Search Results (50,059)

Objectives: Seawater-immersed burn wounds are highly susceptible to contamination, persistent inflammation, oxidative stress, and delayed healing, while current irrigation solutions remain suboptimal for such acute injuries. This study aimed to evaluate the therapeutic efficacy and underlying mechanisms of plasma-activated water (PAW) as a novel irrigation strategy for these complex wounds. Methods: The antibacterial efficacy of PAW against marine pathogens was first evaluated in vitro. Subsequently, a rat model of seawater-immersed burn injury was established in male Sprague-Dawley (SD) rats to assess the therapeutic effects of PAW irrigation on wound healing, infection control, and underlying biological mechanisms. Results: In vitro, PAW significantly eradicated two major marine pathogens, Vibrio vulnificus and Vibrio parahaemolyticus (p < 0.001). In vivo, PAW markedly accelerated wound closure, achieving complete healing in 23.60 ± 6.50 days vs. 38.67 ± 2.08 days (Normal saline group) and 58.33 ± 10.97 days (Model group) (p < 0.05). PAW significantly reduced bacterial burden, modulated inflammation by decreasing interleukin-6 and increasing interleukin-10, and alleviated oxidative stress, as evidenced by reduced malondialdehyde levels and enhanced superoxide dismutase activity. Histological evaluation demonstrated enhanced re-epithelialization, collagen deposition, and increased expression of vascular endothelial growth factor and platelet endothelial cell adhesion molecule-1. No adverse effects on serum biochemistry or major organ histopathology were observed. Conclusions: PAW may be a safe, promising, and multifunctional irrigation strategy that promotes seawater-immersed burn healing through coordinated antibacterial, anti-inflammatory, antioxidant, and pro-angiogenic effects, highlighting its strong potential for clinical translation. Full article

Background: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of hepatic metabolism and disease progression. The hepatocyte nuclear factor 1 alpha antisense 1 (HNF1A-AS1) lncRNA modulates liver-specific transcription factors; however, its physiological role in diet-dependent lipid homeostasis remains poorly defined. Methods: In this study, we investigated the mouse ortholog, Hnf1a opposite strand 1 (Hnf1aos1), using AAV-mediated knockdown in C57BL/6J mice fed either a chow diet (10% kcal from fat) or a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. Metabolic phenotyping included hepatic lipid quantification, histological analysis, serum biochemistry, and quantitative gene expression profiling. Results: Loss of Hnf1aos1 produced distinct, diet-dependent alterations in hepatic lipid handling. Under chow conditions, knockdown mice exhibited selective hepatic cholesterol accumulation (6.10 ± 2.9 mg/g tissue vs. 3.51 ± 1.1 mg/g in controls), accompanied by dysregulation of cholesterol clearance pathways. In contrast, under HFD conditions, knockdown precipitated severe macrovesicular degeneration, with hepatic triglyceride levels approximately doubled relative to HFD-fed controls (51.72 ± 19.8 mg/g vs. 26.34 ± 11.9 mg/g) and a numerically elevated triglyceride-to-cholesterol ratio (TG:TC ≈ 6.1:1; p = 0.0621, trend). Chow/Kd mice gained significantly less weight than chow-fed controls, whereas HFD/Kd mice exhibited weight gain comparable to HFD controls despite severe hepatic steatosis. This paradoxical phenotype suggests impaired metabolic feedback at the post-transcriptional level, in which compensatory upregulation of Hnf1a mRNA is insufficient to suppress lipid-associated genes such as Cd36, despite profound lipid overload; however, HNF1A protein levels were not directly measured in this study. Conclusion: Collectively, these findings identify Hnf1aos1 as a regulator of hepatic lipid homeostasis whose loss produces a phenotype consistent with inappropriate lipid accumulation during nutrient excess, without defining the underlying molecular mechanism. Our results support a role for Hnf1aos1 in shaping hepatic metabolic plasticity and provide insight into lncRNA-associated MASLD phenotypes. Full article

Background/Objectives: Pancreatic adenocarcinoma remains one of the most lethal malignancies, largely due to aggressive biological behavior and limited available insight into biomarker-based prognostic stratification. The aim of our research was to investigate the role of macrophage migration inhibitory factors (MIFs), interleukin-8 (IL-8/CXCL8), and stem cell factors (SCFs) in pancreatic adenocarcinoma. Methods: In this single-center study, sixty hospitalized patients diagnosed with pancreatic adenocarcinoma were prospectively enrolled, and a cross-sectional analysis of baseline cytokine levels was performed. Serum MIF, IL-8/CXCL8, and SCF were assessed in a single analytical run using Luminex xMAP technology. Results: Elevated MIF and IL-8/CXCL8 levels characterized an inflammatory phenotype, associated with leukocytosis, neutrophilia, increased fibrinogen levels, and unequal prevalence of new-onset diabetes. Higher MIF levels were further associated with larger tumor dimension, while IL-8/CXCL8 was associated with increased bilirubin level and recent weight loss (p < 0.05). In contrast, increased SCF predicted a dissemination phenotype as defined by metastasis occurrence (65.4% vs. 28.6%, p = 0.012). SCF demonstrated significant discriminatory ability for metastasis (AUC 0.712, p = 0.013) and remained significantly associated in multivariable analysis. Conclusions: MIF and IL-8/CXCL8 primarily reflect inflammation-driven processes, whereas SCF identifies a dissemination-dominant phenotype, suggesting distinct biological pathways underlying disease progression in pancreatic cancer. Full article

Four algal adsorbents were prepared from two types of green sea algae (Ulva lactuca and Ulva pertusa), either by treatment with concentrated sulfuric acid or without treatment. A comparative study of Au(III) adsorption in an HCl medium was performed. While both untreated adsorbents showed good performance at low HCl concentrations, the treated adsorbents achieved quantitative adsorption and high selectivity for Au(III) across a broad range of HCl concentrations. The adsorption of Au(III) onto the algal biomass adsorbents followed the typical Langmuir monolayer adsorption model. At an HCl concentration of 0.010 M, the maximum adsorption capacities were 1.14, 0.86, 6.57, and 6.28 mol kg^–1 for DUL, DUP, TUL, and TUP, respectively. A kinetic study conducted at different temperatures was consistent with the pseudo-first-order kinetic model and enabled estimation of the activation energy of the adsorption reaction. Structural changes before and after treatment were analyzed using FT-IR spectroscopy. Confirmation of Au(III) adsorption and its subsequent reduction to the elemental state was achieved through XRD and SEM/EDX analyses as well as digital imaging of the Au-loaded adsorbents. Finally, the adsorbed and reduced Au was successfully desorbed using an acidic thiourea solution. Full article

Adenoviruses have been implicated in childhood cancers, primarily leukemia, yet prior neonatal investigations have rarely examined other pediatric tumor types. This study evaluated whether adenoviral early region (E1A) sequences can be detected in archival neonatal Guthrie cards from children who later developed diverse pediatric tumors and in corresponding paraffin-embedded tissues. DNA extraction was optimized for long-stored dried blood spots, and PCR conditions were refined for both Guthrie card and paraffin-derived DNA. Adenoviral E1A was analyzed using conventional and nested PCR, and sequencing of representative amplicons confirmed correspondence to human adenovirus species C. E1A PCR positivity was found in 43% of Guthrie cards from cases (n = 54) and 34% of controls (n = 32), and in 41% of tumor tissues (n = 75) compared with 5% of non-tumor paraffin controls (n = 20). Detection occurred across multiple tumor categories without a clear association with tumor type. Partial concordance was observed between paired neonatal and tumor samples, and cytomegalovirus markers were detected in a subset of E1A-positive specimens. These findings confirm the suitability of Guthrie cards for retrospective viral DNA detection and extend previous leukemia-focused neonatal studies to broader pediatric tumors. The data suggest a potential association between birth-stage adenoviral detection and childhood cancer, though a causal link remains unproven and requires further longitudinal investigation. Full article

IGF1 plays a critical role in cell proliferation and survival. Previous studies show that IGF1 binds to integrin αvβ3 and induces αvβ3-IGF1-IGF1R ternary complex formation. However, how IGF1 binding to αvβ3 leads to IGF1R activation is unclear. Previous studies showed that Gα13, a guanine nucleotide-binding protein of the G12 class of Gα proteins, binds to the integrin β3 tail through the EEE motif upon fibrinogen binding to integrin αIIbβ3 and induces RhoA activation. We discovered that the EEE/AAA mutation of the β3 tail inhibited IGF1-induced cell survival, suggesting that Gα13 binding to the β3 tail is required for IGF1 signaling. Since RhoA activation may not be directly involved in IGF1R activation, we studied if Gα13 binds to molecules other than RhoA. Since Gα13 binds to several cytoplasmic tyrosine kinases, we studied if Gα13 binds to the IGF1R kinase by a docking simulation. The simulation predicted that Gα13 binds to the IGF1R kinase through a new binding site. Mutating the predicted Gα13 binding site in the IGF1R kinase (residues 1020-1022) or the predicted IGF1R kinase binding site in Gα13 (residues 260-279) inhibited Gα13 binding to the IGF1R kinase, which is consistent with the docking model. Notably, the Gα13(260-279A) mutant inhibited IGF1-induced cell survival. We propose that IGF1 binding to αvβ3 induces Gα13 binding to the β3 tail and subsequent Gα13 binding to the IGF1R kinase, leading to IGF1R activation. Interestingly, Gα13(260-279A) mutation inhibited cell survival due to a constitutively active Gα13(Q226L) mutant. We propose that Gα13(Q226L) induces its effect by binding to the IGF1R kinase. We propose that the Gα13 binding site of the IGF1R kinase or the IGF1R binding site in Gα13 may be a novel therapeutic target. Full article

The plague, caused by Yersinia pestis, has resulted in significant mortality over the past century. Despite advances in antimicrobial therapy, plague remains a re-emerging infectious disease with ongoing outbreaks and increasing concerns regarding antimicrobial resistance. Today, plague cases are still being reported, and the loss of effectiveness of treatment methods remains a major challenge. Therefore, effective treatment strategies are needed. In this study, we aimed to develop aptamers specific to Yersinia outer protein M (YopM), a key immunosuppressive protein that is essential for virulence. Our goal was to develop an aptamer that binds to YopM and inhibits its interaction with the human DEAD-box helicase 3 (DDX3) protein. YopM-DDX3 protein interaction was targeted because of its key role in nucleocytoplasmic shuttling of YopM. To achieve this, we developed the YopM16 aptamer using magnetic bead-based (Systematic Evolution of Ligands by Exponential Enrichment) (SELEX). The selected YopM16 aptamer exhibited a half-maximal inhibitory concentration(IC₅₀) value of 103.3 ± 2 nM and effectively inhibited the interaction between YopM and DDX3. The inhibitory effect of the aptamer on protein interaction was confirmed using a pull-down assay and colorimetric test. Given that protein–protein interaction surfaces are considered undruggable, YopM16 is a promising inhibitor with the potential to serve as a molecular tool to investigate the virulence mechanism of YopM, as well as a novel antibacterial agent upon validation of its inhibition in cellular models. Full article

Background/Objectives: Sepsis-associated encephalopathy (SAE) is an acute brain dysfunction during sepsis with high mortality. Klotho protein is notable for its identified neuroprotective effects in chronic neurodegenerative diseases. This study evaluated temporal changes in serum soluble Klotho levels and their association with clinical recovery in SAE. Methods: In this prospective observational study, 750 intensive care unit (ICU) patients were screened and 42 patients with SAE were included. Serum soluble Klotho levels, inflammatory markers, and Glasgow Coma Scale (GCS) scores were recorded on days 1 and 3. Associations between changes in Klotho levels and clinical and inflammatory parameters were analyzed. Results: The median GCS score increased from 11 (IQR: 10–13) on day 1 to 12 (IQR: 10–13) on day 3 (p < 0.001). Serum soluble Klotho levels decreased significantly from 8114.5 ± 3515.7 pg/mL on day 1 to 6452.9 ± 3390 pg/mL on day 3 (p < 0.001). Inflammatory markers, including C-reactive protein and procalcitonin, also showed significant reductions over time (p < 0.001). A moderate negative correlation was observed between changes in Klotho levels and GCS scores (r = −0.56, p < 0.001). Changes in inflammatory markers were not significantly correlated with Klotho dynamics. Conclusions: Serum soluble Klotho levels decrease in parallel with neurological improvements in sepsis-associated encephalopathy and are significantly associated with changes in GCS scores. These findings suggest that Klotho may represent a potential biomarker of disease trajectory and neurological recovery. Full article

Epigenetic mechanisms, including DNA methylation and hydroxymethylation, contribute to inflammation, cardiac remodelling and progression of heart failure. Ten–Eleven Translocation (TET) dioxygenases are key regulators of these processes, but the impact of statins on TET proteins in human heart failure is not well characterised. We investigated how statin therapy relates to TET1, TET2 and TET3 expression in circulating immune cells in heart failure with reduced ejection fraction (HFrEF). In this cross-sectional study, 106 patients with HFrEF were enrolled; 84 were receiving statins and 22 were not. Intracellular TET1/2/3 protein levels were measured by multiparameter flow cytometry in granulocytes, monocytes and lymphocytes, and clinical and laboratory characteristics were compared between groups. Statin-treated patients had lower NT-proBNP concentrations and lower neutrophil, lymphocyte and monocyte counts, and more often received guideline-directed medical therapy. Statin therapy was associated with a distinct TET expression profile, characterised by higher TET1 and TET3 indices in monocytes and lymphocytes and lower TET2 indices in granulocytes and monocytes. This pattern is compatible with a distinct immune-cell TET expression profile aligned with the anti-inflammatory and reparative profile attributed to statins, and the course of disease. These associations do not establish causality and require prospective validation. TET proteins may form part of an epigenetic signature associated with statin treatment in heart failure and warrant further study as potential biomarkers in larger, prospective cohorts. Full article

Poly(lactic-co-glycolic acid) (PLGA) is one of the most extensively investigated biodegradable polymers for biomedical applications, owing to its tunable degradation kinetics, established biocompatibility, and regulatory approval. In implantology, PLGA-based systems have emerged as versatile platforms for scaffolds, coatings, and localized drug delivery, aimed at enhancing osseointegration and tissue regeneration. This review provides a focused and up-to-date analysis of PLGA applications in dental and orthopedic implantology, with particular emphasis on advances reported over the past decade. Unlike previous reviews that predominantly address general drug delivery or broad tissue engineering applications, this work establishes a direct correlation between polymer composition (LA:GA ratio), processing strategies, and biological outcomes, including degradation behavior, mechanical performance, and host response. Special attention is given to multifunctional PLGA systems incorporating antibiotics, growth factors, and bioactive nanoparticles, highlighting their role in improving antibacterial efficacy and osteogenesis. Emerging technologies such as nanostructured composites, additive manufacturing, and stimuli-responsive delivery platforms are critically evaluated. Key limitations—including acidic degradation by-products, burst release kinetics, and translational barriers—are discussed in the context of clinical applicability. By integrating physicochemical design with biological performance and recent clinical trends (2024–2025), this review proposes a framework for the rational development of next-generation PLGA-based implant systems. Full article

Background/Objectives: Type 2 diabetes mellitus (T2-DM) is a continuing national and global health challenge. Retinoic acid (RA), the major transcription-regulating ligand, plays a critical role in energy metabolism, and pancreatic β-cell homeostasis. However, human data linking circulating RA levels to T2-DM and its clinical outcomes are sparse and inconsistent. In this ethically approved cross-sectional study of consented hospital-diagnosed adult T2-DM patients (n = 292) and matched healthy controls (n = 64), variation in plasma RA levels and its relationship with disease and patient characteristics were investigated. Methods: RA concentrations assayed via specific ELISA were related to glycemic control indices [fasting blood glucose (FBG) and HbA1c], the triglyceride–glucose ratio for insulin resistance (TyG-IR), treatment modalities, and complications derived from patients’ medical records. Results: RA concentrations were substantially lower in patients with T2-DM (mean ± SD 2.63 ± 1.54 ng/mL) than in controls (5.21 ± 4.3 ng/mL; p < 0.001). Within the diabetic cohort, RA was inversely correlated with indices of glycemic dysregulation and insulin resistance. Plasma RA exhibited strong discriminatory performance for distinguishing diabetic patients from healthy adults. Its AUC is 0.870 (p < 0.0001 and 95% CI = 0.832–0.902) with a sensitivity of 79.7% and a specificity of 81.3%, at an optimal cutoff of ≤3.061 ng/mL. Conclusions: Circulating RA is associated with metabolic perturbations that define T2-DM, and therefore is promising as a clinically useful biomarker. It may reflect pathophysiological processes linking nutrient signaling, energy handling and β-cell function in T2-DM that merit further evaluation. Full article

The Angiopoietin–Tie2 pathway is a key regulator of postnatal vascular maintenance and remodeling, regulating vascular barrier function and integrity. While the opposing roles of the ligands Angiopoietin-1 (Ang 1) and Angiopoietin-2 (Ang 2) have been recognized for decades, the structural mechanism governing their distinct signaling outputs has only recently been elucidated. As artificial intelligence and protein design continue to develop, emerging evidence suggests that ligand valency and receptor clustering are key determinants of Tie2 pathway activation and endothelial cell function; that is, “form follows function”. This review summarizes the latest discovery in the structural biology and signaling mechanism of the Tie2 pathway using protein design to decode the ligand–receptor interactions. Probing the underlying molecular basis of Tie2 offers new therapeutic opportunities for targeting diseases, featuring vascular dysfunctions such as sepsis, traumatic brain injury, acute respiratory diseases, chronic inflammation, and cancer. This also highlights the next generation of AI-designed protein therapeutics. Full article

Schoenoplectus californicus, a macrophyte from Peruvian marine–coastal wetlands, is traditionally used for medicinal purposes, yet its pharmacological potential remains insufficiently explored. This study evaluated the chemical profile, antioxidant capacity, psychopharmacological effects, and analgesic activity of a hydroethanolic extract from its rhizomes. Phytochemical screening and LC–MS/MS analyses were performed to characterize secondary metabolites. Antioxidant activity was assessed using DPPH and ABTS assays, while in vivo anxiolytic, sedative, and analgesic effects were evaluated in Balb/c mice through open field, elevated plus maze, rotarod, analgesimeter, tail-flick, and hot plate tests, with diazepam and tramadol as reference drugs. In silico PASS and BOILED-Egg analyses were used to predict pharmacological mechanisms and central nervous system permeability. The extract contained flavonoids, phenolic compounds, and stilbenes and exhibited notable antioxidant activity (IC₅₀: 0.7319 mg/mL for DPPH and 0.6207 mg/mL for ABTS). Anxiolytic effects were observed at 50 mg/kg, sedative effects at 200 mg/kg, and significant analgesic activity at 50 mg/kg. Several compounds were predicted to cross the blood–brain barrier, with inhibition of GABA aminotransferase suggested as a potential mechanism. Acute toxicity was detected (LD₅₀ > 2000 mg/kg). These findings support S. californicus as a promising source of neuroactive and analgesic compounds, although further mechanistic and dose-optimization studies are required. Full article

Artificial intelligence (AI) is increasingly used in cancer research, enabling integrative analysis of complex biomedical data to identify actionable therapeutic vulnerabilities. This review specifically examines how AI advances mechanistic cancer target discovery and translational drug development, focusing on: (1) the processing of large-scale genomics, transcriptomics, proteomics, metabolomics, single-cell profiling, spatial, and clinical datasets using machine learning (ML) and deep learning (DL) algorithms; (2) the identification of candidate biomarkers, driver genes, dysregulated pathways, tumor dependencies, and molecular targets that traditional methods often miss; (3) the integration of multi-omics data, network biology, causal inference, and systems-level modeling to refine mechanistic understanding of cancer progression and separate functional driver events from passengers; and (4) applications in drug development, including virtual screening, molecular modeling, structure-informed target validation, drug repurposing, synthetic lethality prediction, and de novo drug design, which collectively may enhance early-stage drug discovery efficiency. The review underscores that AI serves as both a predictive tool and a platform for linking molecular mechanisms to hypothesis generation, target prioritization, and rational treatment design. Challenges such as data heterogeneity, algorithmic bias, interpretability, reproducibility, regulatory requirements, and patient privacy must be addressed for robust translation and clinical use. Future directions may focus on hybrid approaches that integrate causal modeling, explainable AI, multimodal data, and experimental validation to yield mechanistically grounded, clinically actionable insights. AI-driven approaches ultimately aim to accelerate mechanism-based cancer target discovery and enable more precise, biologically informed anticancer therapies. Full article

Chronic heart failure (CHF) remains a leading cause of global mortality, characterized by profound molecular and biochemical disturbances, including nitric oxide (NO) system dysfunction, mitochondrial impairment, and oxidative stress. While standard therapies such as ACE inhibitors, SGLT2 inhibitors, and beta-blockers address clinical symptoms, their capacity to interrupt the underlying biochemical mechanisms of cardiomyopathy is often limited. This review examines the pathophysiological role of impaired NO production and reactive oxygen species (ROS) accumulation in exacerbating myocardial contractile dysfunction and disease progression. Special focus is directed toward the development of next-generation β1-blockers with multifunctional properties, including antioxidant, NO-mimetic, and antiapoptotic effects. Evidence suggests that the novel compound Hypertril (1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide) exhibits significant cardioprotective potential. Experimental data indicate that Hypertril improves eNOS/iNOS expression and enhances NO bioavailability more effectively than conventional β-blockers, leading to stabilized ECG parameters and restored energy metabolism. These findings underscore the clinical relevance of developing NO-mimetic agents to optimize the pharmacological management of CHF. Full article