Uterine fluid microRNAs in repeated implantation failure.

Recurrent implantation failure (RIF) is a significant obstacle in assisted reproductive procedures, primarily because of compromised receptivity. As such, there is a need for a dependable and accurate clinical test to evaluate endometrial receptiveness, particularly during embryo transfer. MicroRNAs (miRNAs) have diverse functions in the processes of implantation and pregnancy. Dysregulation of miRNAs results in reproductive diseases such as recurrent implantation failure (RIF). The endometrium secretes several microRNAs (miRNAs) during the implantation period, which could potentially indicate whether the endometrium is suitable for in vitro fertilization (IVF). The goal of this review is to examine endometrial miRNAs as noninvasive biomarkers that successfully predict endometrium receptivity in RIF.

The role of the endometrial microbiome in embryo implantation and recurrent implantation failure.

There is a suggested pathophysiology associated with endometrial microbiota in cases where repeated implantation failure of high-quality embryos is observed. However, there is a suspected association between endometrial microbiota and the pathogenesis of implantation failure. However, there is still a lack of agreement on the fundamental composition of the physiological microbiome within the uterine cavity. This is primarily due to various limitations in the studies conducted, including small sample sizes and variations in experimental designs. As a result, the impact of bacterial communities in the endometrium on human reproduction is still a subject of debate. In this discourse, we undertake a comprehensive examination of the existing body of research pertaining to the uterine microbiota and its intricate interplay with the process of embryo implantation.

An overview of possible pivotal mechanisms of Genistein as a potential phytochemical against SARS-CoV-2 infection: A hypothesis.

The Coronavirus Disease 2019 (COVID-19) pandemic has been caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is a global problem that humanity has not yet found a definitive solution for it. In this regard, a global effort has been done to find effective or potential adjuvant therapies in order to fight this infection. Genistein is a small, biologically active phytoestrogen flavonoid that is found in high amounts in soy and plants of the Fabaceae family. This important compound is known due to its anti-cancer, anti-inflammatory, and antioxidant effects. Additionally, protective effects of genistein have been reported in different pathological conditions through modulating intracellular pathways such as PI3K, Akt, mTOR, NF-κB, PPARγ, AMPK, and Nrf2. Scientific evidence suggests that genistein could have a potential role to treat COVID-19 through its anti-inflammatory and anti-oxidant effects. Furthermore, it appears to interfere with intracellular pathways involved in viral entry into the cell. This review provides a basis for further research and development of clinical applications of genistein as a potential alternative therapy to decrease inflammation and oxidative stress in COVID-19 patients. PRACTICAL APPLICATIONS: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent for the Coronavirus Disease 2019 (COVID-19), has brought unprecedented untold hardship to both developing and developed countries. The inflammation, cytokine storm, and oxidative stress have an important role in the pathogenesis of this infection. In this regard, finding plant-derived compounds with anti-inflammatory and anti-oxidative effects would be very beneficial in reducing the mortality induced by this infection. Genistein an isoflavone derived from soy-rich products possesses versatile biological activities. It has potent anti-inflammatory and anti-oxidative and immunomodulatory effects. Furthermore, this compound may prevent viral entry to host cells and reduce SARS-CoV2-induced lung injury. Therefore, we suggest further studies on the effects of genistein on SARS-Cov-2 infection.

Pentoxifylline: A Drug with Antiviral and Anti-Inflammatory Effects to Be Considered in the Treatment of Coronavirus Disease 2019.

In December 2019, a new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China, causing pneumonia outbreaks first in the Wuhan region and has now spread worldwide. There are no specific drugs for the disease caused by this virus, coronavirus disease 2019 (COVID-19). Considering that new synthesized drugs cannot be applied immediately to patients, conventional drug in new use is a feasible solution. Chloroquine, remdesivir, favipiravir, lopinavir, ribavirin, and ritonavir have shown efficacy to inhibit coronavirus in vitro. Pentoxifylline, a drug with anti-inflammatory, immunomodulatory, and bronchodilatory effects, has previously been shown to inhibit several viral infections. Immunological studies have shown that most patients with severe COVID-19 exhibit substantially elevated serum levels of pro-inflammatory cytokines. Pentoxifylline is a phosphodiesterase inhibitor that increases the levels of cyclic adenosine monophosphate, which in turn activates protein kinase, leading to a reduction in the synthesis of pro-inflammatory cytokines and immune cell migration. Here, we propose pentoxifylline, a drug with low cost and toxicity, as a possible treatment for COVID-19 based on its interesting properties.

Effects of treatment with hydroxychloroquine on the modulation of Th17/Treg ratio and pregnancy outcomes in women with recurrent implantation failure: clinical trial.

AIM: The imbalance of Th17/Treg cells has been recently suggested as a new risk factors for recurrent implantation failure (RIF). Furthermore Th17/Treg cells are involved in immune regulation in peripheral blood and endometrial tissue of patients with RIF. In this research, we investigated the effects of Hydroxychloroquine (HCQ) on the level and function of Th17 and Treg cells in women with RIF. It may be possible to improve pregnancy outcomes by modulating high cytokine levels. METHODS: Women with RIF received oral HCQ (n = 60) on day 4 of the menstrual cycle and continued until day 20 of the menstrual cycle and 2 days before embryo transfer and continued until the day of the pregnancy test, for a total of 16 days in another cycle. The serum levels of IL-17 and IL-10, the expression of transcription factors related to Th17 and Treg cells and the immune-reactivity of IL-17, IL-21 as Th17 related cytokines and IL-10, TGF- ß as Treg related cytokines in endometrial tissues were evaluated by ELISA, real-time PCR, and fluorescent immunohistochemistry respectively.Results: Treatment with HCQ down-regulated Th17 related cytokines and function and up-regulated Treg related cytokines and function significantly (p < .001). RORγt, the Th17 transcription factor, expression was down-regulated and FOXP-3, the T-reg transcription factor, expression was up-regulated. The biochemical pregnancy rate was not significantly different in RIF patients before and after treatment. CONCLUSION: Our results demonstrated that the administration of HCQ in RIF women with immune cell disorders during pregnancy could affect the Th17/Treg ratio and enhance Treg and diminish Th17 responses which may be associated with successful pregnancy outcomes. However, significant difference in pregnancy outcomes was not observed in the present study.