Disparity of gene expression in coronary artery disease: insights from MEIS1, HIRA, and Myocardin.

INTRODUCTION: Coronary artery disease (CAD) in young adults can have devastating consequences. The cardiac developmental gene MEIS1 plays important roles in vascular networks and heart development. This gene effects on the regeneration capacity of the heart. Considering role of MEIS1 in cardiac tissue development and the progression of myocardial infarction this study investigated the expression levels of the MEIS1, HIRA, and Myocardin genes in premature CAD patients compared to healthy subjects and evaluated the relationships between these genes and possible inflammatory factors. METHODS AND RESULTS: The study conducted a case-control design involving 35 CAD patients and 35 healthy individuals. Peripheral blood mononuclear cells (PBMCs) were collected, and gene expression analysis was performed using real-time PCR. Compared with control group, the number of PBMCs in the CAD group exhibited greater MEIS1 and HIRA gene expression, with fold changes of 2.45 and 3.6. The expression of MEIS1 exhibited a negative correlation with IL-10 (r= -0.312) expression and positive correlation with Interleukin (IL)-6 (r = 0.415) and tumor necrosis factor (TNF)-α (r = 0.534) gene expression. Moreover, there was an inverse correlation between the gene expression of HIRA and that of IL-10 (r= -0.326), and a positive correlation was revealed between the expression of this gene and that of the IL-6 (r = 0.453) and TNF-α (r = 0.572) genes. CONCLUSION: This research demonstrated a disparity in expression levels of MEIS1, HIRA, and Myocardin, between CAD and healthy subjects. The results showed that, MEIS1 and HIRA play significant roles in regulating the synthesis of proinflammatory cytokines, namely, TNF-α and IL-6.

Adherence to EAT-Lancet reference diet and risk of premature coronary artery diseases: a multi-center case-control study.

BACKGROUND: In 2019, a globally sustainable dietary pattern that primarily emphasizes the consumption of plant-based foods was proposed by the EAT-Lancet Commission. However, there is limited evidence regarding the association of this diet with coronary events. OBJECTIVES: To determine the association between the EAT-Lancet Reference Diet (ELD) and premature coronary artery disease (PCAD) risk and its severity. METHODS: This multi-center, case-control study was conducted within the framework of the Iran premature coronary artery disease (I-PAD). A total of 3185 participants aged under 70 years in women and 60 years in men were included. Cases were those whose coronary angiography showed stenosis ≥ 75% in at least one vessel or ≥ 50% in the left main artery (n = 2033), while the controls had normal angiography results (n = 1152). Dietary intake was assessed using a validated food frequency questionnaire. Logistic regression was utilized to examine the association between ELD and presence of PCAD. RESULTS: Compared with individuals in the first quartile, those in the highest quartile of ELD (OR = 0.29, 95% CI: 0.21, 0.39; P for trend < 0.001) and ELD calculated with minimum intake (OR = 0.39, 95% CI: 0.29, 0.52; P < 0.001) had lower risk of PCAD. Individuals in the highest quartile of adherence to the ELD and ELD with minimum intake had 78% and 72% lower risk of having severe PCAD compared with those in the lowest quartile, respectively. CONCLUSION: An inverse association was observed between adherence to the ELD and PCAD risk and its severity. Large-scale prospective cohort studies are required to confirm these findings.

Development of the first Iranian clinical practice guidelines for the diagnosis, treatment, and secondary prevention of acute coronary syndrome.

Background: This article introduces the first national guidelines for the management including diagnosis, treatment, and secondary prevention of acute coronary syndrome (ACS) in Iran. Materials and Methods: The members of the guideline development group (GDG) were specialists and experts in fields related to ACS and were affiliated with universities of medical sciences or scientific associations in the country. They carefully examined the evidence and clinical concerns related to ACS management and formulated 13 clinical questions that were sent to systematic review group who developed related evidence using Grade method. Finally the GDG developed the recommendations and suggestions of the guideline. Results: The first three questions in the guideline focus on providing recommendations for handling a patient who experience chest pain at home, in a health house or center, during ambulance transportation, and upon arrival at the emergency department (ED) as well as the initial diagnostic measures in the ED. Subsequently, the recommendations related to the criteria for categorizing patients into low, intermediate and high-risk groups are presented. The guideline addressed primary treatment measures for ACS patients in hospitals with and without code 247 or having primary percutaneous coronary intervention (PCI) facilities, and the appropriate timing for PCI based on the risk assessment. In addition, the most efficacious antiplatelet medications for ACS patients in the ED as well as its optimal duration of treatment are presented. The guideline details the recommendations for therapeutic interventions in patients with ACS and acute heart failure, cardiogenic shock, myocardial infarction with nonobstructive coronary arteries (MINOCA), multivessel occlusion, as well as the indication for prescribing a combined use of anticoagulants and antiplatelet during hospitalization and upon discharge. Regarding secondary prevention, while emphasizing the referral of these patients to rehabilitation centers, other interventions that include pharmaceutical and nonpharmacological ones are addressed, In addition, necessary recommendations for enhancing lifestyle and posthospital discharge pharmaceutical treatments, including their duration, are provided. There are specific recommendations and suggestions for subgroups, such as patients aged over 75 years and individuals with heart failure, diabetes, and chronic kidney disease. Conclusion: Developing guidelines for ACS diagnosis, treatment and secondary prevention according to the local context in Iran can improve the adherence of our health care providers, patients health, and policy makers plans.

Melatonin/nicotinamide mononucleotide/ubiquinol: a cocktail providing superior cardioprotection against ischemia/reperfusion injury in a common co-morbidities modelled rat.

BACKGROUND: The metabolic and intracellular abnormalities in aging and diabetes cause loss of cardioprotection by routine interventions against myocardial ischemia/reperfusion (I/R) injury. We aimed to evaluate the possible interaction of aging and type-2 diabetes mellitus with cardioprotection and the potential protective effect of a mitochondrial cocktail (melatonin/nicotinamide mononucleotide (NMN)/ubiquinol) on myocardial I/R injury in aged diabetic rats. METHODS: Male Wistar rats (n = 108, 22-24 months old, 400-450 g) received high-fat diet/low dose of streptozotocin to induce type-2 diabetes, then were randomized into 9 groups of 12 rats each with/without I/R and/or melatonin, NMN, and ubiquinol, alone or in dual or triple combinations. Myocardial I/R was induced by LAD occlusion for 30 min followed by 24 h reperfusion. NMN (100 mg/kg/48 h, intraperitoneally) was administered for 28 days before I/R operation. Melatonin (10 mg/kg, intraperitoneally) and/or ubiquinol (30 mg/kg, intravenously) were administered at early reperfusion. Finally, hemodynamic index changes, infarct size, CK-MB levels, mitochondrial functional endpoints, and expression of mitochondrial biogenesis genes (SIRT-1/PGC-1α/NRF-2/TFAM) were assessed. RESULTS: The solo and dual applications of melatonin, NMN, and ubiquinol did not exert remarkable cardioprotective impacts. However, the triple combination improved myocardial function and decreased infarct size and CK-MB levels following myocardial I/R (P < .05 to P < .01). It also improved mitochondrial function and restored mitochondrial biogenesis genes (P < .01). CONCLUSIONS: Combination therapy with melatonin, NMN, and ubiquinol exerted significant cardioprotection and improved mitochondrial function and biogenesis via upregulation of SIRT-1/PGC-1α/NRF-2/TFAM profiles in aged diabetic rats and, thus, offers a promising strategy for providing noticeable cardioprotection against I/R injury also in aged diabetic patients.

The expression levels of PPAR-α/γ and UCP1/2 on the slow coronary flow phenomenon; results from a case-control study.

PURPOSE: The slow coronary flow (SCF) phenomenon is considered a coronary artery disorder. Because of the critical function of peroxisome proliferator-activated receptors (PPARs) in regulating the oxidative stress and inflammatory reactions in cardiovascular disease, The aim of the current study was to investigate the expression of the genes for uncoupling proteins 1 and 2 (UCP1 and UCP2), peroxisome proliferator-activated receptors and (PPAR- PPAR-), and PPAR- in SCF patients. METHODS: In this case-control study, coronary angiography examination was used to analyze 35 individuals with SCF and 35 subjects with normal coronary flow (NCF). SCF was diagnosed using the TIMI (thrombolysis in myocardial infarction frame count) method. The SCF phenomenon is thought to be the TIMI > 27. In the peripheral blood mononuclear cells (PBMCs), the messenger ribonucleic acid (mRNA) expression levels of the PPAR-, PPAR-, UCP1, and UCP2 genes were evaluated. RESULTS: UCP1 and UCP2 expression levels were significantly higher in the SCF group compared to the NCF group (P = 0.034 and P0.001, respectively). The PPAR- and PPAR- levels were found to be significantly lower in the SCF group compared to the NCF group (P = 0.015, P0.001, respectively). According to the results of the logistic regression analysis, high UCP1 and UCP2 levels and low PPAR- and PPAR- levels are each independent predictors of the SCF phenomenon. CONCLUSION: This research provided evidence about the potential role of PPAR-α, PPAR-γ, UCP1, and UCP2 as biomarkers in SCF. More investigations are suggested to assess the functions of these factors in SCF patients mechanistically.

Ethnic differences in the lifestyle behaviors and premature coronary artery disease: a multi-center study.

BACKGROUND: Diverse ethnic groups that exist in Iran may differ regarding the risk factors such as hypertension, hyperlipidemia, dyslipidemia, diabetes mellitus, and family history of non-communicable disease. Premature Coronary Artery Disease (PCAD) is more endemic in Iran than before. This study sought to assess the association between ethnicity and lifestyle behaviors in eight major Iranian ethnic groups with PCAD. METHODS: In this study, 2863 patients aged ≤ 70 for women and ≤ 60 for men who underwent coronary angiography were recruited in a multi-center framework. All the patients' demographic, laboratory, clinical, and risk factor data were retrieved. Eight large ethnicities in Iran, including the Farses, the Kurds, the Turks, the Gilaks, the Arabs, the Lors, the Qashqai, and the Bakhtiari were evaluated for PCAD. Different lifestyle components and having PCAD were compared among the ethnical groups using multivariable modeling. RESULTS: The mean age of the 2863 patients participated was 55.66 ± 7.70 years. The Fars ethnicity with 1654 people, was the most subject in this study. Family history of more than three chronic diseases (1279 (44.7%) was the most common risk factor. The Turk ethnic group had the highest prevalence of ≥ 3 simultaneous lifestyle-related risk factors (24.3%), and the Bakhtiari ethnic group had the highest prevalence of no lifestyle-related risk factors (20.9%). Adjusted models showed that having all three abnormal lifestyle components increased the risk of PCAD (OR = 2.28, 95% CI: 1.04-1.06). The Arabs had the most chance of getting PCAD among other ethnicities (OR = 2.26, 95%CI: 1.40-3.65). While, the Kurds with a healthy lifestyle showed the lowest chance of getting PCAD (OR = 1.96, 95%CI: 1.05-3.67)). CONCLUSIONS: This study found there was heterogeneity in having PACD and a diverse distribution in its well-known traditional lifestyle-related risk factors among major Iranian ethnic groups.

The relationship between nut consumption and premature coronary artery disease in a representative sample of Iranians: Iran-premature coronary artery disease (IPAD) study.

OBJECTIVE: The cardioprotective effects of nuts are well established. However, the positive impacts of nuts in preventing CVD at a younger age, a condition known as premature coronary artery disease (PCAD), is still debated. Therefore, we aim to determine the association between nuts and PCAD occurrence and its severity in different Iranian ethnicities. DESIGN: This case-control study was conducted within the framework of the Iran-premature coronary artery disease (I-PAD) study, an ongoing multi-centric study on Iranian patients of different ethnicities. SETTING: This multi-centric case-control study was conducted in among 3253 persons under the age of 70 years in women and 60 years in men from different ethnicities in Iran. PARTICIPANTS: Information on nut consumption was collected using a validated FFQ. Subjects were selected from among the candidates for angiography. Cases were those whose coronary angiography showed stenosis of more than 75 % in at least one vessel or more than 50 % of the left main artery, while the control group participants had normal angiography results. RESULTS: In the crude model, compared to the first quartile, the highest quartile of nut consumption was significantly associated with a lower risk of PCAD (OR = 0·26, 95 % CI (0·21, 0·32); Pfor trend = 0·001). In the top quartile of nut intake, a substantial decrease in PCAD was observed after controlling for putative confounders (OR = 0·32; 95 % CI (0·24, 0·43); Pfor trend = 0·001). Additionally, a 75 % decrease in the risk of severe PCAD was observed in the participants in the highest quartile of nut intake. CONCLUSION: A significant inverse association was observed between nut intake and the risk and severity of PCAD in the Iranian population. Large-scale clinical trials are required to confirm these findings.

A close-up view of dynamic biomarkers in the setting of COVID-19: Striking focus on cardiovascular system.

Based on the recent reports, cardiovascular events encompass a large portion of the mortality caused by the COVID-19 pandemic, which drawn cardiologists into the management of the admitted ill patients. Given that common laboratory values may provide key insights into the illness caused by the life-threatening SARS-CoV-2 virus, it would be more helpful for screening, clinical management and on-time therapeutic strategies. Commensurate with these issues, this review article aimed to discuss the dynamic changes of the common laboratory parameters during COVID-19 and their association with cardiovascular diseases. Besides, the values that changed in the early stage of the disease were considered and monitored during the recovery process. The time required for returning biomarkers to basal levels was also discussed. Finally, of particular interest, we tended to abridge the latest updates regarding the cardiovascular biomarkers as prognostic and diagnostic criteria to determine the severity of COVID-19.

Sodium selenite and Se-enriched yeast supplementation in atherosclerotic patients: Effects on the expression of pyroptosis-related genes and oxidative stress status.

BACKGROUND AND AIMS: Atherosclerosis as a chronic inflammatory disorder of the arterial wall is the main leading cause of the cardiovascular disease (CVD). Caspase-dependent pyroptosis plays a pivotal role in the pathogenesis of CVD. Selenium (Se) is an important component of the antioxidant defense and plays a crucial role in cardiovascular health. This study aimed to investigate the effects of daily consumption of sodium selenite and Se-enriched yeast on the expression of pyroptosis-related genes, and biomarkers of oxidative stress in patients with atherosclerosis. METHODS AND RESULTS: In this randomized, double-blinded, placebo-controlled clinical trial, 60 patients with atherosclerosis were recruited. Participants received 200 µg/day of sodium selenite, Se-enriched yeast, or placebo for 8 following weeks. The pyroptosis-related genes' mRNA expression in peripheral blood mononuclear cells (PBMCs) was assessed before and after the intervention. Also, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidases (GPX) were measured at baseline and following the intervention. Following sodium selenite and Se-enriched yeast supplementation, the relative expression levels of TLR4, ASC, NLRP3, and NF-κB1 were significantly downregulated (p < 0.05). Furthermore, the changes in GPX were significantly increased after selenite and yeast supplementation (p < 0.05). Also, selenite and yeast consumption caused a statistically significant decrease in the change of MDA level (p < 0.05). CONCLUSION: In summary, these findings showed that Se supplementation may reduce inflammation through down-regulation of some pro-inflammatory genes, improving antioxidant defenses in atherosclerosis patients. Further research is required to come to a definite conclusion of selenium supplementation on the CVD risk. This study was registered on the Iranian Registry of Clinical Trials website (identifier: RCT20110123005670N28; https://www.irct.ir/).

The therapeutic potential of Crocus sativus Linn.: A comprehensive narrative review of clinical trials.

Crocus sativus Linn. (Saffron) is valued worldwide for its potential use in the management of various degenerative disorders, including cardiovascular diseases (CVDs), diabetes, cancer, metabolic syndrome (MetS), neurodegenerative diseases, immune disorders, and sexual dysfunction. Previous reports, based on clinical trials, suggest that crocetin, crocin, picrocrocin, and safranal are the main bioactive components of saffron with antioxidant, anti-inflammatory, and anti-apoptotic effects. In this comprehensive narrative review, we studied the recent clinical trials, investigating the medicinal applications of saffron and/or its components. The present results can provide important insights into the potential of saffron in preventing and treating different disorders, with a special focus on the underlying cellular and molecular mechanisms. However, further high-quality studies are needed to firmly establish the clinical efficacy of saffron in treating some degenerative diseases.

Priority setting in cardiovascular research in Iran using standard indigenous methods.

Background: Determining cardiovascular disease (CVD) research priorities is essential given the high burden of these diseases, limited financial resources, and competing priorities. This study aimed to determine the research priorities in CVD field in Iran using standard indigenous methods. Materials and Methods: An extensive search was done in relevant international and national studies. Then, an indigenous standard multistage approach based on multicriteria decision analysis steps was adapted to local situation and implemented. This process included forming a working group of experts in priority setting methodology, identifying the context and prioritization framework, discussing the methodology with the National Network of CVD Research (NCVDR) members who ultimately determined the priority research topics, weighted topics criteria, ranked topics, and reviewed all determined research priorities for final report. Results: Thirteen cardiovascular research priorities were determined by the NCVDR members. The first five priorities based on their scores include studies in hypertension, prevention and control of ischemic heart disease (IHD) and its risk factors, burden of IHD, Registration of CVDs, and COVID-19 and CVDs. Conclusion: Cardiovascular research priorities were determined using a standard indigenous approach by national experts who are the NCVDR members. These priorities can be used by researchers and health decision makers.

A novel inflammatory signaling pathway in patients with slow coronary flow: NF-κB/IL-1ß/nitric oxide.

PURPOSE: The slow coronary flow (SCF) was identified as delayed opacification of epicardial coronary arteries in the absence of stenotic lesion. Metabolic syndrome (MetS), oxidative stress, and inflammation may be possible known insulting factors for the pathogenesis of SCF. This investigation aimed to assess the relationship between some inflammatory markers, oxidative stress parameters and MetS components with SCF phenomenon. METHODS: A total of 35 patients with SCF and 35 subjects with normal coronary flow (NCF) were included in the study. We assessed some inflammatory markers (IL-1ß, IL-18, TNF-α, and NF-κB mRNA expression in peripheral blood mononuclear cells (PBMCs)). Moreover, blood samples of the participants were tested for total antioxidant capacity (TAC), glutathione peroxidase (GPX) and nitric oxide (NO) levels using enzyme-linked immunosorbent assay (ELISA). Diagnosis of MetS was based on the National Cholesterol Education Program's Adult Treatment Panel III report (ATPIII) criteria, 2005. Diagnostic criteria for coronary flow rates of all subjects were documented by thrombolysis in myocardial infarction (TIMI) frame count method. RESULTS: SCF patients had significantly higher prevalence of MetS (46%, p = 0.048).We found that the level of TAC was significantly higher in the NCF group (p = 0.006). Furthermore, the NO concentration was significantly lower in SCF groups (p = 0.001). A significant incremental difference was detected in IL-1ß (fold change 2.82 ± 0.31, p < 0.05) and NF-κB (fold change 4.62 ± 0.32, p < 0.05) mRNA expression in the SCF group when compared with its level in the NCF group. Furthermore, according to logistic regression analysis, there were significant associations between IL-1ß, NF-κB expression levels and the incidence of SCF (p < 0.05). CONCLUSION: Based on the findings of this study, the pathogenesis of the SCF phenomenon may be closely associated with metabolic syndrome and inflammation. The NF-κB/IL-1ß/nitric oxide & MetS signaling pathway might be considered as potential therapeutic targets in the management of SCF patients but further researches is required to guarantee these findings.

Management of ST-segment-elevation myocardial infarction during the coronavirus disease 2019 (COVID-19) outbreak: Iranian"247" National Committee's position paper on primary percutaneous coronary intervention.

World Health Organization has designated coronavirus disease 2019 (COVID-19) as a pandemic. During the past several weeks, a considerable burden has been imposed on the Iranian's healthcare system. The present document reviewed the latest evidence and expert opinion regarding the management of ST-segment-elevation myocardial infarction during the outbreak of COVID-19 and outlines a practical algorithm for it.

The association between T wave inversion in leads with ST-elevation and patency of the infarct-related artery.

BACKGROUND: Up to over half of the patients with ST-segment elevation myocardial infarction (STEMI) are reported to undergo spontaneous reperfusion without therapeutic interventions. Our objective was to evaluate the applicability of T wave inversion in electrocardiography (ECG) of patients with STEMI as an indicator of early spontaneous reperfusion. METHODS: In this prospective study, patients with STEMI admitted to a tertiary referral hospital were studied over a 3-year period. ECG was obtained at the time of admission and patients underwent a PPCI. The association between early T wave inversion and patency of the infarct-related artery was investigated in both anterior and non-anterior STEMI. RESULTS: Overall, 1025 patients were included in the study. Anterior STEMI was seen in 592 patients (57.7%) and non-anterior STEMI in 433 patients (42.2%). Among those with anterior STEMI, 62 patients (10.4%) had inverted T and 530 (89.6%) had positive T waves. In patients with anterior STEMI and inverted T waves, a significantly higher TIMI flow was detected (p value = 0.001); however, this relationship was not seen in non-anterior STEMI. CONCLUSION: In on-admission ECG of patients with anterior STEMI, concomitant inverted T wave in leads with ST elevation could be a proper marker of spontaneous reperfusion of infarct related artery.

Clinical utility of aVR lead T-wave in electrocardiogram of patients with ST-elevation myocardial infarction.

BACKGROUND: aVR lead is often neglected in routine clinical practice largely because of its undefined clinical utility specifications. Nevertheless, positive T-wave in aVR lead has been reported to be associated with poor clinical outcomes in some cardiovascular diseases. This study aimed to prospectively investigate the prognostic value and clinical utility of T-wave amplitude in aVR lead in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: A total of 340 STEMI patients admitted to a tertiary heart center were consecutively included. Patients were categorized into four strata, based on T wave amplitude in aVR lead in their admission ECG (i.e. < - 2, - 1 to - 2, - 1 to 0, and ≥ 0 mV). Patients' clinical outcomes were also recorded and statistically analyzed. RESULTS: In-hospital mortality, re-hospitalization, and six-month-mortality significantly varied among four T wave strata and were higher in patients with a T wave amplitude of ≥ 0 mV (p 0.001-0.002). The groups of patients with higher T wave amplitude in aVR, had progressively increased relative risk (RR) of in-hospital mortality (RRs ≤ 0.01, 0.07, 1.00, 2.30 in four T wave strata, respectively). T wave amplitude in the cutoff point of - 1 mV exhibited a sensitivity and specificity of 95.83 (95% CI 78.88-99.89) and 49.68 (95% CI 44.04-55.33). CONCLUSION: Our study demonstrated a significant association of positive T wave in aVR lead and adverse clinical outcomes in STEMI patients. Nevertheless, the clinical utility of T-wave amplitude at aVR lead is limited by its low discriminative potential toward prognosis of STEMI.

Protective effects of BiP inducer X (BIX) against diabetic cardiomyopathy in rats.

Diabetic cardiomyopathy (DC) is associated with impaired endoplasmic reticulum (ER) function, development of ER stress, and induction of cardiac cell apoptosis. Preventive effects of BiP inducer X (BIX) were investigated against DC characteristic changes in a type 2 diabetes rat model. To establish diabetes, a high-fat diet and a single dose of streptozotocin were administered. Then, animals were assigned into the following groups: control, BIX, diabetic animals monitored for one, two, and three weeks. Diabetic rats were treated with BIX for one, two, and three weeks. Expressions of various ER stress and apoptotic markers were assessed by immunoblotting method. CHOP gene expression was assessed by Real-time PCR. Tissue expression of BiP was evaluated by immunohistochemistry method. Hematoxylin and eosin and Masson's trichrome staining were performed to assess histological changes in the left ventricle. Cardiac cell apoptosis was examined using TUNEL assay. BIX administration suppressed the activation of the ER stress markers and cleavage of procaspase-3 in the diabetic rats. Likewise, tissue expression of BiP protein was increased, while CHOP mRNA levels were decreased. These results were accompanied by reducing cardiac fibrosis and myocardial cell apoptosis suggesting protective effects of BIX against the development of DC by decreasing cardiomyocyte apoptosis and fibrosis.

Effects of oral butyrate and inulin supplementation on inflammation-induced pyroptosis pathway in type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

PURPOSE: Pyroptosis, a form of inflammatory programmed cell death, is activated in diabetic patients. This study was conducted to investigate the effects of daily consumption of sodium butyrate (NaBut) and high-performance (HP) inulin supplementation, individually or in combination, on the expression of pyroptosis-related genes, microRNA (miR) 146a-5p, miR-9-5p and biomarkers of oxidative stress in patients with type 2 diabetes (T2DM). METHODS: In this study, we conducted a randomized, double-blinded, placebo-controlled clinical involving sixty patients with type 2 diabetes. Participants received 600 mg/d of NaBut (group A), 10 g/d of HP inulin (group B), 600 mg/d of NaBut + 10 g/d of HP inulin (group C) or placebo (group D) for 45 consecutive days. We assessed the pyroptosis-related genes mRNA expression in peripheral blood mononuclear cells (PBMCs), as well as the plasmatic levels of miR-146a and miR-9 before and after the intervention. Moreover, blood samples of the patients at baseline and following the intervention were tested for total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase levels using enzyme-linked immunosorbent assay (ELISA). This study was registered on the Iranian Registry of Clinical Trials website (identifier: IRCT201605262017N29; https://www.irct.ir/). RESULTS: Following butyrate supplementation, the relative expression levels of TLR2/4, NF-κB1, Caspase-1, NLRP3, IL-1ß & IL-18 were significantly downregulated (p < 0.05). Furthermore, butyrate and concomitant use of butyrate and inulin caused a significant increase in the fold change of miR-146a and miR-9 compared with the placebo group (p < 0.05). Interestingly, the changes in total antioxidant capacity (p = 0.047) and superoxide dismutase (p = 0.006) were significantly increased after butyrate and concomitant use of butyrate and inulin supplement, respectively. CONCLUSION: In summary, the change in expression level of miR-146a-5p and miR-9-5p due to butyrate supplementation may have a pivotal role in alleviating of diabetes via inhibiting pyroptosis by targeting TLR2 and NF-κB1. These microRNAs might be considered as potential therapeutic targets in the treatment of type 2 diabetes but further researches is required to prove the link.

SARS-CoV-2 infection in patients with diabetes mellitus and hypertension: a systematic review.

After the emergence of the novel 2019 coronavirus disease in P. R. China, this highly contagious disease has been currently spread out to almost all countries, worldwide. Novel 2019 coronavirus disease, Middle East respiratory syndrome, and severe acute respiratory syndrome are reported to cause a higher risk for severe infections in patients with chronic comorbidities, such as hypertension and diabetes. These severe infections can contribute to higher rates of morbidity and mortality in these patients. In the present review, we discussed the role and underlying mechanisms of the two most common chronic diseases, type-2 diabetes mellitus and hypertension, in clinical manifestations and disease severity of novel 2019 coronavirus disease, Middle East respiratory syndrome and severe acute respiratory syndrome, with the hope to provide evidence for better decision-making in the treatment of this vulnerable population.

Sulforaphane modulates CX3CL1/CX3CR1 axis and inflammation in palmitic acid-induced cell injury in C2C12 skeletal muscle cells.

Studies have shown that sulforaphane (SFN) has potent anti-inflammatory and free radical scavenging effects on obesity and associated disorder such as diabetes, polycystic ovary syndrome, and metabolic syndrome. fractalkine (CX3CL1) and its receptor, CX3CR1, play an important role in muscle metabolism by improving insulin-sensitizing effects. Here, in this study we examined the SFN effect on CX3CL1 and its receptor, CX3CR1, in C2C12 myotubes in palmitic acid (PA)-induced oxidative stress and inflammation. The results showed that PA (750 µM) evoked lipotoxicity as a reduction in cell viability, increased IL-6 and TNF-α expression, and enhanced reactive oxygen species (ROS). However, SFN pretreatment attenuated the levels of, IL-6 and TNF-α in C2C12 myotubes exposure to PA. Moreover, SFN pretreatment up-regulated nuclear factor erythroid related factor 2 (Nrf2) /heme oxygenase-1(HO-1) pathway protein in C2C12 cells as indicated by a decrease in ROS levels. Interestingly, PA also caused an increase in CX3CL1 and CX3CR1 expression that SFN abrogated it. We also found the protective effect of SFN agonist PA-induced lipotoxicity with promotes in UCP3 gene expression in C2C12 cells. Collectively, these findings suggest that SFN hampers the PA-induced inflammation in C2C12 cells by modulation of the Nrf2/HO-1 pathway and CX3CL1/CX3CR1 axis and may propose a new therapeutic approach to protect against obesity-associated disorders in skeletal muscle cells.

Epidemiology of multimorbidity in Iran: An investigation of a large pharmacy claims database.

PURPOSE: Multimorbidity (MM) (presence of more than one chronic condition within a same patient) imposes a heavy burden on patients and health care systems. In contrast to high-income countries, the epidemiology of this phenomenon is unclear in low- and middle-income countries, particularly among Iranian population. METHODS: This was a retrospective cohort study using Iranian Health Insurance Organization claims database. A framework was developed for identifying a set of 18 chronic conditions from the pharmacy claims data in Iran. All 2013 outpatient utilizers (aged 18 years or older) were included. Data were analyzed according to number of chronic conditions, gender, and age. The association between MM and utilizations of health services was examined for 2013 to 2016. RESULTS: In total, 481 733 people were included. Cardiovascular diseases (including hypertension) (19.1%), depression/anxiety/sleep disorders (13.7%), and acid-related disorders (10.3%) were the three most prevalent conditions. MM was present in 21.1%. Although prevalence of MM is higher in older age groups and was present in 40% of individuals aged 65 and older, the absolute number of multimorbid patients was higher in those younger than 65 years (66 271 vs 35 386). MM was more prevalent among women (22.1%) compared with men (19.5). After multivariate adjustment for age group and sex, each additional chronic condition was associated with an increase of 2.23 physician visits, 2.86 drugs dispensed, 2.32 laboratory tests, and 1.6 medical imaging. CONCLUSIONS: Our findings challenge the current single-disease-based assumption implicit in Iranian health care system. To take account of MM, complementary strategies should be designed and implement in health care system.