The Potential Relationship Between Different Human Female Reproductive Disorders and Sperm Quality in Female Genital Tract.

Spermatozoa should travel throughout the female reproductive tract to reach its ultimate goal, fertilization of the oocyte. At the ejaculation moment, millions of sperm within a few milliliters of the ejaculate are deposited at the cranial segment of vagina and make their journey to the fertilization site. This is done by means of various factors, such as sperm motility, the uterine and fallopian tubes contractility, and the ciliary movement of the lining cells. During this migration, spermatozoa interact with the female microenvironment both physically and molecularly. In this regard, the quality of the environmental conditions may affect this interaction. Therefore, some alterations in women's genital tract microenvironment, such as conditions that occur in female reproductive disorders, may have detrimental effects on sperm reproductive function. In this review, human sperm migration through the female tract is described, and the potential effects of different reproductive disorders at reproductive organs, such as vagina, uterine cervix, uterus, fallopian tubes, and ovary on sperm survival and quality, are also argued. The understanding of those conditions that may impair sperm fertility in the female genital tract can provide a more accurate diagnosis of the causes of infertility in couples. This can ultimately lead to the discovery of effective treatment approaches.

An overview on tumor treating fields (TTFields) technology as a new potential subsidiary biophysical treatment for COVID-19.

COVID-19 pandemic situation has affected millions of people with tens of thousands of deaths worldwide. Despite all efforts for finding drugs or vaccines, the key role for the survival of patients is still related to the immune system. Therefore, improving the efficacy and the functionality of the immune system of COVID-19 patients is very crucial. The potential new, non-invasive, FDA-approved biophysical technology that could be considered in this regard is tumor treating fields (TTFields) based on an alternating electric field has great biological effects. TTFields have significant effects in improving the functionality of dendritic cell, and cytotoxic T-cells, and these cells have a major role in defense against viral infection. Hence, applying TTFields could help COVID-19 patients against infection. Additionally, TTFields can reduce viral genomic replication, by reducing the expressions of some of the vital members of DNA replication complex genes from the minichromosome maintenance family (MCMs). These genes not only are involved in DNA replication but it has also been proven that they have a crucial role in viral replication. Also, TTFields suppress the formation of the network of tunneling nanotubes (TNTs) which is knows as filamentous (F)-actin-rich tubular structures. TNTs have a critical role in promoting the spread of viruses through improving viral entry and acting as a protective agent for viral components from immune cells and even pharmaceuticals. Moreover, TTFields enhance autophagy which leads to apoptosis of virally infected cells. Thus, it can be speculated that using TTFields may prove to be a promising approach as a subsidiary treatment of COVID-19.

Anti-IgE monoclonal antibodies as potential treatment in COVID-19.

Coronavirus disease 2019 (COVID-19) is associated with irreversible effects on vital organs, especially the respiratory and cardiac systems. While the immune system plays a key role in the survival of patients to viral infections, in COVID-19, there is a hyperinflammatory immune response evoked by all the immune cells, such as neutrophils, monocytes, and includes release of various cytokines, resulting in an exaggerated immune response, named cytokine storm. This severe, dysregulated immune response causes multi-organ damage, which eventually leads to high mortality. One of the most important components of hypersensitivity is immunoglobulin E (IgE), which plays a major role in susceptibility to respiratory infections and can lead to the activation of mast cells. There is also a negative association between IgE and IFN-α, which can reduce Toll-like receptor (TLR) nine receptor expression and TLR-7 signaling to disrupt IFN production. Moreover, anti-IgE drugs such as omalizumab reduces the severity and duration of COVID-19. In addition to its anti-IgE effect, omalizumab inhibits inflammatory cells such as neutrophils. Hence, blockade of IgE may have clinical utility as an immunotherapy for COVID-19.

Human Tra2 proteins jointly control a CHEK1 splicing switch among alternative and constitutive target exons.

Alternative splicing--the production of multiple messenger RNA isoforms from a single gene--is regulated in part by RNA binding proteins. While the RBPs transformer2 alpha (Tra2α) and Tra2ß have both been implicated in the regulation of alternative splicing, their relative contributions to this process are not well understood. Here we find simultaneous--but not individual--depletion of Tra2α and Tra2ß induces substantial shifts in splicing of endogenous Tra2ß target exons, and that both constitutive and alternative target exons are under dual Tra2α-Tra2ß control. Target exons are enriched in genes associated with chromosome biology including CHEK1, which encodes a key DNA damage response protein. Dual Tra2 protein depletion reduces expression of full-length CHK1 protein, results in the accumulation of the DNA damage marker γH2AX and decreased cell viability. We conclude Tra2 proteins jointly control constitutive and alternative splicing patterns via paralog compensation to control pathways essential to the maintenance of cell viability.

Tra2 protein biology and mechanisms of splicing control.

Tra2 proteins regulate pre-mRNA splicing in vertebrates and invertebrates, and are involved in important processes ranging from brain development in mice to sex determination in fruitflies. In structure Tra2 proteins contain two RS domains (domains enriched in arginine and serine residues) flanking a central RRM (RNA recognition motif). Understanding the mechanisms of how Tra2 proteins work to control splicing is one of the key requirements to understand their biology. In the present article, we review what is known about how Tra2 proteins regulate splicing decisions in mammals and fruitflies.

Co-culture with neurotrophic factor secreting cells induced from adipose-derived stem cells: promotes neurogenic differentiation.

Adipose-derived stem cells (ADSCs) and bone marrow stem cells (BMSCs) can be equally proper in the treatment of neurodegenerative diseases. However, ADSCs have practical benefits. In this study, we attempted to induce the secretion of neurotrophic factors (NTF) in human ADSCs. We then evaluated the effects of co-culture with NTF secreting cells in neural differentiation of human ADSCs. Isolated human ADSCs were induced to neurotrophic factors secreting cells. To evaluate the in vitro effects of NTF-secreting ADSCs on neurogenic differentiation of ADSCs, we used neurogenic induction medium (control group), the combination of neurogenic medium and conditioned medium, or co-cultured NTF-secreting ADSCs which were encapsulated in alginate beads (co-culture) for 7 days. ELISA showed increased (by about 5 times) release of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in NTF-secreting ADSCs compared to human ADSCs. Real time RT-PCR analysis revealed that NTF-secreting ADSCs highly expressed NGF and BDNF. In addition, co-culture with NTF-secreting ADSCs could also promote neuronal differentiation relative to gliogenesis. Overall, NTF-secreting ADSCs secrete a range of growth factors whose levels in culture could promote neuronal differentiation and could support the survival and regeneration in a variety of neurodegenerative diseases.

Expression of Tra2 ß in Cancer Cells as a Potential Contributory Factor to Neoplasia and Metastasis.

The splicing regulator proteins SRSF1 (also known as ASF/SF2) and SRSF3 (also known as SRP20) belong to the SR family of proteins and can be upregulated in cancer. The SRSF1 gene itself is amplified in some cancer cells, and cancer-associated changes in the expression of MYC also increase SRSF1 gene expression. Increased concentrations of SRSF1 protein promote prooncogenic splicing patterns of a number of key regulators of cell growth. Here, we review the evidence that upregulation of the SR-related Tra2 ß protein might have a similar role in cancer cells. The TRA2B gene encoding Tra2 ß is amplified in particular tumours including those of the lung, ovary, cervix, stomach, head, and neck. Both TRA2B RNA and Tra2 ß protein levels are upregulated in breast, cervical, ovarian, and colon cancer, and Tra2 ß expression is associated with cancer cell survival. The TRA2B gene is a transcriptional target of the protooncogene ETS-1 which might cause higher levels of expression in some cancer cells which express this transcription factor. Known Tra2 ß splicing targets have important roles in cancer cells, where they affect metastasis, proliferation, and cell survival. Tra2 ß protein is also known to interact directly with the RBMY protein which is implicated in liver cancer.