Search Results (18,813)

Background: Xanthine oxidase inhibitors (XOIs) may help prevent stroke. However, heterogeneity can be found in the conclusions of different studies. The relevant evidence was summarized in this systematic review and meta-analysis to further clarify the role of XOIs in the prevention and treatment of stroke, with a focus on evaluating the effects of XOIs in primary and secondary prevention of stroke, acute stroke treatment, and reduction of post-stroke complications. Methods: Randomized controlled trials (RCTs) or cohort studies on the effect of XOIs in the prevention and treatment of stroke were searched in PubMed, EMBASE, and Cochrane Library from inception to 3 March 2024, along with hand searching. The analyses were carried out using Review Manager 5.4. Results: The analysis included 14 studies (115,579 patients). While XOIs did not significantly reduce the risk of stroke (RR: 0.89; 95% CI: 0.59–1.34), they improved post-stroke functional outcomes, with a reduction in the modified Rankin scale scores (mean difference: −0.6; 95% CI: −0.8 to −0.4), decreased intercellular adhesion molecule-1 levels (mean difference: −15.2 ng/mL; 95% CI: −22.3 to −8.1), improved augmentation index (AIx) by 4.2% (95% CI: 2.5–5.9%), reduced central blood pressure (mean reduction: 4.8 mmHg; 95% CI: 2.6–6.9), and delayed carotid intima-media thickness progression (mean difference: −0.05 mm/year; 95% CI: −0.08 to −0.02). Full article

Pancreatic cancer is an aggressive tumor with dismal prognosis. Neural invasion is one of the pathological hallmarks of pancreatic cancer. Peripheral nerves can modulate the phenotype and behavior of the malignant cells, as well as of different components of the tumor microenvironment, and thus affect tumor growth and metastasis. From a clinical point of view, neural invasion is translated into intractable pain and represents a predictor of tumor recurrence and poor prognosis. Several molecules are implicated in neural invasion and pain onset in PDAC, including neutrophins (e.g., NGF), chemokines, adhesion factors, axon-guidance molecules, different proteins, and neurotransmitters. In this review, we discuss the role of nerves within the pancreatic cancer microenvironment, highlighting how infiltrating nerve fibers promote tumor progression and metastasis, while tumor cells, in turn, drive nerve outgrowth in a reciprocal interaction that fuels tumor advancement. We outline key molecules involved in neural invasion in pancreatic cancer and, finally, explore potential therapeutic strategies to target neural invasion, aiming to both inhibit cancer progression and alleviate cancer-associated pain. Full article

The MET oncogene, encoding the hepatocyte growth factor (HGF) receptor, plays a key role in tumorigenesis, invasion, and resistance to therapy, yet its full biological functions and activation mechanisms remain incompletely understood. A feature of MET is its extensive interaction network, encompassing the following: (i) receptor tyrosine kinases (RTKs); (ii) co-receptors (e.g., CDCP1, Neuropilin1); (iii) adhesion molecules (e.g., integrins, tetraspanins); (iv) proteases (e.g., ADAM10); and (v) other receptors (e.g., CD44, plexins, GPCRs, and NMDAR). These interactions dynamically modulate MET’s activation, signaling, intracellular trafficking, and degradation, enhancing its functional versatility and oncogenic potential. This review offers current knowledge on MET’s partnerships, focusing on their functional impact on signaling output, therapeutic resistance, and cellular behavior. Finally, we evaluate emerging combination therapies targeting MET and its interactors, highlighting their potential to overcome resistance and improve clinical outcomes. By exploring the complex interplay within the MET network of interacting cell surface proteins, this review provides insights into advancing anti-cancer strategies and understanding the broader implications of RTK crosstalk in oncology. Full article

Uterine infections reduce ruminant reproductive efficiency. Reproductive dysfunction caused by infusion of Gram-negative bacteria is characterized by the failure of embryo implantation and reduced conception rates. Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, is highly abortogenic. In this study, the effects of LPS infusion on the endometrial receptivity of sheep were studied during three critical periods of embryo implantation. The results showed that LPS infusion on d12, d16, and d20 of pregnancy in vivo interfered with the expression of prostaglandins (PGs) and affected the expression of adhesion-related factors (ITGB1/3/5, SPP1), key implantation genes (HOXA10, HOXA11 and LIF), and progestational elongation genes (ISG15, RSAD2 and CXCL10) during embryo implantation. In addition, after LPS infusion on d12, d16, and d20, the phosphorylation level of STAT1 significantly decreased and the protein expression level of IRF9 significantly increased on d12, suggesting that LPS infusion in sheep impairs endometrial receptivity through the JAK2/STAT1 pathway. Sheep endometrial epithelial cells were treated with 17 β-estrogen, progesterone, and/or interferon-tau in vitro to mimic the receptivity of the endometrium during early pregnancy for validation. LPS and the p-STAT1 inhibitor fludarabine were both added to the model, which resulted in reduced p-STAT1 protein expression, significant inhibition of PGE2/PGF2α, and significant suppression of the expression of key embryo implantation genes. Collectively, these results indicate that LPS infusion in sheep on d12, d16, and d20 impairs endometrial receptivity through the JAK2/STAT1 pathway, which is responsible for LPS-associated pregnancy failure. Full article

To investigate the influence of aggregate crystalline surface anisotropy on the interfacial effects and understand the bonding mechanisms, molecular dynamics simulations were employed to analyze the spatial distribution, diffusion, and adhesion properties of asphalt on typical acidic (α-quartz, SiO₂) and weakly alkaline (calcite, CaCO₃) aggregates. The results indicated that different types and crystalline surfaces of aggregates did not alter the distribution patterns of the asphalt components on their surfaces. However, the magnitude of the radial distribution function (RDF) varied with different crystalline surfaces, and a higher RDF value was correlated with better adhesion performance. Different diffusion behaviors were exhibited by asphalt molecules on different crystalline surfaces: slower diffusion was correlated with stronger adhesion and faster diffusion with weaker adhesion. The adhesion performance was significantly affected by the anisotropy of the aggregates. In the asphalt–SiO₂ system, the van der Waals energy and surface atomic density were the major influencing factors, whereas, in the asphalt–CaCO₃ system, the electrostatic energy was significantly influenced by ionic bonding. Overall, alkaline aggregates showed greater adhesion performance with asphalt than acidic aggregates. Full article

Films and coatings based on biopolymers have been extensively studied in recent years since they have less impact on the environment, can be obtained from renewable sources, have good coating and film-forming capacity, are biodegradable and can have interesting nutritional properties. In the present study, sheep’s cheese whey powder (SCWP) was used to produce edible cheese coatings. Six types of cheese samples were produced: without coating (CON); treated with natamycin (NAT); with SCWP coating without antimicrobials (WCO); with SCWP coating with a commercial bioprotective culture (WFQ); with SCWP coating with kombucha tea (WKO); and with SCWP coating with oregano essential oil (WEO). At the end of the ripening period, all the cheeses were classified as full-fat and semihard, according to the Portuguese standard. The higher hardness and adhesiveness values of samples CON, WFQ and WKO were in line with the lower moisture in defatted cheese observed in these samples, indicating that future work should address the improvement of water vapor barrier properties of the whey-based coating. The samples treated with natamycin and with oregano essential oil presented significantly lower values for hardness. Differences were also observed on titratable acidity and a_w, both between samples and because of ripening time. The color parameters of cheese samples also presented differences, chiefly in the rind, but the highest differences observed resulted from ripening time rather than between samples. In all cases, the counts of lactobacilli and lactococci surpassed log 7 CFU/g by the end of ripening. Regarding yeast and mold counts, the samples CON and WCO presented the highest values by the end of the ripening period (>log 4 CFU/g), while sample NAT presented the lowest value (ca. log 3 CFU/g). Samples WFQ, WKO and WEO presented values which were ca. 0.5 log cycles lower than samples CON and WCO. Hence, the use of SCWP alongside bioprotective culture, kombucha tea or oregano essential oil had a positive impact in the reduction of mold counts on cheese surfaces. Future work should also evaluate the joint use of different antimicrobials. Full article

Objectives: Reduced expression of adhesion molecules in tumor vasculature can limit infiltration of effector T cells. To improve T cell adhesion to tumor endothelial cell (EC) antigens and enhance transendothelial migration, we developed bispecific, T-cell engaging antibodies (bsAb) that activate T cells after cross-linking with EC cell surface antigens. Methods: Recombinant T-cell stimulatory anti-VEGFR2–anti-CD3 and costimulatory anti-TIE2–anti-CD28 or anti-PD-L1–anti-CD28 bsAb were engineered and expressed. Primary lines of human umbilical vein endothelial cells (HUVEC) that constitutively express VEGFR2 and TIE2 growth factor receptors and PD-L1, but very low levels of adhesion molecules, served as models for anergic tumor EC. Results: In cocultures with HUVEC, anti-VEGFR2–anti-CD3 bsAb increased T cell binding and elicited rapid T cell activation. The release of proinflammatory cytokines TNF-α, IFN-γ, and IL-6 was greatly augmented by the addition of anti-TIE2–anti-CD28 or anti-PD-L1–anti-CD28 costimulatory bsAb. Concomitantly, T cell-released cytokines upregulated E-selectin, ICAM1, and VCAM1 adhesion molecules on HUVEC. HUVEC cultured in breast cancer cell-conditioned medium to mimic the influence of tumor-secreted factors were similarly activated by T cell-engaging bsAb. Migration of T cells in transwell assays was significantly increased by anti-VEGFR2–anti-CD3 bsAb. The combination with costimulatory anti-TIE2–anti-CD28 bsAb augmented activation and proliferation of migrated T cells and their cytotoxic capacity against spheroids of the MCF-7 breast cancer cell line seeded in the lower transwell chamber. Conclusions: T cells activated by anti-VEGFR2–anti-CD3 and costimulatory EC-targeting bsAb can reverse the energy of quiescent EC in vitro, resulting in improved T cell migration through an EC layer. Full article

We report the discovery of a novel free-living marine nematode, Dracognomus elongatus sp. nov., from the genus Dracognomus Allen & Noffsinger, 1978 (Nematoda: Draconematidae), collected from geniculate coralline algal assemblages in the intertidal zone along the eastern coast of Korea in the Northwest Pacific Ocean. Dracognomus elongatus sp. nov. is distinguished from its congeners by several key features: a relatively long body length (522 µm), densely developed minute spine-like ornamentation along the margins of body annules, small pore-shaped amphids (2 µm) with membranous tubes filled with corpus gelatum extending to the fifth body annule, twelve modified cephalic adhesion tubes located posterior to the rostrum, eight pairs of modified adhesion tubes in the mid-body region, an arrangement of both normal and modified subventral adhesion tubes (three pairs of each), disc-shaped tips on sublateral adhesion tubes, absence of copulatory thorns in males, and the presence of three pairs of short setae with no protuberances on the non-annulated tail end. Morphological details and illustrations were obtained using differential interference contrast microscopy. We also provide information on the geographic distribution and comparative characteristics of species within the genus Dracognomus, along with a schematic ventral view of a congener illustrating the arrangement of posterior adhesion tubes and copulatory thorns. Additionally, we present a species-level pictorial dichotomous key. Dracognomus elongatus sp. nov. is the eighth described species of this rare genus and marks the first record of Dracognomus in the Northwest Pacific Ocean. Full article

Mercury (Hg) is a highly toxic environmental contaminant that can harm human health, ultimately leading to endothelial dysfunction. Hg toxicity is partially mediated by the exposure of the cell membrane’s surface of erythrocytes (RBCs) to phosphatidylserine (PS). In the context of these challenges, hydroxytyrosol, a phenolic compound of olive oil, has the ability to mitigate the toxic effects of Hg. This study aims to analyze the effect of Hg on the adhesion of RBCs and polymorphonuclear cells (PMNs) to the vascular endothelium and the potential protective effect of hydroxytyrosol, as these interactions are crucial in the development of cardiovascular diseases (CVDs). RBCs, PMNs, and human vein endothelial cells (HUVECs) were treated with increasing concentrations of HgCl₂ and, in some cases, with hydroxytyrosol, and their adhesion to HUVECs and the expression of adhesion molecules were subsequently analyzed. Our results demonstrate that HgCl₂ significantly increases the adhesion of both RBCs (2.72 ± 0.48 S.E.M., p-value < 0.02) and PMNs (11.19 ± 1.96 S.E.M., p-value < 0.05) to HUVECs and that their adhesiveness is significantly reduced following treatment with hydroxytyrosol (RBCs, 1.2 ± 1.18 S.E.M., p-value < 0.02 and PMNs, 4.04 ± 1.35 S.E.M., p-value < 0.06). Interestingly, HgCl₂ does not alter the expression of adhesion molecules on either HUVECs or RBCs, suggesting that reduced exposure to PS is a key factor in hydroxytyrosol protection against HgCl₂-induced RBC adhesion to the endothelium. On the other hand, HgCl₂ induces increased expression of several PMN adhesion molecules (CD11b 215.4 ± 30.83 S.E.M. p-value < 0.01), while hydroxytyrosol inhibits their expression (e.g., CD11b 149 ± 14.35 S.E.M., p-value < 0.03), which would seem to be the mechanism by which hydroxytyrosol restricts PMN–endothelium interactions. These results provide new insights into the molecular mechanisms through which hydroxytyrosol mitigates the harmful effects of Hg on cardiovascular health, highlighting its potential as a therapeutic agent that can reduce the cardiovascular risk related to heavy metal exposure. Full article

The human skin is a remarkable organ capable of extensive regeneration, especially after severe injuries such as burns and related wounds. The de-epidermized dermis (DED) model has become a valuable in vitro tool for skin regeneration studies, particularly for testing the mechanism of action and the efficacy of clinical cutaneous cell therapies. To further improve the quality and robustness of these applications, our study focused on optimizing and standardizing DED tissue preparation and storage, enhancing its effectiveness for clinical testing. Therefore, we optimized the air-liquid interfacial culture medium composition by simplifying the historical formulation without compromising keratinocyte (therapeutic cell model) viability or proliferation. Furthermore, we investigated the impacts of adding burn wound exudates in the model by focusing on cell behavior for enhanced translational significance. The results revealed notable differences in keratinocyte adhesion and proliferation between burn wound exudates collected at the early stages and late stages of acute patient treatment, providing new information on a possible therapeutic window to apply cell therapies on burn patients. Generally, this study reported a robust method for the preclinical in vitro assessment of keratinocyte-based cutaneous cell therapies using DED models. Overall, the study underscored the importance of using in vitro models with enhanced translational relevance to better predict the clinical effects of cutaneous cell therapies in burn patient populations. Full article

The vascular cell adhesion molecule-1 (VCAM-1) plays an important role in inflammation, where it facilitates the recruitment of leukocytes to the inflamed area via leukocytes’ VLA-4 and endothelial cells’ VCAM-1 interaction. VCAM-1 expression is also upregulated in certain cancers. VCAM-1 has seven Ig-like domains, with domains 1 and 4 shown to be critical for VLA-4 binding. However, the specific functions of individual VCAM-1 Ig-like domains remain poorly understood. In this study, we identified single-chain variable fragment (scFv) antibodies targeting domains 2, 3, and 5 of VCAM-1, and investigated the ability of these antibodies to block VCAM-1-mediated cell adhesion to macrophages. We show that scFv antibodies against Ig-like domains 2 and 3 interfere with the ability of macrophages to bind endothelial cells, suggesting that these domains also play a role in facilitating this interaction. These results emphasize the need to more carefully study the role of each domain on VCAM-1 function and highlight the potential of targeting these VCAM-1 domains for more tailored therapeutic interventions in inflammatory diseases and cancer. Full article

Mandibular bone defect reconstruction remains a significant challenge for surgeons worldwide. Among multiple biodegradable biopolymers, allogeneic bone scaffolds derived from human sources have been used as an alternative to autologous bone grafts, providing optimal conditions for cell recruitment, adhesion, and proliferation and demonstrating significant osteogenic properties. This study aims to investigate the bone microstructure of the human scapula as a source for allogeneic bone scaffold fabrication for mandibular tissue engineering purposes. We created color-coded anatomical maps of the scapula and the mandible, reflecting the best anatomical and geometrical match. In this pilot study, we hypothesized a microstructural similarity of these bone structures and evaluated the human scapula’s bone tissue engineering potential for mandibular bone tissue engineering by focusing on the microstructural characteristics. Lyophilized human scapular and mandibular bioimplants were manufactured and sterilized. Experimental bone samples from the scapula’s acromion, coracoid, and lateral border from the mandibular condyle, mandibular angle, and mental protuberance were harvested and analyzed using micro-CT and quantitative morphometric analysis. This pilot study demonstrates significant microstructural qualitative and quantitative intra-group differences in the scapular and mandibular experimental bone samples harvested from the various anatomical regions. The revealed microstructural similarity of the human scapular and mandibular bone samples, to a certain extent, supports the stated hypothesis and, thus, allows us to suggest the human scapula as an alternative off-the-shelf allogeneic scaffold for mandibular reconstruction and bone tissue engineering applications. Full article

Background: Adhesion molecules including E-cadherin and N-cadherin have been proven to contribute to the carcinogenesis process. It has been demonstrated that an increased expression or appearance of N-cadherin, as well as a reduction in the expression of E-cadherin, are documented in many cancers, often leading to the loss of intercellular adhesion and acquisition of a more invasive or even metastatic mesenchymal phenotype. The aim of this study was to assess the expression of E-cadherin and N-cadherin, as well as markers of proliferation Ki67 in basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Methods: A total of 123 tumor paraffin specimens, including 73 BCC and 50 SCC cases, were obtained from multiple anatomical locations. The expression of E-Cadherin and N-Cadherin, including the percentage of stained cells, was assessed using a four-grade scale, with Ki-67 assessed on the five-grade scale. Results: A significantly higher expression of N-cadherin was observed in SCC compared to BCC, with 14% of SCC cases having a more than 50% expression of N-cadherin, and 10% with 26–50% expression, in comparison with 2.7% and 8.2% in BCC, respectively (p < 0.001). No significant differences were observed with regard to E-cadherin expression between SCC and BCC. Conclusions: Our results suggest that N-cadherin expression might contribute to the acquisition of the mesenchymal phenotype, SCC, when compared with BCC, with a high expression of E-cadherin in both tumors explaining their overall low rate of metastases; however, further research on the role of adhesion molecules in these tumors is needed. Full article

Epoxy resins have exhibited exceptional performance in engineering applications, particularly as a replacement for traditional mechanical joints in adhesive bonding. This study evaluates the suitability of two innovative adhesives, SikaPower^®-1511 and SikaPower^®-1548, in various graded configurations. The thermal curing behavior of the adhesives was analyzed using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Shear tests and finite element simulations were employed to investigate the strength performance and interfacial stress distribution of four adhesive configurations, including single and graded joints in single lap adhesive joints. The results show that SikaPower^®-1548 reveals a slower heat-curing rate and achieves an average shear limit load of 9 MPa, outperforming the more rigid SikaPower^®-1511, which reaches 4 MPa. Ultimate load predictions indicate that the shear strength of the 1511-1548-1511 graded configuration is slightly lower than that of SikaPower^®-1511, with a decrease of 8.86%. In contrast, the 1548-1511-1548 configuration demonstrates a significant improvement, achieving a 32.20% increase in shear strength, along with a 13.12% reduction in peel stress field intensity at the interface end and a 12.21% reduction in shear stress field intensity. Overall, the experimental and simulation results highlight the significant advantages of graded joints over traditional single joints in alleviating stress concentrations and enhancing joint strength. Additionally, the research confirms the potential of epoxy resins in advanced engineering applications, providing a reliable theoretical foundation and technical guidance for the design of graded adhesives. Full article

Glued wood is one of the most commonly used materials made of wood. Glued wood has many advantages related to its strength characteristics and operation. Nevertheless, due to the use of an adhesive base, it becomes necessary to carefully approach the issue of the fire resistance of building structures made of glued wood. The purpose of this study was to assess the effect of structural fire protection on the fire resistance of glued laminated timber columns; the task of developing methods for experimental and analytical assessments of the fire resistance of glued laminated timber columns, with the possibility of assessing the temperature of the wood under a layer of fire protection, was set, and an analysis of the effectiveness of these methods for assessing the fire resistance of such structures was conducted. The experimental assessment of fire resistance was based on the combined effects of fire and force on structures. The analytical assessment of the fire resistance was carried out using two methods, each of which estimated the time of the beginning of the ignition of the wood, as well as its combustion before the limit state of the structure was reached, but did not ascertain the acting force. As a result of evaluating the effect of structural fire protection on the fire resistance of glued wood columns, data on the heating of wood under a layer of fire protection were obtained, and the relationship between the deformation of the sample and the heating of the layers of fire protection was revealed, consisting of an increase in the ignition time of the wood with an increase in the thickness of the fire protection. Full article