Molecular interaction of cryptophycin 52 with Caspase 8 for the management of lung cancer during coronavirus outbreak : A computational study.

It has been seen that, during COVID-19 outbreak lung cancer (LC) patients are noted as a high-risk population which make a more challenging to treatment of the LC patients. The active form of caspase-8 is involved in lung carcinogenesis in both humans and mice. In this study, the virtual screening was performed among 200 compounds retrieved from several resources for the searching of potent lead against Caspase 8 (Casp8). Cryptophycin 52 was found to have a strong inhibiting efficacy based on the free energy of binding with the active site of Casp8. The lowest binding energy was found to be -8.05 kcal/mole and was further analyzed for molecular dynamic simulation. Casp8 enzyme was determined to interact with cryptophycin 52 through twelve amino acid residues, specifically ARG260, SER316, GLY318, ASP319, THR337, VAL354, PHE355, PHE356, ILE357, GLN358, ALA359 and CYS360 along with six hydrogen bond particular, ILE357:N-UNK1: O7, UNK1: O14-PHE355:O, UNK1: C25-PHE355:O, UNK1: C35-THR337:O, UNK1: H65-HE355:O and UNK1: C25-PHE356. In addition, MD simulations for 50ns were performed for optimization, flexibility estimation and assessment of Casp8-cryptophycin 52 complex stability. This complex was seen as reasonably stable according to the RMSD, RMSF, and radius of gyration graph. Results obtained indicate cryptophycin 52 may be a lead compound with significant anti-cancer ability against Casp8. Further experimental work, however, is expected to support the compound's anti-cancer viewpoint.

Effect of maternal obesity on labor induction in postdate pregnancy.

OBJECTIVE: To test the hypothesis that there is a higher rate of unsuccessful induction of labor (IOL) in post-term obese pregnant women compared to non-obese ones. METHODS: In this prospective cohort study, 144 obese (BMI > 30) and 144 non-obese (BMI < 29.9) post-term (> 41 weeks) pregnant women were recruited. IOL was done by misoprostol or amniotomy and oxytocin infusion according to the Bishop score. Comparison of percentage of failed IOL in both groups (primary outcome) was performed by the Chi-test. Logistic regression and multivariable regression were performed to assess the odds ratio (OR) of cesarean section (CS) and coefficient of delay in labor till vaginal delivery (VD) in obese versus (vs) non-obese groups. Adjustment for gestational age, parity, Bishop Score, membrane rupture and amniotic fluid index was done in both regression analyses. RESULTS: CS rate was significantly higher in obese group [26.4 vs 15.9%; difference in proportion (95% CI) 0.1 (0.01, 0.19); P value 0.02]. 106 (73.6%) obese women and 121 (84.1%) non-obese women delivered vaginally. In addition, the duration till VD was significantly higher in obese group (22 vs 19 h, P value 0.01). After adjustment for possible confounding factors, the CS was still higher in the obese group in comparison to non-obese group (OR 2.02; 95% CI 1.1, 3.7; P value 0.02). This finding suggested that obesity was an independent factor for failure of IOL. In addition, after adjustment for these confounders, obesity had the risk of increasing labor duration by 2.3 h (95% CI 0.1, 4.5) in cases that ended in VD. CONCLUSION: Based on our results, we conclude that there is a higher risk of CS in obese postdate pregnant women undergoing IOL in comparison to non-obese counterparts. Therefore, obstetricians should pay more attention to advising pregnant women about optimal weight gain during pregnancy and counseling about the chances of VD in cases of IOL. CLINCALTRIAL. GOV ID: NCT02788305.

Degradation of antibiotics in aqueous media using manganese nanocatalyst-activated peroxymonosulfate.

ε-MnO2 effectively activates peroxymonosulfate (PMS) for the efficient degradation of emerging pollutants. ε-MnO2 was synthesized by a facile thermal-treatment method and its long-term stability and efficiency for the elimination of emerging pollutants, including sulfamethoxazole (SMX), sulfachloropyridazine (SCP), sulfamethazine (SMT), ciprofloxacin (CIP), and azithromycin (AZI), from aqueous media were evaluated. ε-MnO2 was found to activate PMS more efficiently than α-MnO2, ß-MnO2, or δ-MnO2, owing to its high - OH-group content, unique structure, and high surface area. Sulfate (SO4•-), hydroxyl (•OH), and superoxide (O2•-) radicals, as well as singlet oxygen (1O2) were generated, with O2•- acting as the 1O2 precursor. The ε-MnO2/PMS system proved to be effective in the pH range of 3.5-9.0 and the rate of SMX degradation was not significantly affected by the presence of inorganic anions or natural organic matter. The proposed pathway for the activation of PMS by ε-MnO2 includes inner-sphere interactions between ε-MnO2 and PMS, and electron transfer to PMS via the MnIII â†” MnIV redox cycle, which generates reactive oxygen species. These findings provide new insight into PMS activation by less-toxic metal oxides as catalysts and demonstrate that Mn-based materials can be used to effectively treat water matrices containing emerging pollutants.

Simultaneous reduction of Cr(VI) and oxidization of organic pollutants by rice husk derived biochar and the interactive influences of coexisting Cr(VI).

In this study, biochar derived from rice husk via one-spot calcination treatment at 550 °C (biochar R550), demonstrated a remarkable efficiency in the simultaneous reduction of Cr(VI) and degradation of organic pollutants. With a low Cr(VI) content (0-0.2 mM) coexisting in the biochar (10 g L-1) system, organic pollutants (1 mM) were mostly degraded via a radical process at pH 3, additionally oxidized by Cr(VI) via an electron transfer mediated by biochar, which ultimately promoted the removal of organic pollutants. While further increasing the Cr(VI) content, the radical degradation of organic pollutants was gradually restrained, but partially replaced by the accelerated oxidization of organics by Cr(VI). On the other hand, the Cr(VI) was mainly reduced to Cr (III) by the functional groups on biochar in the absence of organic pollutants. However, the coexisted organic pollutants could take the place of biochar to reduce Cr(VI), resulting in a slight change of Cr(VI) reduction. Further studies indicated that the defective sites on biochar could enhance the reaction between organic pollutants and Cr(VI). These findings are very much interesting and innovative in the ongoing biochar research and demonstrate a new dimension of biochar potential for detoxification of multiple industrial pollutants containing Cr(VI) and organics.

Randomized, controlled trial of priming with 10,000 IU versus 20,000 IU of human chorionic gonadotropin in women with polycystic ovary syndrome who are undergoing in vitro maturation.

Preretrieval priming with 10,000 IU hCG can improve oocyte maturation rates in vitro for women undergoing in vivo maturation treatment, though the optimum dose is unknown. This prospective, randomized, controlled trial demonstrated no improvement in oocyte maturation rates with 20,000 IU of hCG compared with 10,000 IU of hCG and therefore no benefit of the higher dose.

Inhibition of rapamycin-induced AKT activation elicits differential antitumor response in head and neck cancers.

The PI3K/AKT/mTOR pathway is an important signaling axis that is perturbed in majority of cancers. Biomarkers such as pS6RP, GLUT1, and tumor FDG uptake are being evaluated in patient stratification for mTOR pathway inhibitors. In the absence of a clear understanding of the underlying mechanisms in tumor signaling, the biomarker strategy for patient stratification is of limited use. Here, we show that no discernible correlation exists between FDG uptake and the corresponding Ki67, GLUT1, pS6RP expression in tumor biopsies from patients with head and neck cancer. Correlation between GLUT1 and pS6RP levels in tumors was observed but elevated pS6RP was noticed even in the absence of concomitant AKT activation, suggesting that other downstream molecules of PI3K/AKT and/or other pathways upstream of mTOR are active in these tumors. Using an ex vivo platform, we identified putative responders to rapamycin, an mTOR inhibitor in these tumors. However, rapamycin did not induce antitumor effect in the majority of tumors with activated mTOR, potentially attributable to the observation that rapamycin induces feedback activation of AKT. Accordingly, treatment of these tumors with an AKT inhibitor and rapamycin uniformly resulted in abrogation of mTOR inhibition-induced AKT activation in all tumors but failed to induce antitumor response in a subset. Phosphoproteomic profiling of tumors resistant to dual AKT/mTOR inhibitors revealed differential activation of multiple pathways involved in proliferation and survival. Collectively, our results suggest that, in addition to biomarker-based segregation, functional assessment of a patient's tumor before treatment with mTOR/AKT inhibitors may be useful for patient stratification.