Neurotoxic effects of environmental contaminants-measurements, mechanistic insight, and environmental relevance.

Pollution is a significant and growing concern for any population regardless of age because these environmental contaminants exhibit different neurodegenerative effects on persons of different ages. These environmental contaminants are the products of human welfare projects like industry, automobile exhaust, clinical and research laboratory extrudes, and agricultural chemicals. These contaminants are found in various forms in environmental matrices like nanoparticles, particulate matter, lipophilic vaporized toxicants, and ultrafine particulate matter. Because of their small size, they can easily cross blood-brain barriers or use different cellular mechanisms for assistance. Other than this, these contaminants cause an innate immune response in different cells of the central nervous system and cause neurotoxicity. Considering the above critiques and current needs, this review summarizes different protective strategies based on bioactive compounds present in plants. Various bioactive compounds from medicinal plants with neuroprotective capacities are discussed with relevant examples. Many in vitro studies on clinical trials have shown promising outcomes using plant-based bioactive compounds against neurological disorders.

Prepregnancy Counseling Among U.S. Women With Diabetes and Hypertension, 2016-2018.

INTRODUCTION: Individuals who have diabetes or hypertension established before pregnancy are at increased risk for maternal and infant health complications. Guidelines recommend that providers deliver prepregnancy counseling, but little is known about the receipt of those services among patients with chronic conditions. METHODS: Data from the 2016-2018 Pregnancy Risk Assessment Monitoring System, a population-based survey among women with recent live births, were used. Self-reported receipt of prepregnancy counseling on folic acid supplementation, pregnancy desire, contraceptive use, and improving health before pregnancy was examined overall and by diabetes and hypertension status. Multivariable logistic regression examined the association between diabetes and hypertension status and the 4 prepregnancy counseling outcomes. Analyses were conducted in 2020. RESULTS: Overall, 2.1% of women reported having both diabetes and hypertension, 1.3% reported having diabetes alone, and 3.1% reported having hypertension alone. Less than half of the sample reported receiving each prepregnancy counseling outcome. In adjusted models, women with hypertension alone were more likely to report each counseling outcome than women without diabetes or hypertension. Women with diabetes alone were only more likely to report receiving counseling about improving health, and women with both conditions were not more likely to report the receipt of any counseling outcome under study. CONCLUSIONS: Women with prepregnancy diabetes, hypertension, or both reported low levels of the recommended prepregnancy counseling, suggesting an evidence-practice gap that should be addressed to optimize maternal and infant health outcomes. There is a need for evidence-based and patient-centered models of prepregnancy counseling for those with diabetes and hypertension.

Identification and evaluation of novel drug combinations of Aurora kinase inhibitor CCT137690 for enhanced efficacy in oral cancer cells.

Oral cancer is the most prevalent subtype of head and neck cancers and arises mainly from squamous cells of the oral cavity. Patients with advanced metastatic disease have poor overall survival resulting primarily from limited treatment options. Recent advances in the understanding of molecular basis of oral tumorigenesis provide an opportunity for identification and validation of new drug targets. The deregulated expression of the Aurora family of mitotic kinases, for example, has been associated with pathogenesis and poor prognosis in oral cancer. Here, we have evaluated the efficacy of the pan-Aurora inhibitor (CCT137690) alone and in combination with different chemotherapeutic and targeted drugs to identify its synergistic partners in oral cancer cell lines (ORL-48 and ORL-115). CCT137690 effectively inhibits Aurora kinases in both the cell lines and displays potent antiproliferative activity towards them. Prolonged treatment of these cells with CCT137690 results in abrogated mitotic spindle formation, misaligned chromosome attachment and polyploidy that ultimately leads to apoptotic cell death. We further identified that inhibitors of EGFR (gefitinib) and PI3-kinase (pictilisib) synergize with CCT137690 to inhibit the proliferation of the oral cancer cell lines. Moreover, we demonstrate that polyethylene glycol-based nanocapsules harboring combinations of CCT137690 with gefitinib or pictilisib inhibit the growth of oral cancer cell lines in 3D spheroid cultures and induce apoptosis that is comparable to free drug combinations. In conclusion, we have demonstrated the in vitro efficacy of CCT137690 in oral cancer cell lines, identified novel drug combinations with CCT137690 and synthesized nanocapsules containing these drug combinations for co-administration.