Search Results (706)

Background: Inflammatory signaling and oxidative stress machinery are interconnected and play roles in apoptosis, proliferation, redox state control, and the progression of many diseases, including cancer. The marine environment harbors a wealth of organisms that produce a wide variety of bioactive molecules with significant biological activities. Over the last decade, the advent of AI-driven approaches has enhanced the study and analysis of peptides, helping to reduce costly and time-consuming conventional laboratory testing, validation, and synthetic procedures. Methods: In this study, we predicted the antioxidative and anti-inflammatory activities of peptides isolated from proteomic data obtained from circulating cells and humoral components of the sea cucumber defense system using a bioinformatic workflow based on different artificial intelligence tools. Results: We identified 40 top-ranked peptides with antioxidative and anti-inflammatory activity and a sub-class of eight peptides shared by FreD domains. Molecular docking and molecular dynamics simulations showed that they have active binding sites for different key molecules involved in inflammatory and oxidative processes. Conclusions: The results showed that the peptides highlighted by our analysis workflow can be identified as potential molecules used as therapeutic strategies for diseases by targeting both inflammatory and oxidative processes. Full article

Wheat amylase trypsin inhibitors (ATIs) are prominent allergens in Baker’s asthma and contribute to innate inflammation in non-celiac wheat sensitivity (NCWS), linking them to metabolic and autoimmune diseases. Their tetra-, di-, and monomeric forms, stabilized by disulfide bonds, confer resistance to digestion, baking, and heating. Although proteomic studies reveal minor variation in ATI subtypes among cultivars and major variation among species, the influence of environment and wheat genotype on ATI levels and TLR4-stimulating activity remains unclear. We assessed the effect of the environment on the in vitro inflammatory bioactivity of ATIs extracted from 60 German wheat genotypes focusing on breeding over time between 1891 and 2010, and cultivation across three climatically distinct years. We found considerable genotype-dependent variation in ATI bioactivity that did not correlate with ATI subtype abundance, and observed no consistent difference between old and modern cultivars. ATIs from samples grown in 2019, a warm and dry year, showed reduced TLR4 activity, highlighting the significant impact of environmental conditions on inflammatory ATI bioactivity. Full article

Mycotoxin contamination is an important threat to food and feed safety as well as human and animal health, with particular emphasis on oxidative stress, apoptosis, autophagy, inflammation, and dysbiosis. Mycotoxins represent major health threats because they disturb cellular homeostasis and induce oxidative damage. Nutritional factors, such as dietary antioxidants and bioactive chemicals, can influence the body’s reaction to mycotoxin exposure, either reducing or increasing its effects. This study discusses how mycotoxins (aflatoxin B1, deoxynivalenol, and ochratoxin A) induce oxidative stress by producing reactive oxygen species (ROS)-mediated DNA damage, which induces cellular damage and activates apoptosis, an intended cell death process that is critical for tissue integrity. Furthermore, mycotoxins alter autophagy, a cellular degradation process that can be beneficial or destructive depending on the situation, affecting cell survival. The inflammatory response is particularly important because mycotoxin-induced oxidative stress and cell damage activate inflammatory pathways, which contribute to tissue injury and disease progression. Nutritional factors high in antioxidants, anti-inflammatory substances (Lycopene, Curcumin, Thyme oil, Gum Arabic, and Ginger), probiotics, and prebiotics show potential in mitigating these negative consequences by reducing oxidative stress and inflammation. Advances in molecular biology and omics technologies (transcriptomics, proteomics, metabolomics, and single-cell sequencing) can lead to better knowledge of the underlying pathways, allowing for more tailored nutritional recommendations and medicinal interventions. Finally, combining dietary modulation with mycotoxin risk management is a viable path for protecting health and increasing resilience to mycotoxin-related toxicities in animals. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent mucosal inflammation and dysregulated immune–metabolic responses. Koumiss, a traditional fermented mare’s milk, has long been used in ethnomedicine for gastrointestinal disorders; however, its molecular mechanisms in UC remain unclear. In this study, an integrated multi-omics approach combining network pharmacology, quantitative proteomics, and molecular docking was employed to elucidate the therapeutic mechanism of koumiss powder (KP) in a dextran sulfate sodium (DSS)-induced murine colitis model. Network pharmacology identified twelve bioactive compounds targeting fourteen UC-associated proteins, predominantly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In vivo experiments demonstrated that high-dose KP significantly alleviated disease activity, improved colon shortening and histopathological injury, reduced serum TNF-α and IL-6 levels, and restored anti-inflammatory cytokines IL-4 and IL-10. Proteomic analysis further revealed activation of the PPAR signaling pathway, with significant upregulation of Plin4 and Sorbs1. Immunofluorescence staining further confirmed that KP restored the expression of PPARA and increased the levels of Plin4 and Sorbs1 in colonic tissues. Molecular docking confirmed strong binding affinities between key koumiss-derived lipid metabolites, including 13(S)-HOTrE and stearoyl ethanolamide, and PPAR-related target proteins. Collectively, these findings demonstrate that koumiss exerts protective effects against experimental UC primarily through activation of PPAR-mediated lipid metabolic and anti-inflammatory pathways. This study provides mechanistic insight into the biological activity of koumiss and highlights the value of multi-omics integration in natural product research. Full article

Crude glycerin (CG) is an energy-dense ingredient capable of partially or fully replacing corn in high-concentrate diets for ruminants. Its rapid ruminal absorption, favorable fermentative profile, and absence of lactic acid production may support safer adaptation to intensive feeding systems. The aim of this study was to evaluate the effects of replacing corn with CG (300 g/kg DM) on growth performance, feeding behavior, rumen morphometry, and proteomic responses of ruminal papillae in feedlot lambs. Sixty-five Santa Inês × Dorper lambs were assigned to either a control diet or a diet containing CG and were evaluated during pre-adaptation, adaptation, and finishing phases. Replacing corn with CG slightly reduced average daily gain (p = 0.02), without affecting final body weight, dry matter intake, or carcass yield (p > 0.05). Lambs fed CG exhibited lower subcutaneous fat thickness (p = 0.04) and reduced neutral detergent fiber intake during feeding behavior assessments (p < 0.05). Rumen papillae showed higher mitotic index and greater epithelial activity throughout the feedlot period, regardless of treatment. Proteomic analysis revealed upregulation of proteins involved in epithelial integrity (Claudin-1, Occludin) and mitochondrial energy metabolism (ATP synthase β, glycerol kinase) in CG-fed lambs, alongside downregulation of proteins related to oxidative stress and inflammation (HSP70, Annexin A1, SOD1, Peroxiredoxin-6). These findings demonstrate that CG promotes beneficial molecular adaptations in the ruminal epithelium without compromising carcass traits, supporting its use as a safe, functional, and sustainable alternative to corn in lamb finishing systems. Full article

Atypical Parkinsonisms are a diverse group of diseases associated with multiple pathologies, including synucleinopathies and tauopathies. Atypical Parkinsonisms include progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, and dementia with Lewy bodies. The examination of these diseases is complicated due to their overlapping clinical manifestations. Hence, tools enabling reliable supplementary assessment of atypical Parkinsonisms are needed. The most common methods involve neuroimaging; however, these evaluations generally involve basic magnetic resonance imaging and indicate possible morphological changes. Less attention is given to disease background assessment. Biochemical assessment enables a more detailed examination of the factors impacting neurodegenerative processes. The features that may impact the pathophysiology of these diseases include metabolic abnormalities, excessive inflammation, and environmental factors. In this context, proteomic evaluation, as analyzed in this article, could partly address the insufficiently described aspects of the unclear pathological mechanisms related to atypical Parkinsonisms. Full article

The Mediterranean Diet (MD) is recognized for promoting longevity and reducing the risk of chronic disease, yet the mechanisms underlying these benefits remain uncharacterized. This review highlights the diverse nutritional and phytoactive constituents of the MD and research exploring its complex network of polyphenols. It discusses data evaluating MD-derived constituents formulated into a dietary supplement capsule developed using a systems and network biology framework. Component selection was based on their actions on enzyme systems involved in senescence-related pathways and health preservation. This review highlights how MD components synergistically modulate pathways central to antioxidant activity, cognitive health, and aging. Liquid chromatography–mass spectrometry identified phytochemically diverse constituents in capsules (supplied by DailyColors™, Warwickshire, UK and Sebastopol, CA, USA) derived from primary color groups in sixteen Mediterranean plants. These constituents were mapped to bioactive networks targeting enzymes linked to inflammation, metabolic regulation, and cellular senescence. Preclinical studies demonstrated the modulation of mitochondrial and metabolic health markers, with complementary effects on cytokine inhibition and glucose sensitivity. Two clinical studies confirmed broad proteomic and epigenetic effects on pathways governing immunity, skeletal muscle, cognition, and inflammation. Therefore, this review advances a novel perspective that MD polyphenols act through synergistic, multi-pathway interactions that link dietary patterns to coordinated regulation of longevity and healthy aging. Full article

Background: Prostate cancer (PCa) arises from complex interactions among host genetics, androgen signaling, and microbial communities. Emerging genomic evidence supports the presence of microbial consortia within prostate tissue, suggesting that microbial genes, metabolites, and host–microbe interactions may contribute to chronic inflammation, oncogenic signaling, and therapeutic resistance. Methods: We conducted a narrative review using targeted searches of PubMed and Google Scholar for studies published between 2020 and 2025, complemented by selected mechanistic reports published in March 2026. Human studies and experimental research providing mechanistic insights into prostate models were prioritized. Due to the heterogeneous methodologies, evidence was synthesized qualitatively, with an emphasis on genomic and signaling perspectives. Results: Low-biomass microbial DNA is consistently detected in prostate tissue. Proteomic analyses of Corpora amylacea suggest a “fossil record” of past infections through sequestered microbial DNA and antimicrobial proteins, potentially priming tissue for long-term carcinogenic processes, although contamination remains a key limitation. Recurrent bacterial and viral signals, including Cutibacterium acnes, Escherichia coli, Pseudomonas, Acinetobacter, human papillomavirus, Epstein–Barr virus, and cytomegalovirus, appear to converge on a restricted set of tumor-relevant pathways, including TLR–NF-κB, MAPK, PI3K/AKT/mTOR, cGAS–STING, and p53/pRb disruption. These interactions may promote cytokine production, oxidative stress, DNA damage, epithelial–mesenchymal transition, extracellular matrix remodeling, immune evasion, and resistance to therapy. The gut–prostate axis further links intestinal dysbiosis and microbial metabolites with systemic IGF-1 signaling and castration resistance. Conclusions: Microbial genomic consortia in the prostate and gut may shape inflammatory, metabolic, and immune networks that influence PCa initiation and progression. However, most available data remain correlative and are limited by low-biomass sampling, contamination risk, and heterogeneous study designs. Future research should prioritize rigorous contamination control, longitudinal and prostate-specific mechanistic studies, and integrated multi-omic approaches to clarify causality and identify actionable microbial targets for prevention, diagnosis, and therapy. Full article

Neurodegenerative diseases involve progressive neuronal loss associated with oxidative stress (OS) and inflammation. Given the limited efficacy of current therapies, natural compounds with multitarget neuroprotective potential are of growing interest. In this study, we investigated the neuroprotective effects of a standardized Magnolia officinalis (L.) bark extract (MOE) in rat brain cortical slices exposed to hydrogen peroxide-induced OS. MOE significantly recovered tissue viability and reduced ROS and malondialdehyde levels caused by OS while attenuating caspase-3, -8, and -9 activation, suggesting modulation of intrinsic and extrinsic apoptotic pathways. Shotgun proteomics using LC-HRMS/MS identified OS-induced protein expression changes reversed by MOE, with fourteen of thirty-three altered proteins rescued by MOE co-treatment. These proteins participate in several processes, including neuronal survival, OS response, and proteostasis. Bioinformatic analysis demonstrated that genes responsible for protein synthesis regulated by MOE are subjected to transcriptional regulation by factors associated with OS, including FOXO4, NRF2, and SP1. The present findings support the hypothesis that MOE exerts multitarget neuroprotective effects by modulating key proteins involved in OS responses and neuronal survival in an acute ex vivo oxidative injury model, suggesting potential relevance for mechanisms associated with NDs. Full article

Background/Objectives: Trace metal homeostasis is regulated by nutritional status and is crucial for maintaining redox balance, vascular function, and neuroinflammation. Dysregulation of systemic copper (Cu) metabolism, especially an elevated level of non-ceruloplasmin-bound copper (NCC), has been linked to oxidative stress and early cognitive decline. However, the nutritional and molecular pathways that connect Cu imbalance to mild cognitive impairment (MCI) are not well understood. Methods: We compared the serum Cu and zinc levels of individuals with normal cognition (NC; n = 116) and MCI (n = 184). An exploratory serum proteomic analysis using pooled samples was conducted to investigate patterns related to Cu dysregulation. We identified proteins using pattern correlation analysis and then performed a protein–protein interaction analysis using STRING and functional annotation and biological and Kyoto Encyclopedia of Genes and Genomes pathways. Results: The individuals with MCI had higher NCC levels than those with NC, indicating disrupted Cu metabolism influenced by nutrition and metabolism. The proteomic analysis revealed changes in proteins related to lipid transport, metal balance, and inflammation, including transthyretin, transferrin, apolipoprotein A-I, alpha-1 antitrypsin, antithrombin III, and alpha-2-macroglobulin, which respond to oxidative stress and vascular injury. Conclusions: In this cross-sectional analysis of baseline data, NCC levels were associated with cognitive status and specific circulating proteomic profiles. These findings suggest a potential relationship between copper-related biomarkers and mild cognitive impairment; however, longitudinal studies are required to clarify temporal relationships and potential mechanistic pathways. Full article

Cystathionine β-synthase (CBS) deficiency causes classical homocystinuria with severe hyperhomocysteinemia (HHcy) that is inadequately controlled by current therapies. We tested whether liver-targeted CBS gene therapy provides durable biochemical and phenotypic rescue. Using a Cre-inducible adult mouse model of whole-body CBS loss, a single intravenous dose of AAV-DJ-hCBS (3 × 10¹² or 3 × 10¹³ vg/kg) was administered, and the animals were followed for 12 months. Vector biodistribution showed ~100-fold hepatic enrichment over the kidney and spleen. Both doses rapidly normalized plasma homocysteine (<8 µM), maintaining correction throughout the study while preventing alopecia, weight loss, and loss of adiposity. Liver histology showed resolution of inflammation, and only 2 of 19 mice developed anti-hCBS antibodies. Liver proteomics (3998 proteins quantified) revealed CBS deficiency-associated suppression of tRNA aminoacylation and dysregulation of lipid and carbon metabolism with an HNF4A transcriptional signature, all normalized by therapy. Liver metabolomics demonstrated accumulation of S-adenosylmethionine and S-adenosylhomocysteine and disruption of phosphatidylcholine synthesis, also corrected by treatment. Plasma metabolomics revealed systemic disturbances fully normalized by hepatic CBS restoration. These findings identify the liver as the central metabolic control point in CBS deficiency and support liver-targeted gene therapy as a durable corrective strategy. Full article

Sarcopenia is a progressive and multifactorial muscle disorder associated with diminished strength, reduced functional capacity, and increased risk of adverse health outcomes including frailty, falls, and mortality. Despite its clinical burden, the molecular pathogenesis of sarcopenia remains poorly understood, which hinders the development of precise therapeutic strategies. This review examines emerging evidence linking anabolic resistance, mitochondrial dysfunction, neuromuscular instability, and chronic inflammation to impaired regeneration and disrupted proteostasis. While nutritional interventions such as high-quality protein, leucine metabolites, and vitamin D supplementation preserve lean mass, they fail to consistently restore function independently. Although exercise remains the cornerstone therapy, its benefits are often constrained in patients with multimorbidity or reduced mobility. Given the biological heterogeneity of sarcopenia, there is a need to shift from generic supportive care to stratified, mechanism-based therapy. Emerging omics technologies including transcriptomic, proteomic, and metabolic profiling offer a promising avenue to define molecular endotypes. This will guide the development of precision-based management strategies. Full article

Background: Adipose-derived mesenchymal stem/stromal cells (ADSCs) are gaining recognition in regenerative medicine for their potential for adipogenic, osteogenic, and chondrogenic differentiation, as well as their immunomodulatory properties. However, ADSC-based therapies focus either on differentiation for tissue replacement or on counteracting unrestrained inflammation to prevent tissue destruction and initiate regeneration. Here, we aim to examine the immunomodulatory potential of osteogenically differentiated ADSCs by analyzing their proteomic profile. Methods: Using LC-MS/MS, we generated the proteomic profiles of differentiated and undifferentiated ADSCs and compared them with the Reactome database. Transcriptomic analysis was also performed and compared with the proteomic profile. Results: Comparison of the proteomic (499 up-regulated; 355 down-regulated) and transcriptomic (212 up-regulated; 232 down-regulated) profiles showed 60.1% concordance—both proteins and transcripts showed the same trend. Significantly upregulated proteins in differentiating ADSCs (−log₁₀ p > 5 and >10) were grouped into four categories: propensity for osteogenic differentiation; immunomodulation/immune/inflammatory response; cell senescence; and cell cycle regulation. Among those proteins, thirteen were reported to play roles in processes such as immunomodulation, inflammatory signaling, or transplant rejection. Conclusions: We observed that differentiating ADSCs might still exert immunomodulatory effects, which could be used in the treatment of, e.g., bone defects. Full article

Background: Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD). Proteomic studies suggest that Lp(a)-associated proteins mediate inflammation, thrombosis, and vascular calcification, but methodological variability may influence proteome definition. Methods: Lp(a) was immunoprecipitated from human plasma using an apo(a)-specific monoclonal antibody and analyzed by mass spectrometry following either in-gel digestion or automated in-solution proteolysis. Proteins identified by ≥3 unique peptides and consistently detected across all samples by both methods were considered high confidence. Functional enrichment and interaction networks were assessed using STRING. Results: In-solution proteolysis identified 92 proteins and in-gel digestion identified 55 proteins, with 34 proteins shared between methods. These high-confidence proteins were enriched for pathways involved in lipoprotein remodeling, coagulation regulation, vesicle-mediated transport, lipid binding, and extracellular matrix organization, providing biological insight into mechanisms linking Lp(a) to inflammation, thrombosis, and calcification. Conclusions: Proteome composition of Lp(a) is method-dependent; however, a rigorously defined core proteome of 34 proteins was consistently identified across analytical approaches, highlighting biologically relevant pathways that may underlie Lp(a)-mediated ASCVD risk. Full article

Inhibition of inflammation and oxidative stress is increasingly recognized as a promising therapeutic strategy for neurodegenerative diseases. In this study, we isolated two new dimeric naphtho-γ-pyrone (aS)-fonsecinones B and D (1 and 2) and 14 known compounds (3–16) from the deep-sea-derived fungus Aspergillus niger 3A00562. Their structures were unambiguously determined through integrated physicochemical and spectroscopic analyses. Screening for neuroinflammatory inhibitors using a BV2 microglial cell model identified TMC 256 A1 (10) as the most potent candidate. Compound 10 significantly suppressed LPS-induced inflammation in BV2 cells without cytotoxicity. It concurrently inhibited LPS-triggered ROS overproduction and neutrophilic infiltration in zebrafish. Subsequent proteomics revealed that 10 targets NOS2 to modulate Alzheimer’s disease (AD)-associated pathways and the KEAP1-NRF2 axis. Molecular docking and dynamics simulations demonstrated that 10 occupies the NOS2 heme-binding pocket, thereby preventing dimerization and inhibiting enzymatic activity. Finally, 10 ameliorated locomotor deficits in an AD zebrafish model. Collectively, these findings highlight compound 10 as a candidate compound for preventing inflammatory and oxidative stress damage during treatment of neurodegenerative diseases, particularly AD. Full article