The potential use of therapeutics and prophylactic mRNA vaccines in human papillomavirus (HPV).

Cervical cancer (CC) and other malignant malignancies are acknowledged to be primarily caused by persistent human papillomavirus (HPV) infection. Historically, vaccinations against viruses that produce neutralizing antibodies unique to the virus have been an affordable way to manage viral diseases. CC risk is decreased, but not eliminated, by HPV vaccinations. Since vaccinations have been made available globally, almost 90% of HPV infections have been successfully avoided. On the lesions and diseases that are already present, however, no discernible treatment benefit has been shown. As a result, therapeutic vaccines that elicit immune responses mediated by cells are necessary for the treatment of established infections and cancers. mRNA vaccines possess remarkable potential in combating viral diseases and malignancy as a result of their superior industrial production, safety, and efficacy. Furthermore, considering the expeditiousness of production, the mRNA vaccine exhibits promise as a therapeutic approach targeting HPV. Given that the HPV-encoded early proteins, including oncoproteins E6 and E7, are consistently present in HPV-related cancers and pre-cancerous lesions and have crucial functions in the progression and persistence of HPV-related diseases, they serve as ideal targets for therapeutic HPV vaccines. The action mechanism of HPV and HPV-related cancer mRNA vaccines, their recent advancements in clinical trials, and the potential for their therapeutic applications are highlighted in this study, which also offers a quick summary of the present state of mRNA vaccines. Lastly, we highlight a few difficulties with mRNA HPV vaccination clinical practice and provide our thoughts on further advancements in this quickly changing sector. It is expected that mRNA vaccines will soon be produced quickly for clinical HPV prevention and treatment.

Is the Co-administration of Metformin and Clomiphene Superior to Induce Ovulation in Infertile Patients With Poly Cystic Ovary Syndrome and Confirmed Insulin-Resistance: A Double Blind Randomized Clinical Trial.

Objective: This study aimed to compare the effects of clomiphene citrate (CC) combined with metformin or placebo on infertile patients with poly cystic ovary syndrome (PCOS) and insulin resistance (IR). Materials and methods: We included 151 infertile women with PCOS and IR in a university hospital from November 2015 to April 2022 in this prospective, double-blind, randomized, placebo-controlled trial. Patients were randomized into two groups; group A: received CC plus metformin (n = 76) and group B: received CC plus placebo (n = 75). The ovulation rate was the main outcome measure. Clinical pregnancy, ongoing pregnancy, live birth and abortion rates were secondary outcome measures. Results: There was no remarkable difference in ovulation rate in two groups. Moreover, no significant changes were observed in clinical pregnancy, ongoing pregnancy, live birth and abortion rates between two groups. A larger proportion of women in group A suffered from side effects of metformin (9.3% versus 1.4%; p=0.064), although this was not significant. Conclusion: In IR infertile women with PCOS, metformin pre-treatment did not increase the ovulation, clinical pregnancy and live birth rates in patients on clomiphene citrate.

The role of toll-like receptors (TLRs) and their therapeutic applications in endometrial cancer

Endometrial cancer (EC) is developed nations' most prevalent form of gynecologic cancer. Patients are frequently diagnosed with EC when the tumor is still limited to the uterus. Patients without tumor metastasis have a 5-year survival rate ranging from 80 to 90%; however, almost 16.8% of EC patients develop a metastatic form of the tumor. In the early stages of tumorigenesis, the immune system is able to identify aberrant cells as non-self, therefore providing the optimal pro-inflammatory microenvironment for the elimination of cancer cells. Although, chronic inflammation can be a crucial aspect of tumor development. Toll-like receptors (TLRs), as the main pattern recognition receptors (PRRs) in innate immunity, may stimulate an inflammatory response and provide cell survival in the tumor microenvironment (TME). TLRs are vital immunomodulators that may significantly impact the development of gynecologic malignancies. Therefore, TLR inhibitors are being researched for their possible benefits in treating gynecologic cancers. The aim of this study is to review the current knowledge in this field and provide some insight into the therapeutic potential of TLR inhibitors in EC (AU)

The evaluation of CD39, CD73, and HIF-1 α expression besides their related miRNAs in PBMCs of women with recurrent pregnancy loss.

The molecular mechanisms involved in the pathogenesis of recurrent pregnancy loss (RPL) are not completely recognized. The present study aimed to assess the molecules associated with ATP catabolism and hypoxia besides their related miRNAs in patients with RPL. The frequency of Th17 and Treg cells in PBMCs of RPL women and healthy pregnant women were evaluated with Flow cytometry. The expression levels of CD39, CD73, and Hypoxia-inducible factor-alpha (HIF-1α), miR-18a, miR-30a, and miR-206 in PBMCs of two groups were measured with real-time PCR and western blotting. Then, serum levels of IGF-1, TGF-ß, and HIF-1α were measured by ELISA. Our results indicated a higher (p = 0.0002) and lower (p < 0.0001) frequency of Th17 and Treg lymphocytes in RPL women, respectively. The expression level of CD39 decreased in PBMCs of RPL women whereas the level of CD73 and HIF-α increased (p = 0.0010, 0.0023, 0.0006 respectively). The results of CD39 and CD37 were also confirmed by protein analysis (p = 0.0047, 0.0364 respectively). Almost, the same results for CD39 and CD73 expression at mRNA and protein levels were observed in isolated Treg cells. Moreover, we found the higher expression of miR-206 and miRNA-30a (p = 0.0038, 0.0123), but the lower expression of miRNA-18a (p = 0.0101) in RPL. The concentration level of IGF-1, and TGF-ß reduced (p = 0.0017, 0.0065 respectively) while the level of HIF-α elevated (p = 0.0235) in serum samples of RPL. In conclusion, we observed the dysregulation of molecules that are involved in ATP catabolism and hypoxia, including CD39, CD73, and HIF-1a which is related to miR-18a, miR-30a, and miR-206 change in RPL women. It may be potentially used for RPL prognosis by more comprehensive future studies.

The role of toll-like receptors (TLRs) and their therapeutic applications in endometrial cancer.

Endometrial cancer (EC) is developed nations' most prevalent form of gynecologic cancer. Patients are frequently diagnosed with EC when the tumor is still limited to the uterus. Patients without tumor metastasis have a 5-year survival rate ranging from 80 to 90%; however, almost 16.8% of EC patients develop a metastatic form of the tumor. In the early stages of tumorigenesis, the immune system is able to identify aberrant cells as non-self, therefore providing the optimal pro-inflammatory microenvironment for the elimination of cancer cells. Although, chronic inflammation can be a crucial aspect of tumor development. Toll-like receptors (TLRs), as the main pattern recognition receptors (PRRs) in innate immunity, may stimulate an inflammatory response and provide cell survival in the tumor microenvironment (TME). TLRs are vital immunomodulators that may significantly impact the development of gynecologic malignancies. Therefore, TLR inhibitors are being researched for their possible benefits in treating gynecologic cancers. The aim of this study is to review the current knowledge in this field and provide some insight into the therapeutic potential of TLR inhibitors in EC.