Human Papillomavirus Infections in Pregnant Women and Its Impact on Pregnancy Outcomes: Possible Mechanism of Self-Clearance

Young women are at the maximum risk of Human papillomavirus (HPV) infection which are asymptomatic in a majority of cases and spontaneously get cleared. Women in the age between 20 and 35 years are more active sexually and especially in the developing nations, this age group forms a major cohort among the population of pregnant women. The changed hormonal milieu and immune response during pregnancy might favor presence or persistence of HPV infection, while at the same time natural clearance also takes place during pregnancy with an unknown mechanism. Various HPVs have been reported to be associated with preterm rupture of membranes (PROM), fetal growth restriction (FGR), preeclampsia, placental abnormalities and preterm delivery in several populations. The risk factors involved in the intrauterine environment affects fetal development and thus increase the development risk of specific diseases in adult life as per the hypothesis of the fetal origins of adult disease (FOAD). The structural and molecular changes in the feto-maternal interface support and protect the semiallogeneic fetus from immune-mediated or inflammatory injury. On the other hand, the trophoblast cells of placenta facilitate the replication of HPV and the affliction of placenta and the vaginal infection can directly be associated with pregnancy outcomes. So, to optimize better child health care and reproductive outcomes, HPV screening might help during pregnancy. It is therefore important to understand how the HPV is affecting the early pregnancy and immune cells within the feto-maternal interface are educated for self-clearance to fulfill their biological functions or prevalence to affect the pregnancy outcomes and how the persistence of HR-HPV infection overtime increases the development of cervical cancer risk

Pyrazole-based and N,N-diethylcarbamate functionalized some novel aurone analogs: Design, synthesis, cytotoxic evaluation, docking and SAR studies, against AGS cancer cell line

The present study involves the design, synthesis, and biological evaluation of a series of thirty-three, pyrazole-based and N,N-diethylcarbamate functionalized, novel aurone analogs, against AGS cancer cell line. These novel aurone analogs are obtained from the reaction of pyrazole-based 6-hydroxyaurones with diethyl carbamoyl chloride using mild basic reagent. The cytotoxic activities of these compounds were evaluated against a human gastric adenocarcinoma cell line (AGS) and disclosed some potential outcomes as several analogs were found to have cytotoxicity better than the reference drugs Oxaliplatin and Leucovorin. The structure-activity relationship (SAR) study further unveiled the critical role of replacing the hydroxyl group in ring A with a carbamoyl group for cytotoxic activity. Among these aurone analogs, 8e and 8f, with IC50 values of 6.5 ± 0.024 μM and 6.6 ± 0.035 μM, respectively, are identified as the most active compounds. Molecular docking studies were conducted against HER2, a human epidermal growth factor involved in gastric and ovarian cancer, to investigate the binding interactions between the compounds and the protein HER2, where7e and 8e exhibited maximum interactions

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Not AvailableThe functional activity among STAT3 and PIM1, are key signaling events for cancer cell function. Curcumin, a diarylheptanoid isolated from turmeric, effectively inhibits STAT3 signaling. Selectively, we attempted to address interactions of STAT3, PIM1 and Curcumin for therapeutic intervention using in silico and in vitro experimental approaches. Firstly, protein-protein interactions (PPI) between STAT3-PIM1 by molecular docking studies reflected salt bridges among Arg279 (STAT3)-Glu140 (PIM1) and Arg282 (STAT3)-Asp100 (PIM1), with a binding affinity of − 38.6 kcal/mol. Secondly, molecular dynamics simulations of heterodimeric STAT3-PIM1 complex with curcumin revealed binding of curcumin on PIM-1 interface of the complex through hydrogen bonds (Asp155) and hydrophobic interactions (Leu13, Phe18, Val21, etc.) with a binding energy of − 7.3 kcal/ mol. These PPIs were confirmed in vitro by immunoprecipitation assays in MDA-MB-231 cells. Corroborating our results, expression levels of STAT3 and PIM1 decreased after curcumin treatment. We observed that PIM1 in teracts with STAT3 and these functional interactions are disrupted by curcumin. The calculated band energy gap of heterodimeric STAT3-PIM1-Curcumin complex was of 9.621 kcal/mol. The present study revealed the role of curcumin in STAT3/PIM1 signaling and its binding affinity to the complex for design of advanced cancer therapeutics.Not Availabl