Search Results (4,450)

Background: Esophageal squamous cell carcinoma (ESCA) represents one of the most common aggressive malignancies worldwide. Insulin-like growth factor binding protein 1 (IGFBP1), a typical member of the IGF superfamily, is closely linked to adverse prognosis in numerous cancers. Up to now, little is known about its functional relevance to cell migration and tumor progression in ESCA. This work focuses on clarifying the relationship between IGFBP1 expression and the progression and migratory characteristics of ESCA. Methods: mRNA expression profiles from ESCA patients were obtained from the TCGA and GEO databases. Differential expression analysis was performed using R software(version 4.2.2), followed by an intersection of DEGs between datasets. The STRING database was applied to establish PPI networks. Cytoscape software(Version 3.7.2) was then used for visual presentation and hub gene identification. IGFBP1 expression was validated in ESCA tissues versus adjacent normal tissues. Prognostic correlation was assessed using GEPIA, while diagnostic and predictive values were evaluated through ROC analysis and Cox regression. Genetic alterations of IGFBP1 were analyzed via cBioPortal. Immune cell infiltration patterns were investigated using TIMER. Functional enrichment analyses (GO, KEGG) were performed on IGFBP1-associated DEGs. In the in vitro experiments, esophageal cancer cell lines (such as Eca109 and TE-1) and normal human esophageal epithelial cell lines (such as HEEC) were selected. The transcriptional level of IGFBP1 was examined using RT-qPCR, while Western blot analysis was conducted to validate its protein expression changes. Changes in the proliferative capacity of cancer cells after IGFBP1 silencing were detected by the CCK-8 assay, and cell migration capacity was determined via wound scratch assays to clarify the related biological effects. Results: Overall, 2870 DEGs were screened from the GEO database, 153 DEGs were screened from the TCGA database, and 34 genes were found to be common to both databases; 10 core genes were screened from the PPI network. IGFBP1 was abnormally expressed in esophageal cancer. Cox regression confirmed that IGFBP1 is an independent risk factor, and prognostic analysis indicated that IGFBP1 is closely associated with poor prognosis. Gene mutation analysis showed that amplification mutations are the most common type of IGFBP1 gene mutation, and genetic alterations in IGFBP1 in ESCA patients are significantly associated with overall survival (OS) (p = 0.0002568). GO analysis indicated that IGFBP1-related differentially expressed genes were enriched in organic anion transport, epidermal development, apical cell components, and metal ion transmembrane transporter activity. Pathway enrichment based on the KEGG database illustrated the main enrichment of target genes in neuroactive ligand–receptor interactions, calcium signaling and cAMP signaling pathways. Additionally, remarkable differences in immune cell infiltration were observed between IGFBP1 high-expression and low-expression subgroups through tumor immune profiling. IGFBP1 expression differed significantly between esophageal cancer cells and normal esophageal epithelial cells, as detected by RT-qPCR (p < 0.05). Moreover, knockdown of IGFBP1 markedly inhibited the proliferation (p < 0.05) and migration abilities (p < 0.05) of TE-1 and Eca109 cells. Conversely, IGFBP1 overexpression facilitated these cellular processes. Conclusions: As a key oncogenic driver for ESCA, IGFBP1 may participate in the oncogenesis of ESCA, possibly influencing clinical outcomes via IGF signaling and the tumor microenvironment. Its dual functions in tumor and immune systems suggest it might be a candidate for ESCA immunotherapy research. Full article

Empirical management of acute pyelonephritis in Eastern Europe is increasingly constrained by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and by uropathogen phenotypes—such as strong biofilm formation—which may further blunt antimicrobial activity. We aimed to characterise resistance mechanisms, minimum inhibitory concentration (MIC) distributions, biofilm-forming capacity, and the in vitro performance of carbapenem-sparing agents and to test whether these microbiological features improve prediction of clinical failure beyond standard bedside risk scores. We retrospectively analysed 102 Enterobacterales isolates recovered from 129 consecutive culture-confirmed adult pyelonephritis admissions at “Victor Babeș” University Hospital, Timișoara (March 2022–March 2025). MIC values were determined by Vitek 2 and interpreted using EUCAST v13 breakpoints; ESBL, AmpC, and carbapenemase phenotypes were confirmed by combination disk and modified carbapenem inactivation methods. Biofilm formation was quantified by the microtiter-plate crystal-violet assay. Mediation, Restricted Mean Survival Time (RMST), and decision-curve analyses were used to assess added clinical value. ESBL was confirmed in 30/102 (29.4%) isolates, AmpC in 9 (8.8%), and carbapenemase in 4 (3.9%). ESBL+ isolates were more often strong biofilm formers (33.3% vs. 12.5%; p = 0.014) and showed a 4- to 16-fold rightward MIC shift for cefepime, piperacillin–tazobactam, and ciprofloxacin. Among carbapenem-sparing agents, ceftazidime–avibactam (96.7% S), fosfomycin (80.0% S), and amikacin (73.3% S) retained the highest activity against ESBL+ isolates. Strong biofilm formation and the ESBL phenotype were independently associated with worse outcomes (adjusted OR 3.5 and 4.7); an exploratory mediation analysis suggested that biofilm formation may explain part of the observed association between the ESBL phenotype and treatment failure and that delayed effective therapy may account for a further portion of this association. A microbiology-enhanced model that added the ESBL phenotype, biofilm strength, and acquisition setting to routine clinical variables improved discrimination over a clinical-only baseline (AUC 0.89 vs. 0.71) and showed a higher net benefit on exploratory decision-curve analysis across the 10–40% threshold range. These predictive findings derive from a single-centre cohort with a small number of events and were only internally validated; they require validation in independent cohorts before any clinical application can be considered. The ESBL phenotype and strong biofilm formation were each independently associated with worse outcomes in pyelonephritis and may help identify candidate isolates for carbapenem-sparing strategies anchored on ceftazidime–avibactam, fosfomycin, and amikacin; given the observational, single-centre design, these associations should be regarded as hypothesis-generating. Full article

Background: Idiopathic pulmonary fibrosis (IPF) is an incurable disease with limited therapeutic options and a poor prognosis. Current standard therapies are characterized by drugs or surgical strategies with limited effects, as they are either not curative or their use is restricted to a specific subset of the population. The aim of this scoping review is to evaluate the drugs currently under investigation in Phase II and Phase III trials and provide an overview of the mechanisms of new therapeutic strategies for IPF. Methods: The search strategy was conducted in accordance with PRISMA guidelines and included studies conducted on adults with IPF retrieved from the registered ClinicalTrials.gov database up to 31 December 2025. Results: Nineteen studies were included. The clinical trials investigate key signaling pathways and molecular targets, including MAPK, RhoA/ROCK, PDE4B/cAMP, Wnt/β-catenin, Hedgehog/SMO, IL-11/STAT3, and LPA/autotaxin, as well as extracellular receptors and mediators such as CSF1R, TBXA2R, and WISP1. Conclusions: Ongoing clinical research in IPF reflects a broad diversification of molecular targets; however, translational success remains limited. Current evidence suggests that biological complexity, pathway redundancy, and systemic constraints significantly restrict the clinical impact of single-target strategies. Future progress will likely depend on improved patient stratification, combination approaches, and biomarker-guided trial design rather than isolated pathway modulation. Full article

Pediatric acute myeloid leukemia (pedAML) is a childhood malignancy with relapse rates of approximately 30%. CD68, a macrophage marker involved in phagocytosis and macrophage recruitment, may contribute to AML biology. We analyzed CD68 expression using the TARGET database and performed survival analyses, mRNA/protein profiling, and functional assays in AML cell lines, pedAML samples, and cord blood samples. High CD68 transcript levels correlated with KMT2A-rearrangements and inversion 16. Survival analysis showed that high CD68 predicted worse event-free survival, though not independently in a multivariate analysis. Flow cytometry confirmed higher CD68 expression in 7/8 pedAML samples compared to cord blood samples. Functionally, CD68 knockdown reduced proliferation and increased drug sensitivity, while overexpression promoted growth and resistance. Gene set enrichment analysis (GSEA) indicated enrichment of MAPK signaling, AP-1–mediated stress response, and epithelial–mesenchymal transition (EMT)/migration-associated pathways in CD68-high models. Together, these findings suggest that CD68 contributes to a pro-tumorigenic and stress-adaptive phenotype in pedAML and may represent a biologically relevant therapeutic target. Full article

Serratia spp., particularly Serratia marcescens, have emerged as clinically important opportunistic pathogens and are increasingly recognized as causes of healthcare-associated infections, especially among critically ill and immunocompromised patients. Their remarkable ecological adaptability, persistence in hospital environments, and capacity to acquire multiple antimicrobial resistance determinants have contributed to the global emergence of multidrug-resistant strains and complicated therapeutic management. This review aims to comprehensively analyze the epidemiology, virulence mechanisms, antimicrobial resistance patterns, and current and emerging therapeutic strategies associated with Serratia spp. The manuscript is based on a critical review and analysis of previously published literature retrieved from electronic scientific databases focusing on clinically relevant Serratia spp. infections and resistance trends. The reviewed literature demonstrates that Serratia spp. combine intrinsic resistance mechanisms, particularly inducible chromosomal AmpC β-lactamases, with acquired resistance determinants including extended-spectrum β-lactamases, carbapenemases, aminoglycoside-modifying enzymes, and plasmid-mediated quinolone resistance. Horizontal gene transfer and biofilm formation further enhance bacterial persistence, dissemination, and adaptation within healthcare settings. Clinically, these pathogens are associated with device-related infections, bloodstream infections, pneumonia, urinary tract infections, and hospital outbreaks, where increasing multidrug and carbapenem resistance significantly limits therapeutic options. Novel β-lactam/β-lactamase inhibitor combinations and cefiderocol represent promising therapeutic approaches, although treatment success remains highly dependent on accurate identification of underlying resistance mechanisms. This review highlights the growing public health importance of Serratia spp. and underscores the need for improved surveillance, molecular diagnostics, antimicrobial stewardship, and the development of innovative therapeutic strategies in the context of the evolving antimicrobial resistance crisis. Full article

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) dysfunction is increasingly recognized as a key contributor to a broad spectrum of human diseases beyond classical cystic fibrosis (CF). CFTR is a cAMP-regulated chloride and bicarbonate ion channel expressed in both epithelial and non-epithelial tissues, where it regulates ion homeostasis, mucosal hydration, and cellular signaling. Both inherited CFTR mutations and acquired dysfunction resulting from environmental or inflammatory factors can disrupt these physiological processes and drive disease progression. Current evidence linking CFTR dysregulation to respiratory diseases, such as cystic fibrosis, chronic obstructive pulmonary disease (COPD), asthma, and HIV-associated airway disease, as well as cardiovascular, renal, neurological diseases, and cancer, is comprehensively discussed. Mechanistically, impaired CFTR function promotes oxidative stress, chronic inflammation, epithelial barrier dysfunction, altered mucociliary clearance, and dysregulation of signaling pathways, including NF-κB, TGF-β, PI3K/Akt, MAPK, and Wnt/β-catenin. In the context of HIV infection and cigarette smoke exposure, CFTR suppression is mediated in part by TGF-β signaling and miRNA-dependent mechanisms, resulting in compromised airway defense and increased susceptibility to pulmonary complications. Recent studies further demonstrate that CFTR dysregulation alters the expression of genes involved in fibrosis, inflammation, angiogenesis, and epithelial–mesenchymal transition (EMT). Notably, CFTR may act as either a tumor suppressor or a context-dependent oncogene, depending on tissue type and signaling milieu, highlighting its complex role in cancer biology. Advances in CFTR-targeted therapies, including potentiators, correctors, gene therapy, and combination approaches, have markedly improved outcomes in CF and may offer therapeutic potential for diseases associated with acquired CFTR dysfunction. We summarize the systemic consequences of CFTR dysregulation and the need for further mechanistic and translational research to clarify its role across diverse human diseases. Full article

Water management in high-temperature and high-salinity reservoirs remains a critical challenge for oilfield operations, with conventional polymer gel systems exhibiting insufficient thermal stability and salt tolerance under extreme conditions. Here, we establish an integrated computational–experimental platform combining density functional theory (DFT) and molecular dynamics (MD) simulations to rationally design a novel AM/AMPS/AMB (Acrylamide/2-acrylamido-2-methylpropanesulfonic acid/sodium 3-acrylamido-3-methylbutanoate) terpolymer gel plugging agent tailored for the Tahe Oilfield (140 °C, Ca²⁺/Mg²⁺ 10,000 mg L⁻¹). Density functional theory (DFT) calculations of fourteen functional monomers identified AMB as the optimal candidate, achieving further hydrogen bond interactions that stabilize the crosslinked architecture under extreme conditions. This computational pre-screening reduced experimental iterations by over 60% and significantly shortened development cycles compared to conventional trial-and-error approaches. Experimentally, the optimized terpolymer exhibited a 40% increase in storage modulus (150 Pa) relative to AM/AMPS binary systems, 25% improvement in thermal stability (residual carbon at 300 °C), and plugging efficiency exceeding 92% in core flooding tests. Full article

Background: Carbon dots (CDs) are promising fluorescent nanomaterials with great application potential in bioimaging and organelle-targeted diagnostics. This study compares nitrogen-doped (N-CDs) and boron–nitrogen co-doped CDs (BN-CDs) in normal NIH3T3 fibroblasts and KRAS-transformed cells. Methods: CDs were synthesized via a microwave-assisted method. Their fluorescence, cytocompatibility, and intracellular localization were evaluated using confocal microscopy, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and organelle colocalization. Cellular metabolism was assessed by Seahorse analysis. Oxidative stress and cAMP levels were pharmacologically modulated. Results: BN-CDs exhibited stronger intracellular fluorescence than N-CDs, indicating enhanced uptake and imaging performance, with no cytotoxicity up to 100 µg/mL. They localized to multiple organelles, particularly mitochondria. However, fluorescence was significantly reduced in KRAS-transformed cells despite similar mitochondrial mass. BN-CDs did not affect mitochondrial respiration or glycolytic activity. Induced oxidative stress or elevated cAMP in normal cells reduced BN-CD fluorescence. Conclusions: Boron doping improves N-CD imaging properties without affecting cell viability or metabolism. Reduced fluorescence in KRAS cells is associated with altered intracellular conditions, suggesting that BN-CDs could be used to discriminate between normal and cancer cells. Full article

Dietary polyphenols such as quercetin, resveratrol, and (−)-epigallocatechin-3-gallate (EGCG) have shown neuroprotective effects in epidemiologic and experimental studies of Alzheimer’s disease (AD), although clinical evidence remains limited. This review highlights the importance of investigating glucuronide and sulfate conjugates of these polyphenols, as well as their intestinal microbial metabolites, at bioavailable low nanomolar concentrations, particularly those capable of reaching the brain. Although many in vitro studies use micromolar concentrations of aglycones, the relevance of such concentrations to neuroprotection remains uncertain. While polyphenols are redox-sensitive, their direct antioxidant or prooxidant effects may be limited at nanomolar concentrations. Instead, their neuroprotective actions appear to be mediated through high-affinity interactions with molecular targets such as the 67-kDa laminin receptor (67LR). This receptor binds both aglycones and conjugates at low nanomolar concentrations through a peptide G region containing glycosaminoglycan- and palindromic sequence-related motifs. The same region also binds the prion–amyloid-β complex, suggesting that polyphenols may antagonize amyloid-β binding and thereby prevent its neurotoxicity. The peptide G region may also function as a redox sensor. Binding of polyphenols to 67LR activates cAMP signaling and downstream neuroprotective pathways involving CREB, SIRT1, and protein phosphatase 2A. In addition, nanomolar concentrations of resveratrol and quercetin inhibit quinone reductase 2, an enzyme associated with cognitive decline and reported to be elevated in AD. Given their low bioavailability in the brain and their distinct molecular targets, combining multiple polyphenols at low doses may produce additive or synergistic effects, enhance efficacy, and minimize potential toxicity in the prevention of AD. Full article

Co-authored by a French humanitarian anthropologist and a South Sudanese refugee and environmental activist, both writers situated across the Global North and South, this article argues that artistic practices in displacement operate as infrastructures of survival, whose conditions of existence are both enabled and constrained by external actors. Drawing on a case study of Tongogara Refugee Settlement, it argues that the arts—and, more broadly, knowledge production—constitute key survival mechanisms across psychological, psychosocial, and identity-related dimensions. This article further shows that artistic practices in displacement are not only autonomous expressions of resilience but also mediated cultural forms whose visibility and meaning are co-produced through humanitarian, institutional, and epistemic regimes—including the regimes of academic writing itself. First, we examine art’s three interrelated survival dimensions: psychological (personal coherence amid uncertainty and symbolic mobility), psychosocial (collective bonding and mutual support), and identity (cultural representation, memory, heritage, and self-definition in displacement). Second, we examine how these functions are shaped by interactions with external actors—including humanitarian organizations, donors, cultural platforms, and academic institutions—that may increase visibility while favoring curated representation over sustained artistic development, reflecting broader donor-driven logics of accountability. Third, drawing on reflexive notes from the co-authorship process, we show how academic narration can reproduce these asymmetries, thereby positioning co-creation as both an ethical practice and an epistemic condition of equitable knowledge production. Drawing on humanitarian anthropology, aesthetics, and decolonial epistemologies, we argue that processes of symbolic and cultural reconstruction remain structurally under-institutionalized, circulating across humanitarian, developmental, and epistemic regimes without being fully claimed by any of them. Rather than offering normative prescriptions, the article traces how co-production itself becomes a site where these asymmetries are reproduced and made visible. Full article

Background/Objectives: Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is an autosomal recessive disorder of mitochondrial fatty acid β-oxidation caused by pathogenic variants in ACADVL. The clinical spectrum is highly heterogeneous, ranging from lethal neonatal cardiomyopathy to late-onset myopathy. This study aims to characterize the rare c.215C>T (p.Ser72Phe) variant, identified in compound heterozygosity with the common pathogenic allele c.848T>C (p.Val283Ala) in a male neonate detected by newborn screening (NBS). Methods: Genetic analysis was performed using Sanger sequencing on the proband and his family members. The pathogenicity of the p.Ser72Phe variant was evaluated through multiple bioinformatic predictors and interpreted according to ACMG/AMP guidelines. To understand the functional impact on the protein, structural modeling was conducted using FoldX 4.0 for energy calculations and UCSF ChimeraX for the visualization of conformational changes and cofactor-binding site perturbations in the VLCAD homodimer. Results: At the end of the first postnatal week, liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis of dried blood spots of the proband revealed a markedly abnormal acylcarnitine profile, with C14:1 levels (1.837 μmol/L) approximately five times above the reference range. Clinical reports documented hypoketotic hypoglycemia, consistent with VLCADD. Segregation analysis demonstrated transmission of both variants within the family, with additional heterozygous and homozygous carriers identified. Bioinformatic predictions uniformly classified p.Ser72Phe as deleterious. This variant has an extremely low allele frequency and affects a highly conserved residue in the FAD-binding domain. Structural modeling with FoldX yielded a mean ΔΔG of +22.63 ± 5.48 kcal/mol, indicating a significant localized thermodynamic burden. Inspection of the mutant model in ChimeraX showed perturbation of the side-chain orientation and attenuation of the local hydrogen-bonding network at the FAD-binding site, together with increased steric packing around residue 72. Taken together, the clinical, genetic, and structural evidence support reclassification of p. Ser72Phe as likely pathogenic according to ACMG criteria, specifically applying the ClinGen ACADVL VCEP specifications. Conclusions: This study expands the ACADVL mutational spectrum and underscores the value of integrating sequencing, segregation, and structural bioinformatics in interpreting rare variants detected through NBS. Full article

The calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide belonging to the calcitonin family, discovered as a product of alternative splicing of the calcitonin gene. CGRP has emerged as a pleiotropic signaling molecule with widespread distribution in the central and peripheral nervous systems, particularly within primary sensory neurons. This narrative review synthesizes current knowledge on the CGRP system, integrating recent advances in its molecular structure, gene organization, and post-translational processing with high-resolution structural insights into its heterodimeric receptor complex (CLR-RAMP1) obtained through cryo-electron microscopy. We also include long-term safety data on anti-CGRP monoclonal antibodies, emerging cardiovascular risk signals, and novel therapeutic applications in vestibular migraine and pediatric populations. The intracellular signaling cascades activated by CGRP, including the canonical cAMP-PKA pathway, MAP kinase activation, and context-dependent calcium signaling, are discussed in relation to its diverse physiological functions. These encompass vasodilation, nociception modulation, neurogenic inflammation, gastrointestinal motility, bone metabolism, tissue regeneration, and energy homeostasis. The central role of CGRP in migraine pathophysiology is examined to understand the development of targeted therapies. The current pharmacological landscape is reviewed, including the evolution of small-molecule CGRP receptor antagonists (gepants) through three generations and the four approved monoclonal antibodies targeting CGRP or its receptor, with comparative analysis of their efficacy, safety profiles, and clinical positioning. Beyond migraine, emerging and predominantly preclinical roles of the CGRP system are discussed in chronic pain, osteoarthritis, cardiovascular diseases, sepsis, cancer (particularly bone metastases and tumor microenvironment immunomodulation), and neurodegenerative disorders such as Alzheimer’s disease. In these areas, the available evidence remains heterogeneous and, in most cases, is not yet sufficient to support clinical translation. Finally, future directions are discussed, including the development of stable CGRP analogs, allosteric modulators, and the potential expansion of therapeutic applications into oncology, intensive care medicine, and neuroprotection. Full article

Neuritogenesis is essential for neuronal development and circuit formation. Although cAMP signaling downstream of Gs-coupled receptors is considered pro-neuritogenic, activation of these Gs-coupled receptors can produce divergent cellular outcomes. We previously showed that prostaglandin E₂ (PGE₂) induces neurite outgrowth in NSC-34 motor neuron-like cells predominantly through Gs-coupled E-prostanoid receptor 2 (EP2) signaling. The I-prostanoid receptor (IP) is also Gs-coupled, but whether its ligand PGI₂ elicits neuritogenesis remains unclear. Here, we compare the neuritogenic and signaling responses to PGE₂ and PGI₂ in NSC-34 cells. PGE₂ and the EP2 agonist butaprost increased the proportion of neurite-bearing cells, whereas PGI₂ and the IP agonist beraprost had no effect. PGI₂ and PGE₂ induced comparable cAMP accumulation and protein kinase A substrate phosphorylation, and elicited peak cAMP response element binding protein (CREB) phosphorylation at 1 h. However, only PGE₂ maintained significant CREB phosphorylation at 3–6 h. RNA sequencing at 4 h revealed broadly concordant transcriptional responses, while direct comparison identified Fst as the only gene expressed at higher levels under PGE₂ than under PGI₂. These findings suggest that the temporal profile of CREB phosphorylation, rather than the magnitude of early cAMP-PKA signaling, may be associated with differences in neuritogenic outcomes of Gs-coupled prostanoid signaling. Full article

Background/Objectives: Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by abdominal pain, diarrhea, and bleeding. Polydeoxyribonucleotide (PDRN), an adenosine A_2A receptor (A_2AR) agonist, exhibits anti-inflammatory properties. In the present study, we evaluated the therapeutic effects of PDRN in a dextran sodium sulfate (DSS)-induced murine model of UC. Methods: UC was induced by administering 2% DSS in drinking water for 7 days. One day after DSS administration, mice received intraperitoneal injections of PDRN (8 mg/kg) for 7 days. To investigate the involvement of A_2AR, the selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 8 mg/kg) was co-administered with PDRN. Results: DSS administration induced colonic tissue damage and increased disease activity index (DAI) and histological scores. DSS also elevated pro-inflammatory cytokines while reducing anti-inflammatory cytokine levels. PDRN treatment reduced histological damage, restored body weight, colon weight, and colon length, and decreased DAI scores. Furthermore, PDRN treatment inhibited nuclear factor kappa B (NF-κB) activation through suppression of NF-κB inhibitor-α phosphorylation and was associated with activation of the cAMP/PKA/CREB signaling pathway. PDRN treatment attenuated inflammation and was associated with increased expression of vascular endothelial growth factor (VEGF) in colonic tissues. Given the context-dependent role of VEGF in inflammatory bowel disease, this increase is interpreted as contributing to mucosal repair rather than exacerbating inflammation. Co-administration of DMPX abolished these effects, suggesting the involvement of A_2AR-dependent signaling pathways. Conclusions: PDRN attenuated colonic inflammation and improved disease outcomes in DSS-induced UC, potentially through modulation of the PKA/CREB/NF-κB signaling pathway and VEGF-mediated tissue repair mechanisms. Full article

Brain aging is a complex biological process characterised by progressive neuronal and synaptic decline, in which disruption of mitochondrial quality control plays a central role. This system encompasses multiple synergistic components, including mitochondrial biogenesis, dynamic equilibrium, autophagic clearance, and energy metabolism. Aging induces dysfunction across these processes, precipitating mitochondrial fragmentation, functional decline, and energy crises, ultimately driving cognitive deterioration. Exercise is a promising non-pharmacological intervention for preserving brain health during aging, and its benefits may be mediated, at least in part, through modulation of mitochondrial quality control. Specifically, exercise has been shown to activate key signaling pathways such as AMPK/SIRT1/PGC-1α, thereby promoting mitochondrial biogenesis and metabolic adaptation. It may also regulate mitochondrial dynamics and mitophagy via pathways including cAMP/PKA/Drp1 and AMPK/mTOR. In addition, emerging evidence indicates that exercise may influence brain mitochondrial function through activity-dependent regulation of mitochondrial gene expression and systemic signaling factors. Furthermore, this review discusses potential differences between exercise modalities and highlights future directions for personalised intervention strategies, providing a theoretical basis for the application of exercise in delaying brain aging and preventing neurodegenerative diseases. Full article