Jo Aan Goon

Brain aging is a major risk factor for neurodegenerative disorders and is associated with a progressive loss of neuronal homeostasis. Rather than resulting from a single pathological event, brain aging involves coordinated changes across multiple biological processes, including neuroinflammation, proteostasis impairment, mitochondrial dysfunction, neurotransmission deficit, cellular senescence, gut microbiota dysbiosis, extracellular vesicle dysregulation, nutrient-sensing disturbances, and metabolic drift. These processes interact across molecular, cellular, and systemic levels and may progressively increase neuronal vulnerability to neurodegenerative pathology. Age-related biological alterations may increase susceptibility to Alzheimer’s disease and Parkinson’s disease. Disease-associated proteins, including amyloid-β, tau, and α-synuclein, may interact with age-related inflammation, metabolic dysfunction, and loss of proteostasis. This review examines the evidence supporting these mechanisms, their interactions, and their relevance to normal brain aging, Alzheimer’s disease, and Parkinson’s disease. Because much of the current mechanistic evidence derives from animal and cellular models, further longitudinal and human studies are needed to provide a more complete understanding of how these mechanisms operate during human brain aging and neurodegenerative diseases.

Background: Vitamin E has been studied for its role in reducing the growth of colorectal cancer (CRC). CRC is a worldwide health concern. A meta-analysis reported that CRC patients have a lower concentration of serum vitamin E, suggesting it to be a risk factor. Although rodent models are widely used in disease research, their application in studying vitamin E as a preventive or therapeutic agent in CRC is not well characterized. To address this gap, we conducted a scoping review to examine the available evidence, adhering to the PRISMA-ScR checklist. Methods: We searched PubMed, Google Scholar, Scopus, and Web of Science (WoS) for full-text English original articles published before May 2024, using Medical Subject Headings (MeSH) terms and free text. The following search string strategy was applied: (Vitamin E OR tocopherol$ OR tocotrienol$) AND (Colo$ cancer OR colo$ carcinoma) AND (Rodentia OR mouse OR Rodent$ OR mice OR murine OR rats OR guinea OR rabbit OR hamsters OR Animal model OR Animal testing OR animals) AND (neoplasm$ OR “tumor mass” OR tumor volume OR tumor weight OR tumor burden). Data were charted into five categories using a standardized, pretested form. The charted data were synthesized using descriptive and narrative methods. Conclusions: This study highlights that γ- and δ-tocopherols, as well as δ-tocotrienol and its metabolites, were reported to reduce tumor volume and formation in various rodent models. While these results are promising, this scoping review identifies a need for further research to address translational barriers such as dosing, bioavailability, and long-term safety before clinical application.

Background: Stasis eczema, a chronic inflammatory dermatosis associated with chronic venous insufficiency (CVI), remains comparatively underresearched among eczematous dermatoses, particularly in the context of the ideal long‐term management strategy. While the role of emollients in epidermal barrier repair and hydration is well established, there are gaps in knowledge regarding the elucidation of their precise mechanisms for modulating inflammation, preventing exacerbation, and improving adherence in this patient population. Objectives: The pathophysiology of stasis eczema is reviewed here with emphasis on the interlinked relationship between venous hypertension, cytokine imbalance (e.g., TNF‐α, IL‐1, and IL‐6), and epidermal barrier disruption. Emollients, formulated with occlusive agents (e.g., petrolatum), humectants (e.g., urea), and lipid‐replenishing additives (e.g., ceramides), offer targeted skin hydration and barrier repair. The choice of formulations remains paramount with lotions for mild disease, creams for balanced hydration and occlusion in moderate disease, and ointments for maximal protection in severe disease, though potentially at the possible expense of adherence. Methods: A literature review in the narrative approach was carried out by conducting a search on electronic databases such as PubMed, Scopus, Google Scholar, and Web of Science. Various sets of keywords were used to identify appropriate English literature regarding the topics of stasis eczema, CVI, skin barrier dysfunction, and emollient therapy. The review also included clinically useful experimental studies, observational studies, and review articles, in addition to randomized controlled trials, to gain a broad picture of the current evidence. Results: Evidence in this field highlights short‐term outcomes like enhanced skin elasticity and reduced pruritus, but long‐term data regarding flare‐up prevention and combination therapy with adjunctive treatment are sparse. Additionally, limitations to adherence such as cost, cosmetic acceptability, and contact sensitization deserve greater research. Conclusions: This review consolidates the evidence for emollient efficacy, summarizes gaps in knowledge regarding the development of formulations coupled with anti‐inflammatory or antimicrobial agents, and outlines measures to maximize patient adherence by personalizing regimens, postbath application, and patient education on prophylactic use, all aimed at improving outcomes and quality of life.

Background: Tocotrienol, a naturally occurring form of vitamin E, has been extensively studied for its potent antioxidant, anti-inflammatory, and immune-stimulating properties. However, the clinical impact of tocotrienol supplementation on older adults’ overall health and well-being remains relatively unexplored. This research aims to investigate the efficacy of tocotrienol-rich fraction (TRF) on various health parameters associated with general well-being in individuals aged between 50 years and 75 years. Objective: It is hypothesized that TRF supplementation may exhibit positive outcomes on blood biochemistry and several physiological aspects, including lowered levels of oxidative stress and inflammation biomarkers; improvement in vascular age; and enhancement of skin condition, bone mineral density, and cognitive function. Methods: This randomized, double-blind, placebo-controlled trial was designed to investigate the effectiveness of TRF supplementation on overall health in healthy older adults. The study aims to assess the impact of a daily dosage of 200 mg of TRF over a period of 6 months. A total of 220 participants is enrolled in the study, with one-half receiving the placebo and the other one-half receiving TRF supplementation. The study comprises 3 time points: baseline, 3 months, and 6 months. At each time point, various measurements are taken to evaluate different aspects of health. The primary outcome measurements include blood biochemistry assessments, such as liver function tests, renal profile, lipid profile, and full blood count. Oxidative stress markers, including malondialdehyde, advanced glycation end products, protein carbonyl, and isoprostane, are also evaluated. Immune response markers such as interleukin-6 and tumor necrosis factor-α are assessed. Satiety regulation is examined through measurements of leptin and ghrelin. Body composition and skin health parameters, including wrinkling, pigmentation, elasticity, hydration, and sebum secretion, are evaluated. Additionally, arterial stiffness is assessed using arteriography at baseline and 6 months. For secondary outcome measures, bone mineral density is measured using dual x-ray absorptiometry, and cognitive function is assessed using the Montreal Cognitive Assessment, Rey Auditory Verbal Learning Test, and digital span test. Both bone mineral density and cognitive function are also measured at baseline and 6 months. Results: The study is progressing as planned, with 209 participants recruited as of April 2025. The research was funded in 2019, and data collection started in December 2020. Preliminary data analysis has been completed for the first 120 participants, and final results are expected upon completion of data collection and unblinding in 2026. Conclusions: By comprehensively evaluating these health aspects, this study seeks to provide valuable insights into the potential benefits of tocotrienol supplementation for promoting the overall health and well-being of the aging population. Trial Registration: National Medical Research Register (NMRR) NMRR-19-2972-51179; https://tinyurl.com/yy9yueer International Registered Report Identifier (IRRID): DERR1-10.2196/73039

BACKGROUND Tocotrienol, a naturally occurring form of vitamin E, has been extensively studied for its potent antioxidant, anti-inflammatory, and immune-stimulating properties. However, the clinical impact of tocotrienol supplementation on older adults' overall health and well-being remains relatively unexplored. OBJECTIVE This research aims to investigate the efficacy of tocotrienol-rich fraction (TRF), on various health parameters associated with general well-being in individuals aged between 50-75 years METHODS The present study is a randomised, double-blind, placebo-controlled trial designed to investigate the effectiveness of TRF supplementation on overall health in healthy elderly individuals. The study aims to assess the impact of a daily dosage of 200mg of TRF over a period of 6 months. A total of 220 participants are enrolled in the study, with half receiving the placebo and the other half receiving TRF supplementation. The study comprises three endpoints: baseline, 3 months, and 6 months. At each endpoint, various measurements are taken to evaluate different aspects of health. These measurements include blood biochemistry assessments such as liver function tests, renal profile, lipid profile, and full blood count. Oxidative stress markers, including malondialdehyde, advanced glycation end-products, protein carbonyl, and isoprostane, are also evaluated. Immune response markers such as interleukin-6 and tumour necrosis factor-alpha are assessed. Satiety regulation is examined through measurements of leptin and ghrelin. Body composition and skin health parameters, including wrinkling, pigmentation, elasticity, hydration, and sebum secretion, are evaluated. Additionally, arterial stiffness is assessed by arteriography, bone mineral density is measured using dual x-ray absorptiometry, and cognitive function is assessed through the Montreal Cognitive Assessment, Rey Auditory Verbal Learning Test, and digital span, are measured at baseline and at the 6-month endpoint. RESULTS NIL. CONCLUSIONS By comprehensively evaluating these health aspects, this study seeks to provide valuable insights into the potential benefits of tocotrienol supplementation for promoting the overall health and well-being of the ageing population. CLINICALTRIAL National Medical Research Register (NMRR), no. NMRR19-2972-51179

Non-alcoholic fatty liver disease (NAFLD) and its progressive stage, non-alcoholic steatohepatitis (NASH), are becoming one of the most common chronic liver diseases globally. Lifestyle interventions such as weight reduction, increased physical activity, and maintaining healthy diets play a pivotal role in managing NAFLD/NASH. Recent studies suggest that the gut microbiome is associated with the pathogenesis of NAFLD/NASH, prompting microbiome-targeted therapy to emerge as a new therapeutic option for NAFLD/NASH. We conducted a systematic review based on the PRISMA statement and employed network meta-analysis to investigate the effects of traditional probiotics and next-generation probiotics (NGPs) on NAFLD/NASH. Comparative analysis reveals that traditional probiotics primarily reduce liver fat deposition and inflammation by improving gut microbiota composition, enhancing intestinal barrier function, and modulating immune responses. In contrast, NGPs demonstrate a more significant therapeutic potential, attributed to their direct effects on inhibiting oxidative stress and their ability to enhance the production of short-chain fatty acids (SCFAs), NGPs appear as a new potential strategy for the management of NAFLD/NASH through their dual action of directly inhibiting oxidative stress and enhancing SCFA production, highlighting the importance of understanding and utilizing the direct and indirect regulatory mechanisms of oxidative stress in the management of NAFLD/NASH.