Search Results (1,088)

Tropical maize often exhibits photoperiod sensitivity, which limits its adaptation to temperate regions. Understanding its proteomic dynamics under long-day conditions is therefore crucial for germplasm improvement. This study employed a Tandem Mass Tag (TMT)-based proteomic approach to investigate stage-specific protein expression patterns in the tropical maize inbred line QR273 under long-day conditions (16 h light/8 h dark). Seeds were cultivated in climate chambers, and leaves were collected at the four-leaf (P4) and nine-leaf (P9) stages. A total of 2881 differentially expressed proteins (DEPs) were quantified between the P4 and P9 stages, among which only 7 were upregulated and 2874 were downregulated at the P9 stage. Gene Ontology (GO) enrichment analysis revealed that these DEPs were significantly enriched in processes related to proteolysis, membrane components, and ATP binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the enrichment of DEPs in amino acid biosynthesis, secondary metabolite biosynthesis, and aminoacyl-tRNA biosynthesis pathways. Protein–protein interaction (PPI) network analysis identified 60S ribosomal protein L12, adenosine 5′-phosphosulfate reductase, and RuvB helicase as core hub proteins. Based on functional annotation of representative DEPs, the DEPs were classified into four categories: 9 proteins related to storage material protection, 14 proteins related to protein modification, 12 proteins related to photosynthesis, and 25 proteins with other biological functions. Comparative analysis demonstrated a decrease in storage material protection, protein modification, and photosynthetic capacity at the P9 stage relative to the P4 stage. These findings provide insights into the proteomic dynamics underlying tropical maize development under long-day conditions and offer a theoretical basis for genetic improvement of tropical maize germplasm. Notably, inferences regarding nutrient reallocation based on DEP downregulation are derived solely from proteomic data and require further experimental validation. Full article

Methamphetamine (METH) induces neurotoxicity via excessive and incomplete autophagy, although the underlying mechanisms remain unclear. This study investigated cannabidiol (CBD)’s protective effect and the role of the 5-Hydroxytryptamine 1A receptor (5-HT1A)/adenylyl cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway in primary hippocampal neurons. METH (2 mM, 24 h) reduced neuronal viability, downregulated 5-HT1A, activated the AC/cAMP/PKA/CREB pathway, and simultaneously upregulated autophagy-related proteins (Beclin-1, Microtubule-associated protein 1 light chain 3 [LC3], and Sequestosome 1 [p62]) and overall autophagic flux, indicating impaired lysosomal degradation during autophagy. CBD (1–10 μM) reversed METH-induced autophagy, restored viability, and normalized pathway protein expression. 5-HT1A agonist eptapirone synergized with CBD to inhibit autophagy, while the antagonist WAY-100635 abolished CBD’s effects. These findings demonstrate that CBD, acting as an allosteric modulator of 5-HT1A, alleviates METH-induced neuroautophagy by restoring 5-HT1A activity and suppressing excessive AC/cAMP/PKA/CREB activation, highlighting its potential as a therapeutic agent for METH-related neurotoxicity. Full article

Background: Solriamfetol, a dopamine and norepinephrine reuptake inhibitor widely used in narcolepsy management, has not been thoroughly investigated for its anti-fibrotic and anti-inflammatory properties. Herein, we investigated its potential therapeutic applications and underlying mechanisms in both cellular and murine models of pulmonary fibrosis. Methods: To induce fibrosis, C57BL/6 male mice (six-week-old) were administered bleomycin via the intratracheal route. These animals subsequently received solriamfetol orally once per day at dosages of 3 or 10 mg/kg. Histological and immunohistochemical techniques were employed to evaluate inflammatory cell infiltration, collagen accumulation, and α-smooth muscle actin (α-SMA) expression in bronchoalveolar lavage samples and lung tissue sections. Cytokine levels were measured by ELISA, and gene/protein expression of pro-fibrotic markers, A_2A/A_2B adenosine receptors (ARs), adenylate cyclases (ACs), Epac, K_Ca3.1, and adenosine deaminase (ADA) were assessed via quantitative PCR and Western blot. Electrophysiological recordings evaluated K_Ca3.1 channel activity. Purified ADA and normal human lung fibroblasts (NHLFs) were treated with solriamfetol to assess effects on ADA activity and levels of cAMP and adenosine, respectively. Results: Solriamfetol significantly reduced inflammatory cell infiltration, collagen accumulation, and α-SMA expression in fibrotic lungs. Solriamfetol restored downregulated A_2AAR, A_2BAR, ACs, and Epac, while suppressing ADA expression and activity, resulting in elevated extracellular adenosine and intracellular cAMP. The intervention potentiated Epac signaling and inhibited fibroblast activation. Solriamfetol inhibited the K_Ca3.1 current in fibroblasts and reduced K_Ca3.1 protein expression levels in TGFβ-treated fibroblasts and lung tissues from bleomycin-challenged mice. Notably, these effects were abolished by A_2AAR or A_2BAR antagonists, implying that they occur through AR-mediated pathways. Conclusions: Solriamfetol inhibits ADA and reinforces adenosine–cAMP signaling, suppressing pathological fibroblast activation. These findings suggest its therapeutic utility as a novel anti-fibrotic compound for various fibrotic diseases, including pulmonary fibrosis. Full article

The A3 adenosine receptor (A3AR) is a stress-inducible G-protein-coupled receptor that is selectively upregulated in inflamed, hypoxic, and fibrotic tissues as well as in many malignancies, while remaining weakly expressed in most normal organs. This distinctive expression pattern provides a strong biological basis for pathology-selective pharmacology. Activation of A3AR by highly selective agonists, including piclidenoson (IB-MECA) and namodenoson (Cl-IB-MECA), initiates signaling through Gi proteins and phospholipase C (PLC), which in turn regulate a coordinated network of downstream intracellular pathways, including PI3K/Akt, NF-κB, MAPKs, and Wnt/β-catenin, resulting in suppression of inflammation, inhibition of pathological cell survival, and protection of metabolically stressed tissues. Over the three decades, extensive preclinical studies have demonstrated that A3AR agonism exerts anti-cancer, anti-fibrotic, immunomodulatory, neuroprotective, and organ-protective effects across diverse disease models, including hepatocellular carcinoma, pancreatic cancer, psoriasis, osteoarthritis, metabolic dysfunction-associated steatohepatitis, ischemic stroke, neurodegeneration, ophthalmic disorders, and inherited metabolic syndromes. Importantly, these mechanistic insights have been translated into clinical programs, with piclidenoson and namodenoson demonstrating favorable safety profiles and disease-modifying activity in inflammatory, fibrotic, and oncologic indications. This review integrates molecular, cellular, and translational evidence to highlight A3AR activation as a unifying therapeutic principle for diseases driven by inflammation, oxidative stress, hypoxia, and dysregulated cell survival, positioning selective A3AR agonists as first-in-class agents targeting the A3AR, with broad clinical applicability across multiple disease domains. Full article

The purpose of this study was to investigate the adverse effects of 1.5 μg·L⁻¹ environmentally relevant chlorantraniliprole (CAP) on oxidase biomarkers (juvenile, 2.5 g) for 2, 4, and 8 h and transcriptomic response (adult, 254.8 g) for 96 and 192 h in American shad Alosa sapidissima (Wilson, 1981). American shad is sensitive to pollutants and has become an important economic fish in China, especially for recirculating the aquaculture system and photovoltaic farming. For juvenile shad under short-time CAP exposure, acid phosphatase (ACP) and aryl hydrocarbon receptase (AHR) at the protein level significantly increased at 2 h, and for longer-time exposure, alkaline phosphatase (AKP), polyphenol oxidase enzyme (PPO), and tumor necrosis factor alpha (TNFα) at the protein level significantly decreased; ryanodine receptase (RYR) at the protein level was significantly increased at 8 h. Interestingly, malondialdehyde (MDA) contents, biomarkers of oxidative stress, were significantly decreased for depletion at 2 h and 4 h, while they increased for eliminating free radicals at 8 h via longer-time CAP exposure duration. With the same CAP exposure for adult shad, the number of congested and dilated sinuses of the liver changed, with fine granular brown pigmentation and vacuolization of hepatocytes at 96 h, while the sinuses and central veins were dilated and edematous degeneration occurred at 192 h for longer-time exposure. The detected enzymatic activities, except for adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), significantly decreased, and MDA contents significantly increased in adult shad at 96 and 192 h. Ribosome, proteasome, spliceosome, protein processing in endoplasmic reticulum, oxidative phosphorylation, glycerophospholipid metabolism, biosynthesis of amino acids, ferroptosis, peroxisome, apoptosis, necroptosis, and mTOR signaling pathways were the most significantly enriched pathways. For qPCR verification, the genes ppa2, pla1a, psmb13a, pkz and stat1b were significantly upregulated, while hspa8b, capn2, tram2, asns, bcl2l1, diablo, and prkcb were downregulated in adult shad. The results reveal elevated oxidative stress causing time-dependent hepatic damage via 1.5 μg·L⁻¹ CAP exposure both in juvenile and adult shad. Full article

Jiangshan black-bone chicken is well known for its nutritional and health-promoting benefits, and the high melanin content in its muscles gives it a distinctive black appearance. Melanin possesses strong free radical scavenging ability, which may influence the antioxidant capacity and flavor characteristics of muscle tissue. Therefore, we conducted RNA sequencing and non-targeted liquid chromatography–mass spectrometry (LC-MS)-based metabolomics sequencing on the pectoralis major muscles of Jiangshan black-bone chickens and ordinary chickens (Baier buff chickens), to investigate differences in muscle metabolic regulation between two types of chickens. We detected 88 differentially expressed genes (DEGs) and 124 differential metabolites (DMs), identified enrichment in the “Oxidative phosphorylation”, “Glutathione metabolism”, and “Melanogenesis” pathways. As a result, genes CHAC1, GSTA2, DCT, EDNRB, TYRP1, ATP5F1EP2 and metabolites “Adenosine diphosphate (ADP)”, “Phosphate (Pi)”, “Pyrophosphate (PPi)”, “Oxidized glutathione (GSSG)”, “Spermine”, contributed to differences in antioxidant capacity between the pectoralis major muscles of Jiangshan black-bone chickens and Baier buff chickens. Our results indicated that the Jiangshan black-bone chickens could generate more adenosine diphosphate (ADP), thereby enhancing glutathione metabolism and melanin synthesis, which may facilitate the removal of reactive oxygen species (ROS) in muscle tissue. Full article

Background: Cutaneous melanoma (CM) is a highly immunogenic malignant neoplasm. It features high mutational burden and intense lymphocytic infiltration, supporting the use of immunotherapies, especially inhibitors of the programmed cell death protein 1 (PD-1) checkpoint. Despite advances with anti-PD-1 therapies, such as nivolumab and pembrolizumab, many patients still experience resistance. This result highlights additional immunosuppressive mechanisms within the tumor microenvironment (TME) that limit T-lymphocyte-mediated responses. Objectives: The aim was to discuss the immunologic and metabolic bases of PD-1- and CD73-mediated pathways and evidence that CD73 inhibition can boost PD-1 inhibitor efficacy by acting on convergent immunosuppressive pathways. Methods: We conducted a narrative literature review focusing on tumor immunosuppression, purinergic signaling and checkpoint inhibitor-based immunotherapy. Results: The purinergic pathway, mediated by the ectonucleotidase CD73, is a critical regulator of tumor immunosuppression. CD73 converts extracellular adenosine monophosphate (AMP) into adenosine. This adenosine accumulates in the hypoxic and inflamed TME, exerting immunosuppressive effects. Adenosine acts as a “metabolic brake,” inhibiting proliferation, cytokine production, and cytotoxic activity of CD8⁺ T lymphocytes and natural killer (NK) cells. It also promotes the expansion of regulatory T cells (Tregs) and tumor progression. This axis may limit responses to PD-1 blockade, suggesting that complementary pathways are active. Conclusions: Integration of PD-1 and CD73 pathways suggests that CD73 inhibition may enhance PD-1 blockade by targeting convergent immunosuppressive mechanisms. This supports the exploration of combination strategies to broaden the benefits of immunotherapy in CM. Full article

Cordyceps militaris, a medicinal and edible mushroom, is renowned for its bioactive constituents and health-promoting effects. This study investigated the effects of vacuum freeze drying (VF), vacuum drying (VD), oven drying (OV), and sun drying (SU) on the metabolite profiles and antioxidant activities of C. militaris. VF showed the highest levels of total phenolics, total carotenoids, cordycepin, and N⁶-(2-hydroxyethyl)-adenosine, whereas VD better preserved total flavonoids. VF- and VD-treated samples also exhibited stronger antioxidant capacities than those processed by OV and SU in 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS^•+), hydroxyl radical (•OH), and ferric reducing antioxidant power (FRAP) assays. Metabolomics analysis identified 193 significantly altered metabolites after drying treatments. VF, VD, and SU increased carbohydrates, vitamins, and phenolic acids, while leading to reductions in amino acids, nucleotides, and fatty acids. KEGG analysis revealed that drying significantly affected pathways related to purine and pyrimidine metabolism, amino acid biosynthesis, and phenylpropanoid biosynthesis. Network pharmacology further identified 8 key compounds potentially associated with antioxidant effects through interactions with 37 core targets. These findings highlight the importance of selecting appropriate drying methods to preserve the bioactive compounds and functional quality of C. militaris. Full article

Drug resistance remains a significant barrier to achieving durable treatment responses. Traditionally, resistance has been attributed to genetic alterations and clonal selection. However, accumulating evidence suggests that early adaptation to therapy is often mediated by non-genetic state transitions. In this review, we propose a conceptual framework in which resistance emerges through therapy-driven molecular evolution in bladder cancer, characterized by three interconnected axes: non-genetic plasticity, metabolic reorganization, and tumor microenvironment remodeling. Using the Gemcitabine-Resistant Cell (GRC) model as a temporal reference system, we describe a stepwise transition from drug-sensitive states dominated by proliferation to survival-optimized resistant states through a growth–survival trade-off. Early adaptive phases are marked by the attenuation of cell-cycle and glycolytic programs, increased epigenetic flexibility, and metabolic rewiring involving mitochondrial and lipid-associated pathways. Later phases involve the reinforcement of resistance through extracellular matrix remodeling, developmental and stress-response signaling, and immunometabolic interactions within the tumor microenvironment, including adenosine- and lipid-associated mediators. Projecting the GRC score onto a clinical bladder cancer cohort further suggests that these evolutionary patterns may also be reflected in patient tumors. Overall, this framework supports a temporally structured view of chemoresistance and highlights opportunities to therapeutically target transitional adaptive states before resistance becomes stabilized. Full article

Objective: Linezolid (LZD), an oxazolidinone antibiotic widely used against Gram-positive infections, has been associated with mitochondrial dysfunction and hepatotoxicity, particularly during prolonged use. This study aimed to investigate the protective effects of adenosine triphosphate (ATP) and Liv-52 against LZD-induced liver injury, with a focus on oxidative stress, inflammation, and necroptosis pathways. Methods: Twenty-four male Wistar rats were randomly assigned to four groups: healthy control (HG), LZD-treated (LZDG), Liv-52 + LZD (LVLZ), and ATP + LZD (ATLZ). Liv-52 (50 mg/kg, orally) and ATP (5 mg/kg, intraperitoneally) were administered prior to LZD (125 mg/kg, orally) for 14 days. Results: Following LZD administration, malondialdehyde (MDA) levels markedly increased, indicating oxidative stress, while total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) activities significantly decreased. Histopathological examination revealed pronounced hepatocellular damage accompanied by increased NF-κB, NLRP3, RIPK3, and MLKL expression, indicating activation of inflammatory and necroptotic pathways. Treatment with ATP and Liv-52 significantly ameliorated these biochemical, histopathological, and molecular alterations. Conclusions: Treatment with ATP and Liv-52 significantly attenuated oxidative stress, improved histopathological alterations, and suppressed the expression of inflammatory and necroptotic markers. Notably, ATP exhibited a more pronounced protective effect compared to Liv-52. In conclusion, LZD induces hepatotoxicity through oxidative stress-mediated inflammatory and necroptotic mechanisms, while ATP and Liv-52 confer hepatoprotection, with ATP showing superior efficacy. Full article

Cancer cell metabolism represents a critical therapeutic target, particularly under conditions of metabolic stress induced by glycolysis inhibition. Nitroglycerin (glyceryl trinitrate, GTN), a nitric oxide donor, and 2-deoxy-D-glucose (2-DG), a glycolysis inhibitor, have individually demonstrated anticancer potential through modulation of cellular metabolism and redox balance. In this study, we investigated the cytotoxic and combined effects of GTN and caffeine under 2-DG-induced metabolic stress in human cancer cell lines (HeLa, A549, HT29, and MRC-5). Cell viability was assessed using the sulforhodamine B assay after 24 and 48 h treatments, while drug interactions were evaluated using the Chou–Talalay method and combination index (CI) values. 2-DG alone reduced cell viability in a concentration- and time-dependent manner, with IC₅₀ values ranging from 2.01 to 7.05 mM depending on the cell line and exposure period. The combined treatment further enhanced cytotoxicity, particularly in A549 cells, where viability decreased to approximately 63% after 48 h and the calculated IC₅₀ value for GTN in the presence of caffeine reached 0.143 μM. CI analysis demonstrated synergistic interactions in HeLa and A549 cells (CI < 1), whereas HT29 cells predominantly exhibited antagonistic responses (CI > 1). However, strong synergistic effects were also observed in MRC-5 fibroblasts, indicating limited selectivity toward cancer cells. Molecular docking suggested favorable in silico binding of GTN to aldehyde dehydrogenase 2 (ALDH2) and caffeine to the adenosine A2A receptor. Nevertheless, these findings should be considered exploratory and hypothesis-generating because target expression, enzymatic activity, and pathway activation were not experimentally validated. Overall, the results suggest that GTN enhances caffeine-induced cytotoxicity under metabolically stressed conditions through combined metabolic and redox perturbation, although the magnitude of the response depends on cellular context and warrants further mechanistic investigation. Full article

To investigate the role of the adenosine A2A receptor (A2AR) in methamphetamine (MA)-induced microglia-mediated neuroinflammation and to explore the potential signaling mechanism, postmortem human striatal tissue from MA users, a male C57BL/6 mouse model of MA exposure, and the human microglial cell line HMC3 were examined by Western blotting, immunofluorescence, and related assays. Across all three experimental systems, MA exposure significantly upregulated A2AR expression together with alterations in downstream PKA and PKC signaling. These signaling changes were accompanied by parallel upregulation of pro-inflammatory mediators (iNOS, IL-1β, and IL-18) and of anti-inflammatory and repair-associated factors (Arg-1 and IL-10), suggesting that MA did not trigger a simple unidirectional inflammatory program but instead induced multidimensional phenotypic remodeling of microglia that varied with exposure time and dose. Intervention with the selective A2AR antagonist SCH58261 showed that pharmacological inhibition of A2AR markedly attenuated MA-induced alterations in PKA/PKC signaling and suppressed the accompanying shifts in inflammatory mediator expression, thereby mitigating the neuroinflammatory response. These results suggest that A2AR is involved in the modulation of MA-induced microglial inflammatory responses and may contribute to the mixed inflammatory state characterized by simultaneous changes in pro-inflammatory and anti-inflammatory markers, possibly associated with PKA/PKC signaling. This study expands current understanding of the inflammatory basis of MA-related neurotoxicity and suggests A2AR as a potential target for therapeutic intervention in MA abuse. Full article

Cold stress poses a significant challenge to aquatic organisms, affecting their survival, growth, and metabolic processes. This review explores the molecular mechanisms by which fish, crustaceans, and mollusks respond to cold stress, highlighting the shared and species-specific pathways that facilitate adaptation. Common responses to cold stress include modulation of energy metabolism, regulation of oxidative stress, immune responses, and maintenance of proteostasis. In particular, the activation of the adenosine 5′-monophosphate-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) pathways plays a critical role in regulating energy balance and autophagy in response to low temperatures. Furthermore, we examine the specific adaptive mechanisms employed by different groups of aquatic organisms. Fish utilize pathways such as peroxisome proliferator-activated receptor alpha/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPAR/PGC-1α) and fatty acid oxidation to optimize energy utilization and improve cold tolerance. Crustaceans rely on crustacean hyperglycemic hormone (CHH) signaling and AMPK pathway activation, while mollusks employ metabolic suppression and glycogen storage to survive cold exposure. Moreover, the regulation of autophagy and apoptosis, mediated by p53 and cyclin-dependent kinase 1 (Cdk1), ensures the survival of healthy cells under prolonged cold stress, with autophagy maintaining energy homeostasis and apoptosis eliminating damaged cells. This review also discusses the role of molecular chaperones like heat shock protein 70 (HSP70) and the ubiquitin-proteasome system (UPS) in protein homeostasis, highlighting their importance to protect cells under cold stress. The combined action of these molecular pathways allows aquatic organisms to cope with and adapt to cold environments, ensuring cellular integrity and enhancing survival. Future research should focus on integrating molecular, physiological, and ecological approaches to better understand cold tolerance mechanisms and improve aquaculture practices under climate change scenarios. Full article

This review aims to comprehensively examine spent coffee grounds (SCGs) as a sustainable source of antioxidant and immunomodulatory bioactives, with a specific focus on their capacity to modulate membrane-level signaling through ion channels and G-protein-coupled receptors (GPCRs) in the context of lifestyle-related chronic diseases. SCGs, the major solid by-product of coffee brewing, represent an underutilized yet highly abundant source of bioactive compounds, including chlorogenic acids, phenolic acids, melanoidins, diterpenes, and residual alkaloids. Lifestyle-related chronic diseases, including type 2 diabetes, obesity, cardiovascular disease, and chronic inflammatory disorders, are increasingly recognized as immunometabolic conditions driven by persistent low-grade inflammation, redox imbalance, and dysregulated membrane signaling. This review synthesizes current evidence demonstrating that bioactives contained in SCG extracts exert antioxidant and immunomodulatory effects that extend beyond radical scavenging. Crucially, these compounds also act as modulators of membrane-level signaling, representing a mechanistic perspective that has not been previously integrated for SCGs in the context of chronic disease. The different extraction methodologies and the obtained results are evaluated with the aim to identify the most effective experimental approach and extraction conditions. The paper also discusses how SCG compounds regulate redox-sensitive ion channels (including calcium channels, TRP channels, and potassium channels), and key GPCR pathways (such as GPR120, GPR43, and adenosine receptors), thereby influencing immune cell activation, cytokine production, insulin signaling, and metabolic inflammation. Particular attention is given to the role of microbial fermentation and enzymatic processing in enhancing SCG bioavailability, generating postbiotic metabolites that further engage GPCR–ion channel crosstalk. By integrating extraction approaches, antioxidant chemistry, immunology, membrane signaling, and nutritional metabolism, this review positions SCG as a sustainable functional ingredient capable of restoring immune tolerance and metabolic homeostasis. These insights support the valorization of SCGs within the circular economy framework and highlight their potential application in next-generation immunonutrition strategies for chronic disease prevention and management. 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