MicroRNA targeting: A novel therapeutic intervention for ovarian cancer.

Ovarian cancer, a perilous form of cancer affecting the female reproductive system, exhibits intricate communication networks that contribute to its progression. This study aims to identify crucial molecular abnormalities linked to the disease to enhance diagnostic and therapeutic strategies. In particular, we investigate the role of microRNAs (miRNAs) as diagnostic biomarkers and explore their potential in treating ovarian cancer. By targeting miRNAs, which can influence multiple pathways and genes, substantial therapeutic benefits can be attained. In this review we want to shed light on the promising application of miRNA-based interventions and provide insights into the specific miRNAs implicated in ovarian cancer pathogenesis.

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.

Etiology and management of recurrent implantation failure: A focus on intra-uterine PBMC-therapy for RIF.

Infertility is one of the most common problems among couples worldwide. Recurrent pregnancy loss, premature ovarian failure, recurrent implantation failure and etc. are common high prevalence disorders in societies. We will review the definition, causes and treatment of recurrent implantation failure disorder in recent studies. Implantation refers to the attachment of the embryo to the endometrial luminal surface and recurrent implantation failure (RIF) is defined as the failure to achieve a pregnancy after transferring high-grade embryos through at least three in vitro fertilization (IVF) cycles to the endometrium. The embryo factors, maternal age, uterine factors, and multifactorial effectors have been considered as the causes of implantation failure. In this review, we aim to focus on immunological factors and cells such as pro-inflammatory cytokines and dendritic cells, macrophages, decidual and uterine NK cells, as well as Th-1 cells. There are different types of treatment according to the cause of RIF including aspirin and low-molecular-weight heparin therapy, immunosuppressive drugs, intravenous immunoglobulins, and hydroxychloroquine. Among immunological recurrent implantation failure therapy, we will discuss the intrauterine PBMC-therapy in detail.

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.

Current approaches for the treatment of premature ovarian failure with stem cell therapy.

One of the common disorders found in women is premature ovarian failure (POF). Recently some studies have explained premature ovarian insufficiency (POI). The causes of it are unknown although various types of study have been done. The most common causes such as genetic and autoimmune conditions can have a role in POF and can lead to infertility. Some characterization of POF are hypo-oestrogenism (estrogen deficiency), increased gonadotropin level and most importantly amenorrhea. The main purpose of this review is to describe the cause and treatment of POF, especially stem cell therapy proposed in previous studies. Stem cells have self-renewal and regeneration potential, hence they can be very effective in the treatment of ovarian failure and consequently infertility. There are several kinds of stem cells such as, mesenchymal stem cells (MSCs), stem cells from extra-embryonic tissues, induced pluripotent stem cells (iPSCs), and ovarian stem cells that are used in POF stem cell therapy as observed in previous studies. This article reviews the latest studies on POF to summarize current understanding and future directions.