Pancreatic ductal adenocarcinoma (PDAC), which remains undetected till advanced stages of progression, is becoming a more common and aggressive PC with high mortality rates. Trending unhealthy dietary habits, sedentary life, obesity, diabetes, high body mass index (BMI), and perturbed gut microbiota, also known as dysbiosis, increase the PDAC incidences. There is an urgent need to delve into reliable and cost-effective biomarkers and strategies to diagnose and prevent the disease. Microbial remedies and dietary phytonutrients that restore gut microbial balance may be the prospective preventive measures. This article intends to recommend the hypothesis that PDAC is incepted and characterized by microbial signatures and can be managed by integrating evidenced-based complimentary approaches entailing diet, nutraceuticals, microbial interventions and life style modifications with standard therapies. The futuristic longitudinal and mechanistic studies to unravel host-microbiota and the host-microbiome interactions will allow deeper aetiologic and mechanistic insights into PDAC to evolve therapies and recommendations for better pancreatic health.

Introduction: The postprandial phase represents a transient pro-oxidative condition, characterized by an increased vulnerability to oxidative damage following nutrient intake. This state is increasingly recognized as a contributing factor in the early development of atherogenic processes. Alterations in plasma cysteine and glutathione (GSH) redox couples have been shown to correlate with aging and age-related pathologies. Among the principal thiol redox systems regulating plasma redox potential, the reduced cysteine/cystine (CySS) pair predominates, followed by the GSH/oxidized GSH disulfide pair. CySS is considered a marker of systemic oxidative burden, whereas GSH reflects intracellular NADPH-dependent reductive capacity. Objective: This study aimed to assess both intra- and extracellular redox status during the postprandial period in middle-aged and older sedentary individuals adhering to a Mediterranean dietary pattern, with or without supplementation using a patented fermented papaya preparation (FPP). Methods: A total of 90 otherwise healthy participants presenting at least one cardiometabolic risk factor were enrolled. Postprandial assessments were conducted at baseline and after three months. Evaluated parameters included inflammatory biomarkers, adhesion molecules, apoptosis in peripheral blood mononuclear cells, and p53 gene expression. Results: Compared with the Mediterranean diet alone, three months of FPP supplementation resulted in significant reductions in soluble levels of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1. It also effectively prevented the postprandial increase in Annexin V⁺/DAPI⁺ cells and induced a protective downregulation of p53 expression, particularly within the cytoplasmic compartment. Furthermore, CySS concentrations and the CySS:GSH ratio were significantly reduced, while the decline in GSH levels was attenuated under the FPP-supplemented regimen. Conclusion: These findings support the potential benefit of dietary interventions, particularly when combined with redox-modulating nutraceuticals, in reducing postprandial oxidative stress and its associated metabolically deleterious effects.

Background: Skin senescence is a multifaceted process that results from biological aging and exposure to various environmental factors (e.g., smoking, pollution, UV radiation, outer infections, climate change). In addition, skin health is clearly relevant to beauty care, especially—but not exclusively—in women. This has led to the creation of many skincare treatments that lack a rigorous scientific basis. Objective: We aimed to study a patented fermented papaya preparation (FPP®) through in vitro testing and an in vivo pilot study and determine its measurable effects on collagen and the functional characteristics of skin. Methods: Human fibroblasts were subjected to UV irradiation either alone or with FPP® to test collagen production and matrix metallo proteinase (MMP) gene expression. A placebo-controlled clinical study (FPP® vs. dextrose-cellulose: 4.5g twice a day for 3 months) was conducted with 26 women (42–56 years old). The clinical parameters tested were elasticity, moisture, trans-epidermal water loss, glow, and microcirculation. Results: FPP® proved to significantly increase collagen synthesis and protect skin from MMP upregulation in in vitro testing. On a clinical level, it improved all clinical variables tested at a 3-month observation. Novelty of the Study: This study synergized the objective basic science and the related clinical benefits of FPP® intervention in skin aging. Conclusions: Although limited data and limited observation time have been accumulated so far, our study suggests that the oral administration of a long-fermentation-processed papaya preparation may be of interest in an interventional strategy for skin aging. Keywords: collagen synthesis, UVB-elicited MMPs upregulation, elasticity, moisture, trans-epithelial water loss, skin microcirculation, skin glowing, antioxidant capacity, skin texture, skin aging

Sjögren's syndrome (SS) is an autoimmune disease and its management is palliative. There is no specific dietary protocol for SS patients. A gluten-free diet has been tested in SS patients with celiac disease (CD) and indicated modest improvements. Whether gluten-free diets per sè could alleviate autoimmune inflammatory processes in the salivary glands of SS patients with associated CD or even in SS patients without CD is an interesting hypothesis and warrants clinical studies. Hypokalemia in SS patients is among the most frequent sequelae of renal tubular acidosis. Supplementation with potassium (K)-rich diets can reduce inflammation and oxidative stress. K level in CD patients is highly abnormal at diagnosis and gluten-free diets help to normalize its serum level in CD patients. Furthermore, treatment of severe cases of SS requires concomitant glucocorticoid therapy and K supplementation. Results of two separate clinical trials in (i) patients with rheumatoid arthritis (RA) –a disease with similar pathology to SS- indicated that the enhanced serum cortisol followed K supplementation, and in (ii) celiac patients, serum K levels were normalized after the administration of a gluten-free diet. We reviewed the literature extensively on this topic to propose a hypothesis to address this problem and suggest a novel potential for K-rich, gluten-free diets in SS patients. Based on causal associations, we propose that higher K absorption and cortisol secretion following gluten-free diets accompanied by K-rich diets in SS patients with low serum potassium levels, may confer a higher therapeutic potential. Clinical trials are needed to test this hypothesis.

Food preservatives such as nitrites, nitrates, sodium benzoate, and synthetic phenolic antioxidants are widely used to enhance the safety, stability, and sensory properties of foods. Despite these benefits, increasing evidence indicates that chronic or high-dose exposure to preservatives may induce oxidative stress, which plays a central role in the pathogenesis of cancer, metabolic disorders, and reproductive dysfunction. This review summarizes findings from animal, in vitro, and human studies on the relationship between preservatives and oxidative stress, with a focus on nitrites in processed meats and sodium benzoate. Experimental data consistently demonstrate increased lipid peroxidation, suppression of endogenous antioxidant enzymes, mitochondrial dysfunction, and apoptosis following high-dose preservative exposure, although these doses often exceed typical human dietary intake. Epidemiological studies support the association between nitrite-derived N-nitroso compounds and colorectal carcinogenesis, aligning with the International Agency for Research on Cancer (IARC) classification of processed meats as Group 1 carcinogens. In contrast, dietary bioactive compounds such as garlic oil, honey, Nigella sativa, curcumin, berberine, omega-3 fatty acids, and polyphenols have shown protective effects by modulating oxidative pathways and restoring redox balance. However, most of these benefits are observed at pharmacological levels, raising concerns about their practical relevance in human diets. Unlike previous reviews that focus solely on the toxicity of preservatives, this study uniquely integrates the mechanistic evidence of preservative-induced oxidative stress with the mitigating potential of functional food-based dietary strategies. Overall, preservatives may act as pro-oxidants under certain conditions, while antioxidant-rich dietary patterns may offer protective potential. Further human-based studies at realistic exposure levels are essential to strengthen risk assessment and guide public health recommendations. Keywords: Preservatives; Oxidative Stress; Antioxidants; Bioactive Compounds; Nutrition.

Objectives: Physical activity and cardiovascular system efficiency are known to be inversely associated with all-cause mortality. Thus, efforts are focused on preventative strategies for middle-aged and elderly subjects who lead sedentary lifestyles and may be further burdened. This is associated with a decay in mitochondrial efficiency and capacity for adenosine triphosphate (ATP) production, which is associated with decreased performance and overall bioenergetics. Methods: After having confirmed their eligibility, 160 (45-72 years old, m/f: 50/110 participants were admitted into a double blind, 4-month crossover, separated by a one-month washout period, trial, and random assignment to one of two study treatments using a patented fermented papaya preparation (FPP®), endowed with antioxidant properties. Subjects took two sachets per day, each one containing synthetic vitamins (Vitamin C, Vitamin E, alpha-lipoic acid, and dextrose). At the beginning, 1, 2, and 4 months, biochemical assays of oxidized LDL (oxLDL) and nitric oxide (NO) were performed on peripheral blood plasma or red blood cells (RBC) (ATP) on sample aliquots stored at −80°C. Results: FPP® intervention showed a statistically significant increase in RBC-ATP (0.05 vs Multivitamin) at 2 and 4 months of observation. Both treatments significantly improved Total Antioxidant Capacity (TAC) at the 4-month observation with an earlier 2-month increase in the FPP® group (p<0.01). Despite an overall wide scattering of OxLDL values, by clustering the 52-71-year-old participants, this group has significantly higher values than the younger counterpart. Both treatments, particularly FPP® (expressed as percentage change from baseline), led to a significant decrease (p<0,05). While Multivitamin treatment was ineffective in improving FMD or NO levels, these parameters significantly increased during FPP® treatment. Conclusion: The present research study shows that a specific fermented functional food (FPP®) may offer an interesting interventional strategy to tentatively counteract age-related endothelial dysfunction, redox dysregulation, and bioenergetic decline, compared with a synthetic multivitamin mixture.

Chemotherapeutic drugs often cause adverse effects, therefore prompting researchers to find alternative therapeutic strategies. This study examined Curcumin's potential against primary (SW480) and metastatic (SW620) colon cancer cell lines. Curcumin's binding affinity with cancer stem cell (CSC) markers, ALDH1A1, LGR5, EpCAM, ALCAM, CD44, and their transcription factors were studied by molecular docking. SW480 and SW620 cell viability was measured by CCK8 and EZblue assay to find the cytotoxicity after treatment with curcumin, in comparison to Cisplatin. Hyaluronidase, elastase inhibition, and DPPH scavenging assays were studied to determine Curcumin's anti-oxidant properties. Anti-proliferative, apoptotic, and CSC-specific genes were analyzed, and Promin-1 protein, which is involved in colon cancer progression, was quantified to find the potential effects of Curcumin in reducing colon cancer cell proliferation. In-silico studies showed Curcumin has a strong binding affinity to ALDH1A1, LGR5, and transcription factors STAT3, NFYA, and AKT. Curcumin reduced the cell viability in a dose and time-dependent manner. Further it also inhibited hyaluronidase and elastase activities and enhanced DPPH scavenging, confirming its anti-oxidant and possible anticancer activities. It downregulated CCND1, CDK6, PCNA and LGR5, ALDH1A1, ALCAM, CD44 genes expression, and Prominin-1 expression while upregulating pro-apoptotic genes CASP9, BAX, TP53 expression. These findings show Curcumin's potential to reduce the proliferation of colon cancer cells and may suggest its possible use as a bioactive compound in colon cancer treatment. The activity of Curcumin against both primary (SW480) and metastatic (SW620) colon cancer cell lines was examined in this study. Curcumin reduced the proliferation of both SW480 and SW620 cell lines in a dose-dependent manner. Additionally, it inhibited the hyaluronidase and elastase enzyme activities and showed anti-oxidant properties. The treatment also led to a downregulation of CD44, ALCAM, EpCAM, LGR5, and ALDH1A1 and Prominin-1 expression in both the cell lines, which indicates the effectiveness of Curcumin against colon cancer cell proliferation, possibly via regulating cancer stem cell-specific genes. Further detailed in vitro works with more colon cancer cell lines and in vivo works will provide a better understanding of the anti-cancer properties of Curcumin and accelerate the ongoing efforts to use Curcumin as a supportive bioactive compound in colon cancer treatment. Potential role of Curcumin in targeting colon cancer cells.

Background: The increasing consumption of non-caloric sweeteners has raised concerns regarding their potential effects on oxidative stress and related health outcomes. Emerging evidence suggests that artificial sweeteners, particularly aspartame and saccharin, may induce oxidative stress in a dose-, duration-, and tissue-dependent manner. In contrast, natural sweeteners, such as stevia, may offer protective effects. This review synthesizes current findings on the oxidative and metabolic effects of non-caloric sweeteners, outlining key methodological limitations and the need for long-term clinical investigations. It further integrates mechanistic insights to distinguish the differential redox effects of artificial versus natural sweeteners and explores how antioxidant-rich functional foods might mitigate these impacts. This review comprehensively integrates mechanistic, experimental, and dietary evidence linking non-caloric sweeteners to oxidative stress while introducing functional food–based strategies to mitigate redox imbalance. It provides an updated synthesis relevant to evidence-based dietary guidance and regulatory evaluation. Keywords: non-caloric sweeteners, aspartame, saccharin, stevia, antioxidants, oxidative stress, food additives, functional foods, bioactive compounds

Cutting-edge research on oceans and human health is enhancing our comprehension of disease-causing organisms in coastal ecosystems. Coastal areas are affected by pollution resulting from the changes in hydrology and land utilization. In the coastal population, an elevated incidence of diabetes was observed. Diabetes mellitus is a prominent metabolic disease that is causing major burdens for patients as well as physicians. Diabetes is an intricate condition that encompasses several molecular pathways associated with the gut microbiome. The gut microbiome significantly influences the permeability of the gastrointestinal mucosa. Alterations in the wide range of gut microbiomes have been associated with various health issues including diabetes. The two major contributors to type 2 diabetes are insulin resistance and inflammation which may result in metabolic dysregulation due to dysbiosis. Due to gut dysbiosis, diabetes may show high prevalence in individuals living in coastal areas. The correlation between dysbiosis and diabetes can be made, especially considering probiotics have been demonstrated to have some impact in helping diabetic patients with their interrupted metabolism revert to normal. Probiotic intake has reportedly resulted in improved metabolic control among patients with type 2 diabetes. Prebiotics can be non-digestible carbohydrates that are naturally extracted or synthetically produced. Uses of synbiotics show a synergistic impact on type 2 diabetes by altering the gut environment. In coastal communities, the potential effects of probiotic, prebiotic, and synbiotic therapy on the gut microbiome of diabetic patients have been investigated. Although these therapies have demonstrated encouraging results in coastal areas, more research is needed to fully understand their implications for controlling diabetes in this setting. In this review, we describe the role of the gut microbiome in diabetes patients residing in coastal regions and the underlying mechanisms that existed for analysing and predicting the function of the microbiome in diabetic people. The role of pre, pro, and synbiotics in type 1 and type 2 diabetes are precisely summarized. Keywords: Type 1 diabetes, gut microbiome, type 2 diabetes, coastal region, dysbiosis, prebiotics, synbiotics, probiotics.

IntroductionDespite numerous investigations into the impact of drugs/probiotics on the gut microbiota composition in Familial Mediterranean Fever (FMF) patients, the question as to whether there exists a significant bacterial diversity(ies) independent of the placebo effect that can be reliably considered in clinical and nutritional trials remains unresolved.MethodsThis study represents the in augural analysis of the placebo’s influence on the gut microbiota of both healthy individuals and FMF afflicted men, utilizing previously collected data from PhyloChip™ DNA microarray experiments. A total of 15 healthy and 15 FMF male volunteers, aged 18 to 50, participated in this partially randomized placebo trial, which is accessible through the GEO Series accession number GSE111835.Results and DiscussionKey findings from current investigations include i. the anticipated divergence in gut bacteria resistance to placebo between healthy and FMF individuals, ii. the minor impact of placebo on gut bacterial diversities in healthy individuals, with Enterobacteriaceae diversities identified as placebo-resistant among “healthy” gut bacteria, and iii. the comprehensive influence of placebo on all bacterial phyla in the gut microbiome of FMF patients, extending to nearly all bacterial genera, except for the resilience of gut Akkermansia muciniphila spp. to placebo in FMF patients. This study underscores the susceptibility of Faecalibacterium, Blautia, and Clostridium genera to placebo. Consequently, this investigation holds significance for the proper design of placebo-controlled trials and establishes a foundation for further exploration of the gut-brain axis. Furthermore, it contributes valuable insights to discussions regarding proposals for probiotic therapies, particularly focusing on Faecalibacterium spp., Blautia spp., and Clostridium spp.

The aim of this prospective comparative study was to determine whether alterations in ocular microbiota composition affect dry eye disease (DED) in newly married couples. Methods: This study comprised 392 spouses with confirmed dry eye disease (DED) who were either insomniac or hypersomniac, and 196 spouses as controls. We prospectively collected data on ocular surface parameters including tear osmolarity, Schirmer’s test and Ocular Surface Disease Index (OSDI), sleep parameters and ocular microbiota composition on day 1 and after six months follow up. Results: The frequency of moderate-to-severe DED in spouses who had married with an insomniac person was significantly higher than healthy controls and hypersmoniacs (P<0.001). The DED phenotype was positively significantly correlated with species differences in each of the three groups (P value <0.001). At baseline, frequency of both mild and moderate-to-severe DED phenotype was significantly highest in insomniacs. Interestingly, in support of our hypothesis, the frequency of both mild and moderate-to-severe DED phenotype in healthy spouses was significantly increased after six months of marriage with an insomniac person (but not with a hypersomniac person), suggesting that there is a possibility that ocular microbiota alteration might have played a role in occurrence of DED in this group. Conclusions: We for the first time contribute to the existing literature by discovering an association between ocular gut microbiota and DED, possibly through person-to-person contact. In the framework of family medicine and personalized medicine, the practical and theoretical implications of this study cover vast areas of sleep therapy and microbiota-related ocular diseases.