worldwide. The use of stem cells for tissue repair has raised many promises in various medical fields, including skeletal disorders. Mesenchymal stem cells (MSCs) are multipotent stromal cells with mesodermal and neural crest origin. These cells are one of the most attractive candidates in regenerative medicine, and their use could be helpful in repairing and regeneration of skeletal disorders through several mechanisms including homing, angiogenesis, differentiation, and response to inflammatory condition. The most widely studied sources of MSCs are bone marrow (BM), adipose tissue, muscle, umbilical cord (UC), umbilical cord blood (UCB), placenta (PL), Wharton’s jelly (WJ), and amniotic fluid. These cells are capable of differentiating into osteoblasts, chondrocytes, adipocytes, and myocytes in vitro. MSCs obtained from various sources have diverse capabilities of secreting many different cytokines, growth factors, and chemokines. It is believed that the salutary effects of MSCs from different sources are not alike in terms of repairing or reformation of injured skeletal tissues. Accordingly, differential identification of MSCs’ secretome enables us to make optimal choices in skeletal disorders considering various sources. This review discusses and compares the therapeutic abilities of MSCs from different sources for bone and cartilage diseases.

Uterine fibrosis is an acquired disorder leading to menstrual irregularities, implantation impairment, and abortion. Mesenchymal stromal cells (MSCs) have antifibrotic properties through chemokine secretion. MSC-conditioned media (MSC-CM) contain paracrine components—exosomes—with a great potential for repairing damaged tissue or preventing fibrosis. The main goal of this study was to evaluate the preventive effects of bone marrow-derived MSC-CM (BM-MSC-CM) on uterine fibrosis after uterine curettage in rabbits. This study included 12 female rabbits (24 uterine horns in total). Excised uteri of each of the 12 female rabbits were randomly divided into four groups of intact negative control, curettage positive control, BM-MSC injection, and BM-MSC-CM injection in the way that two corresponding uteri from a rabbit were allocated to different groups. The MSC-CM were collected from cultivated BM-MSCs 48 hours after having been washed three times and replaced in serum-free media. Through a surgical approach, the caudal parts of the uteri were submitted to traumatic endometrial curettage, except for the intact negative uteri. After suturing the uterine walls, BM-MSCs or BM-MSC-CM were injected in the curettage site. Endometrial regeneration was histologically evaluated 30 days after treatment. Based on the evaluation of histomorphometric indices, curettage with or without preventive injections increased the growth of endometrial layers. However, the amount of fibrotic tissue in the CM and the BM-MSC injection groups was the same as the normal control groups, and all were less than the curettage group. A single injection of CM of MSCs after 30 days prevented the fibrotic tissue formation induced by curettage in endometrial layers of rabbits. Injecting BM-MSC-CM immediately after curettage prevented and reduced the uterine fibrosis similar to BM-MSCs in a rabbit model.

Aims Incidence of type 2 diabetes is markedly rising worldwide. Some studies suggest that the occurrence of major adverse cardiac events (MACE) after PCI is different in men and women, but data are conflicting. Methods We studied patients with stable coronary artery disease (CAD) who underwent PCI between years 2000 and 2017. Patients with primary PCI were excluded. Drug-eluting stent (DES) and dual antiplatelet therapy were administered in all patients. We followed these patients for a mean of 68 months. MACE as a composite of coronary revascularization, myocardial infarction or cardiovascular death was sought in three time windows. Results We studied 1799 patients, 29.6% of whom with diabetes. Women were 52%. In multivariate analyses, there were no significant differences in the risk of MACE between diabetic and non-diabetic patients, as well as between men and women, neither in different time windows, nor in the whole duration of follow-up. The components of MACE did not show any significant differences between diabetic and non-diabetic patients, as well as between the genders. Conclusion In our patients with stable CAD who received a modern therapeutic management after PCI, neither type 2 diabetes nor gender were associated with an excess risk of MACE.

The importance of venous structure in the heart is usually overshadowed by that of the arterial system. Coronary sinus (CS) is a part of cardiac venous apparatus and connects left atria to the right atria. Other than having role in physiological contractions of both atria, it contributes substantially to cardiac electrical conduction system. Due to unique placement and connections of the CS, it has become growing interest in clinical cardiology. It is used in cardiac resynchronization therapy with biventricular pacing, left-sided catheter ablation of arrhythmias, and administration of retrograde cardioplegia in cardiac surgery. In some individuals, CS is presented with anatomical variants. CS diverticulum is a congenital outpouching that provides muscular connection between atria and ventricle. This connection provides a suitable substrate for occurrence of arrhythmias, which even results in life-threatening events such as sudden cardiac death. Early diagnosis leads to treatment with ablation techniques, which ultimately eliminates origins of arrhythmias.

Background Stem cells has brought promising hope to improve impairment in different organs especially those with limited intrinsic regeneration capacity like nervous system. With the use of mesenchymal stem cells' (MSC) capacity to differentiate toward neural cells, this study aimed to examine the potential of fetal rat brain extract (FBE) as a biological inducer to mimic natural differentiation environment. Methods Bone marrow-MSCs were derived from Rattus norvegicus . After characterization of their mesenchymal nature, three groups were considered including control (culture medium only), differentiation (culture medium supplemented by basic fibroblast growth factor and epidermal growth factor), and treatment (culture medium and FBE). Growth curves as well as expression of glial fibrillary acidic protein (GFAP, marker for astroglial cells), galactocerebridase (GaLc, marker for oligodendrocyte and schwann cells), choline acetyl transferase (ChAT, marker for cholinergic neurons), and tyrosine hydroxylase (TH, marker of dopaminergic neurons) were examined in all the three groups at day 3 and 7 post-exposure. Also, nissl staining was performed in the three groups in order to assess protein synthesis and neurotransmitter production. Results Spindle-shaped cells were seen in the control group. There were neural-like cells in the differentiation group while more developed appearance with axon- and dendrite-like processes were present in the treatment group. To examine cell viability after exposure to FBE, growth curve was delineated. Higher proliferation rate and lower population doubling time were seen in the treatment group compared to other two groups. Regarding expression of neural markers, GaLC and ChAT at day 7 was prominent in the treatment group. Nissl bodies, which are rough endoplasmic reticulum, were seen only in the treatment group. Conclusions FBE might be a safer and more efficient inducer than combination of two well-known growth factors in terms of differentiation of MSCs to functional dopaminergic neurons. Making neural cells in vitro is an attractive approach in improvement of injured nervous system.

Background There are different reports on the occurrence of post-revascularization outcomes of diabetic patients in previous studies. Lesion complexity, which is reflected in stent size, influences the occurrence of outcomes. The aim of the present study was to investigate the occurrence of clinical outcomes in patients with history of diabetes (hDM) after percutaneous coronary intervention (PCI) with emphasis on stent length and diameter. Methods In a retrospective single-center cohort approach, among patients with stable coronary artery disease who underwent PCI with first- and second-generation DES, subjects were included from 2003 until 2019. Outcomes including revascularization, myocardial infarction, and death, totally defined as major adverse cardiac events (MACE), were sought in follow-up phase. All the patients whether with and without hDM received aspirin and clopidogrel as DAPT for at least two years and one year, respectively. Results About 29% out of 1630 participants had hDM and 37.8% of patients who experienced MACE had hDM. Unlike age and time-to-event, there was significant difference in gender between hDM and non-hDM groups. However, no difference was seen in type of MACE between these two groups. Also, after adjusting confounder variables, there was no significant difference in MACE incidence between hDM and non-hDM groups with different stent length and diameter (different lesion length and diameter). Conclusions hDM did not affect MACE incidence significantly in different stent length and diameter. We think that using of DES supplemented by long term DAPT and tight control of glycemic status after PCI are the underlying reasons.

During the last 20 years, stem cell therapy has been considered as an effective approach for regenerative medicine. Due to poor ability of stem cells to survive following transplantation, it has been proposed that beneficial effects of stem cells mainly depend on paracrine function. Therefore, the present study was designed to reinforce mesenchymal stem cells (MSCs) to express higher levels of trophic factors especially the ones with the neurotrophic properties. Here, bone marrow (BM)-MSCs and adipose-MSCs were treated with conditioned medium (CM) of dental pulp stem cells (DPSCs) or hair follicle stem cells (HFSCs) for up to three days. The relative expression of five key trophic factors that have critical effects on the central nervous system regeneration were evaluated using qRT-PCR technique. Furthermore, to assess the impacts of conditioned mediums on the fate of MSCs, expression of seven neuronal/glial markers were evaluated 3 days after the treatments. The obtained data revealed priming of BM-MSCs with HFSC-CM or DPSC-CM increases the BDNF expression over time. Such effect was also observed in adipose-MSCs following DPSC-CM treatment. Secretome preconditioning remarkably increased NGF expression in the adipose-MSCs. In addition, although priming of adipose-MSCs with HFSC-CM increased GDNF expression one day after the treatment, DPSC-CM enhanced GDNF mRNA in BM-MSCs at a later time point. It seemed priming of BM-MSCs with HFSC-CM, promoted differentiation into the glial lineage. Our findings showed that MSCs preconditioning with secretome of neural crest-derived stem cells could be a promising approach to enhance the neurotrophic potential of these stem cells.

Background: People’s lives have become full of risk factors of cardiovascular diseases in the recent years. This situation mainly originates from life style changes, which affect individuals’ health particularly in developing countries. Nutritional transition in terms of high consumption of fast foods and low intake of fruits and vegetables beside insufficient physical activity and sedentary jobs are the potent factors that facilitate the occurrence of diverse disorders. Hypertension is among the most concerning disorders, which affects both physical and mental aspects of health. Objectives: The present study aimed to assess the effects of hypertension, as one of the growing risk factors for diverse disorders, on quality of life. Patients and Methods: In this study, 200 individuals who had referred to Shiraz Healthy Heart House and Imam Reza clinic were selected by convenient sampling. Based on their history of hypertension, relevant therapies, and measurement of blood pressure at the time of enrollment, the participants were allocated to case and control groups. In addition to a general demographic questionnaire, Oxford Happiness Questionnaire was utilized in order to estimate the participants’ happiness status and quality of life. Different statistical methods were used to check the normal distribution of the data and compare the means. Results: The mean score of happiness showed that hypertensive individuals suffered from lower happiness levels compared to those with normal blood pressure (P < 0.05). Conclusions: Not only hypertension imposes serious side effects on different body systems, but it also decreases the quality of life. As many underlying causes of impaired blood pressure are related to lifestyle, it could be easily prevented by addressing the modifiable risk factors.

Objective(s): Adipose tissue-derived mesenchymal stem cells (AT-MSCs) with more potent immunomodulatory effects, greater proliferative potential and secretion of growth factors and cytokines in comparison with bone marrow derived MSCs are more appropriate for cell therapy. The aims of the present study were to evaluate the histomorphometric effect of AT-MSCs allotransplantation on regeneration of germinal layer cells of seminiferous tubules in busulfan-induced azoospermic hamsters. Materials and Methods: In the present experimental case-control study, AT-MSCs were isolated from adipose tissue of two female and six male donor albino hamsters, and testes of the males were simultaneously used as negative control group. Six mature male recipient hamsters received two doses of busulfan with three weeks interval to stop endogenous spermatogenesis. Right testis of hamsters was intratubular injected with AT-MSCs via efferent duct 35 days after induction of azoospermia and was used as cell therapy group. The left testis without cell therapy was served as azoospermia group. Results: After 35 days, testes and epididymis in all groups were removed for histological evaluation. Histomorphometric analyses of AT-MSCs-treated testes and epididymis showed that the epithelial tissue of seminiferous tubules was normally repaired in most cell-treated seminiferous tubules, and spermatozoa were present in epididymis tubes in comparison with intact testes. The untreated seminiferous tubules and epididymis tubes of azoospermia group were empty. Conclusion: Allotransplanted AT-MSCs could successfully induce spermatogenesis in azoospermic seminiferous tubules of hamster. Therefore, AT-MSCs can be suggested as an attractive candidate in cell transplantation of azoospermia.

Background: Endometrial mesenchymal stem stromal cells (EnMSCs) are critical for uterine function, repair, and regeneration. Objective: This study introduced isolation technique of EnMSCs and compared the characteristics of EnMSCs in mature and immature ewes. Materials and Methods: Endometrial tissue samples from the uterus of 10 ewes were collected from the slaughterhouse. Endometrial cells were isolated from tissue using cold incubation and then chopping and treating was performed with collagenase type I. Isolated cells were cultured in cell culture medium and then attached cells to flasks were harvested as EnMSCs and subcultured. To enumerate the cells, the population doubling time (PDT) was determined and 2.2×104 cells in passage 4 were seeded into 24-well culture plates to compare the growth curves of isolated cells. Reverse transcription polymerase chain reaction (RT-PCR) was performed for detection of CD34 and CD73 markers. The osteogenic and adipogenic potential of isolated cells were determined using differentiation tests. Results: EnMSCs adhered to the flasks and displayed spindle-shape. Based on findings of the cell count and the growth curves, the EnMSCs growth was significantly more prominent in immature ewes in comparison to mature sheep. The PDT of EnMSCs in immature ewes was about 21 hr whereas this time period was two times higher (45 hr) in mature sheep. RT-PCR analyses of EnMSCs were positive for CD73 and negative for CD34. EnMSCs were differentiated into osteoblasts and adipocytes. Conclusion: Based on mesenchymal stem cells characters confirmed in EnMSCs, they can be a candidate for cell therapy and regenerative medicine.

Background An abnormality in pulse amplitude and frequency of gonadotropin releasing hormone (GnRH) secretion is the most characteristics of polycystic ovarian syndrome (PCOS). On the other hand, arginine-phenylalanine-amide (RFamide)-related peptide-3 (RFRP3) inhibits the secretion of GnRH in mammalian hypothalamus. The current study performed in order to investigate the expression of RFRP3 mRNA in the dorsomedial hypothalamic nucleus (DMH) after the induction of PCOS in a rat model of constant light exposure, and the possible role of parity on occurrence of PCOS. Materials and Methods In the experimental study, female nulliparous (n=12) and primiparous (n=12) rats were randomly subdivided into control and PCOS subgroups (n=6). PCOS were induced by 90 days exposure to constant light. After 90 days, blood, brain, and ovaries were sampled. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were evaluated. In addition, six adult female ovariectomized rats as a control of real-time polymerase chain reaction (PCR) tests were prepared and in the DMH of all rats, the relative mRNA expression of RFRP3 was assessed. Results Histological evaluation of ovaries represented the polycystic features. In addition, serum concentrations of testosterone in the PCOS subgroups were more than the controls (P < 0.05). Furthermore, the relative expression of RFRP3 mRNA in PCOS subgroups was lower than the controls (P < 0.05). Conclusion Constant light model of the PCOS-induced rats decreased the gene expression of RFRP3 in the DMH that suggests the decrease of RFRP3 may reduce its inhibitory effect on GnRH during the PCOS pathogenesis. This effect was stronger in the nulliparous rats than the primiparous.

BackgroundSeveral studies addressed the association between fragmented QRS (fQRS) on 12-lead EKG and left ventricular (LV) dysfunction in patients with a variety of cardiovascular disorders. We tested such association in healthy individuals.MethodsOut of 500 healthy participants without -overt cardiovascular disease from the Shiraz Heart Study cohort, we identified 20 subjects with fQRS (cases) and 20 peers without fQRS (controls). Global LV longitudinal strain (GLS) was measured by speckle tracking echocardiography in the two groups. Comparison was made between case and control groups by using chi-square or independent sample t-test or ANOVA.ResultsAge, gender, ejection fraction, LV volume and dimensions did not differ between the case and the control groups. Overall, 14 subjects out of 40 had reduced GLS (≤20%) and 10 of them (25%) had fQRS. GLS was significantly lower in the group with fQRS than in the control group (19.9 ± 1.8 vs 21.4 ± 1.6;p = 0.009).ConclusionsHealthy subjects with fQRS present regional LV systolic dysfunction, assessed by GLS, in the presence of a normal ejection fraction. These data suggest that fQRS may be a promising tool to identify apparently healthy subjects with regional LV systolic dysfunction.