FDA-approved cannabidiol [Epidiolex] alleviates Gulf War Illness-linked cognitive and mood dysfunction, hyperalgesia, neuroinflammatory signaling, and declined neurogenesis.

Background: Chronic Gulf War Illness (GWI) is characterized by cognitive and mood impairments, as well as persistent neuroinflammation and oxidative stress. This study aimed to investigate the efficacy of Epidiolex, a Food and Drug Administration (FDA)-approved cannabidiol (CBD), in improving brain function in a rat model of chronic GWI.

Methods: Six months after exposure to low doses of GWI-related chemicals [pyridostigmine bromide, N,N-diethyl-meta-toluamide (DEET), and permethrin (PER)] along with moderate stress, rats with chronic GWI were administered either vehicle (VEH) or CBD (20 mg/kg, oral) for 16 weeks.

A Preliminary Genomic Analysis of the Omicron Variants of SARS-CoV-2 in Central India During the third wave of the COVID-19 Pandemic.

Background: Omicron was detected in South Africa for the first time at the month of November 2021, from then it expanded swiftly over the world, outcompeting other SARS-CoV-2 variants such as Delta. The toxicity, resistance to antiviral medicines, transmissibility, and vaccine-induced immunity of newly developed SARS-CoV-2 variants are major worldwide health concerns.

Aim Of Study: This study investigates the comprehensive explanation of all mutations and their evolutionary linkages between the Omicron variant and recently discovered SARS-CoV-2 variants.

One-year clinical evaluation of bulk-fill composite resin restorations plasticized by preheating and ultrasonics: A randomized clinical trial.

Introduction: Bulk-fill composite restorations displayed substantial annual failure related to imperfect marginal adaptation. Although preheated composites improved, marginal adaptation demonstrated early loss of plasticity. A new technique of ultrasonics plasticization was used for fabricating restorations.

Poloxamer-linked prodrug of a topoisomerase I inhibitor SN22 shows efficacy in models of high-risk neuroblastoma with primary and acquired chemoresistance.

High-risk solid tumors continue to pose a tremendous therapeutic challenge due to multidrug resistance. Biological mechanisms driving chemoresistance in high-risk primary and recurrent disease are distinct: in newly diagnosed patients, non-response to therapy is often associated with a higher level of tumor "stemness" paralleled by overexpression of the ABCG2 drug efflux pump, whereas in tumors relapsing after non-curative therapy, poor drug sensitivity is most commonly linked to the dysfunction of the tumor suppressor protein, p53. In this study, we used preclinical models of aggressive neuroblastoma featuring these characteristic mechanisms of primary and acquired drug resistance to experimentally evaluate a macromolecular prodrug of a structurally enhanced camptothecin analog, SN22, resisting ABCG2-mediated export, and glucuronidation.

Nanocarrier-Based Delivery of SN22 as a Tocopheryl Oxamate Prodrug Achieves Rapid Tumor Regression and Extends Survival in High-Risk Neuroblastoma Models.

Despite the use of intensive multimodality therapy, the majority of high-risk neuroblastoma (NB) patients do not survive. Without significant improvements in delivery strategies, anticancer agents used as a first-line treatment for high-risk tumors often fail to provide clinically meaningful results in the settings of disseminated, recurrent, or refractory disease. By enhancing pharmacological selectivity, favorably shifting biodistribution, strengthening tumor cell killing potency, and overcoming drug resistance, nanocarrier-mediated delivery of topoisomerase I inhibitors of the camptothecin family has the potential to dramatically improve treatment efficacy and minimize side effects.