Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies.

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.

The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review.

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.

COVID-19: Our Current Knowledge of Epidemiology, Pathology, Therapeutic Approaches, and Diagnostic Methods.

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.

Intrauterine administration of autologous hCG- activated peripheral blood mononuclear cells improves pregnancy outcomes in patients with recurrent implantation failure; A double-blind, randomized control trial study.

We aimed to investigate the effect of intrauterine administration of autologous hCG-activated PBMCs in RIF women with low Th-17/Treg cell ratio. 248 women with a history of implantation failure volunteered to receive PBMC-therapy. After immunologic consultation and doing flow cytometry analysis, 100 women with at least three IVF/ET failure who had low Th-17/Treg ratio in comparison with healthy control were enrolled in this study. These 100 patients were randomly divided into two groups as PBMC receiving (n = 50) and controls (n = 50). Then PBMCs were obtained from patients and treated with hCG for 48 h. Afterward, PBMCs were administered into the uterine cavity of the patient in the study group, two days before ET. The concentration of inflammatory cytokines was examined in the supernatant of cultured PBMCs after 2, 24, and 48 h of incubation using the ELISA method. The frequency of Th-17, Treg, and the Th-17/Treg ratio was significantly lower in RIF women than the healthy controls (P < 0.0001). The secretion of inflammatory cytokines was significantly higher after 48 h compared to 2 and 24 h (P < 0.0001). The pregnancy and live birth rate were significantly increased in women undergoing the PBMC-therapy compared to control (PBS-injecting) group (P = 0.032 and P = 0.047, respectively). The miscarriage rate was considerably lower in PBMC-therapy group (P = 0.029). Our findings suggest that intrauterine administration of autologous in vitro hCG-activated PBMCs improves pregnancy outcomes in patients with at least three IVF/ET failures.

Oxidative stress, inflammatory settings, and microRNA regulation in the recurrent implantation failure patients with metabolic syndrome.

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)-1ß, 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-ß, 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.

Metabolic syndrome mediates inflammatory and oxidative stress responses in patients with recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is defined as three or more consecutive pregnancy losses prior to the 20th week of gestation. Exaggerated maternal immune response and oxidative stress status have been proposed as one of the main underlying mechanisms for RPL. The aim of this study was to evaluate the role of inflammatory pathway and oxidative stress imbalance in RPL patients with or without metabolic syndrome (MetS). 21 and 28 RPL patients with (RPL-MS) and without (RPL-NMS) metabolic syndrome were enrolled in this clinical study. 42 healthy women also were considered as the control group. The levels of IL1ß, IL6, IL17, TNFα, CCL2, CXCL8 were evaluated by ELISA method. Additionally, the oxidative stress biomarkers including TAS, TOS, NO, CAT, SOD, AOPP, MPO were analyzed by spectrophotometry. The expression levels of IL1ß, IL6, IL17, TNFα, CCL2, CXCL8, NFĸB, AP1, miR-21, miR-146-a, miR-223 were also assessed by real time PCR. The frequency of Th17 and T-reg cells was also measured by flow cytometry. Significant increase in the expression levels of IL1ß, IL6, IL17, TNFα, CCL2, CXCL8, NFĸB, AP1 and miR-21 was observed in RPL-MS patients. Furthermore, significant decreased expression levels of FoxP3, miR-146-a and miR-223 was also observed in RPL-MS group. The levels of IL1ß, IL6, IL17, TNFα, CCL2, CXCL8, NO, MPO and TOS were found to be higher in RPL-MS group compared to the RPL-NMS and healthy controls. In contrast, the level of CAT and SOD in RPL-MS patients was decreased. The frequency of Th17 and Treg cells was also higher and lower in RPL-MS patients compared to the other groups, respectively. Our results support the concept that subclinical inflammatory state, oxidative stress and metabolic syndrome play a crucial role in the etiopathogenesis of RPL assisting clinicians for pregnancy consequences prediction.

Cyclosporine A improves pregnancy outcomes in women with recurrent pregnancy loss and elevated Th1/Th2 ratio.

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 signaling network in pre-eclampsia: An updated review.

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.

Stem cell therapy in Asherman syndrome and thin endometrium: Stem cell- based therapy.

The endometrium is one of the essential components of the uterus. The endometrium of human is a complex and dynamic tissue, which undergoes periods of growth and turn over during any menstrual cycle. Stem cells are initially undifferentiated cells that display a wide range of differentiation potential with no distinct morphological features. Stem cell therapy method recently has become a novel procedure for treatment of tissue injury and fibrosis in response to damage. Currently, there is massive interest in stem cells as a novel treatment method for regenerative medicine and more specifically for the regeneration of human endometrium disorder like Asherman syndrome (AS) and thin endometrium. AS also known as intrauterine adhesion (IUA) is a uterine disorder with the aberrant creation of adhesions within the uterus and/or cervix. Patients with IUA are significantly associated with menstrual abnormalities and suffer from pelvic pain. In addition, IUA might prevent implantation of the blastocyst, impair the blood supply to the uterus and early fetus, and finally result in the recurrent miscarriage or infertility in the AS patients. It has been evidenced that the transplantation of different stem cells with a diverse source in the endometrial zone had effects on endometrium such as declined the fibrotic area, an elevated number of glands, stimulated angiogenesis, the enhanced thickness of the endometrium, better formed tissue construction, protected gestation, and improved pregnancy rate. This study presents a summary of the investigations that indicate the key role of stem cell therapy in regeneration and renovation of defective parts.