Search Results (10,000)

Down syndrome (DS), caused by trisomy 21, is associated with a wide spectrum of endocrine and gastrointestinal disorders that often arise early in life and significantly impact long-term health. This narrative review examines the pathophysiological mechanisms underlying these conditions, with a particular focus on their bidirectional interactions. Endocrine abnormalities in DS, including thyroid dysfunction, type 1 diabetes mellitus, growth impairment, and altered bone metabolism, occur at higher rates than in the general population and are largely driven by immune dysregulation, chronic inflammation, and gene dosage effects. Similarly, gastrointestinal disorders—ranging from congenital malformations to autoimmune conditions such as celiac disease—are highly prevalent and often present with atypical clinical features. Emerging evidence highlights the central role of gut dysbiosis, characterized by reduced microbial diversity and increased pro-inflammatory taxa, in modulating immune and metabolic pathways. This altered gut environment contributes to a chronic inflammatory state and may promote autoimmunity and endocrine dysfunction through the gut–endocrine–immune axis. Nutritional deficiencies and epigenetic factors, including microRNA dysregulation, further influence disease expression. Understanding this complex cross-talk is essential for improving clinical management. Integrated, multidisciplinary approaches and early screening strategies are crucial to optimize outcomes and guide future research in DS. Full article

Aberrant expression of multiple microRNAs has been reported in gastric cancer. In particular, microRNA-597 has been associated with poor survival rates but is not yet well characterized. Seventy-five clinical samples, four cell lines, and two patient-derived organoids were evaluated for the expression of microRNA-597 and its target genes. microRNA-597 was transiently transfected for analysis of cell migration, invasion, wound healing, colony formation, and cell viability, and its regulation by long non-coding RNAs was explored using the TCGA-STAD and LncBook tools. In clinical samples, low expression of microRNA-597 was associated with the intestinal subtype (p = 0.002) and stages III and IV (p = 0.048). All functional readouts were reduced after microRNA-597 transfection, including colony formation, in patient-derived organoids. Among target genes, RUNX1 was directly regulated by microRNA-597. Other cell invasion genes were dependent on RUNX1 as a hub for regulation. Analysis of the Intersection between long non-coding RNAs co-expressed with RUNX1 and those with the highest microRNA-597 prediction binding identified KCNQ1OT1 as the top transcript. Silencing of KCNQ1OT1 and co-expression in clinical samples suggest the existence of a KCNQ1OT1/microRNA-597/RUNX1 network. The results indicate that microRNA-597 directly suppresses RUNX1, while KCNQ1OT1 modulates this interaction. Our approach enabled the simultaneous analysis of dysregulation in three families of transcripts in gastric cancer progression. Full article

DMG, including DIPG, is a highly aggressive pediatric brain tumor with dismal clinical outcomes. Radiotherapy remains the cornerstone of treatment, yet responses are transient and resistance is nearly universal. Emerging evidence indicates that EVs are key mediators of radiation response, facilitating intercellular communication and the propagation of radioresistant phenotypes within the tumor microenvironment. EVs carry diverse molecular cargo, including RNAs, proteins, and lipids, that can dynamically influence tumor behavior and treatment response. In this review, we focus on the role of EVs in shaping radiation response in DMG, while also examining their broader functions in tumor biology, biomarker development, and therapeutic delivery. We summarize evidence for EV-mediated regulation of tumor growth, invasion, microenvironmental interactions, and immune modulation. We further discuss the potential of EVs as minimally invasive biomarkers for liquid biopsy, highlighting both their advantages and current limitations relative to circulating tumor DNA (ctDNA) approaches. In addition, we review emerging strategies utilizing EVs as therapeutic delivery platforms capable of crossing the blood–brain barrier (BBB) and delivering small molecules and nucleic acid-based therapies. Finally, we explore the role of EVs in modulating radiation response, including their contribution to radioresistance and their potential as biomarkers of treatment efficacy. Although EV-based approaches hold significant promise in DMG, challenges related to standardization, specificity, and clinical validation remain. Continued investigation into EV biology and translational applications may provide new opportunities for improving diagnosis, monitoring, and treatment of this devastating disease. Full article

Tailings remediation alleviates ecosystem degradation and protects species. To conserve terrestrial biodiversity and address sustainability challenges while achieving economic growth, numerous researchers have devoted efforts to monitoring ecological functions and optimizing community structures. This study investigates the microbial characteristics and functional diversity across ecological succession stages of tailings. Selecting three typical restoration stages, including biological crust, moss, and grassland stages, we adopt 16S rRNA and ITS gene amplification, Illumina high-throughput sequencing, spectroscopy, and network correlation analysis to explore the responses of soil multifunctionality index, microbial communities, and carbon metabolism during tailings restoration. The experimental results indicate that the functional diversity index increases with ecological succession and is significantly correlated with the bacterial genera Rubrobacter and Arenimicrobium, whereas no significant correlation is observed with dominant fungi. The network interactions among bacterial communities are gradually strengthened along the succession process. In terms of carbon metabolic functions, the relative abundances of galactose, starch, and sucrose metabolism pathways increase obviously with restoration progression, while inositol phosphate metabolism, peroxisome metabolism, retinol metabolism, glyoxylate and dicarboxylate metabolism, and xenobiotics metabolism exhibit no significant variations. These findings provide novel empirical evidence for explaining microbe-mediated ecological succession in tailing ecosystems and highlight the necessity of multi-perspective analysis for ecological restoration. Policy and practical implications emphasize that the application of specific microorganisms and their interspecific interactions to promote iron tailings ecological restoration should fully consider the spatiotemporal heterogeneity of tailings areas. This study deepens the understanding of differential microbial responses at different tailings restoration stages and provides actionable insights for balancing mining economic development and terrestrial ecosystem conservation. Full article

Background/Objectives: Polychlorinated biphenyls (PCBs) are persistent environmental contaminants associated with chronic toxicity and neurological dysfunction. PCB 153 is among the most prevalent congeners detected in environmental and dietary matrices. Although transcriptional responses to PCB 153 have been described, its potential association with post-transcriptional regulation remains poorly defined. Here, we performed an exploratory computational RNA-seq splicing analysis of previously generated transcriptomic data from retinoic acid-differentiated SH-SY5Y cells exposed to a sub-cytotoxic concentration of PCB 153. Methods: RNA-seq data were analyzed to identify candidate differentially alternative splicing events (DASEs). Candidate events were further examined for retained intron (RI)-related premature termination codons (PTCs), and potential regulatory interactions, including DASE-RNA-binding protein (RBP) motif enrichment. Results: PCB 153 exposure was associated with differential expression of 32 RNA-binding protein (RBP) encoding genes and with 90 candidate DASEs. Disease enrichment analysis indicates that genes affected by candidate splicing alterations overlapped with gene sets annotated to intellectual disability and related neurodevelopmental phenotypes. Among retained intron events, several were predicted to introduce PTCs, suggesting potential effects on transcript stability or coding potential. Motif enrichment analysis identified positional enrichment of motifs corresponding to CELF2, NUMA1, PRPF8, and RBM22 within DASE-associated regions, nominating these RBPs as putative regulators associated with the observed splicing alterations. Conclusions: This computational study identifies candidate PCB 153-associated splicing alterations and RBP-related regulatory hypotheses in a neuron-like in vitro model, suggesting a potential mechanistic link between PCB 153 and neurodevelopmental dysfunction. Full article

Exosomes are small vesicles released by cells that have attracted growing interest as drug delivery vehicles, particularly for brain diseases, where getting therapeutics across the BBB remains a fundamental problem. While conventional platforms such as liposomes, polymeric nanoparticles, and viral vectors often suffer from immune clearance and poor brain accumulation, engineered exosomes leverage natural cellular transport mechanisms to cross the BBB, protect cargo from degradation, and enable biocompatible interactions with target cells. This review takes a mechanistic and translational look at how exosomes are being engineered for CNS disorders, with a particular focus on glioblastoma. We cover exosome biogenesis through ESCRT-dependent and ESCRT-independent pathways, and how the competition between Rab27-driven secretion and Rab7-driven lysosomal degradation determines how many exosomes a cell releases, which has direct consequences for therapeutic production. We then discuss cargo loading strategies, from genetic approaches where donor cells are engineered to package specific molecules during biogenesis to physical methods like electroporation and sonication applied to isolated vesicles, alongside surface modification techniques for directing exosomes toward specific cell types. In glioblastoma, engineered exosomes have shown real promise for delivering chemotherapeutics across the BBB, targeting glioma stem cells, enabling CRISPR-based gene editing, and functioning as combined treatment and imaging tools. Applications in stroke and neurodegenerative diseases, where engineered exosomes carrying microRNAs and neuroprotective cargo have produced encouraging preclinical results, are also discussed. Scalable manufacturing and consistent targeting remain the hardest unsolved problems, and we outline emerging approaches including bioreactor-based production, programmable cargo loading, and patient-specific exosome design that are beginning to address these gaps. Overall, the progress reviewed here suggests that engineered exosomes are moving from an interesting biological concept toward a practically viable platform for CNS drug delivery. Full article

Background/Objectives: Tuberculosis, caused by Mycobacterium tuberculosis, remains a major global health challenge requiring novel prevention strategies. This study aims to developed an immunoinformatics-guided framework coupled with experimental screening to prioritize for multi-epitope mRNA vaccine design. Methods: Eight immunologically relevant antigens were computationally analyzed to predict cytotoxic (CTL) epitopes and helper T lymphocyte (HTL) epitopes. Population coverage, immune simulation, molecular docking, and normal mode analysis (NMA) were performed in silico. To evaluate peptide immunoreactivity, human IFN-γELISPOT assays were conducted using the candidate peptides, though HLA restriction was not experimentally validated. Results: The workflow identified 14 candidate CTL and 8 HTL epitopes, yielding an estimated global population coverage of 82.6% (60.7% in China; 51.2% in Indonesia). Immune simulations predicted robust humoral and Th1-associated cellular responses, though sustained CD8⁺ memory responses appeared limited. Docking and NMA suggested favorable structural interactions with TLR3 and TLR4. Crucially, the IFN-γ ELISPOT assay validated eight reactive epitopes that partially coincided with computational predictions within the tested donor group. Conclusions: This study establishes an integrated computational–experimental workflow for T cell epitope prioritization. The identified reactive epitopes provide a preliminary immunological basis and candidate pool for the future design and evaluation of multi-epitope mRNA vaccine strategies against tuberculosis. Full article

The misuse of antibiotics is causing widespread antibiotic resistance, creating an urgent need for new treatment options such as nanoparticle-based therapies. This study aimed to compare silver nanoparticles (AgNPs) produced via green synthesis methods with those made through traditional chemical processes. Furthermore, the study investigated and contrasted the bacterial responses to these two types of AgNPs over a 21-day period of selection pressure using experimental evolution techniques. Analysis using scanning electron microscopy and transmission electron microscopy revealed a consistent, uniform morphology among the AgNPs produced via chemical methods. In contrast, AgNPs synthesized through green methods displayed an irregular morphology. Despite these morphological differences, all nanoparticles from both synthesis approaches were under 100 nm in diameter. These findings were further supported by the absorption spectrum data, which showed a maximum absorption peak between the 400 and 500 nm wavelength range. E. coli exposed to green synthesized AgNPs for 21 days adapted to their presence, exhibiting both enhanced resistance to the green synthesized AgNPs themselves and the development of cross-resistance to ionic silver, a pattern not observed in chemically synthesized AgNP-selected populations. Populations selected using chemical synthesized AgNPs did not develop increased resistance to either chemically or green synthesized AgNPs; however, they showed a slight increase in resistance to ionic silver. Genomics analysis identified polymorphism in genes in a green synthesized AgNP-resistant line including but not limited to the multidrug efflux transporter system (EmrAB), DUF4756 family protein (D1792_RS05680), putative zinc-binding protein YnfU/cold shock-like protein (ynfU/cspB) and imcF-related family protein (D1792_RS10035). Bacterial resistance to chemical AgNPs involves specific polymorphisms in key bacterial components like the RNA polymerase sigma factor (RpoE) and the EmrAB efflux pump. Collectively, the method used to synthesize the AgNPs influences their antibacterial efficacy and the likelihood of bacteria developing resistance. Understanding this interaction is vital for developing effective and resistance-controlled applications of AgNPs across medicine, environmental science, and industry. Full article

Plastic pollution is an increasing concern in freshwater ecosystems, yet the roles of polymer chemistry, environmental context, and microbial community composition in governing degradation remain poorly resolved. This study examined plastic–microbe interactions across river, creek, and pond environments using gravimetric mass loss, scanning electron microscopy (SEM), and 16S rRNA gene sequencing. Four polymers were evaluated: biodegradable polyhydroxyalkanoate (PHA) and polylactic acid (PLA), and conventional low-density polyethylene (LDPE) and polyethylene terephthalate (PET). Rapid biofilm formation occurred on all plastic surfaces, indicating widespread microbial colonization; however, measurable degradation was strongly polymer-dependent. PHA exhibited rapid and extensive mass loss across environments, approaching complete degradation after four months in river and pond settings, whereas PLA, LDPE, and PET showed limited mass loss despite substantial colonization. Environmental context influenced degradation intensity, but these effects amplified degradation only when polymer chemistry permitted breakdown. Microbial community analyses showed that substrate presence influenced beta diversity more than alpha diversity, and differential abundance patterns revealed overlapping enriched taxa across polymers. Overall, degradation was governed primarily by polymer chemistry and environmental conditions, while microbial composition played a secondary, indirect role. Full article

The vitamin D receptor (VDR) plays a pivotal role in maintaining epidermal barrier homeostasis and regulating cutaneous inflammatory responses. However, the cosmetic application of vitamin D and its active metabolites is limited by photoinstability, formulation challenges, and regulatory considerations. In this study, we evaluated a synthetic VDR-activating peptide (VDR-Pep) as a potential functional cosmetic ingredient capable of modulating VDR-associated signaling pathways in human keratinocytes. In situ proximity ligation assays (PLAs) demonstrated that VDR-Pep enhanced the heterodimerization of VDR and retinoid X receptor (RXR), indicating activation of canonical VDR signaling. Treatment with VDR-Pep significantly increased the expression of S100A3 and key terminal differentiation markers, including filaggrin, involucrin, and loricrin, in a dose-dependent manner. In addition, VDR-Pep stimulated intracellular calcium mobilization at levels comparable to or exceeding those induced by 1,25-dihydroxyvitamin D₃. Under UVB-induced stress conditions, the peptide attenuated the expression of the pro-inflammatory cytokine interleukin-6 (IL-6) and enhanced NRF2-associated transcriptional engagement, as evidenced by increased interaction between NRF2 and RNA polymerase II. Collectively, these findings suggest that VDR-Pep supports epidermal homeostasis through coordinated modulation of VDR/RXR signaling, calcium-mediated differentiation, barrier-related protein expression, inflammatory responses, and antioxidant-associated pathways. The results indicate that VDR-targeting peptides may represent a promising non-hormonal strategy for cosmetic formulations aimed at reinforcing skin barrier function and improving resilience to environmental stress. Future studies should focus on validating these effects in in vivo human skin models, assessing long-term safety and efficacy, and optimizing formulation stability for practical cosmetic applications. Full article

Background/Objectives: NPF proteins are important transporters that mediate nitrate uptake, nutrient allocation, and abiotic stress responses in plants. However, the evolutionary patterns of the NPF gene family in grasses remain largely unclear. This study aimed to clarify the evolutionary expansion and stress response characteristics of NPF genes in Poaceae. Methods: A comprehensive comparative genomic analysis was conducted across nine representative Poaceae species and Arabidopsis thaliana. Multiple analytical approaches were used, including gene family identification, phylogenetic classification, collinearity analysis, Ka/Ks calculation, cis-element prediction, protein interaction analysis, and RNA-seq expression verification. Results: A total of 1109 NPF genes were identified with substantial variation in gene copy number among species, particularly the remarkable expansion observed in hexaploid Triticum aestivum. Phylogenetic analysis classified grass NPF proteins into eight major subfamilies, while collinearity analyses revealed that whole-genome duplication and segmental duplication were the primary drivers of NPF expansion. Most duplicated gene pairs exhibited Ka/Ks values below 1, indicating strong purifying selection during evolution. Promoter analyses identified abundant stress- and hormone-responsive cis-elements, especially in Triticeae species. In addition, protein–protein interaction and RNA-seq analyses suggested potential functional associations among NPF genes and revealed expression variation under low-temperature treatments in rice and wheat. Conclusions: Collectively, this study objectively clarifies the evolutionary expansion, functional conservation, and potential stress-responsive diversification of the NPF gene family in grasses. These findings provide straightforward and reliable insights for further evolutionary and functional research on the NPF gene family in Poaceae. Full article

Cardiovascular remodeling, encompassing vascular remodeling, myocardial remodeling, and fibrosis-associated tissue remodeling, underlies atherosclerosis, pulmonary hypertension, myocardial infarction, myocardial fibrosis, and other cardiovascular diseases. Its regulation has traditionally been studied through transcriptional, inflammatory, metabolic, mechanical, and intercellular signaling mechanisms. Recent advances in epitranscriptomics have identified N6-methyladenosine (m⁶A) RNA methylation as an additional post-transcriptional layer that interacts with microRNA (miRNA) pathways during cardiovascular disease progression. This review summarizes current evidence for m⁶A-miRNA crosstalk in cardiovascular remodeling, focusing on epitranscriptomic checkpoints that regulate miRNA fate, feedback-like regulatory circuits involving miRNAs and the m⁶A machinery, and cell-type-specific programs across endothelial cells, vascular smooth muscle cells, fibroblasts, and cardiomyocytes. We further discuss emerging analytical technologies and translational implications of this regulatory axis. Future studies should clarify causal mechanisms, cell-type and disease-stage specificity, and translational feasibility. Together, this multilayered framework provides a systems-level perspective on how RNA regulatory networks may shape pathological remodeling in cardiovascular disease. Full article

Recent studies have identified microRNAs (miRNAs) in honey, opening a new and promising area of nutrition research. In this view, pasteurized and unpasteurized samples of Eucalyptus, Orange Blossom, Chestnut, and Sulla honeys were analyzed using manual and semi-automated RNA extraction methods. Semi-automated extraction yielded significantly higher RNA amounts than manual methods, while pasteurization selectively affected miRNA presence, depending on the type of honey. The panel of conserved miRNAs monitored was let-7a-5p, miR-1-3p, miR-7-5p, miR-10a-5p, miR-33a-5p, miR-34a-5p, miR-92a-3p, miR-125b-5p and miR-133a-3p, across honey varieties and in their extracellular vesicles with structures approximately 200 nm in diameter that retain four miRNAs in all honey types, miR-1-3p, miR-34a-5p, miR-92a-3p, and miR-133a-3p. Bioinformatic analyses of validated miRNA targets revealed enrichment in pathways related to cytoskeletal organization, transcriptional regulation, protein stability, and immune system processes, with Reactome categories clustering around signal transduction, protein metabolism, and immune interactions. Cell–type–specific enrichment suggested that gastric isthmus progenitor cells, stromal cells, and immune subsets could be potential targets, implying roles in epithelial renewal, immune modulation, and wound healing. Overall, these findings enhance our understanding of honey as a source of conserved miRNAs in extracellular vesicles, highlighting its potential as a natural carrier that protects miRNAs from degradation. This study offers new insights into the health-promoting properties of honey, warranting further preclinical studies. Full article

Cannabinoids, including the psychoactive D9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD), interact with receptors within the endocannabinoid system. The major receptors within this system are CNR1 (cannabinoid receptor 1) and CNR2 (cannabinoid receptor 2), which are both seven-transmembrane G-protein-coupled receptors. In this report, we used the Catalogue of Somatic Mutations in Cancers (COSMIC) to map and analyze mutations arising in CNR1 and CNR2. The goal was to determine if any trends or signatures could be identified. We identified several mutations in both CNR1 and CNR2. In silico 3D structure of proteins reveals that these mutations cluster on the intracellular regions of CNR1 and CNR2, and certain residues may be able to destabilize the interaction with the G-alpha protein due to their close proximity. mRNA expression showed that CNR1 and CNR2 are within normal expression levels in most cancer types except kidney, where there is a tendency towards over-expression. Neither CNR1 nor CNR2 is a driver gene, and our analysis shows that mutations in cancer cells are deactivating (e.g., loss of function). Full article

The red sea urchin Loxechinus albus is a species of high commercial importance in Chilean aquaculture, whose performance is strongly influenced by environmental conditions such as temperature. The gut microbiota plays a central role in host physiology; however, its interaction with stress-induced molecular responses remains poorly understood. This study evaluated the effects of thermal stress on food consumption, gut microbial composition, oxidative status, and immune- and stress-related gene expressions in L. albus gut. Sea urchins were exposed to control (16 °C) and elevated temperature (22 °C) conditions for 7 and 14 days. Gut microbiota was characterized using 16S rRNA sequencing, while oxidative damage to DNA and proteins was quantified. Gene expression analyses targeted markers of apoptosis (casp3, casp10, bak1), cellular growth (mtor, raptor), stress response (hsp70), and immune regulation (nfκb, foxo). Thermal stress induced a marked reduction in microbial alpha diversity and promoted a shift toward opportunistic taxa. Heat-stressed individuals exhibited significantly increased oxidative DNA damage, whereas protein oxidation remained unchanged. Gene expression analyses revealed early upregulation of casp3, casp10, nfκb, foxo, and hsp70, suggesting activation of apoptotic, immune, and stress-response pathways. In contrast, bak1, mtor, and raptor showed limited or no significant modulation. These findings demonstrate that thermal stress disrupts host–microbiota homeostasis and induces oxidative and molecular responses in L. albus. This integrative response provides insight into mechanisms underlying physiological performance under thermal stress, with important implications for aquaculture sustainability. Full article