A glance into the roles of microRNAs (exosomal and non-exosomal) in polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The clinical symptoms include hyperandrogenism, chronic anovulation, and multiple ovarian cysts. PCOS is strongly associated with obesity and insulin resistance. MicroRNAs (miRNAs) are a group of short non-coding RNAs that play a role in the post-transcriptional regulation of gene expression and translational inhibition. They play a vital role in the regulation of multiple metabolic and hormonal processes as well as in oocyte maturation and folliculogenesis in the female reproductive system. miRNAs can be used as diagnostic biomarkers or therapeutic targets because of their stability. The encapsulation of miRNAs in extracellular vesicles or exosomes contributes to their stability. Exosomes are constantly secreted by many cells and size of about 30 to 150 nm. Enveloping miRNAs exosomes can release them for cellular communication. The induced transfer of miRNAs by exosomes is a novel process of genetic exchange between cells. Many studies have shown that along with non-exosomal miRNAs, different types of exosomal miRNAs derived from the serum and follicular fluid can play an essential role in PCOS pathogenesis. These miRNAs are involved in follicular development and various functions in granulosa cells, apoptosis, cell proliferation, and follicular atresia. The present study aimed to comprehensively review the evidence on miRNAs and their affected pathways under both non-exosomal and exosomal circumstances, primarily focusing on the pathogenesis of PCOS.

Relationship between fetal middle cerebral artery pulsatility index and cerebroplacental ratio with adverse neonatal outcomes in low-risk pregnancy candidates for elective cesarean section: A cross-sectional study.

Background: The cerebroplacental ratio (CPR) is an important factor for predicting adverse neonatal outcomes in appropriate-for-gestational-age fetuses. Objective: To evaluate whether there is an association between the CPR level and adverse neonatal outcomes in appropriate-for-gestational-age fetuses. Materials and Methods: This cross-sectional study included 150 low-risk pregnant women candidates for elective cesarean sections at the gestational age of 39 wk. CPR and middle cerebral artery pulsatility index (MCA PI) were calculated in participants just before cesarian section. Postnatal complications were defined as an adverse neonatal outcome such as an Apgar score of the neonate ≤ 7 at 5 min, neonatal intensive care unit (NICU) admission, cord arterial pH ≤ 7/14, and meconium stained liquor. Results: The mean age of participants was 31.53 ± 4.91 yr old. The mean CPR was reported as 1.83 ± 0.64. The Chi-square test analysis revealed that a low MCA PI and a low CPR were significantly associated with decreased cord arterial pH, decreased Apgar score at 5 min, and NICU admission (p < 0.001). There was no significant association between umbilical artery PI with arterial cord pH, Apgar score at 5 min, NICU admission, or meconium stained liquor. The Mann-Whitney test showed that a lower fetal weight appropriate for the women's gestational age was significantly associated with a decreased CPR and MCA PI (p < 0.005). There was no significant association between amniotic fluid index and CPR, umbilical artery PI, or MCA PI. Conclusion: The CPR is a significant factor in predicting adverse neonatal outcomes and ultimately neonatal mortality and morbidity of low risk, appropriate-for-gestational-age fetuses.

Alterations of epigenetic landscape in Down syndrome carrying pregnancies: A systematic review of case-control studies.

OBJECTIVE: Great attention is currently paid to both the pathogenetic mechanisms and non-invasive prenatal diagnosis (NIPD) of Down syndrome (DS). It has been posited that dysregulation of epigenetic signatures including DNA methylation and microRNAs (miRNAs) crucially contribute to the pathomechanism of DS. Therefore, we aimed to perform a systematic review of case-control publications that have examined the differences in epigenetic landscape between pregnancies bearing euploid fetuses and those affected with DS to provide a focused insight into the pathophysiology of DS and also novel biomarkers for NIPD of DS. STUDY DESIGN: Pertinent keywords were utilized to search into PubMed, Scopus, and Google Scholar. We enrolled studies that have compared the pattern of miRNAs expression profile or DNA methylation between pregnant women who carries DS fetuses and those with euploid fetuses. RESULTS: An assessment of 599 articles resulted in, finally, 18 eligible studies (12 miRNAs and 6 DNA methylation). The most investigated miRNAs were those that are encoded by genes on chromosome 21 and more hypermethylation regions in DS fetuses than euploids with nearly evenly distribution on all chromosomes were found. Distinct mechanisms with potential therapeutic purposes have been put forward for the involvement of epigenetic perturbations in the etiopathogenesis of DS. CONCLUSION: There is a disagreement in the recruiting of epigenetic biomarkers for NIPD of DS. This heterogeneity in results of the qualified publications emanates from confounding factors such as differences in demographic data of participants, analytical platforms, and study design. Hence, before harnessing epigenetic signatures for NIPD of DS, more experiments are required.

Adoptive transfer of Tregs: A novel strategy for cell-based immunotherapy in spontaneous abortion: Lessons from experimental models.

Since half of the genes are inherited from the paternal side, the maternal immune system has to tolerate the presence of foreign paternal antigens. Regulatory T cells facilitate the development and maintenance of peripheral tissue tolerance of the fetus during pregnancy. Reduction in regulatory T cells is associated with complications of pregnancy, including spontaneous abortion. Recent studies in mouse models have shown that the adoptive transfer of Tregs can prevent spontaneous abortion in mouse models through improving maternal tolerance. Thus, adoptive cell therapy using autologous Tregs could potentially be a novel therapeutic approach for cell-based immunotherapy in women with unexplained spontaneous abortion. Besides, strategies for activating and expanding antigen-specific Tregs ex vivo and in vivo based on pharmacological agents can pave the foundation for an approach incorporating immunotherapy and pharmacotherapy. This review aims to elaborate on the current understanding of the therapeutic potential of the adoptive transfer of Tregs in the treatment of spontaneous abortion disease.

Exosomal Long Noncoding RNAs: Insights into Emerging Diagnostic and Therapeutic Applications in Lung Cancer.

Lung cancer is the most common cause of cancer-related deaths worldwide. Annually, millions of people die from lung cancer because of late detection and ineffective therapies. Recently, exosomes have been introduced as new therapeutic players with the potential to improve upon current diagnostic and treatment options. Exosomes are small membranous vesicles produced during endosomal merging. This allows for cell packaging of nucleic acids, proteins, and lipids and transfer to adjacent or distant cells. While exosomes are a part of normal intercellular signaling, they also allow malignant cells to transfer oncogenic material leading to tumor spread and metastasis. Exosomes are an interesting field of discovery for biomarkers and therapeutic targets. Among exosomal materials, lncRNAs have priority; lncRNAs are a class of noncoding RNAs longer than 200 base pairs. In the case of cancer, primary interest regards their oncogene and tumor suppressor functions. In this review, the advantages of exosomal lncRNAs as biomarkers and therapeutic targets will be discussed in addition to reviewing studies of their application in lung cancer.

The role of miR-146a in viral infection.

Cellular microRNAs (miRNAs) were identified as a key player in the posttranscriptional regulation of cellular-genes regulatory pathways. They also emerged as a significant regulator of the immune response. In particular, miR-146a acts as an importance modulator of function and differentiation cells of the innate and adaptive immunity. It has been associated with disorder including cancer and viral infections. Given its significance in the regulation of key cellular processes, it is not surprising which virus infection have found ways to dysregulation of miRNAs. miR-146a has been identified in exosomes (exosomal miR-146a). After the exosomes release from donor cells, they are taken up by the recipient cell and probably the exosomal miR-146a is able to modulate the antiviral response in the recipient cell and result in making them more susceptible to virus infection. In this review, we discuss recent reports regarding miR-146a expression levels, target genes, function, and contributing role in the pathogenesis of the viral infection and provide a clue to develop the new therapeutic and preventive strategies for viral disease in the future.