Therapeutic angiogenesis with exosomal microRNAs: an effectual approach for the treatment of myocardial ischemia.

Therapeutic angiogenesis presents a potential approach for treating ischemic heart diseases especially in patients who are not appropriate candidates for traditional approaches of revascularization. This approach acts through inducing the neovascularization or maturation of pre-existing collateral vessels into functional arteries to bypass the blocked arteries and restore perfusion to ischemic myocardium. Successful stimulation of local angiogenesis can be established by the cross talk between stem cells, endothelial cells, and cardiomyocytes, which is mainly mediated by paracrine communication accompanied by secreted exosomes. Exosomes are extracellular vesicles carrying a complex of signaling molecules, such as microRNAs (miRs) that can modulate the function of recipient cells. Such particles have been indicated to exert cardioprotective role through providing signaling cues for angiogenesis, an effect ascribed mainly to their miRs content. Exosomal miRs-mediated therapeutic angiogenesis has been under drastic preclinical and clinical studies. In the current review, it was aimed to summarize pro-angiogenic exosomal miRs released by various cell types mediating angiogenesis, including stem cells, endothelial cells, and cardiomyocytes, which appear to exert a therapeutic effect on the myocardial ischemia. In brief, secreted exosomal miRs including miR-210, miR-23a-3p, miR-424, let-7f, miR-30b, miR-30c, miR-126, miR-21, miR-132, miR-130a-3p, miR-214, miR-378, miR-126, miR-133, and let-7b-5p could protect against myocardial ischemia through inducing cardiac angiogenesis and vascular regeneration resulting in the increase blood flow to ischemic myocardium.

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.

HTLV-1-host interactions facilitate the manifestations of cardiovascular disease.

Atherosclerosis is a multifactorial life-threatening disease which an epidemiologic study in Northeastern Iran showed its association with HTLV-1 infection. Therefore, a cross-sectional study of 39 newly diagnosed subjects with angiography test in three groups including 14 coronary artery disease+HTLV-1+ (CAD+HTLV-1+), 8 CAD-HTLV-1+, and 17 CAD+HTLV-1- patients and 11 healthy subjects (CAD-HTLV-1-) were conducted. In the present study, Tax and proviral load (PVL) as HTLV-1 virulence factors, along with host chemokine receptor 1 (CCR1), and CCR2 were investigated. Real-time PCR TaqMan method was carried out for PVL measurement and HTLV-1-Tax, CCR1, and CCR2 expressions in peripheral blood mononuclear cells (PBMCs). Furthermore, the main risk factors, lipid profile, and complete blood count (CBC) were assessed. Expression of CCR1 in CAD+HTLV-1+ group was higher than CAD-HTLV-1+ (P = 0.01) and healthy subjects (P = 0.02). Expression of CCR1 in CAD+HTLV-1+ was higher in comparison with CAD+HTLV-1-group but did not meet 95% CI (P = 0.02), but meaningful at 91% CI. In addition, expression of CCR2 in CAD+HTLV-1+ subjects was higher than CAD-HTLV-1+ and CAD+HTLV-1- (P = 0.001, P = 0.005, respectively). In CAD+HTLV-1- subjects, CCR2 was higher than CAD-HTLV-1+ (P = 0.03). The mean PVL in CAD+HTLV-1+ group is more than CAD-HTLV-1+ (P = 0.041). In HTLV-1+ patients Tax had a positive correlation with cholesterol (R = 0.59, P = 0.01), LDL (R = 0.79, P = 0.004) and a negative correlation with HDL (R = -0.47, P = 0.04). These correlations were stronger in CAD+HTLV-1+. Findings showed that HTLV-1 could alter the expression of CCR2 and, less effect, on CCR1. Moreover, the strong correlation between CCR2 and HTLV-1-Tax with cholesterol, LDL and HDL showed that Tax as the main HTLV-1 virulence factor in cytokine deregulation might be had indirect effects on cholesterol, LDL, and HDL levels.

The Association between Serum Follistatin-like Proteins and Cardiovascular Diseases: A Systematic Review and Meta-analysis.

BACKGROUND: Follistatin-like proteins (FSTLs) are adipomyokines secreted by adipocytes and myocytes. Previous studies have reported an increase in circulating FSTL1 levels in response to cardiovascular injuries. In this study, we conducted a systematic review and metaanalysis to assess the association between circulating FSTLs and Cardiovascular Diseases (CVDs). METHODS: We performed a comprehensive literature search using PubMed, Web of Science, Scopus, and Embase databases. After screening the articles, we selected eligible studies, extracted relevant data, and calculated the pooled Standardized Mean Difference (SMD). We also conducted a sensitivity analysis to identify sources of heterogeneity and assessed publication bias. RESULTS: Among the 577 articles initially retrieved, we included 5 studies comprising a total of 941 cases with CVDs and 446 controls. All included studies measured FSTL1 levels. The pooled SMD analysis revealed a significant difference in circulating FSTL1 levels between subjects with CVDs and control groups (SMD = 0.853, 95% CI = 0.158-1.548, P = 0.016). Heterogeneity was primarily attributed to a single study that measured FSTL1 levels in heart failure patients with preserved ejection fraction. No publication bias was observed. CONCLUSION: Our findings demonstrate significantly higher levels of FSTL1 in patients with CVD compared to control subjects. This suggests that FSTL1 may have potential as a diagnostic and prognostic biomarker in CVDs. However, further well-designed studies are needed to validate its clinical utility.

Elucidating the Role of Pro-renin Receptors in Pancreatic Ductal Adenocarcinoma Progression: A Novel Therapeutic Target in Cancer Therapy.

Pancreatic cancer is a highly aggressive malignancy with a very poor prognosis. The 5- year survival in these patients is very low, and most patients develop drug resistance to current therapies, so additional studies are needed to identify the potential role of new drug targets for the treatment of pancreatic cancer. Recent investigations have been performed regarding the roles of pro-renin receptors (PRR) in the initiation and development of cancers. PRR is a component of the local renin-angiotensin system (RAS). Local tissue RAS has been known in diverse organ systems, including the pancreas. Various investigations have implicated that PRRs are associated with the upregulation of various signaling pathways, like the renin-angiotensin system pathway, PI3K/Akt/mTOR, and the Wnt-signaling pathways, to contribute to pathological conditions, including cancer. In this review, we presented an overview of the role of PRR in the progression of pancreatic adenocarcinoma.

Evaluation of short and mid-term clinical outcomes in patients with aortic coarctation treated with self-expandable stents.

The present study aimed to evaluate the outcomes of percutaneous treatment of aortic coarctation using self-expandable uncovered Nitinol stents. We conducted a retrospective clinical data review of all patients with aortic coarctation and treated with self-expandable uncovered Nitinol stents at our institution between 2009 and 2019. The gradient pressure across the coarctation site was measured using aortography. Follow-up echocardiography and computed tomography angiography were performed to assess possible stent complications. A total of 127 stents were successfully implanted in 125 patients (64.8% males) with a mean age of 35.36 ± 11.9 years. The gradient across the coarctation site decreased significantly from 67.48 ± 14.79 to 5.04 ± 3.01 mmHg (P < 0.001) after self-expandable stent implantation. Systolic blood pressure (SBP) decreased significantly from 175.53 ± 15.99 to 147.22 ± 12.83 mmHg (P < 0.001) after self-expandable stenting. There were no major technical or clinical complications, including balloon rupture, aneurysmal formation, infection, secondary stent migration, thrombosis, death during the procedure, and in-hospital mortality. On a mean follow-up of 48 ± 23.6 months (12-120 months), the gradient [from 59.43 ± 15.42 to 3.72 ± 1.38 mmHg (P < 0.001)] and SBP [from 175.53 ± 15.99 to 127.99 ± 7.82 mmHg (P < 0.001)] decreased significantly. There was no mortality, aneurysmal formation in the stent site, dislocation, or aortic re-stenosis requiring intervention during mid-term follow-up. Treatment of aortic coarctation using a self-expandable uncovered nitinol stent is safe and effective with promising mid-term outcomes.

DNA fragmentation and apoptosis induced by safranal in human prostate cancer cell line.

OBJECTIVES: Apoptosis, an important mechanism that contributes to cell growth reduction, is reported to be induced by Crocus sativus (Saffron) in different cancer types. However, limited effort has been made to correlate these effects to the active ingredients of saffron. The present study was designed to elucidate cytotoxic and apoptosis induction by safranal, the major coloring compound in saffron, in a human prostate cancer cell line (PC-3). MATERIALS AND METHODS: PC-3 and human fetal lung fibroblast (MRC-5) cells were cultured and exposed to safranal (5, 10, 15, and 20 µg/ml). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to assess cytotoxicity. DNA fragmentation was assessed by gel electrophoresis. Cells were incubated with different concentrations of safranal, and cell morphologic changes and apoptosis were determined by the normal inverted microscope, Annexin V, and propidium iodide, followed by flow cytometric analysis, respectively. RESULTS: MTT assay revealed a remarkable and concentration-dependent cytotoxic effect of safranal on PC-3 cells in comparison with non-malignant cell line. The morphologic alterations of the cells confirmed the MTT results. The IC50 values against PC-3 cells were found to be 13.0 ΁ 0.07 and 6.4 ΁ 0.09 µg/ml at 48 and 72 h, respectively. Safranal induced an early and late apoptosis in the flow cytometry histogram of treated cells, indicating apoptosis is involved in this toxicity. DNA analysis revealed typical ladders as early as 48 and 72 h after treatment, indicative of apoptosis. CONCLUSIONS: Our preclinical study demonstrated a prostate cancer cell line to be highly sensitive to safranal-mediated growth inhibition and apoptotic cell death. Although the molecular mechanisms of safranal action are not clearly understood, it appears to have potential as a therapeutic agent.

Trans-catheter closure of ASD and abnormal connection of left pulmonary vein to vertical vein: A case report.

RATIONALE: Partial anomalous pulmonary venous connection is a rare congenital anomaly in which one or more pulmonary veins are connected to the venous circulation leading to left to right heart shunt. Although correction of anomalous pulmonary venous connection is achieved through surgery, there are rare instances where the abnormal pulmonary vein has dual connection to both left atrium and the major systemic veins. Under these circumstances, catheter-based treatment might become a feasible option. PATIENT CONCERNS: A 22-year-old female presented with exertional dyspnea, holo-systolic murmur in left sternal border, and fixed splitting of S2 in examination. DIAGNOSIS: The patient was diagnosed with secundum type atrial septal defect (ASD) and dual drainage of left upper pulmonary vein. INTERVENTIONS: The patient was candidate for device closure. Under TEE guidance, occluder devices were deployed in the upper part of vertical vein and subsequently in place of ASD. OUTCOMES: Echocardiogram in the next day showed complete occlusion of flow through the vertical vein and ASD. Dual antiplatelet was prescribed on discharge. Follow-up echocardiography after 3 months showed obvious improvement in RV size. Due to suspicion for clot formation, TEE was done and thrombosis with approximate length of extension of 15 mm was detected back to the device. The patient is following for 5 years. Repeated TEE after 2 years did not show any change in the burden of clot. LESSONS: For comprehensive evaluation of patients with ASD, assessment of pulmonic veins is crucial and in the presence of a vertical vein, the dual drainage of pulmonic veins should be considered.

Coronary artery angiographic changes in veterans poisoned by mustard gas.

OBJECTIVES: We aimed to identify coronary artery involvement in mustard gas-poisoned patients. METHODS: We conducted a case-control study on 40 mustard gas-poisoned patients who underwent coronary artery angiography due to cardiac pain. The study was performed during a 3-year interval on patients who were referred to three main hospitals of Mashhad, Iran. The nonexposed control group consisted of 40 normal individuals who had undergone angiography for the same reasons. The primary outcome measurement was coronary artery involvement and its location. Data were collected through studying the angiography films. RESULTS: Among the 40 poisoned patients studied, 15 (37.5%) had coronary artery ectasia, mainly in the left anterior descending artery, but 25 (62.5%) did not. The same values were 2 (5%) and 38 (95%) in the nonexposed group, respectively, which was significantly different compared to the exposed group (p = 0.001). The odds ratio was 11.40. CONCLUSIONS: The prevalence of coronary artery ectasia in mustard gas-poisoned patients was 7.5 times more than in nonexposed controls. Considering the proposed odds ratio, the occurrence of coronary artery ectasia is around 11.4 times greater in mustard gas-poisoned veterans. This is the first study to suggest a strong correlation between mustard gas poisoning and coronary artery ectasia.

High proviral load of human T cell lymphotropic virus type-1 facilitates coronary artery diseases.

OBJECTIVES: Coronary artery disease (CAD) is known as a life threatening disease, worldwide. In this study the role of HTLV-1 infection was evaluated on cardiac involvement in an endemic region of northeastern Iran. MATERIALS AND METHODS: Serologic and molecular tests for HTLV-1 infection were carried out in subjects who had coronary angiography. A real-time PCR, TaqMan method, to quantify HTLV-1 proviral load (PVL), and routine hematological and biochemical tests were performed for study subjects. RESULTS: Twenty nine patients were HTLV-1+CAD+ and 13 cases were HTLV-1+CAD-. Although, there were no significant differences for risk factors like FBS, HDL, triglyceride, systolic and diastolic blood pressure (Cbp, Dbp), waist circumference (WC), hip circumference (WL), cholesterol (P=0.003), and LDL (P=0.007) levels, and monocyte count (P=0.05) had meaningful differences. The mean HTLV-1 PVL in HTLV-1+CAD+ subjects was 992.62±120 which was higher compared with HTLV-1+CAD- group (406.54±302 copies/104 PBMCs). Moreover, HTLV-1 PVL in males (833±108) was lower compared with females (1218±141 copies/104 PBMCs) (P=0.05). Patients with HTLV-1-PVL of more than 500 copies/104 had more diffused atherosclerosis plaque than patients with less than 500 (OR=6.87, 95% CI=1.34-35.05; P=0.016). Furthermore, patients with diffused coronary atherosclerosis had significantly higher levels of HTLV-1 PVL than patients with middle, proximal, and normal location of coronary sclerotic lesions (P<0.05). CONCLUSION: Taken together, in endemic area, HTLV-1 infection, more likely is a facilitating factor for heart complications and the high HTLV-1 PVL might affect CAD manifestations.

Late Cardiac Complications of Sulfur Mustard Poisoning in 38 Iranian Veterans.

It was aimed to investigate possible late cardiac effects of Sulfur mustard (SM) exposure in Iranian veterans. Thirty-eight veterans with late complications of SM exposure were investigated. Clinical history, physical examinations, 12 leads electrocardiography and transthoracic echocardiography were performed. Computed tomography coronary angiography (CTCA) was performed as clinically indicated for angiographic assessment and patients were stratified according to the CTCA findings. Incomplete right bundle branch block and right axis deviation were detected in 3 (7.9%) and 4 (10.5%) cases, respectively. Mean value of left ventricular ejection fraction was 55.7 ± 2.9%. Different degrees of right ventricular dilation was observed in seven (18.4%) patients. All the patients showed mild to moderate degrees of tricuspid regurgitation. Increased pulmonary artery pressure (PAP) was detected in 16 (42.1%) patients. Out of 18 patients who underwent CTCA, non-obstructive and obstructive coronary artery disease (CAD) were observed in three (16.66%) and eight (44.44%) patients, respectively. CAD was stratified to single vessel (5.5%), two vessels (27.8%) and three vessels disease (11.1%). Mean coronary artery calcium score was 50.91 ± 115.58. SM has cardiovascular toxicity, as a delayed complication of this chemical warfare poisoning.

Primary Pulmonary Valve Leiomyosarcoma in a 35-Year-Old Woman.

Primary cardiac leiomyosarcomas are rare, with a high incidence of local recurrence. Herein, we report the case of a 35-year-old woman who was admitted with right ventricular failure and suspected pulmonary embolism. Upon echocardiography, we detected a mass in the pulmonary trunk that involved the pulmonary valve and led to valvular stenosis. The optimal protocol for treating these tumors is as yet unclear. Complete resection can rarely be achieved. However, palliative surgery is usually undertaken because many patients present with mechanical obstruction, such as significant pulmonary stenosis.

Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats.

Cadmium (Cd) is an environmental toxic metal implicated in lipid abnormalities. The present study was designed to elucidate the possible association between chronic exposure to Cd concentration and alterations in plasma lipid, lipoprotein, and oxidative stress indices in rats. Sixteen male rats were assigned to 2 groups of 8 rats each (test and control). The Cd-exposed group obtained drinking water containing cadmium chloride (CdCl2) in the concentration of 2.0 mg Cd/L in drinking water for 3 months. At the end of the experimental period, blood samples were obtained to determine the changes of serum triglycerides (TG), total cholesterol (TC), highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), reduced glutathione (GSH), malondialdehyde (MDA) and also serum Cd contents. The results of the present study indicated that Cd administration significantly increased the serum levels of TG, TC, LDL-C, MDA and Cd with reduction in the HDL-C and GSH levels. In conclusion, evidence is presented that chronic exposure to low Cd concentration can adversely affect the lipid and lipoprotein profile via lipid peroxidation.

The Impact of Remote Ischemic Pre-Conditioning on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography and Angioplasty: A Double-Blind Randomized Clinical Trial.

BACKGROUND AND OBJECTIVE: Contrast-induced nephropathy (CIN) is an acute major complication following intravascular administration of iodinated contrast agents; however, the best approach for preventing CIN is not clear. Remote ischemic pre-conditioning (RIPC) is a new, non-pharmacological method that has been considered for the prevention of CIN following coronary angiography. This study assessed the effects of RIPC with four brief episodes of upper limb ischemia and reperfusion in the prevention of contrast-induced nephropathy (CIN) after coronary angiography and/or angioplasty. METHODS: In this double-blind randomized clinical trial, we enrolled 51 patients with chronic stable angina and non-ST elevation acute coronary syndrome (NSTE.ACS), and they underwent coronary angiography and/or angioplasty. Standard fluid therapy with normal saline was prescribed for all patients before and after the procedure. The patients were divided into two groups, i.e., a study group of patients who had undergone RIPC intervention and a control group of patients who had not undergone RIPC. One hour before the procedure, a sphygmomanometer cuff was placed around one arm and inflated up to 50 mmHg above the systolic pressure for five minutes; then, the cuff was deflated for another five minutes, and this cycle was repeated four times. The patients' serum creatinine levels were measured at baseline and 48 hours after the procedure, and the incidence of CIN was calculated. RESULTS: Twenty-one males and 30 females were studied in two groups, i.e., an RIPC intervention group (n = 25) and a control group (n = 26) that were homogenous considering baseline characteristics. No significant difference was observed in the mean level of serum creatinine between the two groups at a post-intervention time of 48 hours (RICP: 1.74 ± 0.70 mg/dL vs. CONTROL: 1.75 ± 0.87 mg/dL; P = 0.64). However, a lower incidence rate of CIN was observed 48 hours after the administration of the contrast medium in the RIPC group, but it was not statistically significant (RIPC: 23.1% vs. CONTROL: 12.0%; P = 0.30). CONCLUSION: It seems that adequate fluid therapy is still the most effective strategy for preventing CIN and that RIPC might have additional protective effects in very high risk patients, such as those with severe renal insufficiency and heart failure.

A case of left atrial myxoma with unusual tumor vascularity.

A 69-year-old woman presented with a 2-week history of chest pain and mitral and aortic valve replacement 15 and 5 years earlier. Transthoracic echocardiography revealed a well-seated monoleaflet mitral valve and a bileaflet aortic valve with normal function. Cardiac catheterization showed 3-vessel coronary artery disease and an abnormal cluster of new vessels derived from the left atrial circumflex and posterior ventricle branches. Two- and 3-dimensional transesophageal echocardiography identified a semi-mobile oval left atrial mass with multiple internal cystic spaces, attached to the fossa ovalis region in the interatrial septum. The mass was resected. The pathological diagnosis was atrial myxoma.

Transvenous embolization of a carotid cavernous fistula complicated by a hematoma at the tentorial edge.

Indirect (dural) carotid cavernous fistulae are generally treated by endovascular surgery primary transvenous embolization that is safe and effective. We describe here a case of a left indirect carotid cavernous fistula that presented with proptosis and eye redness. The patient underwent transvenous embolization of carotid cavernous sinus. The procedure was complicated by a haemorrhage from the cavernous sinus. The post procedural CT scan showed a haematoma at the tentorial edge. Precise diagnosis and prompt treatment could prevent severe complications.

Patient Safety Culture Based on Medical Staff Attitudes in Khorasan Razavi Hospitals, Northeastern Iran.

BACKGROUND: Since establishing a safety culture in an organization is considered as the first step in patient safety improvement, there is always a need for updated field evaluation to better plan future decisions. METHODS: We performed a cross-sectional, analytic-descriptive study in 25 hospitals related to Mashhad University of Medical Sciences (MUMS) during a 3-month period from April to June 2012. A questionnaire, designed by previous patient safety culture studies with confirmed validity and reliability, was used and distributed among a sample of 922 staff, chosen randomly from the mentioned hospitals. Data were analyzed by SPSS software version 16. RESULTS: "Organizational learning - continuous improvement" and "teamwork within unit" had the highest percentage of positive results as 79.85 ± 12.03% and 71.92 ± 17.08%, respectively; whereas "non-punitive response" to errors (21.57 ± 6.42) and "staffing" (26.36 ± 16.84) came out as the least important factors. There were no meaningful statistical relation between general features of the understudy hospitals including the number of beds, educational level or proficiency status with the general safety culture score. CONCLUSION: Most of the safety culture aspects were reported as low to moderate in terms of importance. If something needs to be modified interventionally in this respect, "the approach to confront errors" would be a wise choice. This could be achieved by establishing an atmosphere of open communication and continuous learning through elimination of the fear for reporting errors and installing a more acceptable approach in hospitals.

Human T Lymphotropic Virus Type I (HTLV-I) is a Risk Factor for Coronary Artery Disease.

OBJECTIVE(S): Few studies have shown the association between HTLV-I infection and coronary artery disease (CAD). HTLV-I has been detected in heart autopsies, particularly in lymphoma\leukemia cases. Mashhad and Neyshabour (Razavi Khorasan Province, Iran) are endemic regions for HTLV-I. Therefore, the present study was carried out to evaluate the impact of HTLV-I on CAD in Neyshabourian patients. MATERIALS AND METHODS: 7590 patients admitted to Razavi and Imam Reza Hospitals (2007-2008) were included in this study. The seroprevalance of HTLV-I infection was determined by the ELISA method and confirmed with the PCR method. Statistical analyses were performed using the SPSS software. RESULTS: Out of the 7590 studied subjects, 564 patients were born and had resided in Neyshabour. The HTLV-I sero-prevalence among these subjects was 13% (n=73). 294 subjects had an abnormal angiography (CAD) and among them 43 (14.6%) were sero-positive for HTLV-I. In the remaining 227 subjects who had a normal angiography, 30 cases were HTLV-I seropositve. The PCR test was performed on 35 cases in order to confirm the presence of infection, which was positive in 31. Regarding the initial population of 294, the rate of PCR-confirmed infection was 10.54%. Conclusion : This sero-prevalence of HTLV-I in subjects with heart complications in Neyshabour was nearly 3 times more than the general population of this city (10.5 % vs 3.4%). However, the results of this study show that in addition to HTLV-I infection, there might be other co-factors leading to the development of heart complications in Neyshabour.