Cross-talk between oxidative stress signaling and microRNA regulatory systems in carcinogenesis: Focused on gastrointestinal cancers

Molecular mechanisms underlying development and progression of gastrointestinal (GI) cancers are mediated by both oxidative stress (OS) and microRNAs (miRNAs) involvement. Notably, OS signaling may regulate the expression of miRNAs, and miRNAs function as imperative players in OS-initiated tumors. Given the defined biological roles of both OS systems and miRNAs in GI carcinogenesis, a possible interplay between these two key cellular networks is considered. A growing body of evidence has indicated a reciprocal connection between OS signaling pathways and miRNA regulatory machines in GI cancer development and progression. Illumination of the molecular cross-talking between miRNAs and the OS would improve our pathophysiological insight into carcinogens. Also, understanding the molecular mechanisms in which these systems are reciprocally regulated may imply in future medical practice mainly GI cancer therapy. Nowadays, therapeutic strategies focusing on miRNA and OS in GI cancer treatment are increasingly delineated. Since the use of antioxidants is limited owing to the contrasting consequences of OS signaling in cancer, the discovery of OS-responsive miRNAs may provide a potential new strategy to overcome OS-mediated GI carcinogenesis. Given the possible interaction between OS and miRNAs in GI cancers, this review aimed to elucidate the existing evidence on the interaction between OS and miRNA regulatory machinery and its role in GI carcinogenesis. In this regard, we will illustrate the function of miRNAs which target OS systems during homeostasis and tumorigenesis. We also discuss the biological cross-talk between OS systems and miRNAs and corresponding cell signaling pathways. © 202

A randomized, double-blind, placebo-controlled study of gelesis100: A novel nonsystemic oral hydrogel for weight loss

Objective: This study aims to assess the efficacy and safety of Gelesis100, a novel, nonsystemic, superabsorbent hydrogel to treat overweight or obesity. Methods: The Gelesis Loss Of Weight (GLOW) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled study in patients with BMI ≥ 27 and ≤ 40 kg/m2 and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co-primary end points were placebo-adjusted weight loss (superiority and 3% margin super-superiority) and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss. Results: Gelesis100 treatment caused greater weight loss over placebo (6.4% vs. 4.4%, P = 0.0007), achieving 2.1% superiority but not 3% super-superiority. Importantly, 59% of Gelesis100-treated patients achieved weight loss of ≥ 5%, and 27% achieved ≥ 10% versus 42% and 15% in the placebo group, respectively. Gelesis100-treated patients had twice the odds of achieving ≥ 5% and ≥ 10% weight loss versus placebo (adjusted OR: 2.0, P = 0.0008; OR: 2.1, P = 0.0107, respectively), with 5% responders having a mean weight loss of 10.2%. Patients with prediabetes or drug-naive type 2 diabetes had six times the odds of achieving ≥ 10% weight loss. Gelesis100 treatment had no apparent increased safety risks. Conclusions: Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile