Factors Determining Primary Coronary Slow Flow Phenomenon among Opium Users and Non-users: A Case Control Study in Northern Iran.

Background: Coronary slow flow phenomenon (CSFP) represents a clinical entity with recurrent chest pain leading to living impairment. The present study aimed to investigate whether opium use correlates with primary CSFP. Methods: This study included Iranian patients with suspected coronary artery disease who underwent myocardial perfusion imaging. Coronary blood flow was measured quantitatively using the thrombolysis in myocardial infarction (TIMI) frame count and slow flow was defined as TIMI grade 2 standard deviations. Age and clinical conditions including diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLP), history of chest pain, and opium use were recorded. First, the characteristics of the two groups were compared and then the main analyses were conducted to examine the relationship between CSFP and opium use. Data were analyzed using t test and chi-square test via SPSS 25.0. The significance level was set at P<0.05. Findings: This study was conducted on 44 male patients with documented CSFP who had no stenotic lesions and 134 control group male patients who had normal coronary arteries with normal flow. The mean age was similar in the two groups (54.25 vs.52.69, P=0.474). Two groups were significantly different in terms of history of chest pain (P=0.003), but there was no significant difference in HTN (P=0.084), DM (P=0.284), HLP (P=0.183), smoking (P=0.696), and opium use (P=0.107). Conclusion: This study indicated that opium use is not associated with primary CSFP.

Investigation of the ionic conditions in SiRNA-mediated delivery through its carriers in the cell membrane: a molecular dynamic simulation.

SiRNA is a new generation of drug molecules and a new approach for treating a variety of diseases such as cancer and viral infections. SiRNA delivery to cells and translocation into cytoplasm are the main challenges in the clinical application of siRNA. Lipid carriers are one of the most successful carriers for siRNA delivery. In this study, we investigated the interaction of siRNA with a zwitterionic bilayer and how ion concentration and lipid conjugation can affect it. The divalent cation such as Mg2+ ions could promote the siRNA adsorption on the bilayer surface. The cation ions can bind to the head groups of lipids and the grooves of siRNA molecules and form bridges between the siRNA and bilayer surface. Our findings demonstrated the bridges formed by divalent ions could facilitate the attachment of siRNA to the membrane surface. We showed that the divalent cations can regulate the bridging-driven membrane attachment and it seems the result of this modulation can be used for designing biomimetic devices. In the following, we examined the effect of cations on the interaction between siRNA modified by cholesterol and the membrane surface. Our MD simulations showed that in the presence of Mg2+, the electrostatic and vdW energy between the membrane and siRNA were higher compared to those in the presence of NA+. We showed that the electrostatic interaction between membrane and siRNA cannot be facilitated only by cholesterol conjugated. Indeed, cations are essential to create coulomb repulsion and enable membrane attachment. This study provides important insight into liposome carriers for siRNA delivery and could help us in the development of siRNA-based therapeutics. Due to the coronavirus pandemic outbreak, these results may shed light on the new approach for treating these diseases and their molecular details.

Neural differentiation of human induced pluripotent stem cells on polycaprolactone/gelatin bi-electrospun nanofibers.

In the present study, for the first time, polycaprolactone (PCL) and gelatin (GEL) were used for neural differentiation of human induced pluripotent stem cells (hiPSCs) in the form of bi-electrospun nanofibers. The electrospun fibers were evaluated by FTIR and tensile analysis. MTT assay was used to evaluate the toxicity on the scaffolds. The hiPSCs were seeded on the fibers and after 14days in neural differentiation medium. To confirm the differentiation, real-time PCR and immunocytochemistry (ICC) analyses were performed. For morphological studies of fibers and cultured cells on them, scanning electron microscopy (SEM) and optical microscopy (OM) were used. Our results indicated that hiPSCs had differentiated to neural cells completely after incubation time. Our study demonstrates that PCL/GEL bi-electrospun nanofibers not only have the capability to support hiPSCs differentiation to neural cells, but they also are able to enhance and improve such process. Overall, PCL/GEL scaffolds seem to be a feasible, reliable and easily accessed composite for further tissue engineering experiments.

Correlation between Obstructive Sleep Apnea Syndrome and Cardiac Disease Severity.

Background. Obstructive sleep apnea (OSA) syndrome is one of the most common respiratory disorders in humans. There is emerging evidence linking OSA to vascular disease, particularly hypertension. The underlying pathophysiological mechanisms that link OSA to cardiovascular diseases such as hypertension, congestive heart failure, and atrial fibrillation are not entirely understood. The aim of this study was to investigate the association of obstructive sleep apnea hypopnea syndrome (OSAHS) with coronary atherosclerotic disease (CAD). Methods. A questionnaire survey based on Berlin questionnaire and Epworth Sleepiness Scale (ESS) was conducted among 406 patients to assess demographic data and the symptoms, such as excessive daytime sleepiness and snoring. Epworth Sleepiness Scale and Berlin questionnaire were completed by all of the patients. Venous blood samples were obtained for biochemical tests. Characteristics of coronary arteries were collected from angiographies' reports. All patients were divided into two groups based on results from Berlin questionnaire: low risk patients for OSA and high risk patients for OSA. Data were analyzed by SPSS software version 13. Results. Mean age of patients was 61.8 ± 10.5. 212 (52.2%) patients were categorized as high risk group for apnea. Also, excessive daytime sleepiness was reported in 186 patients (45.8%). The severity of coronary artery involvement, daytime sleepiness, and electrocardiogram abnormalities was significantly higher in high risk patients for OSA compared with low risk patients. High risk patients had higher level of FBS and LDL and lower level of HDL cholesterol (P < 0.05). Conclusion. Our study found a strong correlation between the number of stenotic vessels and OSA. Based on our findings, OSA can be a predisposing factor for cardiac diseases.

Opium dependency and in-hospital outcome of acute myocardial infarction.

BACKGROUND: Impact of substance abuse on outcome of hospitalized patients with acute myocardial infarction (MI) is a frequent question. Available studies show disagreements over its impact, thus we performed this study to find a clear answer. METHODS: In a cross sectional study, 304 patients (include 152 consecutive opium dependents and equal number of independents) with acute MI admitted to coronary care units (CCU) in Bou-Ali Sina Hospital of Qazvin University of Medical Science were enrolled. Data on demographics (e.g. age, sex and education), identified MI risk factor (smoking and diabetes), clinical findings (e.g. Killip class and in-hospital mortality), ECG findings (e.g. localization of infarction and arrhythmia), echocardiographic examinations (e.g. ejection fraction and regional wall motion abnormality) and laboratory findings (lipid profile, glycemic situation) were gathered. RESULTS: The mean age was 63.01±12 years for opium users and 64.3± 10 for non-users. Educational level was higher in patients who used opium. No significant differences were found between opium users and non-users in rate of hypertension, diabetes mellitus, hyperlipidemia, and cigarette smoking. The mean duration of experienced chest pain in hospital stay was significantly higher in non-opium users compared to opium users (1.78± 0.63 vs.1.52±0.54) (p< 0.001). Higher Killip class and arrhythmia have been identified as the most important independent predictors of early in-hospital mortality (in both groups). CONCLUSION: The higher Killip class and age identified as the most important independent predictors of early in-hospital mortality and addiction do not act as a major risk or protecting factor in this context. Nevertheless, we believe that a more comprehensive study with follow up of patients should be carried out for evaluation of opium addicted patients, their outcome after MI, and a better decision making for their treatment.

Bcr-abl silencing by specific small-interference RNA expression vector as a potential treatment for chronic myeloid leukemia.

BACKGROUND: RNA interference (RNAi) is the mechanism of gene silencing-mediated messenger RNA degradation by small interference RNA (siRNA), which becomes a powerful tool for in vivo research, especially in the areas of cancer. In this research, the potential use of an expression vector as a specific siRNA producing tool for silencing of Bcr-abl in K562 cell line has been investigated. METHODS: siRNA specific for Bcr-abl as short hairpin RNA (shRNA) was designed and cloned in expression vector (pRNAH1.1/Neo). K562 cells were cultured in RPMI media and transfected with shRNA expressing vector using lipofectamin 2000. Successful transfection was confirmed by significant increase of enhanced green fluorescent protein (EGFP) levels in K562-treated cells with expression vector (pEGFP-C1). In vitro studies in human K562 cell line entailed modulation of endogenous Bcr-abl mRNA levels which induced apoptosis. Effects of siRNA treatment on K562 cells were measured by ELISA. RESULTS: Successful expression of siRNA was confirmed by significant reduction of Bcr-abl mRNA levels in K562 cells treated with expression vector (pRNAH1.1/Neo). siRNA directed against Bcr-abl effectively induced apoptosis and reduced viability in human K562 cell lines. CONCLUSION: Expression vector of siRNA can be used in vitro to target specific RNA and to reduce the levels of the specific gene product in the targeted cells. Results of this work suggest that RNAi has potential application for the treatment of a variety of diseases, including those involving abnormal gene expression and viral contamination.