Comparison of three different therapies for cutaneous leishmaniasis and identification of the etiologic isolates in Isfahan, Iran

Background: In Iran, zoonotic and anthroponotic cutaneous leishmaniasis (CL) are caused by Leishmania major and L. tropica respectively. Despite extensive studies, no effective therapies have ever been reported for CL. The main objective of this research was to determine and compare the three different protocols for treatment of CL patients referring to Skin Diseases and Leishmaniasis Research Center (SDLRC), affiliated to Isfahan University of Medical Sciences, Isfahan, Iran from September 2017 to October 2018. Methods: In a randomized controlled parallel groups clinical trial, 150 selected CL patients who met our inclusion criteria were randomly assigned to one of the three therapy groups: A, intra-lesional glucantime plus 50 trichloroacetic acid (TCA), B, intra-lesional glucantime and C, systemic glucantime. All patients in the three groups received the complete course of treatment and were followed for 6 months. To identify the etiologic agents, smears from their lesions were prepared and PCR-RFLP was used after parasite culture. Also, clinical characteristics, history of previous involvement, endemic emigration and demographic data were collected. Results: The results showed that the mean value of healing period was 53.12 ± 25.88 (median: 45, IQR: Q1 = 30-Q3 = 77) days in group A, 57.22 ± 44.02 (median: 42.5, IQR: Q1 = 30-Q3 = 60) days in group B, and 73.56 ± 41.08 (median: 71, IQR: Q1 = 45-Q3 = 90) days in group C; the observed differences were statistically significant (P = 0.024). There was a significant difference between group A and group C (P = 0.049), and between group B and group C (P = 0.047) in terms of mean healing period. Finally, complete recovery rates of 80, 62 and 42 were shown in the three medicinal groups of A, B and C, respectively (P = 0.022). Conclusion: In this study, the average duration of lesion healing among the three groups was the shortest in patients with IL glucantime plus 50 TCA treatment regimen. Also, the use of 50 TCA in patients suffering from CL was associated with a significant improvement in the depth of scars, the time and the percentage of recovery, and the low cost of this agent in the treatment of CL. © 2020 Academy of Medical Sciences of I.R. Iran. All rights reserved

Up-Regulation of Tmevpg1 and Rmrp LncRNA Levels in Splenocytes and Brain of Mouse with Experimental Autoimmune Encephalomyelitis

Background: Two long noncoding (lnc) RNAs, which have been recognized as Tmevpg1/Ifng-AS1/NeST and Rmrp play indispensable roles in the differentiation of TH1 and TH17, respectively. The aim of the present scientific study was to analyze the expression levels of the aforementioned lncRNAs in experimental autoimmune encephalomyelitis (EAE) as an animal model for multiple sclerosis (MS).Materials and Methods: Initially, EAE was induced in C57BL/6 mice via immunization by using MOG peptide. The leukocyte infiltration rate and demyelination of neuronal axons were determined. Secondly, the expression levels of Tmevpg1, Rmrp, Tbx21, and Rorc were analyzed in the cultured splenocytes and brain lysates, by using Real-Time PCR assay; eventually, the levels of interferon-gamma and interleukin-17 evaluated by ELISA.Results: Gene expression analysis revealed that Rorc expression in the splenocytes of EAE mice in comparison to the controls was elevated; however, Tbx21 expression did not show any significant difference. Tmevpg1 and Rmrp levels increased in the splenocytes of EAE mice (4.48 times and 39.70 times, respectively, p = 0.0001). Besides, in the brain lysate, the entire genes that have been mentioned were higher than the controls (Tmevpg1: 3.35 times p = 0.02 and Rmrp 11.21 times, p = 0.0001).Conclusion: The marked up-regulation in Tmevpg1 and Rmrp transcripts suggested the essential roles of lncRNAs in the pathogenesis of EAE and multiple sclerosis indeed. Further investigations are necessary to evaluate the values of these lncRNAs as the target for the therapy or molecular marker for disease monitoring

Mechanisms of hypoxic up-regulation of versican gene expression in macrophages

Hypoxia is a hallmark of many pathological tissues. Macrophages accumulate in hypoxic sites and up-regulate a range of hypoxia-inducible genes. The matrix proteoglycan versican has been identified as one such gene, but the mechanisms responsible for hypoxic induction are not fully characterised. Here we investigate the up-regulation of versican by hypoxia in primary human monocyte-derived macrophages (HMDM), and, intriguingly, show that versican mRNA is up-regulated much more highly (>600 fold) by long term hypoxia (5 days) than by 1 day of hypoxia (48 fold). We report that versican mRNA decay rates are not affected by hypoxia, demonstrating that hypoxic induction of versican mRNA is mediated by increased transcription. Deletion analysis of the promoter identified two regions required for high level promoter activity of luciferase reporter constructs in human macrophages. The hypoxia-inducible transcription factor HIF-1 has previously been implicated as a key potential regulator of versican expression in hypoxia, however our data suggest that HIF-1 up-regulation is unlikely to be principally responsible for the high levels of induction observed in HMDM. Treatment of HMDM with two distinct specific inhibitors of Phosphoinositide 3-kinase (PI3K), LY290042 and wortmannin, significantly reduced induction of versican mRNA by hypoxia and provides evidence of a role for PI3K in hypoxic up-regulation of versican expression

Erratum: COMPARE CPM-RMI trial: Intramyocardial transplantation of autologous bone marrow-derived CD133+ cells and MNCs during CABG in patients with recent MI: A phase II/III, multicenter, placebo-controlled, randomized, double-blind clinical trial. (Cell Journal (2018) 20:3 (449) DOI: 10.22074/cellj.2018.5197)

This article published in Cell J (Yakhteh), Vol 20, No 2, Jul-Sep 2018, on pages 267-277, four affiliations (1, 4, 5, and 10) were changed based on authors request. © 2018 Royan Institute (ACECR). All rights reserved

COMPARE CPM-RMI Trial: Intramyocardial transplantation of autologous bone marrow-derived CD133+ Cells and MNCs during CABG in patients with recent MI: A Phase II/III, multicenter, placebo-controlled, randomized, double-blind clinical trial

Objective: The regenerative potential of bone marrow-derived mononuclear cells (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction (RMI) post-coronary artery bypass graft. Materials and Methods: This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject (time) and group�time interaction terms. Results: There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9 95% confidence intervals (CI): 2.14% to 15.78%, P=0.01 and improved decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The CD133 group showed significantly decreased non-viable segments by 75% (P=0.001) compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed this improvement at both the 6- and 18-month time points. Conclusion: Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the basis for larger studies to confirm definitive evidence about the efficacy of these cell types (Registration Number: NCT01167751). © 2018 Royan Institute (ACECR). All Rights Reserved

Human activated macrophages and hypoxia: a comprehensive review of the literature

Macrophages accumulate in poorly vascularised and hypoxic sites including solid tumours, wounds and sites of infection and inflammation where they can be exposed to low levels of oxygen for long periods. Up to date, different studies have shown that a number of transcription factors are activated by hypoxia which in turn activate a broad array of mitogenic, pro-invasive, pro-angiogenic, and pro-metastatic genes. On the other hand, macrophages respond to hypoxia by up-regulating several genes which are chief factors in angiogenesis and tumorigenesis. Therefore, in this review article we focus mainly on the role of macrophages during inflammation and discuss their response to hypoxia by regulating a diverse array of transcription factors. We also review the existing literatures on hypoxia and its cellular and molecular mechanism which mediates macrophages activation

Evaluation of Inhibitory Effect of Silibinin on Growth and Stemness Property of MCF-7 Cell Line Derived Mammospheres

Introduction: The cancer stem cells are the small population of cells in tumor tissue with the ability of self-renew and differentiation into other tumor cells. Targeting these cells has great importance in the treatment of cancer and prevent cancer recurrence. Milk thistle is the plant of the Asteraceae with the scientific name of Silybum Marianum. However there is no report about the effect of Silibilin on mammospheres. So, the aim of this study was to evaluate the effect of silibinin on the ability of self-renewal, growth and stemness genes expression and markers of MCF-7 cell line derived mammospheres. Methods: In this study, the viability of the MCF7 derived mammospheres were treated with silibinin for 72h using MTS test and 50% lethal dose (IC50) have been evaluated, respectively. Next, untreated and treated mammospheres with silibinin were investigated for the ability of invasion, colony and sphere formation, expression of stemness genes expression includes Oct4 and KLF by real time PCR. Results: Our data showed that silibinin decreased the MCF-7 cells in the mamospheres with a dose dependent manner. Silibinin at dose of 150 µM (IC50) reduced 4.6 and 11.2 fold the ability of sphere and colony formation respectively. Also invasion and expression of stemness genes significantly decreased. Conclusion: Due to reduction of growth, colony and sphere formation, as well as reduction of invasion and expression of stemness genes, Silibinin can be a good candidate for targeting of cancer stem cells

Angiotensin-converting enzyme 2 rs2285666 polymorphism and clinical parameters as the determinants of COVID-19 severity in Iranian population

Host genetic factors may be correlated with the severity of coronavirus disease 2019 (COVID-19). Angiotensin-converting enzyme 2 (ACE2) plays a vital role in viral cell entrance. The current study aimed to evaluate the association of ACE2 rs2285666 polymorphism and clinical parameters with COVID-19 mortality. The ACE2 rs2285666 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism in 556 recovered and 522 dead patients. In this study, the frequency of ACE2 rs2285666 CC was significantly higher than TT genotype in dead patients. The multivariate logistic regression analysis results showed that the higher levels of alanine aminotransferase, alkaline phosphatase, creatinine, erythrocyte sedimentation rate, and C-reactive protein and the low levels of uric acid, cholesterol, low density lipoprotein, 25-hydroxyvitamin D, real-time PCR Ct values, and ACE2 rs2285666 CC genotype were associated with increased mortality rates after COVID-19. In conclusion, our findings demonstrated a possible link between COVID-19 mortality, clinical parameters, and ACE2 rs2285666 CC. Further research is required to confirm these results