Ramyar Azizi

Advancements in adoptive cell therapy over the last four decades have revealed various new therapeutic strategies, such as chimeric antigen receptors (CARs), which are dedicated immune cells that are engineered and administered to eliminate cancer cells. In this context, CAR T-cells have shown significant promise in the treatment of hematological malignancies. However, many obstacles limit the efficacy of CAR T-cell therapy in both solid tumors and hematological malignancies. Consequently, CAR-NK and CAR-M cell therapies have recently emerged as novel therapeutic options for addressing the challenges associated with CAR T-cell therapies. Currently, many CAR immune cell trials are underway in various human malignancies around the world to improve antitumor activity and reduce the toxicity of CAR immune cell therapy. This review will describe the comprehensive literature of recent findings on CAR immune cell therapy in a wide range of human malignancies, as well as the challenges that have emerged in recent years.

Recently, mesenchymal stromal cells (MSCs) and also their exosome has become a game-changing tool in the context of tissue engineering and regenerative medicine. MSCs due to their competencies to establish skin cells, such as fibroblast and keratinocyte, and also their unique attribute to suppress inflammation in wound site has attracted increasing attention among scholars. In addition, MSC’s other capabilities to induce angiogenesis as a result of secretion of pro-angiogenic factors accompanied with marked anti-fibrotic activities, which mainly mediated by the releases matrix metalloproteinase (MMPs), make them a rational and effective strategy to accelerate wound healing with a small scar. Since the chief healing properties of the MSCs depend on their paracrine effects, it appears that MSCs-derived exosomes also can be an alternative option to support wound healing and skin regeneration as an innovative cell-free approach. Such exosomes convey functional cargos (e.g., growth factor, cytokine, miRNA, etc.) from MSCs to target cells, thereby affecting the recipient skin cells’ biological events, such as migration, proliferation, and also secretion of ECM components (e.g., collagen). The main superiorities of exosome therapy over parental MSCs are the diminished risk of tumor formation and also lower immunogenicity. Herein, we deliver an overview of recent in vivo reports rendering the therapeutic benefits of the MSCs-based therapies to ease skin wound healing, and so improving quality of life among patients suffering from such conditions.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) firstly emerged in Wuhan, China at the end of 2019. After going through the experimental process, the virus was named the novel coronavirus (2019-nCoV) by the World Health Organization (WHO) in February 2020 which has created a global pandemic. The coronavirus disease 2019 (COVID-19) infection is challenging the people who are especially suffering from chronic health problems such as asthma, diabetes, and heart disease or immune system deteriorating disorders, including cancers, Alzheimer's, etc. Other predisposing/risk factors consist of smoking and age (elderly people are at higher risk). The 2019-nCoV attacks epithelial cells in all organs, particularly epithelial cells in the lungs, resulting in viral pneumonia. The 2019-nCoV starts its invasion with the attachment and entry into the respiratory tract epithelial cells via Angiotensin-Converting Enzyme 2 (ACE2) receptors on the epithelial cells. The critical problem with 2019-nCoV is its ability in human to human asymptomatic transmission which causes the rapid and hidden spread of the virus among the population. Also, there are several reports of highly variable and tightly case-dependent clinical manifestations caused by SARS-CoV2, which made the virus more enigmatic. The clinical symptoms are varied from common manifestations which occurred in flu and cold, such as cough, fever, body-ache, trembling, and runny nose to severe conditions, like the Acute Respiratory Distress Syndrome (ARDS) or even uncommon/unusual symptoms such as anosmia, skin color change, and stroke. In fact, besides serious injuries in the respiratory system, COVID-19 invades and damages various organs, including the kidney, liver, gastrointestinal, and nervous system. Accordingly, to cut the transmission chain of disease and control the infection spread. One of the major solutions seems to be early detection of the carriers, particularly the asymptomatic people, with sensitive and accurate diagnostic techniques. Moreover, developing novel and appropriate therapeutic approaches will contribute to the suitable management of the pandemic. Therefore, there is an urgent necessity to make comprehensive investigations and study reviews about COVID-19, offering the latest findings of novel therapies, drugs, epidemiology, and routes of virus transmission and pathogenesis. In this review, we discuss new therapeutic outcomes and cover and the most significant aspects of COVID-19, including the epidemiology, biological features, organs failure, and diagnostic techniques.

Problem: Increased oxidative stress (OS) and inflammatory factors in metabolic syndrome (MS) patients are considered as risk factors for recurrent implantation failure (RIF). The aim of this study was to investigate OS markers, inflammatory factors, related microRNAs (miRNA) expression, and cytokine and transcription factors RNA expression.Method of study: We evaluated the frequency of helper T (Th) 17 and regulatory T (Treg) cells in recurrent implantation failure (RIF) women with or without MS. miRNA expression, an inflammatory cytokine, and transcription factors were measured by real‐time PCR. The level of interleukin (IL)‐1β, IL‐6, IL‐17, tumour necrosis factor‐alpha (TNF‐alpha) and chemokine (C‐C motif) ligand 2 (CCL‐2), and C‐X‐C motif chemokine ligand 8 (CXCL‐8) were measured by enzyme‐linked immunosorbent assay (ELISA). OS markers were evaluated by spectrophotometric assay. Th17 and Treg cell frequencies were determined by flow cytometry.Results: The expression of AP1, NF‐κB, FOXP3, miRNA‐21; serum or plasma level of OS markers (ie, nitric oxide, total oxidant status, and myeloperoxidase); serum level of inflammatory factors (ie, IL1‐β, IL‐6, IL‐17, TNF‐alpha, CXCL‐8, and CCL‐2); and frequency of Th17 cells were increased in RIF‐MS patients in comparison with RIF women without MS (RIF‐NMS) and control group. The expression of miRNA‐223 and 146a, antioxidant enzymes, namely superoxide dismutase (SOD) and catalase (CAT), and frequency of Treg also declined in RIF‐MS patients.Conclusion: Overall, our findings suggest that MS in RIF patients causes increased inflammatory factors and OS, which in turn leads to implantation failure.

Recurrent pregnancy loss (RPL) is a one of the most common obstetrical complications. Since, the successful pregnancy occurs in T helper 2 (Th2)‐dominant situation and since, Th1 type immunity is related to pregnancy failure, we investigated the effects of cyclosporine on Th1 and Th2 cells in RPL women. Totally, 76 RPL patients (38 women as treated group and 38 as control group) were included in this study. Flow cytometry was utilized to analyze the frequency of Th1 and Th2 in blood samples. Also, real‐time polymerase chain reaction was carried out to assess the messenger RNA (mRNA) expression of transcription factors and enzyme‐linked immunosorbent assay was used to evaluate Th1 and Th2 related cytokines. Significant decrease in Th1 frequency (p = 0.0004), Th1/Th2 ratio (p < 0.0001), T‐bet mRNA expression (p < 0.0001), interferon‐γ (p = 0.0007), and tumor necrosis factor α (p = 0.0002) secretion level were observed in cyclosporine group. Moreover, significant increase in Th2 frequency (p < 0.0001), mRNA expression of GATA binding protein 3 (p = 0.0001), and interleukin 10 secretion level (p = 0.0027) was also evident in treated group. At the end of the investigation, 31 (81.5%) patients in cyclosporine‐treated group had successful childbirth when compared with 16 (42.1%) women in control group (p = 0.0001). Given this, cyclosporine treatment for RPL patients with elevated Th1/Th2 ratio can result in improved pregnancy outcome.

Toll‐like receptors (TLRs) are innate immune cells receptors. They are expressed on leukocytes, epithelial cells, and more particularly on placental immune cells and chorion trophoblast. Upregulation of innate immune response occurs during normal pregnancy, but its excessive activity is involved in the pathology of pregnancy complications including pregnancy‐induced hypertension and pre‐eclampsia (PE). The recent studies about the overmuch inflammatory responses and aberrant placentation are associated with increased expression of TLRs in PE patients. This review has tried to focus on the relationship between some activities of TLRs and the risk of preeclampsia development.