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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, respectively. There was no significant difference in the expression of miR-181a in the blood samples of UC and HCs. Immunohistochemistry showed high positivity without any significant difference between the 2 groups in the quantitative analysis. Conclusions 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.

Abstract 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.

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 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.

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.

Objective(s): Nowadays much effort is being invested in order to diagnose the mechanisms involved in neural differentiation. By clarifying this, making desired neural cells in vitro and applying them into diverse neurological disorders suffered from neural cell malfunctions could be a feasible choice. Thus, the present study assessed the capability of fetal brain extract (FBE) to induce rat bone marrow-derived mesenchymal stem cells (BM-MSCs) toward neural cells. Materials and Methods: For this purpose, BM-MSCs were collected from rats and cultured and their mesenchymal properties were confirmed. After exposure of the BM-MSCs to fetal brain extract, the cells were evaluated and harvested at days 3 and 7 after treatment. Results: The BM-MSCs that were exposed to FBE changed their appearance dramatically from spindle shape to cells with dendrite-like processes. Those neural like processes were absent in the control group. In addition, a neural specific marker, vimentin, was expressed significantly in the treatment group but not in the negative control group. Conclusion: This study presented the FBE as a natural neural differentiation agent, which probably has required factors for making neurons. In addition, vimentin overexpression was observed in the treated group which confirms neuron-like cell differentiation of BM-MSCs after induction.

Abstract Background The distinction between normal and high blood pressure remains a debated topic, with varying guidelines on when to start medication. Contemporary guidelines advocate for the initiation of antihypertensive therapy in individuals who present with high-normal blood pressure, particularly those exhibiting elevated 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores. Despite these recommendations, there is a notable lack of direct evidence supporting the efficacy of treating high-normal blood pressure to prevent major adverse cardiovascular events (MACE). Methods The PRINT-TAHA9 trial, a unicentric, randomized, open-label, controlled, parallel clinical study, seeks to explore the effects of intensive blood pressure control on MACE in participants with high-normal blood pressure. We will enroll 1620 adults aged 18 years and above with a systolic blood pressure range of 130–140 mmHg, diastolic blood pressure under 90 mmHg, and atherosclerotic cardiovascular disease (ASCVD) risk score exceeding 7.5%. The study will be executed in five distinct phases, with each phase enrolling between 300 and 400 participants. Participants will be randomly assigned to either the treatment group receiving antihypertensive medication (amlodipine/valsartan) and a low-salt/low-fat diet or to the control group receiving a similar diet. Follow-up visits are scheduled every 6 months over a 3-year period to monitor blood pressure, evaluate medication adherence, document any adverse events, and adjust the intervention as necessary. Cox proportional hazards regression analysis will be employed to examine the disparities between the two arms. Discussion Despite guidelines promoting early treatment of elevated blood pressure, the debate continues due to insufficient evidence that such interventions significantly reduce the occurrence of MACE. This trial seeks to address this critical evidence gap. Trial registration The PRINT-TAHA9 trial was registered in October 2019 with the Iranian Registry of Clinical Trials (IRCT.ir) under the registration number IRCT20191002044961N1. https://irct.behdasht.gov.ir/trial/43092 .

Abstract Background The regulation of the circadian clock genes, which coordinate the activity of the immune system, is disturbed in inflammatory bowel disease (IBD). Emerging evidence suggests that butyrate, a short-chain fatty acid produced by the gut microbiota is involved in the regulation of inflammatory responses as well as circadian-clock genes. This study was conducted to investigate the effects of sodium-butyrate supplementation on the expression of circadian-clock genes, inflammation, sleep and life quality in active ulcerative colitis (UC) patients. Methods In the current randomized placebo-controlled trial, 36 active UC patients were randomly divided to receive sodium-butyrate (600 mg/kg) or placebo for 12-weeks. In this study the expression of circadian clock genes (CRY1, CRY2, PER1, PER2, BMAl1 and CLOCK) were assessed by real time polymerase chain reaction (qPCR) in whole blood. Gene expression changes were presented as fold changes in expression (2^-ΔΔCT) relative to the baseline. The faecal calprotectin and serum level of high-sensitivity C-reactive protein (hs-CRP) were assessed by enzyme-linked immunosorbent assay method (ELIZA). Moreover, the sleep quality and IBD quality of life (QoL) were assessed by Pittsburgh sleep quality index (PSQI) and inflammatory bowel disease questionnaire-9 (IBDQ-9) respectively before and after the intervention. Results The results showed that sodium-butyrate supplementation in comparison with placebo significantly decreased the level of calprotectin (-133.82 ± 155.62 vs. 51.58 ± 95.57, P-value

Background: Myocardial infarction (MI) and ischemic stroke are the leading deadly clinical outcomes globally. This study aimed to investigate the association of classic cardiovascular risk factors with MI and ischemic stroke in a general population. Methods: This cross-sectional study used the baseline data of the Shiraz Heart Study, a prospective cohort that investigate risk factors of coronary heart disease in a general population of Iran. Middle-aged citizens of 40–70 years old were included. Univariable and multivariable logistic regression analysis was performed to explore the association between sociodemographic, clinical, and metabolic factors and prevalent MI and stroke. Results: Out of 7225 adults, 1.9 % (n = 135) had prior MI or stroke. Multiple logistic regression revealed that age≥60 years (aOR: 2.22, 95 % CI 1.45–3.20; P

Background: Current treatment methods are not successful in restoring the lost cardiomyocytes after injury. Stem cell-based strategies have attracted much attention in this regard. Smoking, as a strong cardiovascular risk factor, not only affects the cardiac cells adversely but also deteriorates the function of stem cells. Since mesenchymal stem cells (MSCs) are one of the popular candidates in cardiovascular disease (CVD) clinical trials, we investigated the impact of nicotine on the regenerative properties (viability and cardiac differentiation) of these cells.Methods: MSCs were isolated from rat bone marrow and characterized based on morphology, differentiation capability, and the expression of specific mesenchymal markers. The MTT assay was used to assess the viability of MSCs after being exposed to different concentrations of nicotine. Based on MTT findings and according to the concentration of nicotine in smokers’ blood, the growth curve and population doubling time were investigated for eight consecutive days. Cells were treated with 5-azacytidine (an inducer of cardiac differentiation), and then the expressions of cardiac-specific markers were calculated by qPCR.Results: MSCs were spindle-shaped, capable of differentiating into adipocyte and osteocyte, and expressed CD73 and CD90. The viability of MSCs was reduced upon exposure to nicotine in a concentration- and time-dependent manner. The growth curve showed that nicotine reduced the proliferation of MSCs, and treated cells needed more time to double. In addition, the expressions of GATA4 and troponin were downregulated in nicotine-treated cells on day 3. However, these two cardiac markers were overexpressed on day 7.Conclusion: Nicotine decreased normal growth and reduced the expression of cardiac markers in MSCs. This aspect is of eminent importance to smokers with cardiovascular disease who are candidates for stem cell therapy.

Hypertrophic cardiomyopathy (HCM) significantly contributes to an elevated risk of sudden cardiac death. Primary prevention is implemented by using an implantable cardioverter defibrillator (ICD). However, all of the HCM patients do not really need ICD therapy. Providing a superior index for ICD indication compared with the current indices like ejection fraction is essential to differentiate high-risk patients efficiently. The present study assessed the potential of global longitudinal strain (GLS) for the differentiation of HCM patients based on their need for ICD shocks. Patients with HCM were considered in four defined centers between March and June 2021. Those with previous ICD implantation or current candidates for ICD therapy were included in the study. Participants were subjected to speckle-tracking echocardiography, and GLS as well as some other echocardiographic parameters were recorded. Afterwards, data from implanted ICDs were extracted. Patients who received ICD shocks (appropriate) due to ventricular tachycardia (VT)/ventricular fibrillation (VF) were categorized in group A. The remaining patients were constituted group B who received inappropriate shocks, i.e., other than VT/VF. Overall, 34 patients were found eligible to participate with a mean age of 62 ± 16.1 years including 64.7% of males. Among a variety of echocardiographic parameters, GLS was the sole one that was significantly higher in group A compared with that in group B. Our findings revealed that only GLS could predict fatal arrhythmias. To substantiate, the odds of VT were raised by 43% with a single increase in GLS unit. GLS showed the highest accuracy for ICD indication among HCM patients and, therefore, could be a solid and early criterion to predict the incidence of life-threatening arrhythmias. In this regard, identifying appropriate HCM patients with respect to their need for ICD therapy is feasible.

Abstract Background Left ventricular hypertrophy (LVH) is a common diagnosis in patients with cardiovascular disease (CVD). The prevalence of LVH among patients with Type-2 Diabetes Mellitus (T2DM), high blood pressure and aging is higher than the healthy population and has been independently associated with an increased risk for future cardiac event, including stroke. The aim of this study is to identify the prevalence of LVH among T2DM subjects and evaluate its association with related risk factors of CVD patients in the metropolis of Shiraz, Iran. The novelty of this study is that there has been no known published epidemiological study related to the relationship of LVH and T2DM on this unique population. Materials and method This cross-sectional study was designed based on collected data of 7715 free dwelling subjects in the community-based Shiraz Cohort Heart Study (SCHS) from 2015 to 2021, ages 40–70 years. Overall, 1118 subjects with T2DM were identified in the SCHS and after exclusion criteria, 595 subjects remained eligible for study. Subjects with electrocardiography (ECG) results, which are appropriate and diagnostics tools, were evaluated for the presence of LVH. Thus, the variables related to LVH and non-LVH in subjects with diabetes were analyzed using version-22 statistical package for social sciences software program to ensure consistency, accuracy, reliability, and validity for final analysis. Based upon related variables and identifying LVH and non-LVH subjects, the relevant statistical analysis was implemented to ensure its consistency, accuracy, reliability, and validity for final analysis. Results Overall, the prevalence of diabetic subjects was 14.5% in the SCHS study. Furthermore, the prevalence of hypertension in the study subjects aged 40–70 years was 37.8%. The prevalence of hypertension history in T2DM study subjects for LVH compared to non-LVH was (53.7% vs. 33.7%). The prevalence of LVH among patients with T2DM as the primary target of this study was 20.7%. Analytical findings comparing both LVH and non-LVH subjects who have T2DM identified significance for variables in the older (≥ 60) mean and categorical age group (P

IntroductionMetabolic risk factors (MRFs) predispose populations to a variety of chronic diseases with a huge burden globally. With the increasing burden of these risk factors in Iran, in this study, we aimed to report the estimated burden attributed to MRFs at national and subnational scales in Iran, from 1990 to 2019.MethodsBased on the comparative risk assessment method of the Global Burden of Disease (GBD) Study 2019, data of deaths and disability-adjusted life years (DALYs) attributable to four top MRFs in Iran including high systolic blood pressure (SBP), high fasting plasma glucose (FPG), high body mass index (BMI), and high low-density lipoprotein (LDL) for the 1990–2019 period, were extracted. The socio-demographic index (SDI) was used to report the data based on the corresponding socio-economic stratifications. The results were reported in national and subnational 31 provinces of Iran to discover disparities regarding the attributable burden to MRFs. Furthermore, we reported the causes of diseases to which the attributable burden to MRFs was related.ResultsOverall, the age-standardized high LDL, high SBP, high BMI, and high FPG-attributed death rate changed by −45.1, −35.6, +2.8, and +19.9% from 1990 to 2019, respectively. High SBP was the leading risk factor regarding attributed age-standardized death rates reaching 157.8 (95% uncertainty interval: 135.3–179.1) and DALY rates reaching 2973.4 (2652.2–3280.2) per 100,000 person-years, in 2019. All rates increased with aging, and men had higher rates except for the +70 years age group. At the subnational level, provinces in the middle SDI quintile had the highest death and DALY rates regarding all four MRFs. Total deaths, DALYs, YLLs and YLDs number by the causes of diseases linked to MRFs increased over the study period. Cardiovascular diseases, diabetes mellitus, and kidney diseases were the main causes of burden of disease attributable to MRFs.ConclusionHerein, we found divergent patterns regarding the burden of MRFs as well as disparities in different regions, sex, and age groups for each risk factor and related causes. This could provide policymakers with a clearer vision toward more appropriate decision-making and resource allocation to prevent the burden of MRFs in Iran.

Abstract 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.

Objectives This 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.Setting In this cross-sectional study, subjects were enrolled in 25 clinics in Shiraz. I.R. Iran between 2019 and 2021.Participants A 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 measures Primary 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.Results HTN prevalence was 19.3%. Obesity prevalence was estimated to be 28.5%. WHR and lean body mass showed a significant association with HTN (p

Background: This study aimed to investigate the possible relationship between different stent sizes and clinical outcomes after percutaneous coronary intervention (PCI) in patients with diabetes treated with drug-eluting stents (DESs) and dual antiplatelet therapy (DAPT). Methods: Patients with stable coronary artery disease undergoing elective PCI with the DES were entered into a retrospective cohort between 2003 and 2019. Major adverse cardiac events (MACE), defined as the combined endpoint of revascularization, myocardial infarction, and cardiovascular death, were recorded. The participants were categorized according to the stent size: 27 mm for length and 3 mm for diameter. DAPT (aspirin and clopidogrel) was used for at least 2 years for diabetics and 1 year for nondiabetics. The median duration of follow-up was 74.7 months. Results: Out of 1630 participants, 29.0% had diabetes. The diabetics constituted 37.8% of those with MACE. The mean diameter of the stents in the diabetics and nondiabetics was 2.81±0.29 mm and 2.90±0.35 mm, respectively (P>0.05). The mean stent length was 19.48±7.58 mm and 18.92±6.64 mm in the diabetics and nondiabetics, respectively (P>0.05). After adjustments for confounding variables, MACE was not significantly different between the patients with and without diabetes. Although MACE incidence was not affected by stent dimensions in the patients with diabetes, the nondiabetic patients implanted with a stent length exceeding 27 mm experienced MACE less frequently. Conclusion: Diabetes did not influence MACE in our population. Additionally, stents of different sizes were not associated with MACE in patients with diabetes. We propose that using the DES supplemented by long-term DAPT and tight control of glycemic status after PCI could decrease the adverse consequences of diabetes.

Abstract 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.

ABSTRACT Objective: To assess the effect of toothpaste containing 8% arginine on Streptococcus mutans (S. mutans) in dental plaque around orthodontic brackets, and to draw a comparison with a regular fluoride toothpaste. Trial design: A single-center, parallel-arm, triple-blind, randomized controlled trial was conducted. Methods: The clinical trial was conducted at the Orthodontic Clinic, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran. Seventy-two patients (age range: 15-30 years) who required fixed orthodontic treatment were recruited and randomly assigned to arginine and fluoride groups. Randomization was performed using RANDOM.ORG online software, and the participants were divided into two parallel groups, with a 1:1 allocation ratio. Patients were requested to brush their teeth twice daily for 30 days with an experimental toothpaste. Plaque sampling was performed at two intervals, namely at the beginning of the study (T0) and 30 days later (T1). Real-time PCR was used to assess plaque samples in terms of the number of S. mutans surrounding stainless steel brackets in orthodontic patients. A triple-blind design was employed. Results: The baseline characteristics (age, sex, and the relative number of S. mutans) between the groups were similar (p>0.05). Only the arginine group showed a significant decrease in the relative number of bacteria between T0 and T1 (p=0.02). Conclusion: Arginine is an important prebiotic agent in maintaining healthy oral biofilms, and prevent dental caries during fixed orthodontic treatments. Trial registration: The trial was registered at the Iranian Registry of Clinical Trials (IRCT20181121041713N2), https://en.irct.ir/user/trial/42409/view.

Abstract 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.

Abstract Background Several 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. Methods Out 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. Results Age, 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). Conclusions Healthy 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.

The role of exosomes and their mechanism of action at the tumor site have received increasing attention. These microvesicles are produced by a wide range of cells including mesenchymal stem cells (MSCs) and immune cells. In particular, tumor cells release remarkable amounts of exosomes which spread to distant organs through the blood and enhance the possibility of tumor metastasis. In spite of results on tumor promoting properties, there are reports demonstrating the tumor inhibiting effects of exosomes depending on the type of the tumor and cell source. This review aims to have a comprehensive appraisal on the biogenesis, composition, and isolation of exosomes and then highlights the current knowledge of their role in cancer progression or inhibition by special focusing on MSC’s exosomes (MSC-EXOs).

The world is in a hard battle against COVID-19. Endothelial cells are among the most critical targets of SARS-CoV-2. Dysfunction of endothelium leads to vascular injury following by coagulopathies and thrombotic conditions in the vital organs increasing the risk of life-threatening events. Growing evidences revealed that endothelial dysfunction and consequent thrombotic conditions are associated with the severity of outcomes. It is not yet fully clear that these devastating sequels originate directly from the virus or a side effect of virus-induced cytokine storm. Due to endothelial dysfunction, plasma levels of some biomarkers are changed and relevant clinical manifestations appear as well. Stabilization of endothelial integrity and supporting its function are among the promising therapeutic strategies. Other than respiratory, COVID-19 could be called a systemic vascular disease and this aspect should be scrutinized in more detail in order to reduce related mortality. In the present investigation, the effects of COVID-19 on endothelial function and thrombosis formation are discussed. In this regard, critical players, laboratory findings, clinical manifestation, and suggestive therapies are presented.

Background. For decades, cardiovascular diseases (CVD) have been known as men’s disease. However, recent research studies showed that they have become more common in women. Smoking is a strong risk factor for CVD especially that of coronary artery disease (CAD). Several studies reported that women are more susceptible to drastic sequels of smoking than men. There is limited data regarding the impact of smoking on post-revascularization clinical events stratified by gender. This study aimed to investigate if gender significantly changes the incidence of adverse clinical outcomes after percutaneous coronary intervention (PCI) among those with history of smoking. Methods. Participants were selected from two hospitals from 2003 to 2019. Among patients who had PCI (index PCI), those with stable CAD who underwent elective PCI were included. Exclusion criteria were defined as primary PCI and those with multiple prior revascularizations. Participants were followed up seeking for major adverse cardiac events (MACE) including revascularization (PCI or coronary artery bypass grafting), myocardial infarction, and coronary death in three time intervals according to the time of index PCI (short term: up to 24 hours, mid-term: 24 hours to less than 6 months, and long term: more than 6 months). Results. Of the 1799 patients, 61% were men and 47.08% had history of smoking (75% of the smokers were men). At the time of index PCI, smokers were significantly younger than nonsmokers. Also, MACE were significantly higher in smokers than nonsmokers, which was particularly pronounced at the long-term interval. In the nonsmokers group, there was no difference in MACE occurrence between men and women. However, of the smokers, women showed significantly higher MACE rate compared with men peers. Conclusion. Smoking makes women more prone to MACE in comparison to men among patients with stable CAD after PCI with drug-eluting stent.

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.

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.