This study investigated the effect of oral eggshell membrane (ESM) administration on hair health using an in vivo model. C57BL/6N mice were orally administered ESM at different doses for 6 weeks to assess hair growth. ESM treatment increased hair regrowth index and anagen/total ratio and improved hair length, diameter, weight, and density. Scanning electron microscopy revealed reduced hair damage in the ESM groups. At the gene level, ESM upregulated the mRNA expression of hair growth-promoting factors (insulin-like growth factor-1, vascular endothelial growth factor, and fibroblast growth factor-7), the Wnt/β-catenin signaling-related genes (Wnt family member 10b and catenin beta 1), antioxidant enzymes (superoxide dismutase and catalase), and extracellular matrix production-related factors (Has1, Has2, and Has3), while downregulating the inflammatory cytokine interleukin 1 beta. These findings suggest that ESM alleviates oxidative stress and promotes hair growth in vivo by modulating growth factors. Wnt/β-catenin signaling, antioxidant defense, and ECM-related pathways, highlighting its potential as a nutritional supplement for hair and scalp health.

Endothelial nitric oxide synthase (eNOS) deficiency reduces nitric oxide (NO) bioavailability and contributes to vascular dysfunction and prothrombotic signaling. Dietary nitrate may support NO-related pathways through NOS-independent mechanisms. We hypothesized that a fermented beetroot preparation (BRL) would increase urinary nitrate/nitrite (NOx) output and reduce urinary thromboxane B2 more effectively than l-arginine (ARG) in an eNOS-deficient mouse model. In this focused pilot study, a BRL generated from beetroot (BR), carrot, and apple was administered to eNOS-knockout mice in drinking water for 10 days following a 5-day baseline period. Mice were housed individually in metabolic cages for 24-h urine collection, and urinary NOx and thromboxane B2 were measured daily and normalized to creatinine. Compared with l-ARG, the BRL increased urinary NOx and reduced urinary thromboxane B2. The baseline sampling design allowed each animal to serve as its own internal control throughout the longitudinal study. These pilot findings support further investigation of fermented BR-derived functional foods and provide a rationale for larger mechanistic studies examining nitrate exposure, additional molecular endpoints, and the contribution of fermentation-derived constituents.

The aim of this study was to assess the in vitro larvicidal activity of hydroalcoholic extracts (HAE) from four Pleurotus djamor fungal strains against Haemonchus contortus infective larvae (L3) and to evaluate the associated structural alterations in the larval cuticle using scanning electron microscopy (SEM) as an alternative to chemical anthelmintics. HAE were obtained from fruiting bodies through maceration. Larvae/HAE confrontation was carried out in 96 well ELISA plates. Two similar experiments were simultaneously performed to assess the HAE activity against sheathed (ShL3) and exsheathed (ExshL3) H. contortus larvae, respectively. Six well series (n = 4) were confirmed in every assessment. Each well contained 200 H. contortus (L3) in 20 μL of distilled water plus the corresponding HAE as follows: Series 1) Negative control (Distilled water 80 μL); Series 2) Positive control (Ivermectin 10 mg/mL); Series 3) P. djamor ECS-0142 strain (Pd-ECS-0142); Series 4) P. djamor ECS-0143 strain (Pd-ECS-0143); Series 5) P. djamor ECS-0127 strain (Pd-ECS-0127); Series 6) P. djamor ECS-0123 strain (Pd-ECS-0123). The different fungal HAE were assessed at the following concentrations: 20, 40, 80, and 175 mg/mL. Proportions of recovered larvae and larval mortality percentage were estimated, and the medium lethal concentration (LC50) was also estimated. Pd-ECS-0127, Pd-ECS-0142, and Pd-ECS-0143 HAE showed mortality percentages lower than 50%. In contrast, Pd-ECS-0123 HAE showed an in vitro larvicidal activity ranging between 90 and 100% against both ShL3 and ExshL3 H. contortus (L3) after 72 h post-confrontation. LC50 values of the fungal HAE with ShL3 and ExshL3 showed variability ranging from 71.30 to 167.5 mg/mL. The exposure of larvae to the Pd-ECS-0123 HAE at 175 mg/mL produced changes in the normal structural integrity of larvae.

Bee larvae (BL) have a long history of use as both traditional medicine and food. Given that BL contain anti-inflammatory lipids and immune-modulating components, they may be efficacious against hearing loss and tinnitus. In this study, we investigated the effects of enzymatically processed BL on the suppression of hearing loss using mouse models of acute acoustic injury and noise-induced hearing loss (NIHL). In an assay where C57BL/6 mice were exposed to a single 5-min burst of 110 dB white noise, pre-treatment with BL was found to reduce transient acoustic damage. Furthermore, under conditions of repeated 10-min noise exposures to induce NIHL, consumption of enzymatically processed BL mitigated the progression of hearing impairment. Additionally, antioxidant activity was confirmed in the enzymatically processed BL. Cellular assays and analysis of hexane extract fractions suggested that BL reduces noise-induced oxidative stress in the inner ear. Collectively, these findings demonstrate that enzymatically processed BL exert protective effects against the progression of hearing loss.

Edema is characterized by abnormal fluid accumulation in tissues, leading to visible swelling. The pathogenesis of edema is multifactorial, including vascular dysfunction, inflammation, and impaired fluid homeostasis. This study investigated the antiedematous effects of the natural product Centelline[TM] (Centella asiatica extract powder). Centelline exhibited significant antioxidant activity, as demonstrated by its enhanced radical scavenging capacity in the 2,2-diphenyl-1-picrylhydrazyl assay. It preserved the viability of human umbilical vein endothelial cells (HUVECs) under conditions of H2O2-induced oxidative stress. Centelline markedly reduced the production of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in lipopolysaccharide-stimulated RAW264.7 macrophages. It significantly reversed the H2O2-induced upregulation of endothelial adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin) and the reduction of nitric oxide (NO) production in HUVECs. Centelline effectively suppressed H2O2-induced vascular hyperpermeability in vitro while upregulating the expression of VE-cadherin. Furthermore, Centelline significantly attenuated acetic acid-induced vascular permeability in an in vivo model and inhibited carrageenan-induced paw edema in rats in a dose-dependent manner. Centelline suppressed the expression of inducible NO synthase and cyclooxygenase-2, as well as inflammatory cell infiltration at the inflammatory site in carrageenan-induced paw tissues. Taken together, these findings demonstrate the potent antiedematous effects of Centelline, mediated by the inhibition of oxidative stress and inflammatory responses and the reinforcement of the endothelial barrier. Centelline can be further developed as a natural therapeutic candidate for preventing and managing edema.

The global cancer burden is projected to escalate to 27 million new cases annually by 2040, a trajectory that parallels the rising prevalence of obesity, metabolic dysfunction, and related metabolic disorders. While genetic and environmental factors are well-recognized, the systemic metabolic environment is increasingly identified as a critical determinant of tumorigenesis. This review (Part I) systematically delineates the molecular and cellular framework through which metabolic dysfunction orchestrates a tumor-permissive landscape. We evaluate six primary pathophysiological axes: (1) chronic low-grade inflammation that fuels a protumorigenic milieu, (2) oxidative stress and redox imbalance leading to genomic instability, (3) insulin resistance and insulin-like growth factor axis activation which stimulate mitogenic pathways, (4) aberrant lipid metabolism and lipotoxicity-driven cell transformation, (5) gut microbiota dysbiosis and its modulation of the tumor microenvironment, and (6) metabolism-associated epigenetic remodeling that sustains oncogenic gene expression. Unlike previous literature that has focused on isolated pathways, this synthesis emphasizes the synergistic crosstalk among these mechanisms, illustrating how they collectively reinforce cancer initiation and progression. Furthermore, this mechanistic framework provides a biological rationale for targeting metabolism-associated carcinogenesis through dietary phytochemicals and bioactive compounds, which will be comprehensively discussed in Part II. By providing an integrated overview of the metabolic dysfunction-cancer axis, this work establishes a mechanistic foundation for the preventive potential of phytochemicals. These insights are crucial for developing multitarget dietary strategies against metabolism-associated malignancies.

Age-associated reductions in muscle strength and physical function have become an important public health concern among older adults, and gut microbiome-targeted interventions have emerged as a potential strategy to mitigate these declines. We evaluated the effects of Lactiplantibacillus plantarum HY7715 (L. plantarum HY7715) on lower-limb muscle function, serum vitamin B2, and gut microbiome profiles in older adults exhibiting reduced muscle strength. In this 12-week, randomized, double-blind, placebo-controlled trial, 100 adults aged 50-85 years were assigned to receive HY7715 (5.0 × 10[9] CFU/day) or placebo. Compared with placebo, HY7715 supplementation was associated with greater increases in multiple measures of quadriceps strength, with the left and bilateral mean measures remaining significant after baseline adjustment. Selected hamstring strength and quadriceps muscle power outcomes also showed significant improvements in the unadjusted analyses. Overall, the most consistent findings were observed for quadriceps strength, whereas the hamstring strength and quadriceps muscle power findings were less consistent after baseline adjustment. Serum vitamin B2 concentration increased significantly following HY7715 supplementation, and the between-group difference remained significant after adjustment for baseline dietary riboflavin intake. Microbiome analyses demonstrated increased Chao1 alpha diversity, significant within-group shifts in beta diversity, and increased relative abundances of Lactiplantibacillus and L. plantarum. HY7715 supplementation was associated with greater increases in selected quadriceps strength measures and serum vitamin B2 concentrations in adults with reduced muscle strength.

The personalized food industry aims to maintain health and prevent disease through nutritional solutions optimized for individuals' health status and lifestyle. As interest in personalized nutrition grows globally, Asia represents a strategically important hub where traditional medicinal plant knowledge is being translated into natural product-based personalized food innovations. This study analyzed patent filing trends in Asia to examine the development and growth stages of personalized food technologies. Patent databases were searched to identify patents related to natural product-based personalized foods filed in Asia. Of 761 patents identified, 368 were extracted as relevant valid data and categorized by technology field and applicant country. Patent applications began increasing in the mid-2000s, with a marked acceleration since 2015, indicating that the technology is in an early growth stage. Korea (43%) and China (31%) led filing activity. Dietary analysis patents accounted for 79% of valid patents, while food composition patents comprised 21%. This growth is driven by advances in personalized diet information utilizing biometrics and artificial intelligence-based health care technologies. Personalized food technology is currently in a growth phase and is expected to continue expanding.

Helicobacter pylori remains a major cause of chronic gastritis and dyspeptic symptoms, and the effectiveness of standard eradication therapy continues to decline with increasing antibiotic resistance. Lacticaseibacillus paracasei HP7 has shown inhibitory and anti-inflammatory effects on H. pylori in preclinical studies. This study investigated whether 8-week oral HP7 supplementation could improve H. pylori-related outcomes in adults with confirmed infection. Seventy-eight adults with positive [13]C-urea breath test ([13]C-UBT) results and gastric discomfort were randomized to receive low-dose HP7 (HP7-L, 1.5 × 10[9] CFU/day), high-dose HP7 (HP7-H, 5.0 × 10[9] CFU/day), or placebo for 8 weeks. Outcomes included changes in [13]C-UBT values, upper gastrointestinal (GI) symptoms assessed by Korean Gastrointestinal Symptom Rating Scale, pepsinogen I/II ratio, serum tumor necrosis factor-α, and quality-of-life indices. HP7-H significantly reduced [13]C-UBT values compared with placebo. HP7 supplementation was also associated with improvements in gastric mucosal biomarkers and modest changes in selected upper GI symptom and quality-of-life domains. Overall microbial diversity was not significantly altered, although the abundance of L. paracasei increased following supplementation. No treatment-related serious adverse events were observed, and all laboratory findings remained within clinical reference ranges. Complete eradication of H. pylori was not achieved in most participants. These findings support the clinical potential of HP7 supplementation to attenuate H. pylori-related activity and improve gastric biomarkers, with modest benefits in selected dyspeptic symptom domains. HP7 may be a safe and effective functional food option for H. pylori management when antibiotics are contraindicated or ineffective. Further studies are warranted to confirm long-term efficacy and durability of these effects.

Polyporus umbellatus is a traditional medicinal fungus with potential application as a food-related bioactive; however, toxicological data for concentrated extracts remain limited. This study evaluated aqueous P. umbellatus extract using three complementary genotoxicity assays and a 2-week repeated-dose toxicity study. Genotoxicity was assessed using an in vitro chromosomal aberration assay in Chinese hamster lung cells, a bacterial reverse mutation assay, and an in vivo bone marrow micronucleus assay. The repeated-dose toxicity study was performed in F344 rats administered 500, 1000, or 2000 mg/kg/day P. umbellatus extract by oral gavage for 2 weeks. P. umbellatus extract significantly increased structural chromosomal aberrations in vitro under short-term treatment with metabolic activation, and under short-term and continuous-treatment conditions without metabolic activation. In contrast, the extract did not increase revertant colonies of Salmonella typhimurium or Escherichia coli tester strains, and oral administration did not increase micronucleated polychromatic erythrocytes in male or female ICR mice. Repeated oral administration for 2 weeks caused no mortality, treatment-related clinical signs, body weight loss, gross lesions, or consistent hematological or serum biochemical toxicity patterns. Isolated changes in male kidney weight, female salivary gland weight, and male creatine kinase activity were not accompanied by concordant findings and were therefore not interpreted as definitive adverse effects. Overall, the findings indicate an in vitro clastogenic response without evidence of bacterial mutagenicity, bone marrow micronucleus induction, or overt repeated-dose oral toxicity under the investigated experimental conditions, paving the way for long-term studies to complete the toxicological characterization of P. umbellatus.

Dyslipidemia is a significant risk factor for cardiovascular disease. This study evaluated the efficacy of a cholesterol-lowering diet, a supplement containing bergamot and plant sterols, and their combination in managing dyslipidemia. In this 12-week randomized controlled trial, 61 adults with dyslipidemia were assigned to one of three groups: diet-only (Group D, n = 19), supplement-only (Group B, n = 21; 150 mg bergamot flavonoids + 800 mg plant sterols/day), or mixed (Group M, n = 21; Diet + Supplement). Efficacy was assessed via changes in biochemical and anthropometric parameters. The primary finding was the superior efficacy of the mixed group (Group M), which demonstrated significantly greater reductions in total cholesterol (-53.9 mg/dL; -19.8%), low-density lipoprotein cholesterol (LDL-C) (-42.6 mg/dL; -23.3%), and triglycerides (TGs) (-57.2 mg/dL; -29.7%) compared to both diet-only and supplement-only groups (P < .05). While all three groups showed improved total and LDL-C, TG levels decreased significantly only in the supplement-receiving groups (Group B and Group M). Conversely, dietary intervention primarily drove significant improvements in body weight (Group D: -4.2 kg; Group M: -3.4 kg), body mass index (-1.5 and -1.2 kg/m[2], respectively), and fat mass (-3.5 and -2.9 kg, respectively). High-density lipoprotein cholesterol and liver enzymes (alanine aminotransferase, aspartate aminotransferase) remained unchanged across all groups. Combining a cholesterol-lowering diet with a bergamot and plant sterol supplement offers a synergistic and superior strategy for improving the lipid profile in individuals with dyslipidemia, while the dietary component remains essential for improving body composition.

Environmental stress is increasingly recognized as a contributor to auditory dysfunction through disruption of mechanotransduction-related processes and induction of oxidative stress. This study evaluated the protective effects of a γ-aminobutyric acid (GABA)-enriched fermentate (DX3004-GABA), derived from Levilactobacillus brevis DX3004, using a Drosophila melanogaster model of cold stress-induced auditory dysfunction. Auditory-associated phenotypes were assessed by courtship song-induced chaining behavior, and expression of mechanotransduction-related (nan, nompB), ciliary integrity-associated (btv, rempA, ninaC, tilB), and gene expressions related to antioxidant defense (cncC, cat, sod) was analyzed by quantitative real-time polymerase chain reaction. Cold stress markedly impaired chaining behavior, downregulated auditory-related gene expression, and increased both dihydroethidium-reactive and 2',7'-dichlorofluorescein (DCF)-reactive reactive oxygen species (ROS) levels in fly head samples. Supplementation with DX3004-GABA significantly improved auditory dysfunction-associated phenotypes, restored auditory-related gene expression, and reduced ROS accumulation more effectively than purified GABA. In addition, DX3004-GABA enhanced antioxidant defense-associated gene expression, suggesting improved redox regulation. Collectively, these findings indicate that a GABA-enriched fermentate ameliorates cold stress-induced auditory dysfunction-associated phenotypes through coordinated modulation of auditory-related molecular responses and oxidative stress-associated pathways. The enhanced efficacy of DX3004-GABA compared with purified GABA raises the possibility that additional fermentation-derived metabolites contribute to the observed biological activity, highlighting the potential of postbiotic fermentates as functional ingredients for stress-associated conditions.

Prolonged administration of cisplatin, a widely used chemotherapeutic agent, induces nephrotoxicity. Identifying natural compounds that attenuate cisplatin's adverse effects on renal tissues would be of clinical value. Thus, the present study aimed to evaluate the cytoprotective effects of Cudrania tricuspidata leaf-derived polysaccharides (CTP) in human embryonic kidney (HEK) 293T cells to explore their potential as a chemotherapeutic adjuvant. In the cell viability assay, CTP alone showed no inherent cytotoxic effects, whereas co-treatment with cisplatin led to a significant improvement in cell viability. These observations were corroborated by Annexin V/propidium iodide staining, which demonstrated that CTP effectively attenuated cisplatin-induced cell damage in HEK 293T cells. CTP also increased the total antioxidant capacity in the 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and ferric reducing antioxidant power assays in a dose-dependent manner while elevating the activities of intracellular antioxidant enzymes, including catalase and superoxide dismutase, which correlated with the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1. Moreover, CTP reduced malondialdehyde levels, indicating that it protected against oxidative-stress-induced membrane damage. Mechanistically, CTP mitigated cisplatin-induced apoptosis by upregulating B cell lymphoma 2 (Bcl-2) expression while suppressing the expression of Bcl-2-associated X protein, cleaved caspase-3, and caspase-9. Collectively, the findings demonstrate that pretreatment with CTP protected HEK 293T cells from cisplatin-induced damage, highlighting its potential as a functional food ingredient.

Clinical evidence for Salacia reticulata extract (SR) in prediabetes remains limited, particularly with respect to its effects on comprehensive glucose exposure across multiple oral glucose tolerance test (OGTT)-derived intervals. This randomized, double-blind, placebo-controlled trial evaluated the effects of a standardized SR administered for 12 weeks on fasting and postprandial glucose exposure in adults with prediabetes. One hundred participants meeting prediabetes criteria (fasting plasma glucose [FPG] 100-139 mg/dL and postprandial plasma glucose [PPG] 140-199 mg/dL) were selected. Participants with dual fasting and postprandial glycemic impairments were randomly assigned to receive SR (500 mg/day, n = 50) or placebo (n = 50). Efficacy and safety outcomes were assessed at baseline and after the intervention. Compared with placebo, SR significantly reduced FPG and PPG to 90 and 120 min after supplementation (all P < .05). Glucose areas under the curve at 0-30, 0-60, 0-90, and 0-120 min were significantly lower in the SR group compared with placebo, with significant percent reductions in postprandial glucose spikes from baseline to week 12 (all P < .05). Additionally, HbA1c and triglycerides were significantly reduced, while 1,5-anhydroglucitol was significantly increased compared with placebo. Total glucagon-like peptide-1 (GLP-1) levels showed a significant between-group difference. No clinically meaningful safety concerns were observed. Twelve weeks of supplementation with standardized SR attenuated fasting and postprandial glucose concentrations, including significant reductions in OGTT-derived glucose spikes. These findings extend clinical evidence of S. reticulata to early-stage dysglycemia and support its potential role in glycemic stabilization in prediabetes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) develops through systemic metabolic dysregulation and gut-liver axis-mediated inflammation; however, effective preventive strategies remain limited. Probiotics such as Lactiplantibacillus plantarum have emerged as potential modulators of intestinal barrier integrity and hepatic inflammation; however, preventive efficacy during early MASLD progression has not been fully elucidated. The present study evaluated whether L. plantarum Q180 attenuates early high-fat diet (HFD)-induced MASLD in a murine model. Male C57BL/6J mice were fed a normal diet or 60% HFD for 12 weeks, and Q180 was orally administered at 1.0 × 10[9] CFU/day from weeks 5 to 12. HFD feeding induced obesity, hepatic lipid accumulation, and an elevated nonalcoholic fatty liver disease activity score (NAS), confirming early-stage MASLD. Although Q180 did not significantly reduce body weight gain or adipose tissue mass, Q180 did significantly decrease hepatic triglyceride levels and NAS, accompanied by improvements in steatosis, hepatocellular ballooning, and inflammatory infiltration. Hepatic expressions of Dgat1 and Sod were significantly upregulated, whereas Ldlr expression was downregulated. In the colon, Q180 markedly suppressed Tnf-α and Il-6 expression and partially restored Zo-1, Occludin, and Muc2 expressions. Serum endotoxin levels were significantly reduced, and a decreasing trend was observed in fecal endotoxin levels. Overall, Q180 exerted metabolic and immunological benefits during early MASLD progression by reducing hepatic lipid accumulation, enhancing antioxidant defenses, attenuating intestinal inflammation, reinforcing intestinal barrier integrity, and lowering endotoxin exposure. The results support Q180 as a promising probiotic candidate for the prevention and early management of MASLD through gut-liver axis modulation.