Search Results (504)

Background: Residual arrhythmic risk persists in recipients of implantable cardioverter-defibrillators (ICDs) despite guideline-based selection, and inexpensive markers that refine this risk are needed. The monocyte-to-high-density-lipoprotein ratio (MHR) integrates a pro-inflammatory (monocyte) and an anti-inflammatory/antioxidant (HDL) signal in a single index derived from routine blood work. We examined whether MHR is associated with ventricular arrhythmia in ICD patients. Methods: In this cross-sectional study we assessed 382 ICD recipients attending a device outpatient clinic and classified them by a composite ventricular arrhythmia outcome (non-sustained ventricular tachycardia, sustained ventricular tachycardia, or ventricular fibrillation) documented on device interrogation. MHR and comparator inflammatory markers were measured at the same visit. Discrimination was assessed by receiver operating characteristic (ROC) analysis, the optimal threshold by the Youden index, and independence by multivariable logistic regression; internal validity was examined with repeated cross-validation, bootstrap optimism correction, and calibration testing. Results: The ventricular arrhythmia outcome was present in 58 patients (15.2%). MHR was higher in patients with the outcome (median 16.3 vs. 12.3, p < 0.001) and discriminated it with an area under the curve (AUC) of 0.756 (95% CI 0.673–0.828). At the optimal threshold of 15.71, sensitivity was 63.8% and specificity was 83.3%, with a negative predictive value of 92.8%; the outcome was present in 40.7% of patients above versus 7.2% below this cut-off. MHR remained independently associated with the outcome after adjustment for age, left ventricular ejection fraction, etiology, and renal function (odds ratio 1.23 per unit, 95% CI 1.16–1.32; p < 0.001) and outperformed high-sensitivity C-reactive protein (DeLong p < 0.001). Discrimination was preserved in both ischaemic and non-ischaemic cardiomyopathy without interaction by etiology (p = 0.67). The model was stable on internal validation (cross-validated AUC 0.761; optimism 0.021; Hosmer–Lemeshow p = 0.66). Conclusions: MHR is independently associated with documented ventricular arrhythmia in ICD patients and, being derived from routine tests, may warrant prospective evaluation as a low-cost adjunct for risk stratification. Full article

Despite known antioxidant activity, the effects of plant-derived compounds on aging-related physiological functions and mechanisms remain unclear, which necessitates investigation at cellular and organismal levels. To examine whether these compounds can mitigate age-related physiological decline, Nelumbo nucifera Gaertn. (sacred lotus) embryo extract–water-soluble fraction (NEW), stilbene glycoside from Pleuropterus multiflorus (Thunb.) Turcz. ex Nakai (PM-SG), and pterostilbene were investigated through chemical profiling, antioxidant activity, HepG2 liver cells, and Caenorhabditis elegans longevity assays, while principal component analysis (PCA) elaborated on the results. Quantitative LC-MS revealed that NEW extract was rich in alkaloids (neferine and liensinine), while PM-SG mainly contained 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside. PM-SG showed the strongest radical-scavenging activity (DPPH, TEAC, and ORAC), followed by pterostilbene. However, pterostilbene exhibited the strongest cellular antioxidant activity among the three test materials (NEW, PM-SG, and pterostilbene), an effect attributed to its superior cellular uptake, although it was less potent than the reference standards EGCG and quercetin. All samples extended the lifespan of C. elegans dose-dependently, with the strongest effect from pterostilbene (40–50%), then PM-SG (25–35%) and NEW (18–22%). Pterostilbene and PM-SG improved health measures, including enhanced resistance to heat and oxidative stress, and maintained feeding function. Discrepancies between in vitro antioxidant rankings and observed cellular effects indicate that radical-scavenging activity alone cannot fully predict in vivo anti-aging efficacy, which depends on cellular uptake, activation of endogenous defense mechanisms, and modulation of longevity pathways. Further clinical studies are needed to determine the potential relevance of these findings to human health. Full article

Functional fermented foods are increasingly recognized as sources of microbial metabolites with potential biological activity. In this study, MRK2-3, a protease-sensitive anti-Helicobacter pylori component produced by Lactiplantibacillus pentosus MRK2-3 isolated from fermented mushroom sausage, was enriched and preliminarily characterized for in vitro anti-H. pylori activity. Activity appeared during the stationary phase. Sequential ethyl acetate extraction, Sep-Pak C18 chromatography, and reverse-phase HPLC increased specific activity, although the final activity recovery was 0.72%. MALDI-TOF analysis of the active fraction showed a dominant ion at approximately m/z 1848 together with several lower-intensity ions; therefore, chemical homogeneity and sequence identity were not established. The MRK2-3 fraction retained activity after incubation at pH 2–6 and after heating at 80 °C and 100 °C for 30 min, whereas activity decreased under alkaline conditions and after treatment at 121 °C for 15 min. Trypsin, α-chymotrypsin, pepsin and proteinase K reduced activity. The fraction inhibited all tested H. pylori strains (agar-dilution MIC ranged from 12.5 to 100 μg/mL). In a simulated gastric fluid, higher concentrations produced a rapid reduction in viable H. pylori 3949 counts. These findings support MRK2-3 as a fermentation-derived putative antimicrobial peptide candidate with anti-H. pylori activity under gastric-like conditions. However, its amino acid sequence, structural identity, and novelty require confirmation. Antimicrobial mechanism, cytotoxicity, and in vivo efficacy also remain to be established. Full article

Prebiotics are predominantly indigestible carbohydrate-based substrates selectively-utilized by beneficial gut-microbes to support host-health. We previously developed protein-containing prebiotics that co-deliver carbohydrate and protein substrates to the colon, where gut-microbes compete for the limited nitrogen availability, thereby enhancing microbial growth, metabolic activity, and host health compared with conventional carbohydrate prebiotics. Resveratrol is a grape-derived polyphenol with antioxidant, anti-inflammatory, and emerging prebiotic activity. Here, we developed a multifunctional protein-containing prebiotic system based on Maillard conjugates of 2′-fucosyllactose–potato protein hydrolysate (2′-FL-PPH) micelles encapsulating resveratrol, followed by genipin crosslinking. This crosslinked 2′-FL-PPH-resveratrol system is designed to limit premature protein and resveratrol absorption, enhancing their colonic co-delivery. We characterized the encapsulation efficacy, physicochemical properties, digestibility and colonic delivery. The conjugates (10 mg/mL 2′-FL-PPH) effectively entrapped resveratrol (600 µM), exhibiting an average particle size of ~28 nm and an encapsulation efficiency of 79.5 ± 4.9%. Binding studies demonstrated predominantly hydrophobic interactions between resveratrol and 2′-FL-PPH. The conjugates prevented resveratrol crystallization in aqueous media, while genipin crosslinking enhanced resistance to simulated gastrointestinal digestion and inhibited premature resveratrol release, increasing the fraction expected to reach the colon. Collectively, this system enables colonic co-delivery of carbohydrate, peptides, and resveratrol, providing a novel strategy for promoting beneficial-microbiota and gut-health. Full article

Andean crops, including quinoa (Chenopodium quinoa), amaranth species including kiwicha (Amaranthus caudatus), chocho (Lupinus mutabilis), and cañihua (Chenopodium pallidicaule), constitute promising protein matrices for bioactive peptide generation by microbial fermentation and enzymatic proteolysis. These pseudocereals and legumes contain storage proteins, mainly 11S globulins and 2S albumins, enriched in lysine and sulfur-containing amino acids, and therefore provide suitable precursors for multifunctional peptides. In addition, secondary metabolites, such as quinoa saponins and chocho alkaloids, may influence proteolysis, peptide release, and peptide stability during fermentation. This review critically examines LAB fermentation as a food-grade strategy for bioactive peptide production from Andean crops. Evidence from enzymatic hydrolysis and simulated gastrointestinal digestion is included as complementary information and is discussed separately from fermentation-derived evidence. Reported activities include antioxidant, ACE-inhibitory, DPP-IV- and α-glucosidase-inhibitory, antimicrobial and anti-inflammatory activities. Particular attention is given to peptide generation, molecular-weight fractionation, peptidomic characterization, structure–activity relationships, simulated gastrointestinal digestion, and bioaccessibility. Most reported activities were measured in hydrolysates or molecular-weight fractions rather than in defined sequences, and individually validated peptides remain a minority. The strength of evidence differs markedly among crops: fermentation-derived data are more developed for quinoa and amaranth, whereas evidence for chocho and cañihua relies largely on enzymatic hydrolysis. Current limitations, including substrate variability, sensory acceptability, process standardization, peptide identification, bioavailability, and the lack of human validation studies, are also discussed. Andean crop proteins are promising precursors of functional peptide ingredients; however, peptide-specific bioavailability and human efficacy remain largely untested. Full article

Background: This study aimed to investigate the effects of E. stephanianum-derived polyphenols on preventing the progression of collagen-induced arthritis (CIA) in mice and its associated metabolic alterations. Methods: The E. stephanianum plant was extracted, fractionated, and screened in vitro for anti-inflammatory, antibacterial, and antioxidant potential. Fraction 5 (identified as ellagic acid by nuclear magnetic resonance) exhibited the most potent activity and was selected for in vivo study. In the in vivo study, male DBA/1JGpt mice were randomized into five groups: control (CON), CIA (Model), low-dose extract (ES-L), high-dose extract (ES-H), and ellagic acid group. ES-L, ES-H, and ellagic acid were administered by daily oral gavage at 375, 750, and 250 mg/kg body weight, respectively, for 8 weeks. Arthritis severity was evaluated based on paw thickness, clinical score, ankle joint histopathology, and serum proinflammatory cytokine levels. To reveal the associated metabolic alterations, serum metabolites were characterized by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Results: Both the whole extract and ellagic acid revealed pronounced anti-inflammatory, antibacterial, and antioxidant properties. In vivo treatment with ES-L, ES-H, or ellagic acid similarly and significantly ameliorated CIA severity, showing smaller paw swelling, reduced clinical arthritis scores, milder joint histopathological injury, and lower serum tumor necrosis factor-α and interleukin-6 concentrations than the model group. Untargeted metabolomics identified 20 differential metabolites, mainly including triacylglycerols (containing n-3 fatty acids), pro-inflammatory phospholipids, and spermic acid 1. Moreover, the treatments significantly altered amino acid and purine metabolism. Conclusions:E. stephanianum derived polyphenols, like ellagic acid, significantly prevented the progress of CIA in mice. These effects were associated with the alteration of metabolic profiles. Full article

Adonis aestivalis L. is a member of the genus Adonis, traditionally associated with cardiotonic compounds; however, its polyphenolic composition and anti-inflammatory potential warrant further phytochemical and pharmacological evaluation. The aim of this study was to characterise the metabolic profile of A. aestivalis extracts, with a focus on flavonoid-containing components, and to evaluate their anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophages. Aqueous, 50% ethanolic, and absolute ethanolic extracts were analysed by HPLC–ESI–QTOF-MS/MS in positive and negative ionisation modes. The ethanolic extracts exhibited the most diverse chromatographic profiles, with a predominance of flavonoids, including derivatives of kaempferol, quercetin, and apigenin, as well as C-glycosylated flavones such as orientin, isoorientin, vitexin, and isovitexin. Phenolic acids, fatty acid derivatives, organic acids, and adonitol were also tentatively identified. The occurrence of glycosylated, acylated, and glucuronidated flavonoid derivatives indicates marked structural diversity within the flavonoid fraction. In biological assays, the 50% ethanolic extract showed no cytotoxicity towards RAW 264.7 cells at concentrations up to 50 μg/mL and produced a statistically significant but moderate reduction in LPS-induced NO production. Furthermore, it attenuated the release of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, to varying degrees. The data obtained indicate that A. aestivalis is a promising source of flavonoid-containing extracts with anti-inflammatory potential and may provide a foundation for further studies aimed at developing standardised phytochemical preparations with a defined polyphenolic profile. Further quantitative phytochemical analysis, bioactivity-guided fractionation, mechanistic studies, safety assessment, and in vivo evaluation are required to confirm the active constituents and therapeutic relevance of the extracts. Full article

Fenjiu distillers’ grains are a major by-product of Fenjiu production and contain various bioactive components derived from cereal raw materials and microbial fermentation. Colorectal cancer (CRC) remains a global health challenge, and the development of safe and effective therapeutic agents is urgently needed. In this study, we successfully obtained DGAE-1 (distillers’ grains ethanol extract fraction 1), an ethanol-extracted bioactive fraction derived from Fenjiu distillers’ grains, with anti-colorectal cancer activity. LC-MS analysis tentatively annotated the chemical constituents of DGAE-1 fraction based on MS/MS fragmentation patterns and database similarity matching, with the major annotated compounds belonging to carboxylic acids and derivatives, organic nitrogen compounds, organic phosphoric acid derivatives, and other chemical classes. These annotated compounds may contribute to the biological activity of DGAE-1 fraction, although the specific active constituents remain to be further clarified. DGAE-1 fraction inhibited colorectal cancer cell proliferation and induced autophagy. Further studies indicated that the PI3K/AKT pathway is involved in DGAE-1 fraction-induced autophagy. The results of this study demonstrate that DGAE-1 fraction exerts anti-colorectal cancer activity in both cellular and animal models. These findings provide new insights into the development and utilization of Fenjiu distillers’ grains and highlight their potential as a source of bioactive compounds for health-related applications. Full article

Acorns (Quercus spp.) have re-emerged as a sustainable, underutilized food resource, and their lipid fraction has attracted growing scientific interest because of its distinctive composition and technological potential. Acorn lipids typically represent 5–12% of acorn dry weight, ranging from 0.75% (Q. vulcanica) to over 17% (Q. rubra), and are dominated by unsaturated fatty acids, mainly oleic acid (up to ~70% of total fatty acids) and, to a lesser extent, linoleic acid, alongside minor bioactive compounds such as tocopherols (31.60–1486 mg/kg oil), phytosterols (2449–8797.92 mg/kg oil), carotenoids (β-carotene: 473–1421 mg/kg DM), and long-chain aliphatic alcohols (2198.81–2248.87 mg/kg oil) associated with antioxidant, anti-inflammatory, hypocholesterolemic, and cardioprotective effects. Despite their high degree of unsaturation, acorn oils maintain good oxidative stability during up to 180 days of storage under dark conditions at room temperature, partly due to these endogenous antioxidants, and their lipids participate in starch–lipid interactions that influence starch digestibility, glycemic response, and the functional properties of acorn-based foods, including bakery, gluten-free, and pasta products. Based on a comprehensive literature search of the Web of Science database through June 2026, this review provides a comprehensive synthesis of acorn lipids. Critical analysis shows that most evidence derives from whole acorn flour rather than isolated lipids, that reporting units remain inconsistent across studies, and that dedicated intervention trials using acorn oil are lacking—gaps that should guide future research. This review serves as a critical bridge between botanical lipidomics and food engineering, providing a framework for the standardized valorization of Quercus species in the global transition to sustainable, plant-based functional ingredients. Full article

Background/Objectives: Persistent inflammation and impaired tissue regeneration delay mucosal and cutaneous wound healing. Potato (Solanum tuberosum L.) preparations contain bioactive metabolites with anti-inflammatory and regenerative potential, yet their wound-healing mechanisms have not been systematically mapped. This scoping review aimed to map potato-derived bioactive metabolites and their roles in modulating inflammation and promoting tissue regeneration during wound healing. Methods: A scoping review was conducted in accordance with the PRISMA-ScR guidelines. Articles published between 2015 and 2025 were retrieved from the Scopus, PubMed, EBSCO, and ScienceDirect databases combined with hand searching. Eligible studies included in vivo animal models; mechanistically relevant in vitro studies; and limited clinical or human skin safety studies investigating potato-derived extracts, fractions, or defined preparation effects in wound, ulcer, and burn healing. Results: Among the 583 records identified, only 15 met the inclusion criteria. These studies reported five major bioactive metabolite classes—flavonoids/anthocyanins, polyphenols, alkaloids, polysaccharides, and peptides—together with potato-derived exosomal vesicles as an extracellular vesicle/delivery system (not a metabolite class). Potato-derived preparations have been associated with accelerated wound closure, enhanced fibroblast proliferation, collagen deposition, and the attenuation of inflammatory mediators. Molecular evidence, which was included in only six studies, supported the modulation of NF-κB, STAT1/3, COX-2, iNOS, cytokines, and MMP-9. In addition, five priority gaps were identified: lack of standardization, fragmented biomarker profiling, limited compound-specific validation, scarce clinical translation, and absence of omics-based and complex wound models. Conclusions: Potato-derived bioactive metabolites show multi-target preclinical associations with wound healing and warrant further development as potential adjunctive therapies for mucosal and cutaneous wounds after standardization and clinical validation. Full article

Processing herbal medicine generates substantial quantities of by-products that are discarded as waste. These residues may retain polysaccharides, flavonoids, saponins, terpenoids, and other constituents with pharmacological relevance. This review discusses the bioactive potential of by-products derived from single traditional Chinese and Korean herbal medicines, with emphasis on antioxidant, anti-inflammatory, and immunomodulatory mechanisms documented in preclinical in vivo studies. Representative in vivo evidence suggests that selected residues, marc fractions, fermentation products, and re-extracted by-products were reported to modulate oxidative stress markers, inflammatory cytokines, immune responses, and tissue-protective pathways across diverse experimental models. Processing method appears to be a key determinant of activity, as fermentation, high-temperature/high-pressure treatment, re-extraction, and targeted purification may enhance or diversify residual bioactivity. Current evidence remains limited by inconsistent chemical characterization, heterogeneous animal models, and incomplete reporting of experimental design. Re-evaluating herbal medicine processing by-products as bioactive resources may support sustainable herbal medicine manufacturing and circular bioeconomy frameworks. Full article

Aberrant self-assembly of ataxin-3 (ATX3) into amyloid aggregates is a key pathological event in spinocerebellar ataxia type 3 (SCA3). Bioactive nutraceutical compounds, particularly polyphenols, have emerged as promising candidates for targeting protein aggregation and cellular stress responses associated with neurodegenerative disorders. Here, we investigated cinnamon bud extract as a natural source of neuroprotective molecules, focusing on its total extract (Etot) and two bioactive fractions: a polyphenol-enriched fraction (Fr. B) and a cinnamaldehyde-rich fraction (Fr. C). By integrating biochemical and biophysical techniques, we demonstrate that cinnamon-derived compounds modulate ATX3 aggregation by reducing the formation of β-sheet-rich amyloid assemblies and promoting the generation of SDS-resistant, soluble, structurally distinct, non-fibrillar species. NMR profiling identified flavonoids, cinnamaldehyde, and cinnamic acid as key ATX3-interacting molecules, supporting their contribution to the anti-amyloidogenic activity of the extract. Moreover, in a Caenorhabditis elegans SCA3 model, Etot and Fr. B improved locomotor defects and enhanced resistance to oxidative and thermal stress, indicating broader cytoprotective effects beyond direct aggregation modulation. Overall, these findings highlight cinnamon bud extract, particularly its polyphenol-rich fraction, as a promising nutraceutical source of bioactive compounds with potential neuroprotective properties and provide a basis for further investigation of nutraceutical strategies targeting polyglutamine-related neurodegenerative diseases. Full article

Ramanujan’s master theorem is considered to express particular values of the Liouville fractional derivatives. This fact is used to immediately obtain generalizations. Firstly, it is shown that the original formulation is suitable only for anti-causal functions. Consequently, an expression for causal functions is introduced. Secondly, the two formulations are extended to be valid for any real order and related to the Laplace transform, corresponding to transforms with left- or right-sided regions of convergence. This leads to introducing the concept of the unilateral MacLaurin series and the substitution of the Liouville derivative by the (Liouville–)Grünwald–Letnikov derivative, which essentially expresses a discrete formulation that is suitable for numerical implementations. The way in which this procedure arose and its relationship with the Liouville derivatives suggested other approaches, which are briefly discussed, such as replacing the MacLaurin series with the Mittag–Leffler series or the Liouville derivative with the Riesz, Feller, or Hadamard derivatives. Full article

Asphalt binders become stiffer and more brittle during aging, increasing their susceptibility to fatigue and thermal cracking. Rejuvenation is therefore a key strategy for restoring aged bitumen and enabling the effective use of reclaimed asphalt materials. This review examines agricultural by-products, biowastes, and other biogenic materials as bio-rejuvenators for aged bituminous binders. The reviewed materials are classified according to their source, processing route, functional role, chemical characteristics, rejuvenation mechanism, performance effects, and practical limitations. The main groups include waste cooking oils, virgin vegetable oils, reactive bio-oils, biomass-derived bio-oils, agricultural and forestry residues, tree-resin-derived products, animal-based rejuvenators, and other organic waste-derived materials. The literature indicates that these materials can restore aged bitumen through light fraction replenishment, colloidal rebalancing, diffusion, asphaltene deagglomeration, chemical interaction, and anti-aging effects. Waste cooking oils and agricultural/forestry residue-derived rejuvenators provide particularly strong recovery of conventional binder properties, whereas reactive bio-oils and tree-resin-derived systems offer a more balanced rheological response and cracking–rutting balance. However, their effectiveness strongly depends on dosage, feedstock variability, binder compatibility, processing route, and aging condition. Overall, bio-rejuvenators offer a promising pathway for sustainable asphalt recycling, but their practical implementation requires standardized dosage selection methods, long-term aging assessment, mixture- and field-scale validation, and life-cycle evaluation. Full article

Background: Skin photoaging, primarily induced by chronic ultraviolet (UV) radiation exposure, is characterized by dryness, wrinkle formation, pigmentation abnormalities, and reduced skin elasticity, resulting from oxidative stress, inflammation, and degradation of the extracellular matrix. Codonopsis pilosula, a traditional food–medicine homologous plant, is recognized for its anti-aging properties. However, its lipophilic components (designated as CP-L) remain insufficiently explored. Methods: Herein, we developed a thermosensitive nanogel encapsulating CP-L-loaded transferosomes (CP-L nanogel) to enhance topical delivery and evaluated its effects in both a UV-induced photoaging mouse model and UVB-irradiated HaCaT keratinocytes. Results: In UV-induced mice, topical application of the nanogel markedly reduced skin wrinkling and epidermal hyperplasia, with epidermal thickness decreased by 83.2% compared to the model group (p < 0.01), and restored skin elasticity and collagen deposition, as evidenced by a 35.5% increase in collagen area fraction (p < 0.01). Correspondingly, in UVB-irradiated HaCaT cells, it significantly increased cell viability from 53.0 ± 9.6% to 89.4 ± 1.0% (p < 0.01) and suppressed apoptosis from 30.1 ± 0.48% to 12.4 ± 0.66% (p < 0.01). Furthermore, the CP-L nanogel consistently attenuated oxidative stress, with SOD, CAT, and GSH-Px activities increased by 73.1%, 188.1%, and 18.2%, respectively (p < 0.01), and MDA levels reduced by 71.0% (p < 0.01), while inflammatory responses were suppressed, as TNF-α, IL-1α, IL-1β, and IL-6 levels decreased by 28.3%, 22.6%, 12.8% and 31.9%, respectively (p < 0.01). Mechanistically, transcriptomic and molecular analyses revealed that the nanogel potently inhibited the UV-induced activation of the FGFR/PI3K/AKT/mTOR/p70S6K signaling cascade at both transcriptional and protein levels, with the phosphorylation levels of FGFR, PI3K, AKT, mTOR, and p70S6K significantly reduced by 43.9%, 30.9%, 38.8%, 34.9%, and 57.3%, respectively (p < 0.01). Molecular docking and dynamics simulations identified isofuranodienone and aromadendrene oxide-(2) as key constituents with high-affinity, stable binding to FGFR1 and AKT1. The cytoprotective effect of the nanogel was completely abolished by co-treatment with the FGFR inhibitor PD173074, confirming functional reliance on this pathway. Enhanced cellular delivery of the formulation was directly demonstrated by flow cytometry, showing an approximately 1.8-fold increase in cellular uptake compared to the free drug (p < 0.01). Conclusions: Collectively, these results demonstrated that the CP-L nanogel alleviated skin photoaging through a multi-faceted mechanism involving enhanced cellular delivery, potent antioxidant and anti-inflammatory activities, and specific inhibition of the FGFR/PI3K/AKT/mTOR signaling cascade, highlighting its potential as a multitargeted topical agent derived from an edible plant. Full article