Search Results (414)

Soft tissue sarcoma remains challenging to treat due to its heterogeneity, stemness-associated survival programs, and resistance to conventional therapies. Extracellular vesicles (EVs) mediate tumor–stroma communication, yet how stemness-targeted therapies reshape EVs-associated miRNAs networks remains unclear. This study profiled EVs miRNAs cargo from infrapatellar fat pad mesenchymal stem/stromal cells (IFP-MSCs) and sarcoma cells (SCs) under basal conditions and following treatment with a synthetic tyrosine peptide analog (TPA). EVs were isolated, characterized, and subjected to miRNAs profiling and pathway enrichment analyses. TPA induced ≥2-fold regulation of 182 miRNAs, including 49 upregulated and 24 downregulated in IFP-MSC-EVs and 86 upregulated and 23 downregulated in SC-EVs. A conserved core of 149 miRNAs (67.1%) was shared across all EVs groups. Abundant species included miR-3960 and miR-21-5p, while TPA reduced tumor-associated miRNAs such as miR-1246 (~10-fold decrease in IFP-MSC-EVs). Pathway enrichment revealed consistent targeting of cancer, MAPK, Wnt, TGF-β, and immune signaling pathways, with modest increases in mapped gene coverage following TPA treatment. In silico analysis identified distinct EVs miRNA–gene interaction profiles, with VEGFA emerging as a recurrent predicted target. These results demonstrate that stemness-targeted modulation quantitatively reprograms EVs miRNA cargo in a cell-type-dependent manner, reshaping vesicle-mediated signaling networks in sarcoma. Full article

To dissect the molecular mechanisms underlying chicken cecal development, this study used Liangshan Yanying chickens (a local slow-growing breed) and Arbor Acres (AA) chickens (a fast-growing breed) as experimental models. Cecal tissues were collected from healthy chickens at 1, 14, and 28 days of age (n = 10 per breed per day of age) to measure cecal length and perform transcriptome sequencing. Through the screening of differentially expressed genes (DEGs), functional enrichment analysis, construction of protein–protein interaction (PPI) networks, and qRT-PCR validation, temporal changes in cecal development between the two breeds were systematically compared. Results showed that cecal length of both breeds increased significantly with age (p < 0.05), with significant differences between breeds. A total of 18 high-quality samples were obtained from transcriptome analysis (Q30 ≥ 93%), with a mapping efficiency of 86.2–90.5%. The number of DEGs was highest between 1 and 28 days of age (1844 DEGs in Liangshan Yanying chickens and 1747 DEGs in AA chickens), and the number of inter-breed DEGs reached 2133 at 28 days of age. A total of 70 DEGs with consistent expression trends were identified (22 upregulated and 48 downregulated), which were enriched in Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways such as “B cell activation”, “peptide transport”, and “bile acid metabolism”. qRT-PCR validation indicated that the expression trends of genes (e.g., CD79B, IRF4) were highly consistent with sequencing results (R² = 0.91). PPI network analysis suggested that SLC15A1, ACE, and ENPEP were key hub genes, forming a “transport–metabolism” synergistic module. This study reveals the temporal dynamics of chicken cecal development and the molecular basis of inter-breed differences, providing a theoretical foundation for broiler genetic improvement. Full article

Snakebite envenoming remains a critical public health issue, and the molecular variability of venoms limits the cross-species efficacy of conventional antivenoms. Here, we conducted a comparative proteomic analysis of Bitis arietans venom to identify conserved peptide regions derived from enzymatic toxins and evaluate their potential relevance for complementary immunotherapeutic applications. Enzyme-enriched venom fractions were isolated through sequential affinity and ion-exchange chromatography and were subsequently characterized using fluorogenic FRET substrates and inhibitor assays. LC–MS/MS analysis identified 1099 proteins and revealed 36 conserved peptides within snake venom metalloproteinases (SVMPs), serine proteases (SVSPs), and phospholipase A₂ (PLA₂), particularly located near catalytic residues and structurally essential motifs such as the HExxHxxGxxH zinc-binding site in SVMPs, the His-Asp-Ser catalytic triad in SVSPs, and the Ca²⁺-binding loop in PLA₂, across Viperidae venoms. These conserved regions were also observed in homologous toxin isoforms from additional Viperidae genera, supporting the evolutionary conservation of key functional domains. While sequence conservation alone does not guarantee neutralization capacity, the identified regions represent strong candidates for structural epitope mapping and targeted antibody development. This study provides a peptide-level framework for advancing complementary antibody-based therapies designed to broaden cross-species toxin recognition, reduce antivenom dosage requirements, and improve clinical outcomes in snakebite envenoming. Full article

Emerging from millions of years of evolutionary optimization, Natural products (NPs) remain unique, unparalleled sources of bioactive scaffolds. Unlike synthetic molecules engineered around single therapeutic targets, NPs often exhibit multi-target, system-level bioactivity, aligned with the principles of network pharmacology, which modulates pathways in a coordinated, non-disruptive manner. This approach reduces resistance, buffers compensatory feedback loops, and enhances therapeutic resilience. Fungal endophytes represent one of the most chemically diverse and biologically sophisticated NP reservoirs known, producing polyketides, alkaloids, terpenoids, and peptides with intricate three-dimensional architectures and emergent bioactivity patterns that remain exceptionally difficult to design de novo. Advances in artificial intelligence (AI), machine learning, deep learning, and multi-omics integration have redefined the discovery landscape, transforming previously intractable fungal metabolomes and cryptic biosynthetic gene clusters (BGCs) into tractable, predictable, and engineerable systems. AI accelerates genome mining, metabolomic annotation, BGC-metabolite linking, structure prediction, and activation of silent pathways. Generative AI and diffusion models now enable de novo design of NP-inspired scaffolds while preserving biosynthetic feasibility, opening new opportunities for direct evolution, pathway refactoring, and precision biomanufacturing. This review synthesizes the chemical and biosynthetic diversity of major NP classes from fungal endophytes and maps them onto the rapidly expanding ecosystem of AI-driven tools. We outline how AI transforms NP discovery from empirical screening into a predictive, hypothesis-driven discipline with direct industrial implications for drug discovery and synthetic biology. By coupling evolutionarily refined chemistry with modern computational intelligence, the field is poised for a new era in which natural-product leads are not only rediscovered but systematically expanded, engineered, and industrialized to address urgent biomedical and sustainability challenges. Full article

Background/Objectives: Early childhood caries (ECC) and saliva have been studied across disparate domains, including microbiome, fluoride, immune, oxidative-stress, and neuroendocrine research. However, the ECC–saliva literature has not previously been mapped as a connected system using modern natural language processing (NLP). This study treats PubMed titles and abstracts as data to identify major themes, emerging topics, and candidate neuroimmune axes in ECC–saliva research. Methods: Using the NCBI E-utilities API, we retrieved 298 PubMed records (2000–2025) matching (“early childhood caries” [Title/Abstract]) AND saliva [Title/Abstract]. Text was cleaned with spaCy and embedded using a transformer encoder; BERTopic combined UMAP dimensionality reduction and HDBSCAN clustering to derive thematic topics. We summarised topics with class-based TF–IDF, constructed keyword co-occurrence networks, defined an internal topic-level Novelty Index (semantic distance plus temporal dispersion), and mapped high-novelty topics to gene ontology and Reactome pathways using g:Profiler. Prophet was used to model temporal trends and forecast topic-level publication trajectories. Finally, we generated a fully synthetic neuroimmune salivary dataset, based on realistic ranges from the literature, to illustrate how the identified axes could be operationalised in future ECC cohorts. Results: Seven coherent ECC–saliva topics were identified, including classical microbiome and fluoride domains as well as antioxidant/redox, proteomic, peptide immunity, and Candida–biofilm themes. High-novelty topics clustered around total antioxidant capacity, glutathione peroxidase, superoxide dismutase, and peptide-based host defence. Keyword networks and ontology enrichment highlighted “Detoxification of Reactive Oxygen Species”, “cellular oxidant detoxification”, and cytokine-mediated signalling as central processes. Temporal forecasting suggested plateauing growth for classical epidemiology and fluoride topics, with steeper projected increases for antioxidant and peptide-immunity themes. A co-mention heatmap revealed a literature-level Candida–cytokine–neuroendocrine triad (e.g., Candida albicans, IL-6/TNF, cortisol), which we propose as a testable neuro-immunometabolic hypothesis rather than a confirmed mechanism. Conclusions: AI-assisted topic modelling and network analysis provide a reproducible, bibliometric map of ECC–saliva research that highlights underexplored antioxidant/redox and neuroimmune salivary axes. The synthetic neuroimmune dataset and modelling pipeline are illustrative only, but together with the literature map, they offer a structured agenda for future ECC cohorts and mechanistic studies. Full article

Microbiota-derived indoles and short-chain fatty acids (SCFAs) modulate intestinal immunity via the aryl hydrocarbon receptor (AhR) and vitamin D receptor (VDR). This review proposes an operational AhR–VDR axis—three testable models (sequential, parallel, reciprocal)—to explain how indoles (AhR) and SCFAs/vitamin D (VDR) may cooperate to drive IL-22–mediated repair, antimicrobial peptide production, autophagy, and tight-junction restoration. We critically evaluate prebiotics, probiotics, and postbiotics: prebiotics shift fermentation toward SCFAs but show context-dependent effects; probiotics can supply indole-type AhR ligands yet are strain-specific; postbiotics offer standardized ligand delivery but face formulation challenges. We distinguish Salmonella-specific findings (e.g., SCFA suppression of SPI-1) from general colitis data and prioritize molecular validation, temporal mapping, multi-omics responder stratification, and standardized postbiotic development for clinical translation. Full article

Plant-based fermented foods are increasingly promoted for glycemic control, yet their mechanisms and clinical impact remain incompletely defined. This narrative review synthesizes mechanistic, preclinical, and human data for key matrices—kimchi and other fermented vegetables, tempeh/miso/natto, and related legume ferments, kombucha and fermented teas, plant-based kefir, and cereal/pulse sourdoughs. Across these systems, microbial β-glucosidases, esterases, tannases, and phenolic-acid decarboxylases remodel polyphenols toward more bioaccessible aglycones and phenolic acids, while lactic and acetic fermentations generate organic acids, exopolysaccharides, bacterial cellulose, γ-polyglutamic acid, γ-aminobutyric acid, and bioactive peptides. We map these postbiotic signatures onto proximal mechanisms—α-amylase/α-glucosidase inhibition, viscosity-driven slowing of starch digestion, gastric emptying and incretin signaling, intestinal-barrier reinforcement, and microbiota-dependent short-chain–fatty-acid and bile-acid pathways—and their downstream effects on AMPK/Nrf2 signaling and the gut–liver axis. Animal models consistently show improved glucose tolerance, insulin sensitivity, and hepatic steatosis under fermented vs. non-fermented diets. In humans, however, glycemic effects are modest and highly context-dependent: The most robust signal is early postprandial attenuation with γ-PGA-rich natto, strongly acidified or low-glycemic sourdough breads, and selected kombucha formulations, particularly in individuals with impaired glucose regulation. We identify major sources of heterogeneity (starters, process parameters, substrates, background diet) and safety considerations (sodium, ethanol, gastrointestinal symptoms) and propose minimum reporting standards and trial designs integrating metabolomics, microbiome, and host-omics. Overall, plant-based ferments appear best positioned as adjuncts within cardiometabolic dietary patterns and as candidates for “purpose-built” postbiotic products targeting early glycemic excursions and broader metabolic risk. Full article

Bovine mastitis remains a major challenge in dairy production despite extensive antimicrobial use, with therapeutic failure increasingly attributed to factors beyond classical antimicrobial resistance (AMR). Growing evidence indicates that treatment inefficacy arises from the combined effects of pharmacokinetic/pharmacodynamic (PK/PD) constraints, biofilm-mediated tolerance, intracellular persistence, and the adaptive capacity of mastitis pathogens. Intramammary therapy is particularly limited by poor tissue penetration, episodic drug elimination via milk flow, and inactivation by milk components, frequently resulting in subtherapeutic exposure at the site of infection. These limitations are amplified in chronic and subclinical mastitis, where biofilms and intracellular reservoirs reduce antimicrobial susceptibility and promote relapse and resistance selection. This narrative review integrates current knowledge on pharmacokinetic and pharmacodynamic (PK/PD) barriers, microbial survival strategies, and antimicrobial resistance (AMR) mechanisms that underlie treatment failure in bovine mastitis. It critically evaluates conventional antimicrobial therapies alongside emerging approaches, including antimicrobial peptides, bacteriophages and endolysins, nanoparticle-based delivery systems, immunomodulators, CRISPR-guided antimicrobials, and drug repurposing strategies. Overall, available evidence highlights the potential of these approaches to enhance therapeutic durability, particularly in settings where biofilm formation, intracellular persistence, and resistance limit conventional treatment efficacy. By mapping research coverage across mastitis phenotypes and therapeutic outcomes, this review identifies key gaps in long-term efficacy and resistance mitigation and underscores the need for PK/PD-guided, biofilm-aware, and resistance-conscious strategies to support durable next-generation mastitis management. Full article

Artificial intelligence (AI) and machine learning (ML) are reshaping cancer research and care. In pediatric oncology, early evidence—most robust in imaging—suggests value for diagnosis, risk stratification, and assessment of treatment response. Pediatric endocrine tumors are rare and heterogeneous, including intra- and extra-adrenal paraganglioma (PGL), adrenocortical tumors (ACT), differentiated and medullary thyroid carcinoma (DTC/MTC), and gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). Here, we provide a pediatric-first, entity-structured synthesis of AI/ML applications in endocrine tumors, paired with a methods-for-clinicians primer and a pediatric endocrine tumor guardrails checklist mapped to contemporary reporting/evaluation standards. We also outline a realistic EU-anchored roadmap for translation that leverages existing infrastructures (EXPeRT, ERN PaedCan). We find promising—yet preliminary—signals for early non-remission/recurrence modeling in pediatric DTC and interpretable survival prediction in pediatric ACT. For PGL and GEP-NEN, evidence remains adult-led (biochemical ML screening scores; CT/PET radiomics for metastatic risk or peptide receptor radionuclide therapy response) and serves primarily as methodological scaffolding for pediatrics. Cross-cutting insights include the centrality of calibration and validation hierarchy and the current limits of explainability (radiomics texture semantics; saliency ≠ mechanism). Translation is constrained by small datasets, domain shift across age groups and sites, limited external validation, and evolving regulatory expectations. We close with pragmatic, clinically anchored steps—benchmarks, multi-site pediatric validation, genotype-aware evaluation, and equity monitoring—to accelerate safe, equitable adoption in pediatric endocrine oncology. Full article

Smart nucleic acid hydrogels (SNAHs), endowed with stimulus responsiveness, function as programmable molecular switches that can perceive diverse external stimuli and undergo rapid, reversible, and highly specific conformational or performance changes. These dynamic properties have enabled the rational design of biosensors with bionic behaviors, facilitating cascaded “recognition–decision–execution” processes that support advanced biological analysis. Consequently, SNAHs are recognized as a core breakthrough for the next generation of intelligent biosensing units. However, a systematic mapping between SNAH design strategies, specific stimuli, and application fields remains lacking. This review mainly analyzes advances in SNAH-based biosensors over the past five years, proposing flexible and feasible design strategies and key trends in customization. Firstly, we systematically summarize molecular recognition modules involved in the construction of SNAHs, including aptamers, DNAzymes, antibodies, and specific binding peptides. Subsequently, we elaborate on the responses of these modules to external stimuli, so as to further facilitate the signal transduction of signals derived from physical, chemical, and biological sources involving temperature, light, magnetic fields, pH, nucleic acids, proteins, other biomolecules, and pathogens. Additionally, the review outlines the research progress of SNAHs in environmental monitoring, food safety, and medical diagnostics. Finally, we provide an integrated perspective on future opportunities and challenges, highlighting the innovative framework for designing SNAH-based biosensors and offering a practical roadmap for next-generation intelligent sensing applications. Full article

African swine fever virus (ASFV) is a highly contagious pathogen causing African swine fever in wild boars, warthogs and domestic pigs. The disease leads tosubstantial economic losses to the global pork industry and poses a grave threat to biodiversity. The early-encoded structural protein p22, owing to its immunodominant characteristics and high conservation across most genotypes, represents a promising diagnostic target and subunit vaccine candidate. In this study, the soluble extracellular domain of p22 protein (aa 30–177) was successfully expressed and purified, yielding 1.220 g/L. Eleven strains of monoclonal antibodies against p22 were generated, with four selected for B-cell epitope screening. Bioinformatic prediction-guided design was employed to generate overlapping truncations and peptides for epitope mapping. Based on those strategies, three novel linear B-cell epitopes were identified to be ³⁰KKQQPPKK³⁷, ¹³⁰WGTDDCTG¹³⁷ and ¹⁵⁰YVYNNPHH¹⁵⁷ by monoclonal antibodies. Sequence alignment across ASFV isolates revealed 100% evolutionary conservation in genotypes I/II, with minor variation in genotypes IV/VIII/XX/XXII. This study provided valuable data for broadening the ASFV antigen spectrum and identifying immunological targets for subunit vaccine formulation strategies. Full article

Cerebral ischemia represents a major mortality and disability cause; oxidative stress is the main intensifier mechanism of excitotoxicity, neuroinflammation, blood–brain barrier failure, and neuronal loss; under these circumstances, firm, mechanism-anchored neuroprotection is an absolute necessity. The work includes a exhaustive, PRISMA (Preferred reporting items for systematic review and meta-analysis)-adherent presentation of the effects of antioxidant peptides and small molecules on tissues, unifying disparate readouts into a coherent tissue-level narrative. A systematic interrogation was performed across major databases over a prespecified interval, applying transparent eligibility criteria to studies that quantified canonical endpoints—infarct volume, neuronal integrity (NeuN/MAP2), apoptosis (TUNEL/cleaved caspase-3), gliosis (GFAP/Iba1), and ultrastructural preservation. The evidence coalesces around a strikingly consistent signal: antioxidant strategies converge on smaller infarcts, robust preservation of neuronal markers, attenuation of apoptotic burden, dampened astroglial–microglial reactivity, and stabilization of mitochondrial and axonal architecture—patterns that align with antioxidative, anti-apoptotic, anti-inflammatory, and ferroptosis-modulating mechanisms. While early clinical data echo these benefits, translation is tempered by heterogeneity in models, timing and dosing windows, and outcome batteries. By consolidating the histological landscape and pinpointing where effects are durable versus contingent, this work elevates antioxidant peptide and small-molecule neuroprotection from promising fragments to an integrated framework and sets an actionable agenda—standardized histological endpoints, protocol harmonization, head-to-head comparisons of peptide versus small-molecule strategies, and adequately powered randomized trials embedded with mechanistic biomarkers to decisively test efficacy and accelerate clinical adoption. Full article

African swine fever virus (ASFV) is the only member of the family Asfarviridae and can cause African swine fever, a disease with a consistently high mortality rate. The pE248R protein, a myristoylated integral membrane protein of ASFV, is required for virus infectivity and some early postentry event, making it a key target for studying the prevention and treatment of ASFV. In this study, BALB/c mice were immunized with purified recombinant pE248R protein, leading to the generation of five monoclonal antibodies (mAbs). Selected mAbs were subsequently subjected to further characterization. By identifying the reactivity of different pE248R protein peptide segments with these monoclonal antibodies, we screened and identified a linear B cell epitope (⁸⁷QEVALTQWMDAG⁹⁸) on the pE248R protein. These results provide a new theoretical basis for analyzing the structure and function of pE248R protein, particularly contributing to the construction of a comprehensive B-cell epitope map for ASFV immunogens. Full article

Background/Objectives: Marine-derived bioactive peptides have been reported to possess blood pressure-regulatory effects. However, most studies have focused on the antihypertensive effects after single-dose administration, and research on long-term administration and its protective effects against hypertension-induced tissue damage remains limited. Therefore, this study aimed to investigate the long-term antihypertensive efficacy of IGTGIPGIW, a bioactive peptide derived from Hippocampus abdominalis (H. abdominalis), and its protective effects on hypertension-related tissue damage. Methods: To evaluate the blood pressure-regulatory effects, spontaneously hypertensive rats (SHRs) were orally administered a high-dose (50 mg/kg) IGTGIPGIW peptide group (H-IGTGIPGIW) for 8 weeks. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were monitored weekly. Serum levels of angiotensin II (Ang II), angiotensin-converting enzyme (ACE), and angiotensin-converting enzyme 2 (ACE2) were measured to assess the peptide’s regulatory effects on the renin–angiotensin system. Histological analyses of the aorta and heart tissues were performed to evaluate the protective effects against hypertension-induced tissue damage. Results: After 8 weeks of treatment, H-IGTGIPGIW significantly reduced SBP, DBP, and MAP compared with SHRs. Serum Ang II and ACE levels were significantly decreased, while ACE2 levels were significantly increased. Histological analyses demonstrated that IGTGIPGIW alleviated aortic wall thickening and reduced renal and cardiac tissue damage in SHR. Conclusions: IGTGIPGIW, a bioactive peptide derived from H. abdominalis, effectively regulated blood pressure by modulating serum Ang II, ACE, and ACE2 levels. Moreover, it protected against hypertension-induced aortic, renal and cardiac tissue damage, suggesting its potential as a functional ingredient for managing hypertension. Full article

The growing interest in functional foods has driven research into protein hydrolysates produced by enzymatic hydrolysis, especially from agro-industrial by-products. These compounds stand out for their antioxidant, antihypertensive, and other bioactive properties, which are relevant to the food, pharmaceutical, and nutraceutical industries. In this context, a bibliometric analysis of 1498 articles indexed in the Web of Science (WoS) database (2015–2025, collected up to June) was conducted to map the evolution of knowledge, identify consolidated and emerging thematic lines, and recognize the most influential actors in the field. The methodology combined an advanced search strategy with Biblioshiny (RStudio) and VOSviewer to generate co-occurrence maps, collaboration networks, and citation analyses. The results show sustained growth since 2018, with a predominance of research on functional properties, bioactive peptides, and antioxidant activity, along with a growing interest in sustainability, process optimization, and in silico methodologies. Six thematic clusters were identified, encompassing process optimization, biofunctional validation, circular economy, and non-conventional protein sources. The study concludes that the field demonstrates significant thematic maturity, with opportunities for innovation, particularly in functional validation and the integrated use of by-products through sustainable enzymatic technologies. Full article