ABSTRACT
Skin cancer and other skin-related inflammatory pathologies are rising due to heightened exposure to environmental pollutants and carcinogens. In this context, natural products and repurposed compounds hold promise as novel therapeutic and preventive agents. Strengthening the skin's antioxidant defense mechanisms is pivotal in neutralizing reactive oxygen species (ROS) and mitigating oxidative stress. Sunset Yellow (SY) exhibits immunomodulatory characteristics, evidenced by its capacity to partially inhibit the secretion of proinflammatory cytokines, regulate immune cell populations, and modulate the activation of lymphocytes. This study aimed to investigate the antioxidant and anti-genotoxic properties of SY using in-silico, in vitro, and physiochemical test systems, and to further explore its potential role in 7,12-dimethylbenz(a) anthracene (DMBA)/ 12-o-tetradecanoylphorbol-13-acetate (TPA)-induced two-stage skin carcinogenesis. In vitro experiments showed that pre-treatment of SY significantly enhanced the cell viability of HaCaT cells when exposed to tertiary-Butyl Hydrogen Peroxide (tBHP). This increase was accompanied by reduced ROS levels, restoration of mitochondrial membrane potential, and notable reduction in DNA damage in (SY + tBHP) treated cells. Mechanistic investigations using DPPH chemical antioxidant activity test and potentiometric titrations confirmed SY's antioxidant properties, with a standard reduction potential ( E o ) of 0.211 V. Remarkably, evaluating the effect of topical application of SY in DMBA/TPA-induced two-step skin carcinogenesis model revealed dose-dependent decreases in tumor latency, incidence, yield, and burden over 21-weeks. Furthermore, computational analysis and experimental validations identified GSK3ß, KEAP1 and EGFR as putative molecular targets of SY. Collectively, our findings reveal that SY enhances cellular antioxidant defenses, exhibits anti-genotoxic effects, and functions as a promising chemopreventive agent.
Subject(s)
Antioxidants , Azo Compounds , Skin Neoplasms , Humans , Kelch-Like ECH-Associated Protein 1/metabolism , Antioxidants/adverse effects , Antioxidants/metabolism , Reactive Oxygen Species/metabolism , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/therapeutic use , 9,10-Dimethyl-1,2-benzanthracene/toxicity , Skin Neoplasms/chemically induced , Skin Neoplasms/drug therapy , Skin Neoplasms/prevention & control , Tetradecanoylphorbol Acetate/adverse effects , Oxidative Stress , Chemoprevention , CarcinogenesisABSTRACT
Randomized trials constitute approximately 3% of the orthopaedic literature Concerns regarding quality of the orthopaedic literature stem from a widespread notion that the overall quality of the surgical literature is in need of improvement. Limitations in surgical research arises primarily from two pervasive issues: 1) A reliance on low levels of evidence to advance surgical knowledge, and 2) Poor reporting quality among the high level surgical evidence that is available. The scarcity of randomized trials may be largely attributable to several unique challenges which make them difficult to conduct. We present characteristics of the orthopaedic literature and address the challenges of conducting randomized trials in surgery.
ABSTRACT
Several checklists have been developed in an effort to help journals and researchers improve the quality of reporting in research. The CONSORT statement and the CLEAR NPT evaluate randomized trials. The MOOSE and QUOROM checklists evaluate meta-analyses. The STROBE checklists assists readers in evaluating observational studies and the STARD checklist was developed for diagnostic test evaluation. The checklists presented here provide an invaluable source of guidance to authors, journal editors and readers who are seeking to prepare and evaluate reports. As evidence-based medicine continues to establish itself as the new paradigm by which medicine is practiced, the need for good reporting for all research designs must also become commonplace as opposed to the exception.
