Coronavirus Disease 2019 Pandemic and Reduced Surgical Site Infection After Cardiac Surgery: A Potential Blessing in Disguise.

Background: The coronavirus disease 2019 (COVID-19) pandemic has brought about drastic hygienic measures, one upside of which might be the mitigated occurrence of surgical site infection (SSI). This study investigated the association of the pandemic with SSI occurrence after cardiac surgeries. Patients and Methods: From 2014 to 2022, patients undergoing cardiac surgery were included and categorized into pre-pandemic and during-pandemic groups. Surgical site infections were classified into harvest-site, superficial sternal, and complex sternal infection. Multiple logistic regression and inverse probability weighting assessed the association of the pandemic with SSI. Results: Among a total of 26,143 patients, 793 SSIs occurred. The during-pandemic patients were younger (61.87 ± 10.58 vs. 65.64 ± 11.82) with a higher male proportion (70.1% vs. 67.4%) and a higher prevalence of all studied comorbidities/risk factors (expect cigarette smoking). Total SSI rate decreased substantially from 3.3% before COVID-19 to 1.8% afterward (p < 0.001). Inverse probability weights analyses evinced an independent association of the pandemic with a reduced risk of total (adjusted odds ratio [OR]; 0.59; 95% confidence interval [CI], 0.45-0.78), harvest-site (adjusted OR, 0.36; 95% CI, 0.19-0.70), and superficial sternal infection (adjusted OR, 0.60; 95% CI, 0.43-0.81). No significant association was observed with complex sternal site infection (adjusted OR, 1.05; 95% CI, 0.55-2.01). Multivariable regression recapitulated these findings. Conclusions: The COVID-19 pandemic independently pertained to more than a 40% reduction in SSI occurrence, particularly affecting harvest-site and superficial sternal infections. However, there remains the possibility of the implications of other known and unknown confounders on the observed association. To some extent, the decrease in SSIs after the pandemic can be justified by reinforced hygienic precautions, emphasizing the necessity of extending the adherence to these measurements into the post-COVID-19 era to maintain the status quo.

Efficacy of curcumin for amelioration of radiotherapy-induced oral mucositis: a preliminary randomized controlled clinical trial.

BACKGROUND: Oral mucositis (OM) is one of the main problems in almost all patients undergoing head and neck radiotherapy (RT). Owning to the antioxidant and anti-inflammatory properties of curcumin, the effect of both oral and topical formulations of curcumin was assessed on radiation-induced OM (ROM) in this study. METHODS: The safety and efficacy of curcumin mouthwash 0.1% (w/v) and curcumin-nanocapsule were evaluated in ameliorating severity and pain/burning associated with OM during RT. The current randomized, placebo-controlled trial was conducted on 37 patients with head and neck cancers. Patients with grades 1 to 3 of ROM were randomized to receive one of the three interventions: curcumin mouthwash (0.1% w/v); Sinacurcumin soft gel containing 40 mg curcuminoids as nano-micelles (SinaCurcumin®40); or placebo mouthwash with a similar transparent appearance to curcumin mouthwash for 1 min three times daily during RT. Study evaluations were conducted at baseline and weekly thereafter for up to 3 weeks using the Numeric rating scale (NRS) and world health organization (WHO) scale. RESULTS: Among the 45 patients randomized, 37 (mean (SD) age of 53.36 (15.99) years; 14 [37.8%] women) completed the treatment according to the protocol. Patients treated with either oral or topical curcumin showed a significantly reduced severity and burning related to OM during the first 3 weeks after administration (P-Value < 0.001) as compared with the placebo. At study termination, more than 33% of subjects utilizing curcumin mouthwash and 15% of patients utilizing curcumin-nanocapsule remained ulcer free while all of the placebo-receiving subjects had OM. The reduction of NRS and WHO scale between curcumin groups was comparable without significant differences. CONCLUSION: Both curcumin mouthwash and nanocapsule were effective, safe, and well-tolerated in the treatment of radiation-induced OM. Higher doses of curcumin and larger sample sizes can be used for further investigation in future studies. TRIAL REGISTRATION: https://irct.ir/ IRCT20190810044500N17 (13/08/2021).

Opium as a risk factor for early-onset coronary artery disease: Results from the Milano-Iran (MIran) study.

The spreading of opium use poses new health related concerns. In some areas of Asia its use is believed to protect from cardiovascular disorders, such as coronary artery disease (CAD). However, whether opium use has an association with CAD is unclear. We aimed to investigate the association between non-medical opium use and CAD. We set up a case-control analysis, i.e., the Milano-Iran (MIran) study by enrolling consecutive young patients who underwent a coronary angiography at the Tehran Heart Center, between 2004 and 2011. Incident cases with CAD were contrasted with controls for opium use. Relative risks were calculated in terms of odds ratios (ORs) by logistic regression models adjusted for age, sex, cigarette smoking, body mass index, hypertension, hyperlipidaemia, and diabetes. Interaction analyses were performed between opium and major cardiovascular risk factors. 1011 patients with CAD (mean age 43.6 years) and 2002 controls (mean age 54.3 years) were included in the study. Habitual opium users had a 3.8-fold increased risk of CAD (95%CI 2.4-6.2) compared with non-users. The association was strongest for men, with a fully adjusted OR of 5.5 (95%CI 3.0-9.9). No interaction was observed for the combination of opium addiction and hypertension, or diabetes, but an excess in risk was found in opium users with hyperlipidaemia (OR 16.8, 95%CI 8.9-31.7, expected OR 12.2), suggesting supra-additive interaction. In conclusion, despite common beliefs, we showed that non-medical opium use is associated with an increased risk of CAD, even when other cardiovascular risk factors are taken into account.

Patient education information material assessment criteria: A scoping review.

BACKGROUND: Patient education information material (PEIM) is an essential component of patient education programs in increasing patients' ability to cope with their diseases. Therefore, it is essential to consider the criteria that will be used to prepare and evaluate these resources. OBJECTIVE: This paper aims to identify these criteria and recognize the tools or methods used to evaluate them. METHODS: National and international databases and indexing banks, including PubMed, Scopus, Web of Science, ProQuest, the Cochrane Library, Magiran, SID and ISC, were searched for this review. Original or review articles, theses, short surveys, and conference papers published between January 1990 and June 2022 were included. RESULTS: Overall, 4688 documents were retrieved, of which 298 documents met the inclusion criteria. The criteria were grouped into 24 overarching criteria. The most frequently used criteria were readability, quality, suitability, comprehensibility and understandability. CONCLUSION: This review has provided empirical evidence to identify criteria, tools, techniques or methods for developing or evaluating a PEIM. The authors suggest that developing a comprehensive tool based on these findings is critical for evaluating the overall efficiency of PEIM using effective criteria.

Orphan GPR26 Counteracts Early Phases of Hyperglycemia-Mediated Monocyte Activation and Is Suppressed in Diabetic Patients.

Diabetes is the ninth leading cause of death, with an estimated 1.5 million deaths worldwide. Type 2 diabetes (T2D) results from the body's ineffective use of insulin and is largely the result of excess body weight and physical inactivity. T2D increases the risk of cardiovascular diseases, retinopathy, and kidney failure by two-to three-fold. Hyperglycemia, as a hallmark of diabetes, acts as a potent stimulator of inflammatory condition by activating endothelial cells and by dysregulating monocyte activation. G-protein couple receptors (GPCRs) can both exacerbate and promote inflammatory resolution. Genome-wide association studies (GWAS) indicate that GPCRs are differentially regulated in inflammatory and vessel cells from diabetic patients. However, most of these GPCRs are orphan receptors, for which the mechanism of action in diabetes is unknown. Our data indicated that orphan GPCR26 is downregulated in the PBMC isolated from T2D patients. In contrast, GPR26 was initially upregulated in human monocytes and PBMC treated with high glucose (HG) levels and then decreased upon chronic and prolonged HG exposure. GPR26 levels were decreased in T2D patients treated with insulin compared to non-insulin treated patients. Moreover, GPR26 inversely correlated with the BMI and the HbA1c of diabetic compared to non-diabetic patients. Knockdown of GPR26 enhanced monocyte ROS production, MAPK signaling, pro-inflammatory activation, monocyte adhesion to ECs, and enhanced the activity of Caspase 3, a pro-apoptotic molecule. The same mechanisms were activated by HG and exacerbated when GPR26 was knocked down. Hence, our data indicated that GPR26 is initially activated to protect monocytes from HG and is inhibited under chronic hyperglycemic conditions.

Patients' perspectives on the quality of online patient education materials: A qualitative study.

BACKGROUND: Access to online patient education information can lead to more effective self-care and disease management. However, the large amount of online information provided through unknown or unreliable sources can challenge patients to trust and use this information. This study was designed to examine the opinions of Iranian gastrointestinal patients about the quality of online information used. MATERIALS AND METHODS: A qualitative study was conducted using thematic analysis. Data were gathered via a semi-structured interview with 29 gastrointestinal patients, and data analysis was performed by qualitative content analysis using open coding with MAXQDA 2018 software. RESULTS: Based on the study, 22 codes were extracted in nine subcategories named as: "Emphasis on the identity of providers," "Nature of online information," "Distrust on online information," "Poor quality of information," "Giving misinformation," "False impact," "Improve communication," "Positive effect on the patient," "Better Diagnosis." CONCLUSIONS: In the current situation, Iranian patients are not confident enough about the quality of available online information. They believe that the use of current poor-quality information has negative consequences. However, they tend to use online patient education materials are produced in Persian by reputable scientific authorities. Using online information can increase patients' knowledge and lead to better communication with medical staff and other similar patients. They can use this information for self-care with more confidence, and such an approach can also have significant benefits for the national health system.

Marketing methods for electronic resources in medical libraries: a study on the application of the analytical hierarchy process.

Objective: Paired with the high cost of providing access to electronic resources in medical libraries, the inefficient use of these resources highlights the need for more efforts to promote these resources than ever before. In this study, electronic resource marketing methods were prioritized and the best strategies were determined using the analytical hierarchy process (AHP). Methods: Using an analytical survey of officials of medical libraries, the most common methods for marketing electronic resources in libraries were determined and divided into categories of strategies. Five important criteria for marketing strategies were also selected. Using the analytical hierarchy process, pairwise comparisons were performed between the alternatives (i.e., strategies), which were evaluated against the selected criteria. Data analysis was performed using Expert Choice 11 software. Results: A total of 44 electronic resource marketing methods were identified and categorized into 4 strategies. On average, 43.9% of these methods were used by the surveyed libraries. The analytical hierarchy process showed that simplicity was the most important criterion and that communication networks were the best electronic resource marketing strategy. Home/off-campus access, group training, library search stations, and marketing by individual librarians were the most preferred methods of marketing electronic resources. Conclusion: With the availability of a variety of different methods for marketing electronic resources, medical libraries must select strategies based on important criteria depending on the characteristics of the library, librarians, and users. Thus, the analytical hierarchy process can be an effective and practical solution to decision-making by mathematically prioritizing the selection of the best strategies from a set of alternatives based on differentially weighted criteria.

Isolation of Novel Probiotic Lactobacillus and Enterococcus Strains From Human Salivary and Fecal Sources.

Probiotics are non-pathogenic microorganisms that can interact with the gastrointestinal microbiota. They have numerous beneficial health effects that include enhancement of the host immune response, antiallergic, antimicrobial, anti-cancer, and anti-inflammatory properties. Probiotics are capable of restoring the impaired microbiome of a dysbiotic gut. They can be isolated from different environments. However, it is frequently suggested that probiotics for human use should come from human sources. The objective of this study was to isolate and characterize novel probiotic strains from the saliva and feces of healthy human individuals. To meet the criteria for probiotic attributes, the isolates were subjected to numerous standard morphological and biochemical tests. These tests included Gram staining, catalase tests, antibiotic susceptibility testing, hemolytic and antagonistic evaluation, tolerance tests involving temperature, NaCl levels, pH and bile salts, adherence ability assays, and genotypic characterization involving 16S rRNA gene sequencing. From 26 saliva and 11 stool samples, 185 microbial strains were isolated. Based on morphological and biochemical characteristics, 14 potential probiotic candidates were selected and identified genotypically. The new strains belonged to Lactobacillus fermentum, Enterococcus faecium, and Enterococcus hire. The selected strains were non-hemolytic, showed high tolerance to low pH and bile salts, and strong adherence abilities. Furthermore, the strains displayed a wide range of antimicrobial activities, particularly against antibiotic-resistant pathogens such as methicillin resistant Staphylococcus aureus (MRSA). Moreover, five of the selected isolates demonstrated antiproliferative features against human colon cancer cell line (Caco-2). The results of this investigation confirm the diversity of microbial populations in the human gut and saliva, and since these strains are of human origin, they will highly likely display maximal activities in food and drugs set for human use. Hence, the new strains of this study require additional in vivo experiments to assess their health-promoting effects.

Ratio of Serum Aspartate to Alanine Aminotransferase as a Marker of Isolated Coronary Artery Ectasia and its Severity.

BACKGROUND: Several studies have reported an association between elevated liver enzymes and increased risks for developing inflammatory diseases. The aim of our study was to examine how serum liver transaminases, as inexpensive and routinely measured markers, and the De Ritis ratio are associated with the presence of coronary artery ectasia (CAE) and its severity. METHODS: Participants were recruited from patients admitted to Tehran Heart Center for diagnostic coronary angiography due to suspected myocardial ischaemia. These participants also underwent concurrent laboratory routine biochemical and liver enzyme tests. RESULTS: A total of 104 participants were included; 59 had CAE and 45 were controls without coronary artery disease (CAD). The CAE group was split into a further two subgroups: those with isolated CAE (n=27) and those with CAD and coexisting CAE (n=32). In the adjusted multivariate analysis, a lower ratio of aspartate aminotransferase to ALT (AST/ALT) was, uniquely among the variables, a statistically significant marker for isolated CAE. In the CAD + CAE group, the AST/ALT ratio was not significant after adjustments for the confounding factors. The multivariate linear regression for the Markis score showed that the AST/ALT ratio was inversely associated with the severity of CAE. CONCLUSIONS: We conclude that the AST/ALT ratio and, to some extent, ALT independently of other inflammatory factors, can be associated with the presence and severity of isolated CAE.

Amikacin resistance due to the aphA6 gene in multi-antibiotic resistant Acinetobacter baumannii isolates belonging to global clone 1 from Iran.

BACKGROUND: TnaphA6-carrying repAci6 plasmids have been detected in Acinetobacter baumannii isolates belonging to global clones, GC1 and GC2, worldwide. Here, we examined whether RepAci6 plasmids family play a role in the dissemination of the aphA6 in GC1 A. baumannii isolates from Iran. RESULTS: We found that 22 isolates carried the repAci6 gene, suggesting that they contain a RepAci6 plasmid family. Using the primers linking the aphA6 gene to the backbone of repAci6 plasmid, it was revealed that 16 isolates from different hospitals harbored TnaphA6 on a repAci6 plasmid. CONCLUSIONS: This study provides evidence for the dissemination of TnaphA6 on the plasmids encoding RepAci6 in Iranian A. baumannii isolates. Furthermore, it seems that TnaphA6 might be acquired by distinct plasmids separately as it was found to be located on the variants of repAci6 plasmids.

Integrin Beta-3 Gene Polymorphism and Risk for Myocardial Infarction in Premature Coronary Disease.

BACKGROUND: Contradictory results have been obtained regarding the role of integrin, beta 3 (ITGB3) gene polymorphisms in occurrence of myocardial infarction (MI). OBJECTIVES: We aimed to assess the association between 1565C/T polymorphism of ITGB3 gene and increased risk for acute MI in patients with premature coronary artery disease (CAD). MATERIAL AND METHODS: Our study included 1000 premature CAD patients that classified into two groups with history of MI (n = 461) and without of MI (n = 539). The polymorphism variants in 10% of samples were determined by PCR-RFLP technique and genotyping of the polymorphism in all subjects was conducted by High Resolution Melting method. Given the two conditions of patients residing in Tehran and also faced with their first episode of MI, 640 out of 1000 study samples that had been previously followed-up were assessed in a retrospective cohort phase regarding long-term major adverse cardiac events (MACE). RESULTS: There was no significant difference in the frequency of 1565C/T polymorphism between the MI and non-MI groups. The frequency of wild genotype was 69.2% and 72.2%, the frequency of homozygous genotype was 21.3% and 18.4%, and the frequency of mutant genotype was 9.5% and 9.5%, respectively (P = 0.505). No significant difference was also found in total-MACE free survival rate between the patients with different genotypes of 1565C/T polymorphism in both MI and non-MI group. CONCLUSIONS: The carriage of the 1565C/T polymorphism of ITGB3 gene seems unlikely to be a significant risk factor for the development of MI in Iranian patients with premature CAD.

Characterization of Clostridioides difficile isolates recovered from hospitalized patients and the hospitals environment and air: A multicenter study.

In healthcare settings, contamination of environment with toxigenic and hypervirulent Clostridioides difficile strains is a serious concern. Here, we assessed whether patients with C. difficile have a role to play in the dissemination of C. difficile in our settings or other sources are implicated in its circulation. A total of 700 fecal specimens and 1435 environmental samples from surfaces, equipment and air of rooms occupied by patients suspected of C. difficile infection were taken from 4 tertiary hospitals in Tehran, Iran between April 2016 and August 2017. Antibiotic susceptibility testing and detection of resistance genes were performed for the environmental isolates. The clinical and environmental isolates of C. difficile were subjected to Pulsed Field Gel Electrophoresis (PFGE) analysis. Forty three (6.14%) and 2 (0.13%) isolates of C. difficile were recovered from the clinical and environmental samples, respectively. In the clinical settings, 2 patients were suspected of recurrent C. difficile infection. Thirty distinct pulsotypes were found among the C. difficile isolates including 28 singletons and 2 common types. One of the two environmental isolates was isolated from floor in the Medical ward, of pulsotype/ribotype/toxinotype PT10/New ribotype/toxinotype V, harbored cdtA/B and tcdC-A, and resistant to ciprofloxacin. The other one was isolated from air of a room in ICU, assigned to PT11/RT001/toxinotype 0, belonged to tcdC-sc3 genotypes and resistant to metronidazole. The environmental isolates did not generate amplicons in PCR assays targeting vanA and nim genes. This study provided evidence for dissemination of genetically diverse strains of C. difficile in hospitalized patients, presence of C. difficile in hospital air, existence of binary toxin positive/antibiotic-resistant isolate on the floor and intra-hospital dissemination of this pathogen.

ASGR1 but not FOXM1 expression decreases in the peripheral blood mononuclear cells of diabetic atherosclerotic patients.

BACKGROUND: The ASGR1 was recently shown to play a key role in the development of coronary artery disease (CAD), but its exact mechanism of action in the CAD pathogenesis is not yet known. This study evaluates the possible association between the expression level of ASGR1 and its downstream transcription factor FOXM1 in the inflammatory cells of peripheral blood (PBMC) and the pathogenesis of CAD in the Diabetic condition. METHODS: Blood samples were taken from the candidates who had visited the Tehran Heart Center and had underwent diagnostic tests with respect to diabetes and CAD. The peripheral blood cells were harvested, RNA was extracted, and cDNA was synthesized. The qRT-PCR was performed on 79 cDNA samples taken from 49 CAD+ patients and 30 CAD- patients. RESULTS: In this study, we observed a significant decrease of ASGR1 expression in the PBMC of CAD+ patients compared to the CAD- patients. We did not identify any considerable differences in the expression of FOXM1 in patients' subgroups with respect to the diabetes and CAD. CONCLUSION: The results of our study determine the association of ASGR1 expression and CAD pathogenesis. However, we do not know whether this result is the cause or the effect of CAD.

Nutrient sensing pathway genes expression dysregulated in patients with T2DM and coronary artery disease.

AIMS: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder and its prevalence is rapidly increasing worldwide. Patients with T2DM suffer from an increased risk of vascular complications. Of these, the development of coronary artery disease (CAD) causes the most mortality in patients with T2DM, however, its underlying molecular mechanisms are not fully understood. Nutrient sensing pathways which play a key role in sensing cellular energy and nutrients levels are reported to dysregulated in metabolic disease like T2DM. The aim of this study was to investigate the expression levels of nutrient sensing genes including SIRT1, PRKAB1, PRKAB2 and mTOR in CAD+ versus CAD-T2DM patients. METHODS: Sixty-five people with T2DM who referred to Tehran heart center were participated in this study. Based on coronary angiography data these individuals were classified into two groups: CAD+ T2DM (n = 34) and CAD-T2DM (n = 31). Peripheral blood mononuclear cells were isolated from these patients and the expression levels of genes were evaluated by RT-qPCR. RESULTS: Significant down-regulations of the SIRT1 (3.1-fold, p = 0.0013) and PRKAB1 (3.5-fold, p = 0.0001) mRNA expression were observed in CAD+ T2DM group in comparison with CAD-T2DM patients. Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve was 0.8529 (p = 0.0001) and 0.7078 (p = 0.004) for PRKAB1 and SIRT1 respectively. CONCLUSION: Our results suggest that the dysregulation of genes involved in nutrient sensing pathway may be associated with the pathogenesis of CAD in patients with T2DM. Furthermore, the expression levels of these genes could be consider as potential biomarkers.

Visfatin as marker of isolated coronary artery ectasia and its severity.

Several studies have demonstrated the relationship between visfatin and increased risk of diseases caused by inflammation, however, the relationship between visfatin and coronary artery ectasia (CAE) is still unknown. The aim of our study is to investigate the association between serum visfatin with presence of coronary ectasia and its severity. We enrolled 85 individuals including 35 CAE patients (mean age: 58.40 ±â€¯9.82 years) and 50 control persons (mean age: 53.24 ±â€¯8.81 years). These participants underwent some biochemical tests including visfatin, fasting blood glucose and lipid profiles. In univariate analysis, the serum level of visfatin was significantly associated with ectasia in all patients with CAE and CAD coexisting with CAE groups, but a trend toward significance in isolated CAE group. In multivariate analysis, visfatin showed independently significant association with presence of ectasia in all patients with ectasia and in CAD coexisting with ectasia groups, but not significant in isolated CAE group. Visfatin was also independently associated with severity of ectasia according to MARKIS classification. We conclude that visfatin independently can be the useful predictor for the presence and severity of coronary ectasia.

Catheter-related candidemia and identification of causative Candida species in patients with cardiovascular disorder.

BACKGROUND AND PURPOSE: Catheter-related blood circulation infection is the most dangerous and serious side-effects of vascular catheters, which leads to the enhancement of the costs, mortality, and hospital stay duration, especially in the Intensive Care Unit. Regarding this, the aim of the current study was to identify the prevalence of catheter-induced candidemia in the Tehran Heart Center, a heart hospital in Tehran, Iran. MATERIALS AND METHODS: This study was conducted on patients admitted to Tehran Heart Center for a minimum of 7 days during 18 months. To detect the fungal elements, blood culture and catheter culture were performed in the patients receiving central or peripheral venous catheter. Then, the polymerase chain reaction (PCR) was applied to determine the possible diagnosis. RESULTS: The investigation of 223 samples led to the identification of a total of 15 (6.7%) yeast isolates obtained from 9 (60%), 4 (26.6 %), and 2 (13.4%) catheter, blood, and skin (of the catheter insertion areas) cultures, respectively. Out of nine Candida isolates obtained from the catheter samples, 1 (11.1%), 1 (11.1%), 2 (22.2%), and 5 (55.6%) cases were identified as C. tropicalis, C. membranifaciens, C. glabrata, and C. albicans, respectively, using the internal transcribed spacer region sequencing. Furthermore, the four yeasts isolated from the blood culture included C. tropicalis, C. carpophila, C. membranifaciens, and Cryptococcus albidus. Additionally, one case of C. glabrata and one case of C. albicans were isolated from the skin culture of the catheter insertion areas in patients with positive catheter culture. We reported two cases of catheter-related candidemia caused by C. membranifaciens and C. tropicalis on the basis of the genetic similarity of the species isolated from the blood and catheter. These cases were treated successfully with intravenous fluconazole and catheter removal. CONCLUSION: There is some evidence indicating the growing prevalence of non-albicans Candida infections. Many risk factors, including prior antibiotic therapy, use of a central venous catheter, surgery, and parenteral nutrition, are considered to be associated with candidemia in hospitalized heart failure patients. The identification of the route of infection in candidemia is difficult. In the current study, the positive blood and catheter cultures for Candida isolates and the similarity of the ITS region of ribosomal DNA sequence of Candida isolated from two patients confirmed the diagnosis of intravenous catheter-related candidemia.

Non-invasive diagnosis of early-onset coronary artery disease based on cell type-specific gene expression analyses.

A non-invasive diagnostic method based on biomarkers related to endothelial and mononuclear cell dysfunction can provide opportunities for screening and early treatment of atherosclerosis. This study aimed to construct a risk scoring model based on clinical risk factors and molecular markers (lncRNA SENCR and CD markers) at single-cell level for early diagnosis of early-onset coronary artery disease (EOCAD). A single-cell expression analysis was performed on peripheral blood mononuclear cell subsets derived from 253 young individuals (Males ≤45 and Females ≤55 years old) in two training and validation sets using FISH-Flow assay. Concurrent quantifications of intracellular SENCR and surface/intracellular CD31, CD146, CD45 and CD14 in mononuclear cell fractions (Circulating endothelial cell, Monocyte and Lymphocyte) showed a significant reduction in intra-CEC SENCR, increased in intra-monocyte SENCR and also increased surface/intracellular CD146 and CD14 in patients with EOCAD as compared to the controls. Altered biomarkers were combined together as a risk scoring model. The ROC curve analysis on the combination model showed a high-performance in the distinction of our patients with EOCAD and healthy controls. A positive correlation between SENCR and CD14 in monocytes led us to find a binding site corresponding to SENCR and CD14 mRNA interaction. Our study suggested that combination of our molecular and clinical factors can be benefit to early diagnosis of EOCAD. CECs in peripheral blood as the novel approach could reflect molecular alteration in vascular endothelium. Bimodal variation in intracellular SENCR at the single-cell transcriptional level suggests that SENCR has cell-specific function(s) in its epigenetic gene regulation mechanisms.

The role of lnc-DC long non-coding RNA and SOCS1 in the regulation of STAT3 in coronary artery disease and type 2 diabetes mellitus.

AIMS: Coronary artery disease (CAD) can be classified as an inflammatory disease, which affected by type 2 diabetes mellitus (T2DM). Elevated levels of many inflammatory molecules were found in the serum of patients with CAD. STAT3 molecule as a transcription factor plays an important role in the cytokines expression. Here, we examined the expression levels of STAT3 and its important regulatory genes lnc-DC and SOCS1, in patients with CAD and T2DM. METHODS: Blood samples were obtained from 37 CAD+ and 36 CAD- patients. These patients were enrolled in this study based on angiography findings and categorized based on T2DM status. The expression levels of STAT3, lnc-DC and SOCS1 genes were examined with Real time PCR method. RESULTS: A significant increase was observed in expression of STAT3 and lnc-DC genes but not SOCS1 in CAD+ versus CAD- patients. These results replicated partially in some groups categorized based on T2DM and CAD status. However, severity of CAD had no effect on expressions of these genes. Moreover, we found some significant correlations between expressions of lnc-DC with SOCS1 and STAT3, which confirmed by in silico analysis. CONCLUSION: Our results shed further light to the inflammatory aspects of CAD and T2DM with emphasis to JAK/STAT pathway and the regulatory role of long non-coding RNAs in the physiopathology of these diseases.

Association of ANRIL Expression with Coronary Artery Disease in Type 2 Diabetic Patients.

OBJECTIVES: ANRIL is an important antisense noncoding RNA gene in the INK4 locus (9p21.3), a hot spot region associated with multiple disorders including coronary artery disease (CAD), type 2 diabetes mellitus (T2DM) and many different types of cancer. It has been shown that its expression is dysregulated in a variety of immune-mediated diseases. CAD is a major problem in T2DM patients and the cause of almost 60% of deaths in these patients worldwide. The aim of the present study was to compare the expression level of ANRIL between T2DM patients with and without CAD. MATERIALS AND METHODS: In this case-control study, we examined ANRIL expression in peripheral blood mononuclear cell samples by quantitative reverse transcription- polymerase chain reaction (RT-qPCR) in 64 T2DM patients with and without CAD (33 CAD+ and 31 CAD- patients respectively, established by coronary angiography). RESULTS: Expression analysis revealed that ANRIL was up regulated (2.34-Fold, P=0.012) in CAD+ versus CADdiabetic patients. Data from receiver operating characteristic (ROC) curve analysis has shown that ANRIL could act as a potential biomarker for detecting CAD in diabetic patients. CONCLUSIONS: The expression level of ANRIL is associated with presence of CAD in diabetic patients and could be considered as a potential peripheral biomarker.

Association of R279Q and C1562T polymorphisms of matrix metalloproteinase 9 gene and increased risk for myocardial infarction in patients with premature coronary artery disease.

BACKGROUND: A number of matrix metalloproteinase (MMP) gene polymorphisms has been identified which may be probably related to premature myocardial infarction (MI). OBJECTIVE: We assessed the relationship between the two polymorphisms of the MMP9 gene including R279Q and C1562T and occurrence of premature MI. METHODS: The study has two phases including a case-control study as the first phase and cohort study as the second phase. Initially, 1000 patients with premature coronary artery disease were classified into MI and non-MI groups. Genotyping of the polymorphism was conducted by PCRRFLP and high-resolution melting techniques. Given the two conditions of patients residing in Tehran and faced with their first episode of MI, 640 of 1000 study samples previously followed up with a median follow-up time of 45.74 months were assessed in a retrospective cohort phase regarding long-term major adverse cardiac events (MACE). RESULTS: The prevalence of wild, heterozygous, and mutant genotypes of R279Q polymorphism in MI group was 14.5%, 57.3%, and 28.2% and in non-MI group was 36.9%, 38.4%, and 24.7%, respectively, with a considerable difference (P<.001). There was a significant difference in the prevalence of wild, heterozygous, and mutant genotypes of C1562T polymorphisms in MI group (12.4%, 41.2%, and 46.4%, respectively) and in non-MI group (46.8%, 38.6%, and 14.7%, respectively; P<.001). No difference was found in total MACE-free survival rate between genotypes of R279Q and C1562T polymorphisms. CONCLUSION: C1562T and R279Q polymorphisms are associated with the susceptibility to premature MI, but cannot predict long-term cardiac events in these patients.