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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).

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.

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 P P P P P P P = 0.3112), diastolic blood pressure mean (P = 0.7722) and body mass index (BMI) mean and categorical BMI (P = 0.2888 and P = 0.4080, respectively). Conclusion The prevalence of LVH in the study increases significantly among T2DM patients with hypertension, older age, years of hypertension, years of diabetes, and higher FBS. Thus, given the significant risk of diabetes and CVD, evaluation of LVH through reasonable diagnostic testing with ECG can help reduce the risk of future complications through the development of risk factor modifications and treatments guidelines.

Atherosclerotic lesions of the coronary arteries are still in charge of significant annual morbidity and mortality despite intense therapeutic advancements. Genome-born elements contribute substantially to the atherosclerosis process. ANRIL is one of the long non-coding RNAs with outstanding functions particularly regulation of genes involved in atherosclerosis development. In this study, we measured ANRIL expression (circular-, linear-, and circular/linear ratio) in hypertensive patients with coronary artery disease (CAD) compared with peers without CAD. Among hypertensive patients who were candidates of angiography, 25 subjects with CAD and the equal number without CAD were considered as the case and control groups, respectively. Different categories of data were recorded through a predefined questionnaire. Before angiography, blood samples were obtained. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for circular and linear ANRIL. Age and gender were not different between the groups. Most of the parameters of the lipid profile besides creatinine and blood urea nitrogen were remarkably worse in the case group. Circular ANRIL was significantly lower in the case group while linear counterparts were significantly higher in this group. Circular/linear ratio was also significantly lower in the case group. To overcome growing devastating trend of CAD, scrutinizing different factors involved in the initiation and development of atherosclerosis is a must. Atheroprotective role of circular ANRIL and atheroprogressive role of linear ANRIL were shown in our patients with hypertension.

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.

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. 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.

ObjectiveWe aimed to reveal the potential of four different metabolic syndrome (Mets) definitions to differentiate subjects according to 10-year risk of cardiovascular disease.DesignA cross-sectional analysis of a prospective cohort.SettingThis study used baseline data from the Shiraz Heart Study, a prospective cohort study in Shiraz, Iran. Participants were screened against Mets definitions including modified WHO, National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), American Heart Association (AHA) and International Diabetes Federation (IDF). Also, Framingham risk score (FRS) and atherosclerotic cardiovascular disease (ASCVD) risk score were determined for each participant.ParticipantsA total number of 7225 participants of both genders entered the study. They were selected through defined family physician centres in different geographical areas. Urban residents with no migration plan were included. Those who were far from study centres or with disabilities that made them incapable to cooperate were excluded.ResultsParticipants were 47.68% (N=3445) male with the mean age of 52.13±8.00 years. The number of subjects with Mets identified by WHO was the lowest (N=1676), while the percentage of subjects with high risk score was the highest, 17.1% (N=282) in FRS and 9.8% (N=162) in ASCVD risk score. There were statistically significant differences in the mean risk scores between participants with and without Mets according to AHA, WHO and NCEP ATP III definitions (pConclusionsIDF was not the appropriate definition for discrimination of subjects with Mets and/or those at high risk of future cardiovascular events. AHA, WHO and NCEP ATP III definitions were effective to discriminate subjects with Mets from peers without Mets.

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.

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.

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. RESUMO Objetivo: Avaliar o efeito de um dentifrício contendo arginina a 8% no Streptococcus mutans (S. mutans) da placa bacteriana ao redor de braquetes ortodônticos, e compará-lo a um dentifrício fluoretado convencional. Desenho do estudo: Foi conduzido um estudo unicêntrico, com braços paralelos, triplo-cego, controlado e randomizado. Métodos: O ensaio clínico foi conduzido na Clínica de Ortodontia da Faculdade de Odontologia da Universidade de Ciências Médicas de Shiraz, no Irã. Setenta e dois pacientes (com idades variando de 15 a 30 anos) que necessitavam de tratamento ortodôntico com aparelho fixo foram recrutados e alocados aleatoriamente nos grupos arginina ou flúor. A randomização foi feita usando o programa on-line RANDOM.ORG, e os participantes foram divididos em dois grupos paralelos, com proporção de alocação de 1:1. Solicitou-se aos pacientes que escovassem os dentes duas vezes ao dia com a pasta experimental, durante 30 dias. Amostras da placa bacteriana foram coletadas em dois intervalos: ao começo do estudo (T0) e após 30 dias (T1). Um PCR em tempo real foi usado para avaliar as amostras de placa, em termos de números de S. mutans ao redor dos braquetes de aço inoxidável nos pacientes ortodônticos. Um desenho de estudo triplo-cego foi usado. Resultados: As características iniciais (idade, sexo e quantidade relativa de S. mutans) foram semelhantes entre os grupos (p>0,05). Apenas o grupo arginina mostrou uma redução significativa na quantidade de bactérias entre T0 e T1 (p=0,02). Conclusão: A arginina é um agente prebiótico importante na manutenção de biofilmes bucais saudáveis, e previne as cáries dentárias durante o tratamento ortodôntico com aparelho fixo. Registro do ensaio: O ensaio foi registrado no Iranian Registry of Clinical Trials (IRCT20181121041713N2), https://en.irct.ir/user/trial/42409/view.

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.

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.

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.

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.

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 Uterine fibrosis is a uterine acquired disorder with symptoms of implantation disturbances, menstrual irregularities and abortion. Mesenchymal stem cells (MSCs) have antifibrotic properties by secretion of chemokines. MSCs-conditioned media (MSC-CM) contains paracrine components, exosomes, with a great potential for repairing damaged tissue or prevention of 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. Methods This study included 12 female rabbits (24 uterine horns) that double uteri of each 12 female rabbits were randomly divided into four groups of intact negative control, curettage positive control, BM-MSCs injection, and BM-MSC-CM injection in the way that two corresponding uteri from a rabbit were assigned in different groups. The MSC-CM was collected from cultivated BM-MSCs 48 h after three times washing and replacement of serum free media. Through a surgical approach, except intact negative uteri, the caudal part of the uteri was submitted traumatic endometrial curettage. After suturing of uterine wall, BM-MSC or BM-MSC-CM were injected in the curettage site. Endometrial regeneration was histologically evaluated 30 days after treatment. Results Curettage with or without preventive injections increased the growth of endometrial layer based on the histomorphometric indices evaluation. However, the amount of fibrotic tissue in the BM-MSC-CM injection group was lower than the BM-MSC and the curettage group, single injection of CM of MSCs after 30 days prevented the fibrotic effects of curettage on endometrial layer of rabbits. Conclusions Injecting BM-MSC-CM immediately after curettage prevented and reduced the uterine fibrosis better than BM-MSC in a rabbit model.

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.

Background: The burden of cardiovascular diseases have been become a concerning health challenge throughout the world. Stopping this condition needs applying early, yet inexpensive diagnostic methods. The aim of this study is to evaluate the capacity of fragmented QRS (fQRS) on 12-lead EKG for detecting left ventricular dysfunction in healthy individuals.Methods: Out of 500 healthy participants without detected cardiovascular disorders from Shiraz Heart Study cohort, 20 subjects diagnosed with fQRS (case) and 20 peers without fQRS (control) were participated. Global longitudinal strain was measured by speckle tracking echocardiography for two groups. Comparison was made between case and control groups by using chi-square or independent sample t-test or ANOVA. P value of less than 5% considered statistical significance. Results: There was no difference between the case and the control groups in terms of age, gender, ejection fraction, left ventricular volume and dimensions. Out of 40 subjects, 14 had reduced GLS (≤20%) with 10 of them had fQRS. GLS in the case group was significantly lower than in the control group.Conclusions: Apparent healthy subjects with fQRS diagnosed with left ventricular systolic dysfunction with respect to GLS despite normal ejection fraction. It seems that EKG, as one of the simplest way toward assessing heart function, could be a prominent informative clue to detect high-risk individuals among healthy population in advance.

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.

The aim of the present study was to investigate the larvicidal effect of aqueous and dimethyl sulfoxide extracts of Peganum harmala on larvae of Dictyocaulus filaria. Seed extract was prepared, and serial dilutions of 200, 100, 50, 25, 12.5, 6.25, and 3.12 mg/ml were prepared using distilled water and dimethyl sulfoxide (DMSO). Two genders of D. filaria were collected from sheep lung and cultured with Escherichia coli bacteria as parasites nutrition source. Ten juveniles were placed in deep slide to assess the larvicidal effects based on disability in the movement, degranulation, and appearance of the wrinkles on the body and narrowing of the body especially at the extremities every 20 min until 180 min. The larvicidal effect was reached to 100% for 200 mg/ml at more than 80 min, for 100 mg/ml at more than 100 min and for 50 mg/ml at more than 160 min for both extracts. The DMSO extract in all concentrations had significantly more potent than aqueous extract after 40 and 60 min for 200 mg/m, after 20, 60, and 80 min for 100 mg/ml, after 20, 40, 100, and 120 min for 50 mg/ml, after 40, 80, 120, 140, 160, and 180 min for 25 mg/ml, all time except at 20 min for 12.5 and 6.25 mg/ml, and at time more than 80 min for 3.12 mg/ml (P

Multilineage properties of mesenchymal stem cells (MSCs) cause their contribution in repair of different tissue. Adipose tissue is considered a good source of MSCs because of its abundance and easy access. The aims of this study were to characterize and determine the differentiation properties and growth kinetics of adipose tissue-derived stem cells (AT-SCs) from Syrian hamster. Fat tissue was isolated from the abdominal and pelvic regions of the hamster and by using type I collagenase, and cells were isolated and cultured. AT-SCs were characterized by morphology, cell surface markers, and adipogenic and osteogenic differentiations. AT-SCs were transferred to 24 well plates, and the growth kinetic was assessed by evaluation of the population doubling time (PDT). To show the chromosome stability of the AT-SCs, karyotyping was done. Hamsters’ AT-SCs showed fibroblast like morphology and expressed CD73 and CD29 but not CD45. AT-SCs could be differentiated to adipocytes and osteoblasts verified by Alizarin Red and Oil Red O staining methods. The PDT of the passages 2 and 3 of the AT-SCs were 51.6 and 80.6 h, respectively. The karyotyping was normal until passage 4. Hamsters’ AT-SCs showed mesenchymal properties denoting to these cells as a good source for the cell transplantation purposes in experimental and preclinical studies in hamster as an animal model.

The incidence of cardiovascular disorders, especially coronary artery disease and atherosclerosis, is increasing alarmingly. Clarifying the underlying causes is of the utmost importance and should be elucidated in order to reduce this growing trend. Periodontitis is known as a chronic destructive disease with sophisticated pathophysiological mechanisms that slowly impose negative effects not only on the oral tissues but also on distant organs. Additionally, it has been shown in many studies that atherosclerosis and periodontitis utilized common inflammatory signaling pathways and mediators. Several lines of evidence have demonstrated the signatures of periodontitis-related bacteria in atherosclerotic plaque specimens. It is proposed that virulent proteins of these bacteria probably accelerate the initiation or development of plaque formation on the inner walls of the coronary arteries. Proteomics techniques are very sensitive and have a global point of view. They can help to discover host factors and pathogenrelated biomarkers. This review summarizes the studies focused on the three most important bacterial species involved in both diseases and presents recent findings about the proteomic evaluation of virulence factors of these bacteria. The known mechanisms of action of the virulence factors are also described.

Mesenchymal stem cells (MSCs) have been isolated from various tissues of different species. The mammalian endometrium has morphological and functional modifications throughout the estrous cycle undergoing periodic proliferation and degeneration. The aim of this study was to isolate, culture, and characterize and to determine adipogenic differentiation of endometrial mesenchymal stem cells (En-MSCs) in heifers. Uteri of healthy heifers were collected from Shiraz Slaughterhouse, Iran and transferred to Stem Cell Laboratory of Stem Cell and Transgenic Technology Research Center to isolate En-MSCs from endometrial tissue samples. The tissue samples were exposed to collagenase type IA to reach the primary culture of En-MSCs. Isolated En-MSCs were sub-cultured up to passage 4. A specified number of En-MSCs were seeded into 12- and 24-well culture plates, and the number of cells was counted to evaluate the growth behavior of isolated cells and the population doubling time (PDT). RT-PCR for CD45 marker (hematopoietic stem cells) and CD73 marker (MSCs) and differentiation to adipocytes were performed for MSCs confirmation of En-MSCs of heifer. After cell culture, spindle-shape En-MSCs were visible adherent to the culture flasks. The cell count and the growth curves using 12- and 24-well culture plates showed that the PDT of En-MSCs was 37, 159.5, 52.9, and 136.3 h after seeding 2.2 × 104 and 20 × 104 (12-well) and 5 × 104 and 10 × 104 (24-well) En-MSCs, respectively. Using RT-PCR, heifer En-MSCs were negative for CD45 marker and positive for CD73 marker. Moreover, after culture of En-MSCs in differentiation medium, the cells differentiated toward adipocytes as verified by positive staining with Oil Red O staining. The morphology, growth kinetic, and differentiation of bovine En-MSCs demonstrated that these cells may be a good choice in bovine cell therapy and if necessary, they can be easily and safely administered in bovine tissue regeneration.

Phoenix dactylifera is a useful traditional medicinal plant, mainly the fruit is used, which is the edible part of the plant (Ajwa date). It is now considered to be a valuable source of natural medicinal products against various diseases. Phytochemical investigations have shown that the fruit contains anthocyanins, phenolics, sterols, carotenoids, and flavonoids. The fruits are a rich source of carbohydrates, vitamins, and proteins. P. dactylifera is considered as a complete diet because it also contains different fatty acids, amino acids, proteins, and steroidal substances. This review highlights the phytochemical composition, nutritional significance, and potential health benefits of P. dactylifera and discusses its potential as a functional food for disease prevention, management, and treatment.

IntroductionThe significant increase in the rate of morbidity and mortality due to cardiovascular diseases has become a health challenge globally. Lack of enough knowledge on the underlying causes in Iran and taking the unique characteristics of the Shiraz metropolitan city (the capital city of Fars Province) into consideration prompted us to conduct the Shiraz Heart Study. The aim of this study is to determine the predisposing elements leading to coronary heart disease, cerebrovascular disease and peripheral arterial disease.Methods and analysisIn this population-based, prospective study, family physician clinics will become the executive arms. Participants aged 40–70 years old will be recruited to achieve a sample size of 10 000. Socioeconomicta and anthropometric indices supplemented by physical activity, nutritional and psychological questionnaires, as well as routine blood laboratory tests, medical history and electrocardiographic records, will be collected at enrolment in clinics. In addition, blood samples will be obtained to explore the possible role of genetics in outcome occurrence. Follow-up with blood sampling, completion of a lifestyle questionnaire and evaluation of clinical risk factors will be carried out five times in a 2-year interval for all participants. Advanced statistical methods such as mixed model and time-to-event models will be used for data analysis.Ethics and disseminationThis study is in accordance with the Helsinki Declaration and has been approved by the Research Ethics Committee of Shiraz University of Medical Sciences (No: 2017–358). Signing a written informed consent is the preliminary step. Participants are free to withdraw on their request at any time. Collected data are kept encrypted in a software with authorities’ access only. Findings of the study will be published at a national or international scale through peer-reviewed journals.