Search Results (2,111)

Background/Objectives: Renal ischemia–reperfusion injury (IRI) and infection-associated renal damage are characterized by persistent inflammation, oxidative stress, microvascular dysfunction, and impaired tissue regeneration, creating a hostile microenvironment that limits effective repair. We developed an injectable, photocrosslinkable methacrylated chitosan (CSMA) hydrogel for the localized co-delivery of cerium oxide nanoparticles (CeO₂NPs) and vascular endothelial growth factor (VEGF), aiming to integrate redox modulation, antibacterial activity, and regenerative support. Methods: Gelation, microstructure, rheology, degradation, and CeO2NP/VEGF were characterized. Tubular epithelial and fibroblast migration and endothelial network formation, angiogenic gene expression, and antibacterial activity against Staphylococcus aureus and Escherichia coli were evaluated in vitro. Theraputic performance was assessed by renal surface application in a rat renal IRI model and catheter-mediated interavsical administration in an ascending urinary tract infection model. Systematic biocompatibility was evaluated separately in a 14-day subcutaneous implantation study. Renal response were further investigated using transcriptomic and targeted molecular analyses. Results: The CSMA/VEGF/CeO₂NPs hydrogel exhibited rapid in situ gelation, interconnected porous architecture, stable viscoelasticity, gradual degradation, and sustained release of both CeO₂NPs and VEGF. The formulation enhanced tubular epithelial and fibroblast migration, promoted endothelial network formation and angiogenic gene expression and effectively inhibited both S. aureus and E. coli. In a surgically controlled rat renal IRI model, direct renal-surface application of the hydrogel reduced tubular injury, inflammatory infiltration, and fibrotic remodeling. In a separate ascending urinary tract infection model, catheter-based intravesical administration reduced the ascending renal bacterial burden and infection-associated inflammatory injury. No detectable adverse systemic effects observed under the tested conditions over the 14-day observation period in the subcutaneous implantation. Transcriptomic analyses further revealed that CSMA/VEGF/CeO₂NPs treatment was associated with marked remodeling of the renal injury microenvironment, characterized by suppression of antigen presentation and immune activation pathways, alongside restoration of metabolic programs associated with amino acid, lipid, and purine metabolism. These molecular changes were accompanied by downregulation of CIITA/CD74/MHC-II signaling, recovery of metabolic regulators AGXT and ACOX1, modulation of Hippo/YAP- and ECM-associated pathways, and preservation of renal structural markers including nephrin and WT1. Conclusions: The localized CSMA-mediated co-delivery of CSMA/VEGF/CeO₂NPs hydrogel promotes renal repair through resolution of maladaptive immune activation, metabolic reprogramming, angiogenic enhancement, and preservation of renal structural integrity, providing a promising biomaterial strategy for the treatment of ischemic and infection-associated renal injuries. Full article

Chronic hyperglycemia disrupts the retinal neurovascular unit, making diabetic retinopathy (DR) the leading cause of adult vision loss. The hallmarks of DR include pathological angiogenesis, vascular leakage, and neurodegeneration. Although vascular endothelial growth factor A (VEGF-A) is a key mediator of these abnormalities and anti-VEGF therapies remain the standard treatment, many patients exhibit incomplete responses, and these therapies do not adequately address inflammation or fibrosis. Placental growth factor (PlGF), a VEGF family member that selectively binds to VEGFR1, has emerged as an important contributor to retinal neovascularization, vascular dysfunction, barrier breakdown, and microinflammation in DR. Unlike VEGF-A, PlGF modulates distinct responses among retinal neurons, glial cells, and vascular cells, with its abnormal expression closely associated with disease progression from non-proliferative to proliferative DR. This review summarizes the context-dependent functions of PlGF in the diabetic retina, compares PlGF–VEGFR1 signaling with VEGF-A–VEGFR2 pathways, and discusses preclinical and clinical evidence supporting PlGF inhibition as a potential complementary approach to existing anti-VEGF therapy. Full article

Fracture healing depends on coordinated osteogenesis and restoration of the vascular microenvironment. Endothelial cells support skeletal repair through angiogenesis, tissue perfusion and angiocrine signaling that regulates osteoprogenitor recruitment and differentiation. This narrative review examines endothelial dysfunction (ED) as a potential systemic contributor to impaired fracture healing by integrating evidence from vascular biology, experimental models and clinical studies. ED is characterized by reduced nitric oxide (NO) bioavailability, oxidative stress, inflammation and impaired vascular repair. These changes may disrupt angiogenic–osteogenic coupling through altered hypoxia-inducible factor 1-alpha subunit (HIF-1α)/vascular endothelial growth factor (VEGF) signaling, endothelial Notch activity, platelet-derived growth factor (PDGF)-mediated vascular remodeling and endothelial progenitor cell (EPC) mobilization. Conditions associated with endothelial dysfunction, including diabetes, aging, chronic kidney disease (CKD), smoking, obesity and chronic inflammatory disease, are also linked to delayed union, nonunion and poorer orthopedic outcomes. Cardiovascular disease and perioperative cardiovascular instability may further impair perfusion and physiological reserve during repair. However, the available evidence is predominantly experimental or observational, and direct causal evidence in fracture patients remains limited. Prospective studies combining standardized endothelial assessments with fracture-healing outcomes are needed to clarify clinical relevance and identify potential therapeutic targets. Full article

Semen cryopreservation is widely used in canine breeding, but individual variation in post-thaw semen quality limits its efficiency. This study investigated whether testicular artery Doppler-derived blood-flow parameters and circulating vascular endothelial growth factor (VEGF) concentrations are associated with semen quality and sperm freezability in clinically healthy dogs. Sixty-four privately owned male dogs underwent reproductive screening, semen collection, testicular Doppler ultrasonography, blood sampling, fresh and post-thaw semen analysis, and plasma VEGF quantification. Testicular artery Doppler parameters were not significantly associated with fresh or post-thaw semen quality or with most freezability outcomes. Plasma VEGF concentration was positively correlated with fresh linearity (LIN) (p = 0.034), straightness (STR) (p = 0.031), and beat-cross frequency (BCF) (p = 0.043). Higher VEGF concentrations were associated with greater post-thaw declines in progressive motility (PM) (p = 0.036), straight-line velocity (VSL) (p = 0.032), LIN (p = 0.001), STR (p = 0.005), and wobble (WOB) (p = 0.010). In multivariable analysis, VEGF was associated with linearity decline (B = 0.595, 95% CI: 0.254–0.937; p = 0.001). Circulating VEGF may therefore be associated with individual variation in canine sperm cryotolerance, whereas testicular artery Doppler assessment showed limited value. Full article

Alveolar bone resorption after tooth extraction complicates subsequent dental implant placement. OsteoBiol^® GTO^® (Tecnoss^®, Giaveno, Italy) is an innovative pre-hydrated heterologous collagenated bone mix blended with a thermosensitive copolymer (OsteoBiol^® TSV Gel) that has demonstrated osteoconductive properties. Despite direct contact with blood vessels upon socket filling, its pro-angiogenic potential has not been directly investigated on endothelial cells. Thus, in this study, an in vitro model, consisting of the EA.hy926 endothelial cell line exposed to different OsteoBiol^® GTO^® soaking preparations [original soaking (OS), centrifuged soaking (CS), and diluted soaking (DS)] at multiple concentrations (1, 5, 10, and 20 mg/mL) was established to identify optimal experimental conditions and characterize the underlying molecular mechanisms. Cell viability and collagen release quantification led to the selection of 10 mg/mL OS as the most suitable condition. Under this condition, OsteoBiol^® GTO^® induces an early increase in Cyclooxygenase-2 (COX-2) protein expression and Prostaglandin E-2 (PGE2) secretion, followed by upregulation of Vascular Endothelial Growth Factor (VEGF) protein expression and phosphorylation of Endothelial Nitric Oxide Synthase (eNOS) at serine 1177. The tube formation assay confirmed the pro-angiogenic functional outcome. These results suggest an association between the pro-angiogenic response of endothelial cells to OsteoBiol^® GTO^® and modulation of the COX-2/PGE2/VEGF axis. This effect could be attributed to collagen accumulation in the OS, thereby representing a novel and promising pro-angiogenic mechanism with potential implications for wound healing and guided bone regeneration following tooth extraction. Full article

The European Pathfinder THOR project envisages the creation of a vascularized fragment of tissue that can be implanted in a patient using regenerated silk fibers as its building blocks. The selection of regenerated silk as the main building block of the scaffold relies heavily on its outstanding biocompatibility in comparison with either other artificial polymeric fibers or even natural silk fibers. Additionally, regenerated fibers produced through the Dynamic Dope Destabilization Spinning (D3S^TM) process are shown to exhibit high mechanical performance as reflected in values of strain at breaking and work to fracture comparable to those of the natural material. It is further shown that these fibers are endowed with the unique property of self-adhesion whereby hydrated fibers attach to one another and may sustain detachment forces of up to a few tens of MPa, a property that facilitates the generation of the scaffold with the fibers as its basic building block. Lastly, regenerated silk fibers are shown to be efficiently decorated with either peptides or small proteins, such as the vascular endothelial growth factor (VEGF), or with antibodies. The performance of both non-functionalized and decorated silk fibers is assessed in two different in vitro biological systems: (1) endothelial cell cultures, and (2) organotypic brain slice cultures. Together, these results support the use of regenerated silk fibers as versatile building blocks for biofunctional tissue scaffolds and provide experimental validation of the tissue engineering strategy established by the THOR project. Full article

Background: Age-related macular degeneration (AMD) is a leading cause of visual impairment among older adults. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are widely used for neovascular AMD; however, their potential effects on the conjunctival microbiota remain poorly understood. This study evaluated the impact of intravitreal anti-VEGF therapy on conjunctival microbial composition and antimicrobial resistance patterns. Materials and Methods: Ninety patients with AMD were enrolled and assigned to three groups: bevacizumab-treated (n = 30), aflibercept-treated (n = 30), and untreated dry-type AMD controls (n = 30). Conjunctival swab samples were collected two months after the last injection in treated patients and during routine examination in controls. Bacterial identification and antimicrobial susceptibility testing were performed using automated microbiological systems. Results: Culture positivity rates were comparable among groups, although a lower growth rate was observed in the bevacizumab group (83.3%) than in the aflibercept and control groups (100% each). Staphylococcus epidermidis was significantly more prevalent in both treatment groups than in controls (p = 0.014). Most other bacterial species were detected more frequently in controls. Levofloxacin resistance among staphylococcal isolates was significantly higher in the aflibercept group (p = 0.007), whereas erythromycin and fusidic acid resistance were significantly higher in controls (p = 0.040 and p = 0.001, respectively). Resistance in treated eyes was predominantly associated with S. epidermidis and S. hominis. Conclusions: Intravitreal anti-VEGF therapy may be associated with transient alterations in conjunctival microbiota composition and antimicrobial resistance patterns. These findings may have implications for infection prevention in patients undergoing repeated intravitreal injections. Full article

Myeloid-derived growth factor (MYDGF) is a monocyte- and macrophage-secreted protein with anti-apoptotic and pro-angiogenic properties that has demonstrated protective effects in models of myocardial ischemia, but its role in peripheral ischemic injury has not been evaluated. We investigated the effects of recombinant human MYDGF (hMYDGF) in a murine hindlimb ischemia model. Male C57BL/6 mice underwent femoral artery ligation and were treated with continuous subcutaneous infusion of recombinant hMYDGF, vehicle control, or vascular endothelial growth factor (VEGF) as a positive control. Limb perfusion was assessed longitudinally using laser speckle contrast imaging, and functional recovery was evaluated using standardized limb function scoring. Recombinant hMYDGF significantly improved blood flow recovery in the ischemic limb compared with vehicle at all post-surgical time points, achieving levels of perfusion comparable to VEGF. Improved perfusion translated into accelerated early functional recovery, with a greater proportion of recombinant hMYDGF-treated mice retaining normal toe flexion. Immunohistochemical analyses revealed significantly increased CD34⁺ endothelial cell staining in both quadriceps and gastrocnemius muscles in recombinant hMYDGF-treated mice, consistent with enhanced angiogenesis, while alpha-smooth muscle actin staining did not differ between groups. Collectively, these findings demonstrate that recombinant hMYDGF restores blood flow and accelerates functional recovery following ischemic injury, supporting its therapeutic potential for ischemic diseases. Full article

This study aimed to determine the action of a single dose of human chorionic gonadotropin (hCG) on follicular dynamics, CL functionality, ovarian (OV.A) and uterine arteries (MUA) blood flow, hormones (estradiol [E2] and luteinizing hormone [LH]), nitric oxide (NO), and vascular endothelial growth factor (VEGF) levels in Thoroughbred mares. Animals were subjected to ultrasonography scanning, when the dominant follicle (F1) reached 35 mm in diameter, mares were injected with hCG (hCG group; n = 7) at hour 0, while others were injected with saline (control; n = 7). The examination was performed a those points at hours −24 h, −12 h, 0 h, 12 h, 24 h, 36 h, 48 h, 72 h, and 96 h. Blood sampling, ultrasound scanning, hormone assaying, and statistical analysis were performed. F1 was ruptured at 12 h after injection compared to 24 h in the control, with an elevation in its diameter (p ≤ 0.05) and a colored area surrounding F1. The amount of color Doppler area around CL and its diameter were increased (p ≤ 0.05) at 24 and 48 h after injection with an increase (p ≤ 0.05) in the ipsilateral uterine horn colored area from 6 to 36 h after injection. OV.A and MUA Doppler velocity parameters were elevated (p ≤ 0.05) at 24 h. Both NO and VEGF levels were elevated at 24 h after injection, with the elevation (p ≤ 0.05) of E2 occurring only before injection and then declining. hCG and LH levels were increased after injection at 12 and 24 h, respectively, with an interaction (p ≤ 0.05) effect. hCG may speed up and hasten the ovulation process by elevating follicular color amount and CL morphometry via elevating ovarian flow and uterine body total coloration via elevating uterine blood flow (declining Doppler indices) in mares. Full article

Background/Objectives: A substantial proportion of eyes with exudative macular diseases show a suboptimal response to standard-dose anti-vascular endothelial growth factor (anti-VEGF) therapy, and evidence regarding clinical outcomes after same-agent double-dose escalation remains limited. We evaluated the functional and anatomical outcomes of same-agent double-dose anti-VEGF therapy in such eyes. Methods: In this observational real-world cohort study, we retrospectively reviewed eyes with exudative macular diseases that were switched to same-agent double-dose anti-VEGF therapy because of a suboptimal response to prior standard-dose treatment. Eligibility required clinician-assessed persistent or recurrent exudative activity during the standard-dose treatment course despite at least three prior anti-VEGF injections, based on the longitudinal treatment and imaging history. Insufficient visual response and inadequate durability were considered additional, potentially overlapping features supporting dose escalation. Primary outcomes were functional and anatomical changes after switching. Secondary outcomes included injection interval, time-to-event outcomes, and associated baseline factors. Results: A total of 104 patients (111 eyes) were included. Mixed-effects modeling showed a small longitudinal improvement in BCVA of 0.007 logMAR per month (p = 0.028) and an estimated CST decrease of approximately 2.1% per month (p < 0.001). In visit-specific analyses, BCVA did not differ significantly from baseline at the first three post-switch visits and differed significantly only at the final follow-up (p = 0.004); however, the median BCVA was 0.70 logMAR at both baseline and final follow-up, and the median within-eye change was 0.00 logMAR (IQR, −0.25 to 0.10). CST was significantly lower than baseline at all post-switch visits (all p < 0.01). Among the 73 eyes with calculable paired interval data, injection intervals did not differ significantly between the standard-dose and double-dose phases (p = 0.289). Baseline pigment epithelial detachment was associated with a less favorable BCVA change (p = 0.002), and worse baseline visual acuity was associated with a higher risk of subretinal fibrosis (hazard ratio, 2.854; p = 0.002). Conclusions: In this uncontrolled pre–post cohort, anatomical changes after same-agent double-dose escalation were more consistent than functional changes. The BCVA change was statistically detectable but small in magnitude and of uncertain clinical relevance. No significant interval extension was observed among the 73 eyes with complete paired interval data during the relatively short follow-up. Full article

APG157DS is a multi-component investigational drug which is currently the subject of multiple cancer trials. It has shown promising efficacy in patients with head and neck cancer. We report its immuno-modulatory effect in a syngeneic mouse model of glioblastoma (GBM). Long-term treatment with APG157DS led to durable tumor remission in 50% of mice, while all vehicle-treated mice reached humane endpoints within 42 days. Mechanistically, the drug induced selective repolarization of tumor-associated macrophages (TAMs) from an immunosuppressive Arg1^high/iNOS^low phenotype to a tumoricidal Arg1^low/iNOS^high state, accompanied by increased intratumoral recruitment of activated (NKp46+) natural killer cells and CD8+ cytotoxic T-cells. APG157DS also suppressed vascular endothelial growth factor (VEGF) and Hypoxia-inducible factor 1-alpha (HIF-1α) expression in tumors, further impairing tumor growth. Notably, APG157DS did not elicit off-target macrophage activation in peripheral tissues such as the spleen, highlighting its selective immune targeting. These findings provide a mechanistic rationale for further clinical development of APG157DS in GBM and potentially other immune-evasive cancers. Full article

This study aimed to optimize the extraction and purification of TSG-enriched Polygonum multiflorum extract and evaluate its therapeutic potential against androgenetic alopecia. P. multiflorum Thunb. has long been used in traditional Chinese medicine to promote hair growth and preserve hair pigmentation. Microwave-assisted extraction (MAE) was optimized to obtain a 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG)-enriched P. multiflorum extract (PME). The crude extract was further purified by medium-pressure liquid chromatography and semipreparative high-performance liquid chromatography. Phytochemical profiling by HPLC demonstrated a 3.75-fold increase in TSG content, from 22,770.0 ± 815 ppm to 85,387.5 ± 192 ppm, and the identity of the enriched TSG was confirmed by LC–MS and ¹H NMR spectroscopy. PME exhibited potent dose-dependent inhibition of 5α-reductase activity, reaching 92.7% inhibition at 1 μg/mL, comparable to that of finasteride. In a testosterone (TES)-induced androgenetic alopecia (AGA) mouse model, PME markedly accelerated hair regrowth and increased both the number and size of hair follicles. Mechanistically, PME suppressed the conversion of TES to dihydrotestosterone (DHT) through 5α-reductase inhibition and promoted GSK3β inactivation, β-catenin stabilization, and nuclear translocation, indicating activation of the Wnt/β-catenin signaling pathway. Consequently, the expression of hair growth-related proteins, including Ki67 (1.98-fold), epidermal growth factor (EGF, 1.54-fold), insulin-like growth factor-1 (IGF-1, 1.21-fold), and vascular endothelial growth factor (VEGF, 1.34-fold), was significantly upregulated. These findings demonstrate, for the first time, that TSG-enriched PME obtained through optimized MAE and chromatographic purification promotes hair regeneration through a dual mechanism involving 5α-reductase inhibition and Wnt/β-catenin activation, highlighting its potential as a natural therapeutic candidate for androgenetic alopecia. Full article

Hepatic fibrosis is a pathological process involving the systemic reconfiguration of the liver microenvironment under chronic liver injury. It is a pathological wound healing response characterized by the excessive deposition of extracellular matrix (ECM) driven by the activation of hepatic stellate cells (HSCs), starting with the capillarization of liver sinusoidal endothelial cells (LSECs). This process can lead to liver structure destruction, portal hypertension, and even liver dysfunction, and is a major driving factor for death related to liver diseases. During this process, hypoxia initiates the transcriptional upregulation of effector molecules such as vascular endothelial growth factor (VEGF) and Lysyl oxidase (LOX) by stabilizing hypoxia-inducible factors (HIFs), inducing changes in LSEC phenotype and activation of HSCs, thus becoming a core driving factor. Activated HSCs not only exacerbate the capillarization of LSECs and tissue hypoxia but also strengthen the transcriptional activity of HIFs through autocrine/paracrine signaling, establishing a positive feedback loop linking hypoxia to HIFs and HSC activation, continuously driving the progression of liver fibrosis and significantly increasing the probability of chronic liver diseases evolving into cirrhosis and the risk of death. This review will analyze the mechanism of liver fibrosis driven by hypoxia, integrate the current treatment landscape, focus on exploring the therapeutic targets related to hypoxia-induced activation of hepatic stellate cells leading to liver fibrosis, and evaluate their translational potential. It is expected to provide information for future effective anti-fibrotic intervention strategies. Full article

Background/Objectives: Hypoxia-inducible factor 1-alpha (HIF-1α) is a transcription factor that escapes proteasomal degradation under hypoxic conditions, translocates to the nucleus, and activates genes involved in anaerobic glycolysis (e.g., GLUT1 and LDH-A) and vascular endothelial growth factor (VEGF) expression. Through its role in tumor progression, angiogenesis, and metabolic reprogramming, elevated HIF-1α levels have been reported in various malignancies; however, its serum concentration in malignant salivary gland neoplasms remains unexplored. This study aimed to assess serum HIF-1α levels in patients with salivary gland malignancies. Methods: Serum samples were collected from 30 patients diagnosed with malignant salivary gland neoplasms. HIF-1α concentration was determined using an enzyme-linked immunosorbent assay (ELISA). Results: The mean serum HIF-1α concentration was 89.20 ± 44.56 pg/mL. Exploratory analyses demonstrated higher HIF-1α levels in stage III tumors compared with stage II tumors and in high-grade tumors compared with lower-grade lesions. Conclusions: This is the first study to quantify serum HIF-1α levels in patients with malignant salivary gland neoplasms. The findings suggest that while HIF-1α may have potential as a biomarker, its potential as a biomarker of tumor aggressiveness or of malignant salivary gland neoplasms is limited due to high interindividual variability. Further studies with larger cohorts and standardized methodologies are necessary to establish reference values and clarify the clinical significance of HIF-1α in salivary gland malignancies. Full article

Background & Objectives: Endovascular embolization has matured into a sophisticated, precision-guided discipline that is central to the management of complex neurovascular pathologies. This review synthesizes contemporary treatment strategies, evaluating the advanced material characteristics of conventional inert liquid polymers, specifically non-adhesive ethylene vinyl alcohol (EVOH) copolymers and adhesive cyanoacrylates, alongside their targeted clinical applications in brain arteriovenous malformations (bAVMs), dural arteriovenous fistulas (dAVFs), hypervascular intracranial tumors, and chronic subdural hematomas (CSDHs). Furthermore, it examines the critical material and hemodynamic constraints that limit these agents in cerebral aneurysm repair. Methods: A comprehensive literature synthesis through 3 July 2026 was integrated with peer-reviewed clinical illustrations to evaluate both procedural mechanics and the necessity of post-procedural physiological management. Review Findings: Embolization serves a critical dual role: as a definitive curative therapy and as an essential preoperative or radiosurgical adjunct. As demonstrated by recent clinical validations, technical angiographic success must be closely coupled with vigilant neurocritical oversight to manage profound, localized hemodynamic shifts. While these conventional methods represent established clinical practice, the field is evolving away from inert mechanical occlusion toward a highly integrated approach. The convergence of stimuli-responsive “smart” hydrogels and endovascular robotics is being evaluated for potential roles in transforming these interventions into dynamic, bioactive platforms capable of modulating disease-specific mechanisms, such as Rat Sarcoma-Mitogen-Activated Protein Kinase (RAS-MAPK) and Bone Morphogenetic Protein (BMP) signaling in bAVMs or the Von Hippel-Lindau/Vascular Endothelial Growth Factor (VHL/VEGF) axis in hypervascular tumors. This review further analyzes landmark data, including the Squid Trial For the Embolization of the Middle Meningeal Artery for Treatment of Chronic Subdural Hematoma (STEM) trial for CSDH, providing a synthesis for translating these advanced material sciences into standardized, multidisciplinary neurointerventional care. Full article