The pathologic changes in the coronary arteries of three patients who died 5, 17 and 62 days, respectively, after percutaneous transluminal coronary angioplasty were studied. Changes in the vessel wall seen early after angioplasty included focal denudation of the endothelium, splits in the intima extending to and along the inner aspect of the media, focal intimal necrosis and adventitial hemorrhage. Extensive medial dissections were seen in the coronary arteries of the two patients who died 5 and 17 days after coronary angioplasty. Fibrin was deposited on the surface of the intima, within intimal cracks and in areas of intimal and medial necrosis. Focal proliferation of smooth muscle cells was prominent on neointimal surfaces of the coronary artery from the patient who died 17 days after angioplasty. The previously dilated coronary segment from the patient who died 62 days after angioplasty was stenosed by an extensive recent proliferation of smooth muscle cells that were distributed over the entire circumference of the intimal surface as well as within gaps in the old atherosclerotic plaques. This type of intimal proliferation would appear to be responsible for the recurrent coronary artery stenosis that develops in some patients after coronary angioplasty.

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Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

A set of unique sequences in bacterial genomes, responsible for protecting bacteria against bacteriophages, has recently been used for the genetic manipulation of specific points in the genome. These systems consist of one RNA component and one enzyme component, known as CRISPR (“clustered regularly interspaced short palindromic repeats”) and Cas9, respectively. The present review focuses on the applications of CRISPR/Cas9 technology in the development of cellular and animal models of human disease. Making a desired genetic alteration depends on the design of RNA molecules that guide endonucleases to a favorable genomic location. With the discovery of CRISPR/Cas9 technology, researchers are able to achieve higher levels of accuracy because of its advantages over alternative methods for editing genome, including a simple design, a high targeting efficiency and the ability to create simultaneous alterations in multiple sequences. These factors allow the researchers to apply this technology to creating cellular and animal models of human diseases by knock‐in, knock‐out and Indel mutation strategies, such as for Huntington's disease, cardiovascular disorders and cancers. Optimized CRISPR/Cas9 technology will facilitate access to valuable novel cellular and animal genetic models with respect to the development of innovative drug discovery and gene therapy.

Background: MicroRNA-126, a microRNA implicated in blood vessel integrity and angiogenesis is significantly up/down regulated in different physiological and pathological conditions related to angiogenesis such as cardiovascular formation and angiogenesis dependent diseases like Cancer, diabetic microvascular complication, cardiovascular disease, atherosclerosis and stroke. MicroRNA-126 plays a critical role in angiogenesis via regulating the proliferation, differentiation, migration, and apoptosis of angiogenesis related cells such as endothelial cells, vascular smooth muscle cells and pericytes. Objective: The aim of this review is to investigate the molecular mechanisms and effects of microRNA-126 in angiogenesis process in pathophysiological conditions. Methods: To conduct this review, related articles published between 2001 and 2019 were collected from the PubMed, Web of Science, Google Scholar, Scopus and Scientific Information Database using search terms such as microRNA-126, angiogenesis, cardiovascular disorders, hypoxia, VEFG-A, endothelial cells, VEGF pathway, gene silencing. Then, the qualified articles were reviewed. Result: MicroRNA-126 regulates the response of endothelial cells to VEGF, through directly repressing multiple targets, including Sprouty-related EVH1 domain-containing protein 1 (SPRED1) and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-b). MicroRNA-126 -3p and microRNA-126 -5p have cell-type and strand-specific functions and also various targets in angiogenesis that lead to regulate angiogenesis via different pathways and consequently diverse response. Conclusion: MicroRNA-126 can bind to multiple targets and potentially be both positive and negative regulators of gene expression. Thus, microRNA-126 could cause the opposite biological effects depending on the context. As a result, understanding the different cellular pathways that microRNA-126 regulate angiogenesis through them in various situations is a critical aspect in the development of novel and effective treatments for diseases with insufficient angiogenesis. So it is critical to understand its role in governing angiogenesis during pathological and even physiological conditions.

Male infertility is an important factor accounting for 40-50% of infertility cases that may be due to disturbance in one of the parameters as concentration, motility and morphology observed in one or two semen analysis with an interval of 1 and 4 weeks. COVID-19 may affect male fertility through virus division, cytotoxic effects on testicular tissue and immunopathological effect. N-acetyl cysteine (NAC) improved sperm concentration and acrosome reaction while reducing reactive oxygen species (ROS) and oxidation of sperm DNA. This interventional study was conducted on 200 men who were referred to private infertility clinics for female factor (their previous semen analysis was normal) and got COVID-19 infection in the last 3 months showing an impairment of the latest semen analysis due to COVID. Men were placed in two groups of control (n = 100) and intervention (NAC consumption). Subjects who got COVID-19 infection had a significant impairment of sperm quality (sperm concentration, sperm motility, and normal sperm morphology) compared to their semen analysis evaluated before the COVID-19 infection. NAC consumption significantly improved sperm total motility, sperm morphology and sperm concentration. COVID-19 infection has a negative effect on sperm parameters. NAC supplementation may have positive effect on sperm parameters.

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Exosomes are small vesicles covered by a lipid bilayer, ranging in size from 50 nm to 90 nm, secreted by different cell types in the body under normal and pathological conditions. They are surrounded by cell-segregated membrane complexes and play a role in the pathological and physiological environments of target cells by transfer of different molecules such as microRNA (miRNA). Exosomes have been detected in many body fluids, such as in the amniotic fluid, urine, breast milk, blood, saliva, ascites, semen, and bile. They include proteins, lipids, and nucleic acids such as DNA, RNA, and miRNA, which have many functions in target cells under pathological and physiological conditions. They participate in pathological processes such as tumor growth and survival, autoimmunity, neurodegenerative disorders, infectious diseases, inflammation conditions, and others. Biomarkers in exosomes isolated from body fluids have allowed for a more precise and consistent diagnostic method than previous approaches. Exosomes can be used in a variety of intracellular functions, and with advances in molecular techniques they can be used in the treatment and diagnosis of many diseases, including cancer. These vesicles play a significant role in various stages of cancer. Tumor-derived exosomes have an important role in tumor growth, survival, and metastasis. In contrast, the use of stem cells in cancer treatment is a relatively new scientific area. We hope to address targeted use of miRNA-carrying exosomes in cancer therapy in this review paper.