Search Results (197)

One of the main targets for snake venoms in animal and human organisms is the circulatory system. Mechanisms of circulatory system injury within the victim’s body include, among others, the direct effect of snake toxins on structures in blood vessel walls. The interaction of a toxin with cells and the extracellular matrix of the vessel wall may manifest as cytotoxicity, leading to cell death by necrosis or apoptosis, and damage to vascular wall structures. Such interactions may increase capillary permeability, promoting hemorrhage or edema, and may also induce alterations in vascular tone, resulting in changes in blood pressure. Snake toxins may also affect the growth, function, and regenerative ability of the endothelium, thus modulating angiogenesis; some toxins exert protective or anti-atherosclerotic effects. Toxins interacting with the vasculature may be classified as enzymes (phospholipases A₂, metalloproteinases, L-amino acid oxidases, and hyaluronidases), proteins without enzymatic activity (vascular endothelial growth factors, disintegrins, C-type lectins and snaclecs, three-finger toxins, etc.), peptides (bradykinin-potentiating peptides, natriuretic peptides, sarafotoxins), and low-molecular-weight substances. This review summarizes the data on the vascular effects, particularly on the blood vessel wall, exhibited by various classes and groups of snake toxins. Full article

Blood–brain barrier (BBB) deterioration with increasing age is an important factor contributing to vascular dementia. Previous studies show that endothelial nitric oxide synthase (eNOS) facilitates vascular endothelial growth factor-mediated angiogenesis and increased vascular permeability. In contrast, recent work has shown that aged hemi-deficient hemizygous eNOS^+/− mice manifest BBB disruption in association with increased incidence of thromboembolic events in the brain. To unravel whether eNOS contributes to or protects against hypoxia-induced cerebrovascular damage, we compared chronic mild hypoxia (CMH)-induced cerebrovascular angiogenic remodeling and BBB breakdown in aged (20 months old) eNOS^+/− and wild-type (WT) mice. This revealed that CMH strongly enhanced eNOS expression in cerebral blood vessels with much lower levels in eNOS^+/− mice. eNOS hemi-deficiency resulted in greater CMH-induced BBB disruption, but unexpectedly, had no effect on endothelial proliferation. eNOS^+/− mice also displayed enhanced endothelial expression of the endothelial activation markers MECA-32, VCAM-1, and β3 integrin in cerebral blood vessels, indicating greater vascular inflammation, and this correlated with increased levels of microglial activation and demyelination. Taken together, our results support the concept that eNOS plays an important protective function in the aged brain by suppressing endothelial activation and maintaining cerebrovascular health. Full article

Traditional Chinese courtyard theaters in Taiwan possess a unique architectural and performative identity, distinct from Western-style proscenium theaters that dominate contemporary performance venues. These Western configurations often impose spatial and acoustic constraints that hinder the authentic expression of traditional Chinese opera. In contrast, courtyard-style theaters—characterized by open-air layouts and architectural enclosures—offer inherent acoustic advantages rooted in structural coupling and boundary reflections. This study focuses on the Da-Hua Hall at the Wu-Feng Lin Family Mansion, employing on site acoustic measurements to characterize its sound environment not only distribute sound energy and calibrate a sound tracing and a wave-based simulation model. The finite element method framework enables precise modeling of low-frequency acoustic phenomena, including modal behavior and resonance, which were conducted to assess the impact of stage permeability, vessel geometry, and wall-mounted resonators on acoustic parameters. The results demonstrate that the interaction between sub-stage resonators and architectural elements, specifically the width of stage floorboard joints and the presence of embedded jars, significantly influences acoustic performance, notably affecting the distribution of sound waves. These findings underscore the acoustically responsive architectural design in preserving the sonic integrity of traditional Chinese opera and highlight the value of simulation-based approaches in heritage research. Full article

The Gliomas account for 81% of all malignant central nervous system tumors and are classified by WHO into four grades of malignancy. Glioblastoma multiforme (GBM), the most common grade IV glioma, exhibits an extremely aggressive phenotype and a dismal five-year survival rate of only 6%, underscoring the urgent need for novel therapeutic approaches. Immunotherapy has emerged as a promising strategy, and photodynamic therapy (PDT) in particular has attracted attention for its dual cytotoxic and immunostimulatory effects. In GBM models, PDT induces immunogenic cell death characterized by the release of damage-associated molecular patterns (DAMPs), which promote antigen presentation and activate T cell responses. Additionally, PDT transiently increases blood–brain barrier permeability, facilitating immune cell infiltration into the tumor microenvironment, and enhances clearance of waste products via stimulation of meningeal lymphatic vessels. Importantly, PDT can reprogram or inactivate immunosuppressive tumor-associated macrophages, thereby counteracting the pro-tumoral microenvironment. Despite these encouraging findings, further preclinical and clinical studies are required to elucidate PDT’s underlying immunological mechanisms fully and to optimize treatment regimens that maximize its efficacy as part of integrated immunotherapeutic strategies against GBM. Full article

Zebrafish are model organisms for drug screening owing to their transparent bodies, rapid embryonic development, and genetic similarities with humans. However, using standard polystyrene culture plates can limit the oxygen supply, potentially affecting embryo survival and the reliability of assays conducted in zebrafish. In this study, we evaluated the application of a novel, highly oxygen-permeable culture plate (InnoCell^TM) in zebrafish development and drug screening assays. Under both normal and oxygen-restricted conditions, zebrafish embryos cultured on InnoCell^TM plates exhibited significantly improved developmental parameters, including heart rate and body length, compared with those cultured on conventional polystyrene plates. The InnoCell^TM plate enabled a significant reduction in medium volume without compromising zebrafish embryo viability, thereby demonstrating its advantages, particularly in high-throughput 384-well formats. Drug screening tests using antiangiogenic receptor tyrosine kinase inhibitors (TKIs) revealed enhanced sensitivity and more pronounced biological effects in InnoCell^TM plates, as evidenced by the quantification of intersegmental blood vessels and gene expression analysis of the vascular endothelial growth factor receptor (vegfr, also known as kdrl). These results indicate that the InnoCell^TM highly oxygen-permeable plate markedly improves zebrafish-based drug screening efficiency and assay reliability, highlighting its potential for widespread application in biomedical research. Full article

This study investigates the hydrogen permeability of injection-molded polyamide 6 (PA6) nanocomposites reinforced with organo-modified montmorillonite (OMMT) at varying concentrations (1, 2.5, 5, and 10 wt. %) for potential use as Type IV composite-overwrapped pressure vessel (COPV) liners. While previous work examined their mechanical properties, this study focuses on their crystallinity, morphology, and gas barrier performance. The precise inorganic content was determined using thermal gravimetry analysis (TGA), while differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), and scanning electron microscopy (SEM) were used to characterize the structural and morphological changes induced by varying filler content. The results showed that generally higher OMMT concentrations promoted γ-phase formation but also led to increased agglomeration and reduced crystallinity. The PA6/OMMT-1 wt. % sample stood out with higher crystallinity, well-dispersed clay, and low hydrogen permeability. In contrast, the PA6/OMMT-2.5 and -5 wt. % samples showed increased permeability, which corresponded to WAXD and SEM evidence of agglomeration and DSC results indicating a lower degree of crystallinity. PA6/OMMT-10 wt. % showed the most-reduced hydrogen permeability compared to all other samples. This improvement, however, is attributed to a tortuous path effect created by the high filler loading rather than optimal crystallinity or dispersion. SEM images revealed significant OMMT agglomeration, and DSC analysis confirmed reduced crystallinity, indicating that despite the excellent barrier performance, the compromised microstructure may negatively impact mechanical reliability, showing PA6/OMMT-1 wt. % to be the most balanced candidate combining both mechanical integrity and hydrogen impermeability for Type IV COPV liners. Full article

Orthoflavivirus omskense (Omsk hemorrhagic fever virus, OHFV) is a tick-borne flavivirus that causes Omsk hemorrhagic fever (OHF), a severe zoonotic disease endemic to Western Siberia. Despite the fact that the role of NS1 proteins of various mosquito-borne flaviviruses in pathogenesis was investigated and their ability to affect human endothelial permeability was shown, the role of the NS1 protein of OHFV in pathogenesis is unstudied. In this work, the ability of OHFV NS1 to induce human endothelial permeability was investigated for the first time. It was shown that recombinant OHFV NS1 produced in eucaryotic cells directly affects both human lung microvascular endothelial cells (HLMVEC) and human umbilical vein endothelial cells (HUVEC) in vitro. RNAseq of endothelial cells treated with OHFV NS1 indicated that OHFV NS1 enhances the expression of genes associated with cellular stress responses, vascular signaling, and cell–cell junction regulation, resulting in a nonspecific increase in the endothelial permeability of various vessels. These results suggest that the NS1 protein may contribute to OHFV pathogenesis by disrupting endothelial barrier function and promoting vascular leakage, potentially playing a role in the hemorrhagic manifestations of Omsk hemorrhagic fever. Full article

Liquid hydrogen (LH₂) storage using carbon-fiber-reinforced composite pressure vessels is facing increasing demands in aerospace engineering. However, hydrogen permeation in epoxy resin matrixes seriously jeopardizes the function and safety of the cryogenic vessels, and the micro-behavior of hydrogen permeation in epoxy resins remains mysterious. This study performed molecular dynamics (MD) simulations to investigate the hydrogen molecule permeation behaviors in two types of epoxy resin systems, with similar epoxy reins of bisphenol A diglycidyl ether (DGEBA) and different curing agents, i.e., 4,4′-diaminodiphenylmethane (DDM) and polypropylene glycol bis(2-aminopropyl ether) (PEA). The influencing factors, including the cross-linking degrees and temperatures, on hydrogen permeation were analyzed. It was revealed that increased cross-linking degrees enhance the tortuosity of hydrogen diffusion pathways, thereby inhibiting permeation. The adsorption characteristics demonstrated high sensitivity to temperature variations, leading to intensified hydrogen permeation at low temperatures. By triggering defects in the epoxy resin systems by uniaxial tensile simulation, high consistency between the simulation results and the results from helium permeability experiments can be achieved due to the micro-defects in the simulation model that are more realistic in practical materials. The findings provide theoretical insights into micro-scale permeation behavior and facilitate the development of high-performance epoxy resins in liquid hydrogen storage. Full article

Aquaporin 1 is a membrane water channel protein, which was studied here in spiny dogfish (Squalus acanthias) osmoregulatory tissues using a variety of techniques. The cloning of aquaporin 1 (AQP1) in the spiny dogfish identified a splice variant version of the mRNA/protein (AQP1SV1/AQP1SV1). Polymerase chain reaction (PCR) in a range of tissues showed AQP1 to be expressed at very high levels in the rectal gland with ubiquitous mRNA expression at lower levels in other tissues. Northern blotting showed that AQP1 had a mRNA size of 5.3 kb in kidney total RNA. The level of AQP1 mRNA was significantly lower in the rectal glands of fish acclimated to 120% seawater (SW; vs. 75% SW (p = 0.0007) and 100% SW (p = 0.0025)) but was significantly higher in those fish in the kidney (vs. 100% SW (p = 0.0178)) and intestine (vs. 75% SW (p= 0.0355) and 100% SW (p = 0.0285)). Quantitative PCR determined that AQP1SV1 mRNA levels were also significantly lower in the rectal glands of both 120% (p = 0.0134) and 100% SW (p = 0.0343) fish in comparison to 75% SW-acclimated dogfish. Functional expression in Xenopus oocytes showed that AQP1 exhibited significant apparent membrane water permeability (p = 0.000008–0.0158) across a range of pH values, whereas AQP1SV1 showed no similar permeability. Polyclonal antibodies produced against AQP1 (AQP1 and AQP1/2 antibodies) and AQP1SV1 had bands at the expected sizes of 28 kDa and 24 kDa, respectively, as well as some other banding. The weak AQP1 antibody and the stronger AQP1/2 antibody exhibited staining in the apical membranes of rectal gland secretory tubules, particularly towards the periphery of the gland. In the gill, the AQP1/2 antibody in particular showed staining in secondary-lamellar pavement-cell basal membranes, and in blood vessels and connective tissue in the gill arch. In the spiral valve intestine side wall and valve flap, the AQP1/2 antibody stained muscle tissue and blood vessel walls and, after tyramide signal amplification, showed some staining in the apical membranes of epithelial cells at the ends of the luminal surface of epithelial folds. In the rectum/colon, there was also some muscle and blood vessel staining, but the AQP1 and AQP1/2 antibodies both stained a layer of cells at the base of the surface epithelium. In the kidney convoluted bundle zone, all three antibodies stained bundle sheath membranes to variable extents, and the AQP1/2 antibody also showed staining in the straight bundle zone bundle sheath. In the kidney sinus zone, the AQP1/2 antibody stained the apical membranes of late distal tubule (LDT) nephron loop cells most strongly, with the strongest staining in the middle of the LDT loop and in patches towards the start of the LDT loop. There was also a somewhat less strong staining of segments of the first sinus zone nephron loop, particularly in the intermediate I (IS-I) tubule segment. Some tubules appeared to show no or only low levels of staining. The results suggest that AQP1 plays a role in rectal gland fluid secretion, kidney fluid reabsorption and gill pavement-cell volume regulation and probably a minor role in intestinal/rectal/colon fluid absorption. Full article

In recent years, chemo-photodynamic combinational therapy has become increasingly popular in treating breast cancer. However, the limited accumulation of nanodrugs into tumors (less than 1% of the injected dose) impacts therapeutic efficacy to an extreme extent. Herein, the photosensitizer Chlorin e6 (Ce6) and the chemotherapeutic drug rhein were self-assembled to form a carrier-free nanodrug (RC NPs) with good stability and a high drug loading rate (nearly 100%). In vitro, the phototoxicity of RC NPs resulted in a mere 17.8% cell viability. Ultrasound (US) irradiation was applied to increase the permeability of tumor blood vessels, thus greatly enhancing the drug accumulation of RC NPs in tumor tissues (1.5 times that of the control group). After uptake by tumor cells, Ce6 could produce a significant amount of reactive oxygen species (ROS) when exposed to laser irradiation, while rhein could inhibit tumor cell proliferation and affect mitochondrial membrane potential, inducing tumor cell apoptosis through the mitochondria-dependent apoptosis pathway, thus effectively realizing the combined effect of PDT and chemotherapy. The final tumor inhibition rate reached 93.7%. Taken together, RC NPs strengthen the enhanced permeability and retention (EPR) effect when exposed to US irradiation and exhibit better tumor suppression, which provides new insights into chemo-photodynamic combination treatment for clinical breast cancer. Full article

Background/Objectives: This study evaluated the potential of a polysaccharide (PCS) extracted from the brown alga Cystoseira spinosa as an antioxidant and anti-inflammatory agent. Collected off the coast of Alkhoms, Libya, PCS was investigated for its wound-healing and pro-angiogenic properties, addressing the need for natural bioactive compounds in therapeutic applications. Methods: The monosaccharide composition of PCS was analyzed using HPLC-RID, identifying glucuronic acid and xylose as major components. In vitro tests assessed antioxidant activity, while in vivo experiments on 24 rats evaluated wound healing. Rats were divided into four groups: control (saline), standard drug (CYTOL CENTELLA cream), glycerol, and glycerol+PCS. Wound healing was analyzed macroscopically, histologically, and biochemically. The chick chorioallantoic membrane (CAM) model assessed pro-angiogenic effects, and computational analyses explored COX-2 and VEGF pathways. Pharmacokinetic properties were also evaluated. Results: PCS demonstrated significant antioxidant activity and accelerated wound healing after 16 days, with improved wound appearance scores and increased collagen content. Histological analysis confirmed PCS outperformed the standard drug. The CAM model showed PCS increased blood vessel density, length, and junctions while reducing lacunarity. Computational analyses supported involvement of COX-2 and VEGF pathways. Pharmacokinetic assessments indicated good bioavailability, non-inhibition of CYP enzymes, and favorable skin permeability. Conclusions: PCS shows promise as a natural bioactive polymer for wound healing and tissue regeneration. Its antioxidant, anti-inflammatory, and pro-angiogenic properties, combined with favorable pharmacokinetics, highlight its therapeutic potential. This study provides new insights into the mechanisms of C. spinosa polysaccharides and their application in promoting tissue repair. Full article

The lymphatic system, a complex and dynamic network comprising lymphatic vessels, lymph nodes (LNs), and associated lymphoid tissues, plays a pivotal role in regulating interstitial fluid balance and providing immune surveillance across the body. In cancer, however, the lymphatic system often transforms into a pathway for malignant cell dissemination, leading to lymphatic metastasis—a significant step in tumor progression associated with worse patient prognoses. Mechanistically, tumor cells exploit lymphangiogenic pathways to facilitate their entry and spread within the lymphatic network. Key mechanisms in this process include the upregulation of vascular endothelial growth factors C and D (VEGF-C/D), which promote lymphatic endothelial proliferation, vessel dilation, and increased permeability. This review seeks to provide an in-depth examination of the biological mechanisms underpinning lymphatic metastasis, explore its impact on cancer progression, and highlight current and emerging strategies aimed at managing metastatic disease. Full article

Background/Objectives: Raynaud’s phenomenon (RP) is characterized by an exaggerated vasoconstrictive response of small blood vessels in the fingers and toes to cold or stress. Oral therapy with tadalafil (TDL), a phosphodiesterase-5 inhibitor, is limited by systemic side effects and reduced patient compliance. This study aimed to develop and evaluate a TDL-loaded nanoemulgel for transdermal delivery as a non-invasive treatment alternative for cold-induced vasoconstriction. Methods: TDL-loaded nanoemulsions were prepared using the aqueous titration method with cinnamon oil as the oil phase and Cremophor RH40 and Transcutol as the surfactant–cosurfactant system. The optimized nanoemulsion was incorporated into a carbopol-based gel to form a nanoemulgel. The formulation was characterized for droplet size, morphology, thermodynamic stability, rheological properties, in vitro drug release, skin permeation, and pharmacokinetic behavior. Infrared thermography was employed to assess in vivo efficacy in cold-induced vasoconstriction models. Results: The optimized TDL nanoemulsion exhibited a spherical morphology, a nanoscale droplet size, and an enhanced transdermal flux. The resulting nanoemulgel displayed suitable physicochemical and rheological properties for topical application, a short lag time (0.7 h), and a high permeability coefficient (Kp = 3.59 × 10⁻² cm/h). Thermal imaging showed significant vasodilation comparable to standard 0.2% nitroglycerin ointment. Pharmacokinetic studies indicated improved transdermal absorption with a higher C_max (2.13 µg/mL), a prolonged half-life (t_1/2 = 16.12 h), and an increased AUC_0–24 compared to an oral nanosuspension (p < 0.001). Conclusions: The developed TDL nanoemulgel demonstrated effective transdermal delivery and significant potential as a patient-friendly therapeutic approach for Raynaud’s phenomenon, offering an alternative to conventional oral therapy. Full article

Upregulation of leucine-rich alpha-2-glycoprotein-1 (LRG1) contributes to aberrant neovascularization in many different diseases. In contrast, LRG1 is not involved in developmental angiogenesis. Here, we investigated the vasculopathic properties of LRG1 by examining its effect on developing retinal blood vessels. By injecting recombinant protein or an expression vector into the mouse retina during vascular development, we showed that exogenous LRG1 reduces pericyte coverage and NG2 expression. It leads to diminished collagen IV sheathing, fewer adhesion and gap junctions, and reduced vessel calibre and vascular density. Moreover, in mouse retinae containing exogenous LRG1, the developing blood–retinal barrier remains more permeable with significantly higher numbers of transcytotic vesicles present in microvascular endothelial cells. These results reveal that exogeneous LRG1 is sufficient to interfere with the maturation of developing retinal vessels and drive vessel development towards a dysfunctional phenotype. These observations deliver further evidence that LRG1 is an angiopathic factor and highlight the therapeutic potential of blocking LRG1 in diseases characterized by pathogenic angiogenesis or vascular remodelling. Full article

Vascular graft failure rates remain unacceptably high due to thrombosis and poor integration, necessitating innovative solutions. This study optimized plant-derived extracellular matrix scaffolds as a scalable and biocompatible alternative to synthetic grafts and autologous vessels. We refined decellularization protocols to achieve >95% DNA removal while preserving mechanical properties comparable to native vessels, significantly enhancing endothelial cell seeding. Leatherleaf viburnum leaves were decellularized using sodium dodecyl sulfate-based and Trypsin/Tergitol-based treatments, achieved via clearing in bleach and Triton X-100 for 6 to 72 h. To assess the environmental influence on scaffold performance, leaves from multiple collection sites were processed using sodium dodecyl sulfate-based protocols. Scaffold performance was evaluated through tensile testing and histological analysis to assess structural integrity, while DNA quantification and endothelial cell recellularization measured biological compatibility. Sodium dodecyl sulfate-treated scaffolds with shorter clearing durations demonstrated the highest DNA removal (≥95%) while preserving mechanical properties, significantly outperforming Trypsin/Tergitol treatments. Longer clearing times reduced fiber diameter by 60%, compromising scaffold strength. Shorter clearing times preserved extracellular matrix integrity and significantly improved endothelial cell seeding efficiency. Larger leaves supported significantly higher endothelial cell densities than smaller leaves, highlighting the need for standardized material sources. Permeability tests demonstrated minimal leakage at 120 mmHg and structural stability under dynamic flow conditions, suggesting their suitability for vascular applications. These findings establish a reliable framework for optimizing plant-derived grafts, improving their reproducibility and performance for tissue engineering applications. Full article