Search Results (47)

Background/Objectives: Endothelial activation by lipopolysaccharides (LPS) contributes to inflammation and the development of cardiovascular disease, making n-3 polyunsaturated fatty acids (PUFAs) potential modulators capable of mitigating endothelial dysfunction. The current study examines the effects of long-chain eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), along with their precursor, α-linolenic acid (ALA), on oxidative stress, adhesion molecule expression, and cytokine milieu in LPS-stimulated human aortic endothelial cells (HAECs). Methods: HAECs (fifth passage) were cultured in control medium under standard conditions: ~37 °C, 5% CO₂, ≥80% humidity. Cells were incubated in control basal cell medium or medium supplemented with ALA, EPA, DHA, and their combination (50 µM; n = 5 per group). After 48 h, cells were treated overnight (~16 h) with LPS from E. coli (0.75 and 1 µg/mL). HAECs and supernatants were collected for flow cytometry, Luminex, and ELISA assays. Significance was assessed using two-way analysis of variance ANOVA, followed by post hoc analyses (p < 0.05). Spearman’s correlation analysis was performed between markers, and p-values were adjusted using the Benjamini–Hochberg (BH) correction. Results: PUFA supplementation, particularly with DHA and ALA, significantly reduced intracellular reactive oxygen species (ROS) production and the expression of adhesion molecules (ICAM-1, E-selectin) in HAECs under both basal and LPS-stimulated inflammatory conditions. All PUFAs reduced pro-inflammatory cytokine levels (IFNγ, TNFα, IL-6), while ALA increased IL-1α and endoglin expression, indicating differential immunomodulatory effects. EPA exhibited antioxidant and anti-inflammatory effects primarily at higher LPS concentrations. Correlation analysis demonstrated strong interdependence between oxidative stress, inflammatory markers, and vascular activation, further confirming PUFA-mediated endothelial protection. Conclusions: PUFA supplementation produced molecule-specific effects on endothelial inflammation. DHA and ALA consistently showed anti-inflammatory and antioxidative effects, while EPA’s beneficial effect was more pronounced under inflammatory conditions, emphasising the importance of PUFA type and context in managing vascular inflammation. Full article

Background/Objectives: Transferrin is a multi-task protein commonly known for binding iron; however, it is involved in multiple crucial processes, including antimicrobial activity, the growth of different cell types, differentiation, chemotaxis, the cell cycle, and cytoprotection. Vascular cell adhesion molecule 1 (VCAM-1) is a cell surface glycoprotein which participates in inflammation and the trans-endothelial movement of leukocytes. Neither transferrin nor VCAM-1 has been studied in the context of progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS). This study aimed to evaluate the utility of transferrin and VCAM-1 assessment for the in vivo examination of tauopathic atypical Parkinsonian syndromes. Methods: This study included 10 patients with clinically probable PSP-RS, 10 with clinically probable PSP-P, and 8 with probable CBS. Patients’ blood and urine were collected and analyzed. Twenty-four serum samples (from twelve males and twelve females) were obtained from age-matched healthy volunteers. Peripheral blood inflammatory ratios, including the neutrophil-to-lymphocyte ratio, the platelet-to-lymphocyte ratio, the neutrophil-to-monocyte ratio, the neutrophil-to-high-density lipoprotein ratio, and the monocyte-to-high-density lipoprotein ratio, were calculated. VCAM-1 and transferrin concentrations were measured in the serum and urine. The urinary biomarker results are not included in the main analysis due to the absence of a control group. Results: The highest concentrations of transferrin in the serum were observed in patients with PSP-P, followed by PSP-RS and CBS. Statistically significant differences were found between PSP-P and healthy controls (p < 0.0001) and PSP-RS and healthy controls (p < 0.0001). The highest levels of serum VCAM-1 were observed in the PSP-P group. Significant differences were found between PSP-P and healthy controls (p < 0.0001), PSP-P and CBS (p < 0.001), and PSP-RS and healthy controls (p < 0.001). Serum VCAM-1 levels were negatively correlated with the NLR in CBS patients (p < 0.03; r = −0.74). Serum transferrin levels were negatively correlated with the NHR in CBS patients (p < 0.04; r = −0.64). ROC curve analyses were conducted to evaluate the diagnostic utility of serum transferrin and VCAM-1 in distinguishing tauopathic APS patients from controls. Transferrin showed excellent diagnostic performance, with an AUC of 0.975 (95% CI: 0.888–0.999; p < 0.0001), a sensitivity of 96.4%, and a specificity of 95.8% at the optimal cut-off (>503.0). VCAM-1 demonstrated good accuracy, with an AUC of 0.839 (95% CI: 0.711–0.926; p < 0.0001), a sensitivity of 75.0%, and a specificity of 91.7% at the optimal cut-off (>463.9). Conclusions: The obtained results indicate the potential role of transferrin and VCAM-1 in the pathogenesis of tauopathic APSs and highlight the need for further exploration in this field. Full article

Background: Type 2 diabetes mellitus (DM) is a major cardiovascular risk factor that induces monocyte dysfunction and contributes to their accumulation in atherosclerotic lesions. Monocyte recruitment and accumulation in the tissues contribute to chronic inflammation and are essential to the pathobiology of diabetes-induced atherosclerosis. However, the mechanisms that drive the accumulation of monocytes in the diabetic environment are not clearly understood. Methods: Primary monocytes from type 2 (T2) DM and non-T2DM individuals were isolated using magnet-assisted cell sorting. To examine the influence of a diabetic milieu on monocyte function, monocytes from T2DM patients, db/db mice, or human monocytes subjected to hyperglycaemia were analysed for their responses to pro-atherogenic cytokines using Boyden chamber assays. Furthermore, the interactions of non-diabetic and diabetic monocytes with TNFα-inflamed endothelium were studied using live-cell imaging under physiological flow conditions. RT-qPCR and FACS were used to study the expression of relevant molecules involved in monocyte-endothelium interaction. Results: CD14⁺CD16⁻ monocytes isolated from T2DM patients or monocytes exposed to hyperglycaemic conditions showed reduced chemotactic responses towards atherosclerosis-promoting cytokines, CCL2 and CX3CL1, indicating monocyte dysfunction. Under flow conditions, the transendothelial migration (TEM) capacity of T2DM monocytes was significantly reduced. Even though these monocytes adhered to the endothelial monolayer, only a few transmigrated. Interestingly, the T2DM monocytes and monocytes exposed to hyperglycaemic conditions accumulated in the ablumen following transendothelial migration. The time period in the ablumen of T2DM cells was prolonged, as there was a significant impairment of the reverse transendothelial migration (rTEM). Mechanistically, the T2DM milieu specifically induced the activation of monocyte integrins, Macrophage-1 antigen (Mac-1; integrin αMβ2 consisting of CD11b and CD18), and Lymphocyte function-associated antigen 1 (LFA-1; αLβ2 consisting of CD11a and CD18). Furthermore, elevated levels of CD18 transcripts were detected in T2DM monocytes. Junctional Adhesion Molecule 3 (JAM-3)–MAC-1 interactions are known to impede rTEM and T2DM milieu-potentiated JAM-3 expression in human coronary artery endothelial cells (HCAEC). Finally, the overexpression of JAM-3 on HCAEC was sufficient to completely recapitulate the impaired rTEM phenotype. Conclusions: Our results revealed for the first time that the enhanced T2DM monocyte accumulation in the ablumen is not secondary to the elevated transmigration through the endothelium. Instead, the accumulation of monocytes is due to the direct consequence of a dysfunctional rTEM, potentially due to enhanced JAM3-MAC1 engagement. Our results highlight the importance of restoring the rTEM capacity of monocytes to reduce monocyte accumulation-dependent inflammation induction and atherogenesis in the T2DM environment. Full article

(1) Background: Prompt acute coronary syndrome (ACS) recognition remains challenging. This study evaluated the diagnostic and prognostic performance of novel biomarkers for non-ST-elevation myocardial infarction (NSTEMI). (2) Methods: Patients with suspected ACS presenting to Heidelberg University Hospital’s Emergency Department between August 2014 and February 2023 were analyzed. The biomarker panel included high-sensitivity cardiac troponin T (hs-cTnT), cardiac myosin-binding protein C (cMyBP-C), pro-B-type natriuretic peptide (proBNP), total N-terminal pro-B-type natriuretic peptide (t-NtproBNP), Angiotensin II (Ang2), Bone morphogenetic protein 10 (BMP10), Endothelial cell-specific molecule 1 (ESM1), fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor 15 (GDF15), and Copeptin. Negative predictive values (NPVs), sensitivities, and area under the curve (AUC) values were calculated for NSTEMI discrimination. Effectiveness and prognostic performance were assessed based on cardiovascular events at 30 days and 1 year. (3) Results: Of 1765 patients, 212 (12%) were diagnosed with NSTEMI. The European Society of Cardiology (ESC) 0/1 h and 0/3 h algorithms achieved sensitivities of 100% and 96.8%, NPVs of 100% and 99.3%, and effectiveness values of 54.8% and 66.0%. Hs-cTnT (AUC: 0.922) and cMyBP-C (AUC: 0.917) exhibited the highest diagnostic accuracy, followed by FABP3 (AUC: 0.759) and Copeptin (AUC: 0.624). Other biomarkers had lower performance (AUC: 0.516–0.617). At 1 year, event rates ranged from 0.0% to 3.4%, with the ESC algorithms demonstrating superior prognostic performance (0.8%, 2.4%). (4) Conclusions: The ESC 0/1 h and 0/3 h algorithms remain the most effective NSTEMI diagnostic strategies, balancing high sensitivity, prognostic reliability, and effectiveness. Among novel biomarkers, only cMyBP-C demonstrated comparable accuracy to hs-cTnT, supporting its potential as an adjunct to troponin assays. Full article

Salt-sensitive hypertension (SSH) is closely associated with arterial inflammation, yet its molecular mechanisms remain unclear. In this study, we utilized deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice, which exhibited elevated blood pressure and significant arterial inflammation. Single-cell RNA sequencing (scRNA-seq) identified interferon regulatory factor 5 (IRF5) and its downstream targets, signal transducer and activator of transcription (STAT), as key regulators of these inflammatory changes. In vivo, IRF5 levels were significantly elevated in the DOCA group, while STAT1 and STAT2 protein levels were comparable to those in the normal salt group. However, nuclear levels of phosphorylated STAT1 (pSTAT1) and phosphorylated STAT2 (pSTAT2) were markedly higher in the DOCA group. Furthermore, scRNA-seq analysis showed increased IRF5 expression in endothelial cells (ECs) in both human and mouse aorta samples. In vitro, IRF5 knockdown in artery ECs led to a reduction in nuclear pSTAT1 and pSTAT2 expression. These results suggest that IRF5 promotes STAT1 and STAT2 phosphorylation, enabling their nuclear translocation. Additionally, RNA sequencing indicated a positive correlation between endothelial cell-specific molecule 1 (ESM1) and STAT1/STAT2. Using the UCSC and JASPAR databases, we identified multiple binding sites for the STAT1::STAT2 dimer on the ESM1 promoter. Luciferase reporter assays revealed enhanced ESM1 transcription following pSTAT1::pSTAT2 binding, and pinpoint potential binding sites. Chromatin Immunoprecipitation Quantitative PCR (ChIP-qPCR) further confirmed the specific binding sites between the pSTAT1::pSTAT2 dimer and the ESM1 promoter. These findings highlight the critical role of the IRF5-pSTAT1::pSTAT2-ESM1 pathway in the pathogenesis of SSH and suggest potential therapeutic targets. Full article

Chronic venous disease (CVD) is among the most common diseases in industrialized countries and has a significant socioeconomic impact. The diversity of clinical symptoms and manifestations of CVD pose major challenges in routine diagnosis and treatment. Despite the high prevalence and the huge number of venous surgical interventions performed every day, a substantial proportion of the etiopathogenesis remains unclear. There are several widely advocated and generally valid theories of “peri-capillary fibrin cuffs” and “white cell trapping hypothesis”, which consider the role of venous reflux/obstruction, inflammation, vascular remodeling, hemodynamic changes, genetic and social risk factors. There are several specific provoking factors for the development of venous reflux: incompetence of the valve system, inflammation of the vascular wall, and venous hypertension. Over the past few years, increasing scientific data has demonstrated the link between oxidative stress, endothelial dysfunction, and vascular inflammation. High levels of oxidants and persistent inflammation can cause cumulative changes in hemodynamics, resulting in permanent and irreversible damage to the microcirculation and endothelial cells. Production of reactive oxygen species and expression of inflammatory cytokines and adhesion molecules are involved in a vicious cycle of venous wall remodeling. The interaction of ROS, and in particular, the superoxide anion radical, with nitric oxide leads to a decrease in NO bioavailability, followed by the initiation of prolonged vasoconstriction and hypoxia and impairment of vascular tone. This review addresses the role of ED, oxidative, and hemodynamic stress in the CVD mediation. Based on predefined inclusion and exclusion criteria, we conducted a systematic review of published scientific articles using PubMed, PMC Europe, Scopus, WoS, MEDLINE, and Google Scholar databases in the interval from 24 April 2002 to 1 April 2025. The current review included studies (n = 197) scientific articles, including new reviews, updates, and grey literature, which were evaluated according to eligibility criteria. The selection process was performed using a standardized form according to PRISMA rules, the manual search of the databases, and a double-check to ensure transparent and complete reporting of reviews. Studies had to report quantitative assessments of the relationship between vascular endothelial dysfunction, inflammation, oxidative stress, and shear stress in a chronic venous disease. Full article

Bone marrow stromal antigen 2 (BST2) is a host-restriction factor that plays multiple roles in the antiviral defense of innate immune responses, including the inhibition of viral particle release from virus-infected cells. BST2 may also be involved in the endothelial adhesion and migration of monocytes, but its importance in the immune system is still unclear. Immune cell adhesion and migration are closely related to the initiation of immune responses. In this study, we found that the expressions of the lymph node homing marker chemokine receptor 7 (CCR7) and an adhesion molecule intercellular adhesion molecule 1 (ICAM-1) in conventional dendritic cells (cDCs) were associated with BST2 expression. Interestingly, Bst2^−/− cDCs showed lower chemotactic ability, including velocity and accumulative distance toward chemokine ligand 19 (CCL19) gradient in vitro, compared to wild-type cDCs. Bst2^−/− cDCs also showed reduced migration and reduced retention capacity in draining lymph nodes in vivo. As a result, Bst2^−/− cDCs as antigen-presenting cells induced lower antigen-specific B cell and T cell responses compared to Bst2^+/+ cDCs. Notably, mice administered the influenza vaccine via Bst2^−/− cDCs exhibited substantially inefficient virus clearance compared to mice administered the Bst2^+/+ cDCs vaccine. Therefore, we propose that BST2, which plays a critical role in the effective migration and retention of cDCs, is involved in the development of optimal immunological effects in draining lymph nodes. 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

PEAR1, also known as platelet endothelial aggregation receptor 1, is known to play a crucial role in the migration and differentiation of muscle satellite cells (MuSCs). However, its specific effects on skeletal muscle development and regeneration require further exploration. In this study, the expression of PEAR1; the proliferation marker proteins of Pax7, CCNB1, and PCNA; and the key molecules of N1-ICD, N2-ICD, and Hes1 were all increased gradually during the process of C2C12 cell proliferation. Furthermore, Western blotting and EdU results showed that when PEAR1 was over-expressed or inhibited, the proliferation status of C2C12 cell was increased or reduced respectively. This implied that PEAR1 could regulate myoblast proliferation and might be relate to Notch cell signaling pathway. A subsequent immunoprecipitation experiment result showed that the interaction between PEAR1 and Notch1 or Notch2, respectively. Then Western blotting and EdU results showed that the proliferation of C2C12 cell was inhibited under the treatment of Notch signaling pathway inhibitor RIN1. Meanwhile, the proliferation capacity of C2C12 cell could not be improved by treatment with RIN1 even though PEAR1 was over-expressed. These results showed that PEAR1 may regulated C2C12 cell proliferation though Notch signaling pathway. Additionally, a mouse model of muscle injury repair injected with bupivacaine hydrochloride was established in this study. Immunohistochemistry results exhibited that PEAR1 may regulate skeletal muscle post-injury regeneration relevant to Notch1 and Notch2 in different patterns. These findings provide valuable insights into the potential involvement of PEAR1 in skeletal muscle development and post-injury regeneration. Full article

Non-HLA antibodies against heterogeneous targets on endothelial cells have been associated with allograft injuries. The endothelial cell crossmatch (ECXM) is used in the detection of non-HLA antibodies but remains non-discriminatory for specific antibody identification. The primary objective of this study was to delineate the specific non-HLA antibody signatures associated with ECXM positivity and to determine the correlation of ECXM status and non-HLA antibody signatures on allograft health. Serum specimens from 25 lung transplant recipients (LTRs) and 13 renal transplant recipients (RTRs) were collected as part of clinical evaluation, and testing for angiotensin II receptor type 1 (AT1R) and donor-specific MHC class I chain-related gene A (MICA) antibodies and ECXM was performed. Remnant sera were tested for non-HLA antibodies using the LABScreen™ Autoantibody (LSAUT) Group 1, 2, and 3 kits (One Lambda, Inc., Los Angeles, CA, USA). In both cohorts, the concordance of AT1R and MICA together or individually with ECXM+ status was poor (<0.7), suggesting the presence of other unaccounted antibodies. Autoantibody profiling revealed three distinct clusters targeting fibrotic products, cytoskeletal proteins, and cell signaling molecules. A comparative analysis of ECXM+ and ECXM− specimens identified nine and five differentially expressed antibodies in the LTR and RTR cohorts, respectively. Employing machine learning techniques (variable importance, feature selection, ROC-AUC), we derived a five-antibody panel (TNFα, collagen V, CXCL11, GDNF, GAPDH) and a two-antibody panel (TNFα, CXCL9) that effectively discriminated between ECXM+ and ECXM− status in the LTR and RTR cohorts, respectively. Distinct antibody signatures were identified in LTR and RTR cohorts that correlated with ECXM+ status and were associated with allograft dysfunction. Full article

Cutaneous hypersensitivity reactions (CHRs) are complex inflammatory skin disorders that affect humans and dogs. This study examined the inflammatory and immune responses leading to skin damage, inflammation, and irritation by investigating gene expression through quantitative PCR (qPCR) and protein localization through the immunohistochemistry (IHC) of specific receptors and molecules involved in CHRs. Formalin-fixed paraffin-embedded (FFPE) samples from canine CHR skin (n = 20) and healthy dog skin (n = 3) were analyzed for expression levels of eight genes, including members of the pattern recognition receptor (PRR) family, CD209 and CLEC4G, the Regakine-1-like chemokine, and acute phase proteins (APPs), LBP-like and Hp-like genes. Additionally, we examined the local involvement of IL-6, Janus Kinase 1 (JAK1), and the signal transducer activator of transcription 3 (STAT3) in the CHR cases. The study demonstrated statistically significant increases in the expression levels of CD209, Hp-like (p < 0.01), LBP-like, Regakine-1-like, and CLEC4G (p < 0.05) genes in CHRs compared to healthy controls. Conversely, IL-6, JAK1, and STAT3 showed no significant difference between the two groups (p > 0.05). Protein analysis revealed JAK1 and STAT3 expression in CHR hyperplastic epithelial cells, dermal fibroblasts, and endothelial cells of small capillaries, indicating a possible involvement in the JAK/STAT pathway in local inflammatory response regulation. Our findings suggest that the skin plays a role in the development of CHRs. Full article

Current clinical diagnostic imaging methods for lung metastases are sensitive only to large tumours (1–2 mm cross-sectional diameter), and early detection can dramatically improve treatment. We have previously demonstrated that an antibody-targeted MRI contrast agent based on microparticles of iron oxide (MPIO; 1 μm diameter) enables the imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Using a mouse model of lung metastasis, upregulation of endothelial VCAM-1 expression was demonstrated in micrometastasis-associated vessels but not in normal lung tissue, and binding of VCAM-MPIO to these vessels was evident histologically. Owing to the lack of proton MRI signals in the lungs, we modified the VCAM-MPIO to include zirconium-89 (⁸⁹Zr, t_1/2 = 78.4 h) in order to allow the in vivo detection of lung metastases by positron emission tomography (PET). Using this new agent (⁸⁹Zr-DFO-VCAM-MPIO), it was possible to detect the presence of micrometastases within the lung in vivo from ca. 140 μm in diameter. Histological analysis combined with autoradiography confirmed the specific binding of the agent to the VCAM-1 expressing vasculature at the sites of pulmonary micrometastases. By retaining the original VCAM-MPIO as the basis for this new molecular contrast agent, we have created a dual-modality (PET/MRI) agent for the concurrent detection of lung and brain micrometastases. Full article

Radiotherapy (RT) may have a cardiotoxic effect on the heart and cardiovascular system. Postulated mechanisms mediating these complications include vascular endothelium damage and myocardial fibrosis. The aim of our study was to assess endothelial damage and myocardial fibrosis in the early period after RT on the basis of cardiac biomarkers and in relation to the radiation dose applied to individual heart structures in patients treated for non-small-cell lung cancer. This single-center prospective study included consecutive patients with lung cancer (LC) who were referred for treatment with radiochemotherapy (study group) or chemotherapy (control group). The study protocol included performing an echocardiographic examination, a standard ECG examination, and collecting blood samples for laboratory tests before starting treatment for lung cancer in the first week after completing RT (after four cycles of chemotherapy in the control group) and after 12 weeks from the end of treatment. The study included 23 patients in the study group and 20 patients in the control group. Compared to the baseline values, there was a significant increase in total cholesterol concentration in the study group immediately after the end of RT, which persisted for three months after the end of therapy. After taking into account the use of statins in the analysis, it was found that an increase in total cholesterol concentration after oncological treatment was observed only among patients who did not use statins. Taking into account the assessment of myocardial fibrosis markers, there were no significant changes in the concentration of matrix metallopeptidase 9 (MMP-9) and tissue inhibitors of metalloproteinases 1 (TIMP-1) in the study group. In patients treated with radiochemotherapy, there was a significant increase in the concentration of intercellular adhesion molecule 1 (ICAM-1) immediately after RT, when compared to the baseline. After taking into account the use of statins, an increase in ICAM-1 concentration immediately after RT was observed only in patients who did not use statins. There was also a significant correlation between the radiation dose received by the left anterior descending coronary artery (LAD) and left circumferential coronary artery, and vascular cell adhesion protein 1 (VCAM-1) concentration measured at three months after the end of RT. Immediately after completion of radiotherapy, a significant increase in the level of ICAM-1 is observed indicating endothelial damage. The radiation dose to coronary arteries should be minimized, as it correlates with the concentration of VCAM-1. The use of statins may prevent the increase in total cholesterol and ICAM-1 concentration after irradiation for lung cancer; however, further studies designed for this specific purpose are necessary to confirm the effectiveness of statins in this area. Full article

Background: The prevailing etiological model of both acute and chronic urticaria implicates specific allergen exposure that triggers the local release of vasoactive factors and inflammatory adhesion molecules, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), endothelial leukocyte adhesion molecule 1 (ELAM-1), P-selectin and E-selectin in the superficial dermis. This study focused on the possible role of VCAM-1 and ICAM-1 as biomarkers in children with acute and chronic urticaria. Methods: This study involved 184 children, 40 with acute urticaria, 71 with chronic urticaria, and 73 matched comparison subjects. The serum levels of ICAM-1 and VCAM-1 were determined in venous blood in all the participants on enrollment. Antihistamine treatment was administered to all the patients. In the children with chronic urticaria, the Urticaria Activity Score Questionnaire (UAS7) was completed daily by the parents. In 16 of the patients with acute urticaria and 43 with chronic urticaria, the serum levels of ICAM-1 and VCAM-1 were determined at follow-up after 6–8 weeks of treatment. Results: The mean serum levels of both VCAM-1 and ICAM-1 were higher in both groups of children with urticaria than in the comparison subjects at the start of the study. In the chronic urticaria group, the levels decreased significantly (p = 0.03 and p = 0.01, respectively) following treatment. Similarly, the acute urticaria group exhibited significant reduction in the mean levels of VCAM and ICAM (p < 0.001). In both groups, the mean level of ICAM after treatment was comparable with that of the comparison group. Conclusions: VCAM-1 and ICAM-1 are suggested as promising biomarkers for monitoring both acute and chronic urticaria in children. Future research should explore their utility in larger cohorts and investigate their role in personalized treatment strategies. Full article

The peritoneum is the most common metastatic site of advanced gastric cancer and is associated with extremely poor prognosis. Endothelial-specific molecule 1 (ESM1) was found to be significantly associated with gastric cancer peritoneal metastasis (GCPM); however, the biological functions and molecular mechanisms of ESM1 in regulating GCPM remain unclear. Herein, we demonstrated that ESM1 expression was significantly upregulated in gastric cancer tissues and positively correlated with platelet endothelial cell adhesion molecule-1 (CD31) levels. Moreover, clinical validation, in in vitro and in vivo experiments, confirmed that ESM1 promoted gastric cancer angiogenesis, eventually promoting gastric cancer peritoneal metastasis. Mechanistically, ESM1 promoted tumor angiogenesis by binding to c-Met on the vascular endothelial cell membrane. In addition, our results confirmed that ESM1 upregulated VEGFA, HIF1α, and MMP9 expression and induced angiogenesis by activating the MAPK/ERK pathway. In conclusion, our findings identified the role of ESM1 in gastric cancer angiogenesis and GCPM, thus providing insights into the diagnosis and treatment of advanced gastric cancer. Full article