The impact of acemannan, an extracted product from Aloe vera, on proliferation of dental pulp stem cells and healing of mandibular defects in rabbits.

OBJECTIVES: Dental pulp stem cells (DPSCs) were shown to play an important role in regenerative medicine including reconstruction of various bone lesions. This study determined the impact of acemannan, an extracted product from Aloe vera, on in vitro proliferation of DPSCs and in vivo healing of mandibular defects in rabbits. METHODS: DPSCs were isolated and characterized. The growth kinetics of cells exposed to acemannan (8 mg/mL) and Hank's balanced salt solution (HBSS) were compared in vitro. Fifteen male rabbits were divided into 3 groups. Five animals were left as control group without any therapeutic intervention. Five rabbits were considered as experimental group 1 and received 20 µL of a cell suspension containing 106 DPSCs in the bone defect. Another 5 rabbits were regarded as experimental group 2 and were injected in the bone defect with 20 µL of a cell suspension containing 106 DPSCs treated with acemannan for 24 h. After 60 days, the animals were assessed by radiography and histologically. RESULTS: The mesenchymal properties of DPSCs were confirmed. Population doubling time (PDT) of DPSCs treated with acemannan (29.8 h) was significantly shorter than cells were just exposed to HBSS (45.9 h). DPSCs together with acemannan could significantly accelerate the healing process and osteogenesis in mandibular defects. CONCLUSIONS: As DPSCS showed an increased proliferation when treated with acemannan and accelerated the healing process in mandibular defects, these findings can open a new avenue in dentistry regenerative medicine when remedies of bone defects are targeted.

The impact of high nicotine concentrations on the viability and cardiac differentiation of mesenchymal stromal cells: a barrier to regenerative therapy for smokers.

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.

The impact of diabetic glucose concentration on viability and cardiac differentiation of mesenchymal stem cells.

INTRODUCTION: Hyperglycemia may be a stumbling block for delivery of regenerative benefits of mesenchymal stem cells (MSCs) to diabetic patients with cardiovascular diseases. Our study aims to assess the viability and cardiac differentiation potential of MSCs after being exposed to diabetic glucose concentration. METHODS: MSCs were extracted from rat bone marrow. Cells were characterized based on morphology, differentiation potential, and expression of mesenchymal specific markers. MTT assay was done to evaluate the viability of MSCs after treatment with different glucose concentrations. Case group was MSCs treated with diabetic concentration of glucose versus cells treated with PBS as the control group. Growth curve and population doubling time were calculated in both groups. Expression of GATA4 and troponin, as the early and late markers during cardiac differentiation, were measured following 5-azacytidine exposure. RESULTS: Proliferated cells at passage three had fibroblastic-shape, was able to differentiate into adipocytes or osteocytes, and expressed CD73 and CD90. MSCs viability was gradually decreased by increasing glucose concentration. Irrespective of nicotine concentration, three-day exposure imposed more severe detrimental effects on viability compared with one-day treatment. Proliferation rate of the MSCs was lower in the case group, and they need more time for population doubling. Expression of both cardiac markers were downregulated in the case group at day three. However, their expression became higher at day seven. CONCLUSION: Diabetic glucose concentration inhibits normal proliferation and cardiac differentiation of MSCs. This effect should be considered in stem cell therapy of cardiovascular patients who are concurrently affected by hyperglycemia, a common comorbidity in such individuals. Why carry out this study? What was learned from the study?

Global Longitudinal Strain May Be the One that Appropriately Identifies Candidates of ICD Implantation.

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.

Cell Proliferation, Viability, Differentiation, and Apoptosis of Iron Oxide Labeled Stem Cells Transfected with Lipofectamine Assessed by MRI.

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.

The prevalence of left ventricular hypertrophy associated with type-2 diabetes in Shiraz, Iran: a cross-sectional study.

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 < 0.0001), history of hypertension (P < 0.0001), mean and categorical duration of hypertension in years (P < 0.0160), status of controlled versus uncontrolled hypertension level (P < 0.0120), the mean systolic blood pressure (P < 0.0001) as well as mean duration years of T2DM and categorical duration of diabetes in years (< 0.0001 and P < 0.0060), mean fasting blood sugar (< 0.0307) and categorical status of FBS Level (mg/dl): controlled and uncontrolled FBS status of controlled vs. uncontrolled FBS levels P < 0.0020). However, there were no significant findings for gender (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.

Premature Death, Underlying Reasons, and Preventive Experiences in Iran: A Narrative Review.

Premature mortality (PM) has emerged as a global health challenge. This is of eminent importance in low- and middle-income countries, where nearly three fourths of the deaths occur. The concerning issue is the early occurrence of fatal events in productive age. Fatal events before the age of 70 are called PM, which mainly result from cardiovascular diseases (CVDs). Iran as a middle- income country greatly suffers from the cardiovascular burden, which accounts for almost 50% of all PM. Despite substantial success in reducing mortality due to communicable diseases across different age ranges, urbanization and pervasiveness of cardiovascular risk factors have increased the death rate in adults in recent years. Undoubtedly, such lifestyles have imposed heavy costs on the healthcare system; it is possible that PM reduction, as one of the fundamental elements of sustainable development goals defined by the World Health Organization (WHO), would not be reached by the due date. Recently, researchers have introduced a cost-effective fixed-dose drug combination, the so-called polypill, in order to attenuate the detrimental effects of hypertension and hyperlipidemia, as two strong cardiovascular risk factors. PolyIran and PolyIran-Liver studies are two pivotal clinical trials that revealed the feasibility of primary and secondary prevention of premature cardiovascular mortality, both in an urban and a rural population. In the present narrative review, we tried to present a comprehensive appraisal on PM status, its underlying reasons, and the impact of polypill strategy on PM prevention in Iran.

Prevalence of Microorganisms in Atherosclerotic Plaques of Coronary Arteries: A Systematic Review and Meta-Analysis.

Background: In this systematic review and meta-analysis, the existence of pathogens in atherosclerotic plaques of coronary arteries was investigated in coronary arteries diseases (CAD) patients. Methods: This study was designed and implemented up to 31 August 2020. The findings present according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) checklist. Two independent reviewers (I.RJ and S.H) performed a comprehensive search on four different English databases including PubMed, ISI, Scopus, and Embase. In order to assess the quality of the articles, a checklist prepared by The Joanna Briggs Institute (JBI) was used. Results: Finally, 44 studies were selected. The prevalence of different microorganisms in coronary arteries were as follows: Aggregatibacter actinomycetemcomitans (46.2%), Campylobacter rectus (43.0%), Chlamydia pneumonia (42.8%), Cytomegalovirus (29.1%), Helicobacter pylori (18.9%), Herpes simplex virus type 1 (5.9%), Porphyromonas gingivalis (42.6%), Prevotella intermedia (47.6%), Tannerella forsythia (43.7%), and Treponema denticola (32.9%). Conclusion: Based on the result of this meta-analysis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans are the most common microorganisms in atherosclerotic plaques of coronary arteries and may have an important role in the development of atherosclerosis.

Can anthropometric indices predict the chance of hypertension? A multicentre cross-sectional study in Iran.

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<0.05). Receiver operating characteristic for WHtR yielded an area under the curve of 0.62 (95% CI 0.61 to 0.64) and 0.63 (95% CI 0.62 to 0.65) for males and females, respectively. The optimal threshold value yielded 0.54 in men and 0.61 in women. The sensitivity was 72.3% and 73.9% in women and men, with specificity of 48.4% and 44.3%, respectively. CONCLUSION: HTN had a meaningful association with all the noted anthropometric indices. WHtR performed well as a predictor of HTN.

Composition, Biogenesis, and Role of Exosomes in Tumor Development.

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).

Effect of 8% arginine toothpaste on Streptococcus mutans in patients undergoing fixed orthodontic treatment: randomized controlled trial.

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.

Effect of performing high-intensity interval training and resistance training on the same day vs. different days in women with type 2 diabetes.

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, IL1ß, 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-1ß, 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.

Drug resistance in cancer therapy: the Pandora's Box of cancer stem cells.

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.

Immune system and atherosclerosis: Hostile or friendly relationship.

Coronary artery disease has remained a major health challenge despite enormous progress in prevention, diagnosis, and treatment strategies. Formation of atherosclerotic plaque is a chronic process that is developmentally influenced by intrinsic and extrinsic determinants. Inflammation triggers atherosclerosis, and the fundamental element of inflammation is the immune system. The immune system involves in the atherosclerosis process by a variety of immune cells and a cocktail of mediators. It is believed that almost all main components of this system possess a profound contribution to the atherosclerosis. However, they play contradictory roles, either protective or progressive, in different stages of atherosclerosis progression. It is evident that monocytes are the first immune cells appeared in the atherosclerotic lesion. With the plaque growth, other types of the immune cells such as mast cells, and T lymphocytes are gradually involved. Each cell releases several cytokines which cause the recruitment of other immune cells to the lesion site. This is followed by affecting the expression of other cytokines as well as altering certain signaling pathways. All in all, a mix of intertwined interactions determine the final outcome in terms of mild or severe manifestations, either clinical or subclinical. Therefore, it is of utmost importance to precisely understand the kind and degree of contribution which is made by each immune component in order to stop the growing burden of cardiovascular morbidity and mortality. In this review, we present a comprehensive appraisal on the role of immune cells in the atherosclerosis initiation and development.

The Role of ANRIL in Atherosclerosis.

There is a huge number of noncoding RNA (ncRNA) transcripts in the cell with important roles in modulation of different mechanisms. ANRIL is a long ncRNA with 3.8 kb length that is transcribed in the opposite direction of the INK4/ARF locus in chromosome 9p21. It was shown that polymorphisms within this locus are associated with vascular disorders, notably coronary artery disease (CAD), which is considered as a risk factor for life-threatening events like myocardial infarction and stroke. ANRIL is subjected to a variety of splicing patterns producing multiple isoforms. Linear isoforms could be further transformed into circular ones by back-splicing. ANRIL regulates genes in atherogenic network in a positive or negative manner. This regulation is implemented both locally and remotely. While CAD is known as a proliferative disorder and cell proliferation plays a crucial role in the progression of atherosclerosis, the functions of ANRIL and CAD development are intertwined remarkably. This makes ANRIL a suitable target for diagnostic, prognostic, and even therapeutic aims. In this review, we tried to present a comprehensive appraisal on different aspects of ANRIL including its location, structure, isoforms, expression, and functions. In each step, the contribution of ANRIL to atherosclerosis is discussed.

Preconditioning with secretome of neural crest-derived stem cells enhanced neurotrophic expression in mesenchymal stem cells.

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.

Expression ratio of circular to linear ANRIL in hypertensive patients with coronary artery disease.

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.

Potential of four definitions of metabolic syndrome to discriminate individuals with different 10-year cardiovascular disease risk scores: a cross-sectional analysis of an Iranian cohort.

OBJECTIVE: We aimed to reveal the potential of four different metabolic syndrome (Mets) definitions to differentiate subjects according to 10-year risk of cardiovascular disease. DESIGN: A cross-sectional analysis of a prospective cohort. SETTING: This 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. PARTICIPANTS: A 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. RESULTS: Participants 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 (p<0.001). In IDF definition, the risk scores of subjects with Mets were not statistically different compared with peers without Mets, neither based on FRS (p=0.247) nor ASCVD risk score (p=0.193). CONCLUSIONS: IDF 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 Impact of Diabetes Mellitus on Clinical Outcomes after Percutaneous Coronary Intervention with Different Stent Sizes.

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.

Effect of 8% arginine toothpaste on Streptococcus mutans in patients undergoing fixed orthodontic treatment: randomized controlled trial

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.

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.