Search Results (3,454)

Immune checkpoint inhibitors (ICIs) for cancer therapy may induce immune-related adverse events including myocarditis, which occurs infrequently but carries a high mortality rate. Crocins are the active constituents derived from Crocus sativus L. (saffron), and have demonstrated various bioactivities including anti-tumor, anti-inflammation, antioxidation, anti-ischemia, anti-aging, and neuroprotective effects. This study established a subcutaneous xenotransplanted tumor model of human liver cancer in nude mice to better mimic ICI-related myocarditis. Animal experimental results revealed that crocins improved cardiac function, relieved myocardial damage and autoimmune response, and suppressed oxidative stress and inflammatory reaction. Quantitative proteomics and Western blotting verification confirmed that crocins ameliorated experimental ICI-related myocarditis by targeting the Hpx/Nrf2/HO-1 pathway. Molecular docking revealed that the best docking activities were demonstrated by crocin I–HO-1, crocin II–Hpx, and crocin III–Nrf2. These findings shed new light on the development of therapeutic strategies for treating ICI-related myocarditis and provided the fundamental basis for expanding the clinical application of crocins. Full article

Nucleic acids are essential dietary components with diverse physiological functions. Numerous studies have focused on the biological functions of nucleotides, nucleosides, and functional RNAs such as microRNAs. However, the nutritional value of ribosomal RNA (rRNA)-derived oligonucleotides, which are likely the predominant nucleic acid-derived components in foods, remains largely unexplored. Here, yeast was used as a food-associated eukaryotic model organism to investigate the uptake and utilization of rRNA-derived oligonucleotides. Yeast efficiently utilized short RNA oligonucleotides (approximately 5–30 nt) as nutrient sources, supporting robust cell growth. Confocal microscopy confirmed rapid uptake of Cy5-labeled RNA oligonucleotides by yeast cells. Proteomic analysis further revealed marked upregulation of proteins involved in endocytosis and autophagy in yeast cultured with RNA oligonucleotides. Collectively, these findings demonstrate that yeast can internalize and metabolize rRNA-derived oligonucleotides as efficient nutrient sources, likely through coordinated endocytic and autophagic pathways. This study highlights the nutritional potential of rRNA-derived oligonucleotides and provides a foundation for their future application in functional foods and fermentation systems. Full article

Overwinter Syndrome (OWS) affects grass carp (Ctenopharyngodon idellus) aquaculture in China, causing high mortality and economic losses under low temperatures. Failure of antibiotic therapies shows limits of the ‘low–temperature–pathogen’ model and shifts focus to mucosal barrier dysfunction and host–microbiome interactions in OWS. We compared healthy and diseased grass carp collected from the same pond using histopathology, transcriptomics, proteomics, and metagenomics. This integrated approach was used to characterize intestinal structure, microbial composition, and host molecular responses at both taxonomic and functional levels. Results revealed a three-layer barrier failure in OWS fish: the physical barrier was compromised, with structural damage and reduced mucosal index; microbial dysbiosis featured increased richness without changes in diversity or evenness, and expansion of the virobiota, notably uncultured Caudovirales phage; and mucosal immune dysregulation indicated loss of local immune balance. Multi-omics integration identified downregulation of lysosome-related and glycosphingolipid biosynthesis pathways at transcript and protein levels, with disrupted nucleotide metabolism. Overall gut microbial richness, rather than individual taxa abundance, correlated most strongly with host gene changes linked to immunity, metabolism, and epithelial integrity. Although biological replicates were limited by natural outbreak sampling, matched high-depth multi-omics datasets provide exploratory insights into OWS-associated intestinal dysfunction. In summary, OWS entails a cold-triggered breakdown of intestinal barrier integrity and immune homeostasis. This breakdown is driven by a global restructuring of the gut microbiome, which is marked by increased richness, viral expansion, and functional shifts, ultimately resulting in altered host–microbe crosstalk. This ecological perspective informs future mechanistic and applied studies for disease prevention. Full article

Secondary hair follicle stem cells (HFSCs) are essential for cashmere fiber regeneration, yet the molecular mechanisms governing their activation and lineage progression remain poorly understood. Here, we identify S100a4 as a key regulator of secondary HFSCs in cashmere goat. S100a4 expression peaks during anagen and is markedly enriched in secondary HFSCs relative to hair matrix cells (HMCs), suggesting a role in initiating follicle regeneration. Functional assays show that S100a4 promotes HFSCs into a dynamically regulated state that activates stem cell competence while facilitating differentiation, with overexpression upregulating epidermal and follicular differentiation markers (Ivl, Cux1, K14, Klk5), as well as pluripotency genes (Itga6, Krt15), while knockdown suppresses these programs. Proteomic analysis further reveals direct interactions between S100A4 and keratins critical for hair follicle and epidermal development (KRT5, KRT14, KRT8, KRT18), suggesting a structural and regulatory interface through which S100A4 modulates HFSC fate. Collectively, these results establish S100a4 as a central modulator of secondary HFSC function and provide mechanistic insight into the molecular control of hair follicle regeneration, with potential implications for improving cashmere fiber production. Full article

Redox (reduction–oxidation) processes underlie all forms of life and are a universal regulatory mechanism that maintains homeostasis and adapts the organism to changes in the internal and external environments. From capturing solar energy in photosynthesis and oxygen generation to fine-tuning cellular metabolism, redox reactions are key determinants of life activity. Proteins containing sulfur- and selenium-containing amino acid residues play a crucial role in redox regulation. Their reversible oxidation by physiological oxidants, such as hydrogen peroxide (H₂O₂), plays the role of molecular switches that control enzymatic activity, protein structure, and signaling cascades. This enables rapid and flexible cellular responses to a wide range of stimuli—from growth factors and nutrient signals to toxins and stressors. Mitochondria, the main energy organelles and also the major sources of reactive oxygen species (ROS), play a special role in redox balance. On the one hand, mitochondrial ROS function as signaling molecules, regulating cellular processes, including proliferation, apoptosis, and immune response, while, on the other hand, their excessive accumulation leads to oxidative stress, damage to biomolecules, and the development of pathological processes. So, mitochondria act not only as a “generator” of redox signals but also as a central link in maintaining cellular and systemic redox homeostasis. Redox signaling forms a multi-layered cybernetic system, which includes signal perception, activation of signaling pathways, the initiation of physiological responses, and feedback regulatory mechanisms. At the molecular level, this is manifested by changes in the activity of redox-regulated proteins of which the redox proteome consists, thereby affecting the epigenetic landscape and gene expression. Physiological processes at all levels of biological organization—from subcellular to systemic—are controlled by redox mechanisms. Studying these processes opens a way to understanding the universal principles of life activity and identifying the biochemical mechanisms whose disruption causes the occurrence and development of pathological reactions. It is important to emphasize that new approaches to redox balance modulation are now actively developed, ranging from antioxidant therapy and targeted intervention on mitochondria to pharmacological and nutraceutical regulation of signaling pathways. This article analyzes the pivotal role of redox balance and its regulation at various levels of living organisms—from molecular and cellular to tissue, organ, and organismal levels—with a special emphasis on the role of mitochondria and modern strategies for influencing redox homeostasis. Full article

ATP-dependent chromatin remodeling complexes regulate gene expression by altering chromatin structure through ATP hydrolysis. They are classified into four families—SWI/SNF, ISWI, CHD, and INO80—which remodel chromatin via nucleosome sliding, eviction, assembly, and editing to control transcription. These complexes play critical roles in DNA repair, tumorigenesis, and organogenesis. Recent advances in low-input proteomics have highlighted their importance in vertebrate embryonic development. In mammals, they regulate embryonic genome activation, lineage specification, and stem cell fate determination. In non-mammalian models (e.g., Xenopus laevis), they function from blastocyst formation to pre-organogenesis stages (gastrulation and neurulation)—key windows for chromatin reprogramming and cell fate decisions. This review provides a systematic overview of chromatin remodeling complexes, detailing their classification and conserved mechanisms, and discusses their functions in early embryogenesis and embryonic stem cell maintenance. The collective evidence underscores the implications of these chromatin remodelers for understanding developmental defects and advancing regenerative medicine. Full article

Background: ALG13-CDG is an X-linked N-linked glycosylation disorder caused by pathogenic variants in the glycosyltransferase ALG13, leading to severe neurological manifestations. Despite the clear CNS involvement, the impact of ALG13 dysfunction on human brain glycosylation and neurodevelopment remains unknown. We hypothesize that ALG13-CDG causes brain-specific hypoglycosylation that disrupts neurodevelopmental pathways and contributes directly to cortical network dysfunction. Methods: We generated iPSC-derived human cortical organoids (hCOs) from individuals with ALG13-CDG to define the impact of hypoglycosylation on cortical development and function. Electrophysiological activity was assessed using MEA recordings and integrated with multiomic profiling, including scRNA-seq, proteomics, glycoproteomics, N-glycan imaging, lipidomics, and metabolomics. X-inactivation status was evaluated in both iPSCs and hCOs. Results: ALG13-CDG hCOs showed reduced glycosylation of proteins involved in ECM organization, neuronal migration, lipid metabolism, calcium homeostasis, and neuronal excitability. These pathway disruptions were supported by proteomic and scRNA-seq data and included altered intercellular communication. Trajectory analyses revealed mistimed neuronal maturation with early inhibitory and delayed excitatory development, indicating an E/I imbalance. MEA recordings demonstrated early network hypoactivity with reduced firing rates, immature burst structure, and shortened axonal projections, while transcriptomic and proteomic signatures suggested emerging hyperexcitability. Altered lipid and GlcNAc metabolism, along with skewed X-inactivation, were also observed. Conclusions: Our study reveals that ALG13-CDG is a disorder of brain-specific hypoglycosylation that disrupts key neurodevelopmental pathways and destabilizes cortical network function. Through integrated multiomic and functional analyses, we identify early network hypoactivity, mistimed neuronal maturation, and evolving E/I imbalance that progresses to compensatory hyperexcitability, providing a mechanistic basis for seizure vulnerability. These findings redefine ALG13-CDG as disorders of cortical network instability, offering a new framework for targeted therapeutic intervention. Full article

To identify pancoronaviral inhibitors, we sought to identify peptides that bound the evolutionarily conserved SARS-CoV-2 spike fusion peptide (FP). We screened the NEB PhD-7-mer random combinatorial phage display library against FP, synthesised as a D-peptide, to identify peptides from the L-library to be synthesised as proteolytically resistant D peptides. We selected the top ten peptides that were not seen in another published screen with this library, as these were more likely to be specific. All ten D-peptides had no impact on the infection of Vero-E6/TMPRSS2 cells by SARS-CoV-2. Screening of a proteomic-derived phage display library from the disordered regions of human proteins identified two overlapping 14mer peptides from a region of OTUD1. While a synthetic peptide based on their sequences failed to markedly inhibit viral entry, molecular dynamics structural modelling highlighted a stable binding mode where positive residues on one side of the OTUD1 helix interacted with hydrophobic residues of the FP triple-helical wedge. Thus, while the two phage display strategies failed to yield peptide sequences that are themselves strong inhibitors of viral infection, they led to the development of a computational model that can underpin future designs of potential pancoronaviral FP disruptors. Full article

Although calpain-5/CAPN5 is widely expressed in mammals, little is known regarding its functions. Pathogenic mutations of CAPN5 are causal for a devastating autoimmune eye disease, neovascular inflammatory vitreoretinopathy (NIV). To provide insight into both the physiological and pathological roles of CAPN5, it is essential to identify candidate interaction partners and possible substrates. Human SH-SY5Y neuroblastoma cells, transfected with full-length catalytically dead (Cys81Ala) CAPN5-3×FLAG, were used for anti-FLAG co-immunoprecipitation (co-IP) and quantitative proteomics using Sequential Window Acquisition of all THeoretical mass spectra (SWATH-MS). Fifty-one proteins were enriched at least four-fold, p < 0.01, relative to cells transfected with an empty FLAG vector. A high proportion (24/51) of candidate CAPN5 interaction partners are associated with protein quality control, including components of the chaperonin, chaperone, and ubiquitin–proteasome systems. Additional candidate interactors include tubulins, kinases, phosphatases, G proteins, and mitochondrial proteins. CAPN5 interactions for 14 of the candidate proteins were confirmed by co-IP and immunoblotting. Of these 14 proteins, 11 exhibited in vitro calcium-induced proteolysis following co-IP with WT CAPN5-3×FLAG. Impaired calcium-induced proteolysis of co-IP proteins was observed for the pathogenic CAPN5 variants R243L and R289W. Further studies are needed to validate the association of candidate CAPN5 interactors with proteins and complexes suggested by the SWATH-MS and co-IP results, and the possible role of CAPN5 within such complexes. The possible involvement of CAPN5 in protein quality control is relevant to NIV, as defects in protein quality control have been implicated in inherited retinal disorders. Proteomic data are available via ProteomeXchange with identifier PXD068008. Full article

Cancer remains one of the most common causes of death worldwide and imposes enormous social and economic burdens. Human tumor-associated NADH oxidase (ENOX2, also known as tNOX) is a cancer cell-specialized NADH oxidase that is expressed on the membranes of cancer cells. In this study, we investigated the potential role of ENOX2 in regulating stemness properties in oral cancer through a combination of in vitro, in vivo, and bioinformatics approaches. We found that ENOX2 physically interacted with the stem cell transcription factor, SOX2, in co-immunoprecipitation experiments. The expression and activity of ENOX2 were elevated in p53-functional SAS and p53-mutated HSC-3 oral cancer cell spheroids compared with their monolayer counterparts. Consistently, SIRT1, a downstream effector modulated by ENOX2 through NAD⁺ generation, was also upregulated in spheroid cultures. Functional studies further established that ENOX2 overexpression significantly enhanced spheroid formation, self-renewal properties, stem cell marker expression, and PKCδ expression, whereas ENOX2 knockdown produced the opposite effects. In xenograft models, ENOX2-overexpressing oral cancer cell spheroids exhibited enhanced tumorigenicity, while ENOX2-silenced spheroids formed significantly smaller tumors. Complementary analyses of public transcriptomic and proteomic datasets revealed elevated ENOX2 expression in human head and neck tumor tissues compared with adjacent normal tissues. Based on these findings and literature-supported correlations, we propose a putative ENOX2-SIRT1-SOX2 regulatory framework that may contribute to the acquisition and maintenance of stem-like properties of oral cancer cells. While the ENOX2–SOX2 interaction was experimentally validated, the roles of SIRT1 and other downstream components are inferred from bioinformatic analyses and prior studies; thus, this axis represents a hypothetical model that warrants further mechanistic investigation. Collectively, our results identify ENOX2 as a potential regulator of oral cancer stemness and provide a conceptual foundation for future studies aimed at elucidating its downstream pathways and clinical relevance in head and neck tumors. Full article

RNA viruses are major pathogens in fish, causing high mortality and substantial economic losses in aquaculture. To uncover conserved antiviral mechanisms, we investigated the response of turbot (Scophthalmus maximus) to viral hemorrhagic septicemia virus (VHSV), infectious pancreatic necrosis virus (IPNV), and red-spotted grouper nervous necrosis virus (RGNNV) using a comparative proteomic approach complemented by in vivo and in vitro functional assays. Proteomic analyses revealed the central, conserved role of proteins involved in reactive oxygen species (ROS) production and redox homeostasis during early infection. Functional assays using head kidney-derived leukocytes identified neutrophils and macrophages as the primary ROS producers and showed that the modulation of cytoplasmic and mitochondrial ROS, as well as ROS-dependent DNA release, follows virus-specific patterns. The pharmacological inhibition of NADPH oxidase and mitochondrial ROS significantly affected viral replication, demonstrating the direct role of ROS in viral pathogenicity. Collectively, these findings highlight redox modulation as a conserved host response in teleost fish during RNA virus infection, linking oxidative stress regulation to viral progression. This knowledge provides a foundation for developing broad-spectrum therapeutic or preventive strategies to enhance disease resistance and promote sustainable aquaculture. Full article

The integration of omics technologies, including genomics, proteomics, metabolomics, and microbiomics, has transformed sports science, particularly soccer, by providing new opportunities to optimize player performance, reduce injury risk, and enhance recovery. This systematic literature review was conducted in accordance with PRISMA 2020 guidelines and structured using the PICOS/PECOS framework. Comprehensive searches were performed in PubMed, Scopus, and Web of Science up to August 2025. Eligible studies were peer-reviewed original research involving professional or elite soccer players that applied at least one omics approach to outcomes related to performance, health, recovery, or injury prevention. Reviews, conference abstracts, editorials, and studies not involving soccer or omics technologies were excluded. A total of 139 studies met the inclusion criteria. Across the included studies, a total of 19,449 participants were analyzed. Genomic investigations identified numerous single-nucleotide polymorphisms (SNPs) spanning key biological pathways. Cardiovascular and vascular genes (e.g., ACE, AGT, NOS3, VEGF, ADRA2A, ADRB1–3) were associated with endurance, cardiovascular regulation, and recovery. Genes related to muscle structure, metabolism, and hypertrophy (e.g., ACTN3, CKM, MLCK, TRIM63, TTN-AS1, HIF1A, MSTN, MCT1, AMPD1) were linked to sprint performance, metabolic efficiency, and muscle injury susceptibility. Neurotransmission-related genes (BDNF, COMT, DRD1–3, DBH, SLC6A4, HTR2A, APOE) influenced motivation, fatigue, cognitive performance, and brain injury recovery. Connective tissue and extracellular matrix genes (COL1A1, COL1A2, COL2A1, COL5A1, COL12A1, COL22A1, ELN, EMILIN1, TNC, MMP3, GEFT, LIF, HGF) were implicated in ligament, tendon, and muscle injury risk. Energy metabolism and mitochondrial function genes (PPARA, PPARG, PPARD, PPARGC1A, UCP1–3, FTO, TFAM) shaped endurance capacity, substrate utilization, and body composition. Oxidative stress and detoxification pathways (GSTM1, GSTP1, GSTT1, NRF2) influenced recovery and resilience, while bone-related variants (VDR, P2RX7, RANK/RANKL/OPG) were associated with bone density and remodeling. Beyond genomics, proteomics identified markers of muscle damage and repair, metabolomics characterized fatigue- and energy-related signatures, and microbiomics revealed links between gut microbial diversity, recovery, and physiological resilience. Evidence from omics research in soccer supports the potential for individualized approaches to training, nutrition, recovery, and injury prevention. By integrating genomics, proteomics, metabolomics, and microbiomics data, clubs and sports practitioners may design precision strategies tailored to each player’s biological profile. Future research should expand on multi-omics integration, explore gene–environment interactions, and improve representation across sexes, age groups, and competitive levels to advance precision sports medicine in soccer. Full article

Bacteriophages are a key ecological factor in the legume rhizosphere, controlling bacterial populations and affecting introduced inoculant strains. Despite their importance, rhizobiophage genomic diversity remains poorly characterized. We report the complete genome of a novel predicted temperate Sinorhizobium phage, AP-202, isolated from agricultural Chernozem. This siphovirus infects the symbiont Sinorhizobium meliloti. Its 121,599 bp dsDNA genome has a strikingly low GC content (27.1%), likely reflecting adaptive evolution and a strategy to evade host defenses. The linear genome is flanked by 240 bp direct terminal repeats (DTRs), and its DNA packaging follows a T7-like strategy. Annotation predicted 178 protein-coding genes and one tRNA. Functional analysis revealed a complete lysogeny module and a divergent, two-pronged codon-usage strategy for translational control. A significant part of the proteome (74.2%) comprises hypothetical proteins, with 50 CDSs having no database homologs, underscoring its genetic novelty. Complete-genome comparison shows minimal similarity to known rhizobiophages, defining AP-202 as a distinct lineage. Phenotypic analysis indicates AP-202 acts as a selective ecological filter, with host resistance being more prevalent in agricultural than in natural soils. The AP-202 genome provides a unique model for studying phage–host coevolution in the rhizosphere and is a valuable resource for comparative genomics and soil virome research. Full article

Marine flora is a significant source of bioactive metabolites. These compounds have been demonstrated to have outstanding bioactivity and biocompatibility, enabling their use in various therapeutic applications. Therefore, examining the biological potential of marine natural compounds remains important, with particular emphasis on their interaction profiles to identify the macromolecular partners they can modulate. This study focused on the interactome profiling of the marine alkaloid caulerpin (CAU), isolated from the alga Caulerpa cylindracea. Along with the discovery of its antitumor properties, this metabolite has garnered attention for its potential therapeutic applications, including modulation of MAO-B and PPARs involved in inflammatory responses, as well as the discovery of its antitumor properties. Two complementary MS-based proteomic approaches were used to identify CAU target proteins in cancer cells: DARTS, which enabled proteome-wide screening to identify proteins interacting with the compound, and t-LIP-MRM-MS, which pinpointed the target protein regions involved in ligand binding. RUVB-like 1 (RUVBL1), a protein that regulates the essential mechanism of carcinogenesis, including chromatin remodeling, DNA repair, and transcriptional control, was discovered as an intriguing CAU target. These results were corroborated via in silico and biological investigations that elucidated CAU role in the regulation of RUVBL1 activity, highlighting its promising therapeutic relevance. Full article

Fisheries bycatch, while representing a major ecological concern due to the incidental capture of non-target species, also constitutes an underexplored source of marine biomass with biotechnological potential. This study aimed to generate and characterize bioactive peptides from the muscle tissue of three common bycatch species from the Brazilian coast: Paralonchurus brasiliensis, Micropogonias furnieri, and Hepatus pudibundus. Muscle homogenates were hydrolyzed using either Alcalase or Protamex to produce peptide-rich hydrolysates, which were analyzed through SDS-PAGE, HPLC-UV, MALDI-TOF, and LC-MS/MS. De novo sequencing and bioinformatic analyses predicted bioactivities that were subsequently validated by in vitro assays. The results demonstrated that enzyme selection strongly influenced both peptide profiles and bioactivity. The Protamex hydrolysate of P. brasiliensis (PBP) exhibited potent antifungal activity, inhibiting Candida albicans growth by 81%, whereas the Alcalase hydrolysate (PBA) showed moderate inhibition of Staphylococcus aureus (29%). No significant effect was observed against Escherichia coli. Overall, this study highlights a sustainable strategy for the valorization of fisheries bycatch through the production of bioactive marine peptides and identifies P. brasiliensis hydrolyzed with Protamex as a promising source of anti-Candida peptides for pharmaceutical and nutraceutical applications. Full article