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Epithelioid hemangiosarcoma (EH), a rare histological variant of hemangiosarcoma, is reported in various animal species, including humans, dogs, cows, horses, and cats. Epithelioid hemangiosarcomas are composed of highly pleomorphic epithelioid cells arranged in cords, islands, nests, or solid cellular areas, similar to epithelial neoplasms. Moreover, in humans, approximately 50% of EHs have cytoplasmic immunolabeling for cytokeratin AE1/AE3 (CK AE1/AE3), making it challenging to distinguish them from carcinomas. This retrospective study assessed the CK AE1/AE3 immunolabeling in canine EH cases from 5 veterinary institutions. Immunohistochemistry for CD31 and CK AE1/AE3 was performed on 30 cases. CK AE1/AE3 immunolabeling was detected in 43% (13/30) of cases, with cytoplasmic labeling ranging from 5% to 100% of neoplastic cells. All tumors consistently had membranous immunolabeling for CD31. The CK AE1/AE3 immunolabeling pattern in canine EHs closely resembled those documented in humans, indicating a similar diagnostic challenge. Therefore, it is recommended to include a vascular immunohistochemistry marker, such as CD31, whenever EH is suspected, particularly in small incisional cutaneous and subcutaneous biopsies. [ABSTRACT FROM AUTHOR]

Extracranial arteriovenous malformations (eAVMs) are complex vascular lesions characterized by anomalous arteriovenous connections, vascular instability, and disruptions in endothelial cell (EC)-to-mural cell (MC) interactions. This study sought to determine whether eAVM-MCs could induce endothelial-to-mesenchymal transition (EndMT), a process known to disrupt vascular integrity, in the eAVM microenvironment. eAVM and paired control tissues were analyzed using RT-PCR for EC (CD31, CD34, and CDH5) and EndMT-specific markers (SNAI1, SNAI2, ACTA2/α-SMA, N-cadherin/CDH2, VIM). Immunohistochemistry (IHC) was also performed to analyze MC- (PDGFR-β and α-SMA), EC (CD31, CD34, and CDH5), and EndMT-specific markers (CDH2 and SNAI1) in sequential paraffin-embedded sections of eAVM patient biopsies and in adjacent normal tissue biopsies from the same patients. Furthermore, eAVM-MCs and MCs from normal paired tissues (NMCs) were then isolated from fresh human surgical samples using flow cytometry and co-cultured with normal human umbilical vein vascular endothelial cells (HUVECs), followed by analysis of CD31 by immunofluorescence. RT-PCR analysis did not show a significant difference in the expression of EC markers between eAVM tissues and controls, whereas expression of EndMT-specific markers was upregulated in eAVM tissues compared to controls. IHC of eAVMs and paired control tissues demonstrated regions of significant perivascular eAVM-MC expansion (PDGFR-β+, and α-SMA+) surrounding dilated, morphologically abnormal vessels. These regions contained endothelium undergoing EndMT as evidenced by loss of CD31, CD34, and CDH5 expression and upregulation of the EndMT-associated genes CDH2 and SNAI1. Isolated eAVM-MCs induced loss of CD31 in HUVECs when grown in co-culture, while NMCs did not. This study suggests that the eAVM endothelium surrounded by expanded eAVM-MCs undergoes EndMT, potentially leading to the formation of dilated and fragile vessels, and implicates the eAVM-MCs in EndMT initiation and eAVM pathology. [ABSTRACT FROM AUTHOR]

Background: Chronic wounds pose a significant surgical challenge, often requiring traditional treatments with limited efficacy. This study explores the promising impact of Shixiang plaster, a classic Chinese ointment, on wound healing. We investigated the cluster of differentiation 31 (CD31) expression, serum fibronectin (FN), and vascular endothelial growth factor (VEGF) levels in SPF rats with induced wounds to elucidate the mechanism behind Shixiang plaster's effectiveness. We investigated the effect and explored the role of Shixiang plaster on the expression of CD31, serum FN, and VEGF in chronic wounds. Methods: The study involved 36 SPF rats divided into model, rb-bFGF, and Shixiang plaster groups. Penicillin was injected into the rats before modelling for 3 days to prevent infection. The skin was excised 2 cm below the horizontal line of the inferior border of the shoulder bone in the middle of the rat column up to the deep fascial layer and inoculated with a certain concentration of Staphylococcus aureus; the wound was covered aseptically for 3 days. The trauma area of the rats was observed at 3, 7, and 14 days, respectively. Histopathology was observed using haematoxylin eosin and Masson staining. CD31 expression was detected using immunohistochemistry staining. FN and VEGF expression was detected using serum ELISA. Statistical analyses were carried out by the method of SPSS. Results: Regarding wound morphology, at 3 days, the recovery area of the Shixiang plaster group was larger than that of the other two groups, at 7 days, the wound healing rate of the Shixiang plaster group was significantly higher, and at 14 days, the wounds of the Shixiang plaster group had been mostly healed, with a healing rate of 98.3%. Haematoxylin eosin staining revealed a large amount of granulation tissue at 3 days in the Shixiang plaster group, and the epidermal scales disappeared at 14 days, with thinner epidermal thickness at 1 lesion and a large reduction in inflammatory cell infiltration. Masson staining showed that at 3, 7, and 14 days, blue staining was the most abundant and deeper in the Shixiang plaster group, with richer collagen and a compact tissue matrix. Immunohistochemical testing showed strong positive expression of CD31 in the Shixiang plaster group, with abundant neovascularisation and large official lumens extending towards the surface of the wound. Statistically significant elevated expression of FN at 7 and 14 days was determined by ELISA in the Shixiang plaster group, and VEGF expression was significantly increased at 7 days, but expression had been expressed at a low level at 14 days. Conclusion: Shixiang plaster exhibits remarkable efficacy in healing chronic wounds. The proposed mechanism involves FN's promotion of angiogenesis and cell proliferation, VEGF's impact on angiogenesis and inflammation, and CD31's regulatory role in inhibiting inflammation while promoting angiogenesis. [ABSTRACT FROM AUTHOR]

Background: Studying microvessel density (MVD) as an angiogenesis indicator enhances insights into tumor diversity, predicting invasive or metastatic tendencies. It assists in tailoring treatment approaches based on angiogenesis expression in different tumors. Objectives: This study aimed at assessing MVD using the CD31 marker and its associated factors in individuals with endometrial malignancies. Methods: This cross-sectional study involved 118 patients with endometrial cancer (EC) at Imam Hussein Educational and Medical Center, Tehran, Iran spanning from 20I8 to 2023. Data, gathered from patient medical flies using a researcher-made checklist, included a quantitative assessment of angiogenesis using the CD31 endothelial marker for MVD. Linear regression models were utilized to identify predictors of MVD-CD31 in patients with EC. Results: Patients had a mean age of 5735 ± 11.16 years. The overall mean MVD-CD31 was 157.06 ± 9431 (range, 32 - 385). Those with over 50% invasion depth exhibited a higher MVD-CD31 (79.59 units) compared to those with no invasion depth (P = 0.003). Higher MVD-CD31 levels were also associated with lymph node involvement and metastasis to other organs (P < 0.001). In comparison to grade 1 tumors, grade 2 tumors showed elevated MVD-CD31 (mean difference: 64.85, P = 0.007). Clear cell carcinoma tumor type had significantly higher MVD-CD31 than low-grade endometrioid carcinoma (mean difference: 225.84, P = 0.005). Conclusions: Our results suggest that some tumor characteristics such as invasion depth, lymph node involvement, tumor grade, and tumor type may play a role in angiogenesis in patients with EC. These findings suggest that tumor features play a crucial role in modulating angiogenesis in EC. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β (TGFβ) and FoxP3 regulatory T cells (Treg) are involved in human breast carcinogenesis. This topic is not well documented in canine mammary tumors (CMT). In this work, the tumoral TGFβ expression was assessed by immunohistochemistry in 67 malignant CMT and its correlation to previously determined FoxP3, VEGF, and CD31 markers and other clinicopathologic parameters was evaluated. The high levels of TGFβ were statistically significantly associated with skin ulceration, tumor necrosis, high histological grade of malignancy (HGM), presence of neoplastic intravascular emboli and presence of lymph node metastases. The observed levels of TGFβ were positively correlated with intratumoral FoxP3 (strong correlation), VEGF (weak correlation) and CD31 (moderate correlation). Tumors that presented a concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31 markers were statistically significantly associated with parameters of tumor malignancy (high HGM, presence of vascular emboli and nodal metastasis). Additionally, shorter overall survival (OS) time was statistically significantly associated with tumors with an abundant TGFβ expression and with concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31. The presence of lymph node metastasis increased 11 times the risk of disease-related death, arising as an independent predictor of poor prognosis in the multivariable analysis. In conclusion, TGFβ and Treg cells seem involved in tumor progression emerging as potential therapeutic targets for future immunotherapy studies.

Objective To investigate the effect of the Piezo1 channel on tension-side angiogenesis and osteogenic remodeling during orthodontic tooth movement, so as to provide an experimental basis for accelerating orthodontic periodontal tissue remodeling. Methods This study was approved by the Animal Ethics Committee. Sixty healthy male Sprague-Dawley rats with bilateral maxillary incisors as the anchorage were selected, and nickel titanium tension springs were used to apply 0.5 N of force to the right maxillary first molar of the rats and construct an orthodontic tooth movement model. The rats were randomly divided into three groups (n = 20 per group). On Days 0 and 8 of force application, equal volumes of saline (control group), 100 μmol/L Piezo1 channel agonist (Yoda1 group), and 48 μmol/L Piezo1 channel inhibitor (GsMTx4 group) were injected into the buccal and palatal submucosa of the right maxillary first molar. Tooth movement distances were recorded on Days 1, 3, 7, and 14. Five rats from each group were sacrificed at each time point to obtain maxillary tissue samples. Hematoxylin and eosin (HE) staining was performed to observe the histophysiological changes in the tension-side periodontal tissues. Immunohistochemical staining was used to mark and count CD31-positive cells (microvascular quantification) and to detect the expression of osteocalcin (OCN) in the tension side. Results Measurements of tooth movement distance showed that the Yoda1 group exhibited significantly increased tooth movement distances on Days 3, 7, and 14 (0.238 ± 0.008 mm, 0.406 ± 0.011 mm, and 0.746 ± 0.013 mm, respectively) compared to the control group (PPPPPP

Background and Aim: Glioma is one of the most prevalent and refractory brain cancers with a high recurrence rate. Current limitations of experimental in vitro models include their inability to remodel the heterogeneity of the parental tumors and their incapacity to effectively reflect antitumor effects and mechanisms observable in vivo. Organoid models, as a new technology developed in recent years, can preserve the histological characteristics, cellular diversity, and gene expression of parental tumors to the fullest extent, thereby delivering more reliable data. This study intends to construct a simple organoid model developed from glioma patient material. Materials and Methods: Glioma samples were taken intraoperatively and cultured in the organoid medium using a continuous horizontal shaker. Sample collection and scientific research were authorized and approved by the Ethics Committee of Kowloon Hospital, China (Approval No. KY-2021-007). Immunofluorescence was applied to identify CD31 and Sox2 protein expression in the organoid model. The differences between primary glioblastomas and transplanted organoid tumors were analyzed by hematoxylin and eosin (H and E) staining. Immunohistochemistry (IHC) and Western blot assay were used to analyze the Sox2, Ki67, and CD31 protein expression levels. Results: The success rate of establishing organoid models was 90.9% in the primary glioblastomas, 75.0% in the WHO Grade III gliomas, and 42.9% in the Grade I–II gliomas. Immunofluorescence demonstrated that in vitro cultured organoids expressed CD31 and Sox2. Similarly, IHC and Western blot assay showed that orthotopically transplanted organoid tumors could exhibit high expressions of Sox2, Ki67, and CD31. There were no significant differences regarding the pathological features of primary glioblastomas and glioma organoid model as judged by H and E staining. Conclusions: This study presents a simple in vitro organoid model established from glioma patient samples. The success rate of constructing an organoid model is correlated with the degree of glioma malignancy. The established organoid model displays original model properties and simplifies the development of new experimental platforms that can support preclinical glioma treatment studies.

The tissue preparations of the pelvic veins obtained during laparoscopy were examined. The expression of markers of proliferation (Ki-67), apoptosis (p53), and angiogenesis (CD31, CD34), as well as estrogen and progesterone receptors in women with pelvic varicose veins was assessed by the immunohistochemical method. A decrease in the median expression of the proliferation marker (Ki-67) and estrogen and progesterone receptors and simultaneous increase in the expression of apoptosis marker (p53) and activation of angiogenesis processes (markers CD31 and CD34) were observed with increasing the severity of the disease. These data extend our understanding of the pathogenetic mechanisms of pelvic varicose veins and contribute to the development of methods of pathogenetically based targeted therapy. [ABSTRACT FROM AUTHOR]

Background: Basal Cell Carcinoma (BCC) is the most common form of skin cancer, characterized by its low metastatic potential yet considerable diversity in clinical and dermatoscopic presentation. Advances in dermatoscopy have significantly improved the early detection of BCC, revealing specific patterns that guide diagnosis and management. Parallelly, immunohistochemical markers have been explored for their potential to elucidate the underlying tumor biology and prognosis, with particular focus on angiogenesis, melanocytic activity, and lymphangiogenesis. Objective: This study aims to investigate the correlations between dermatoscopic features and the immunohistochemical expressions of CD34, CD31, Melan-A, and D2-40 in BCC, through a comprehensive analysis of 100 cases We sought to determine whether visual dermatoscopic patterns correlate with the molecular characteristics defined by immunohistochemical staining, potentially enhancing diagnostic accuracy. Methods: A total of 100 cases of clinically and histopathologically confirmed BCC were prospectively analyzed, employing standard dermatoscopic techniques for lesion evaluation and immunohistochemical staining for CD34, CD31, Melan-A, and D2-40 to assess tumor angiogenic potential, melanocytic activity, and lymphangiogenesis. The study was conducted with adherence to ethical standards and informed consent from all participants. Results: Dermatoscopic examination revealed a variety of vascular patterns and pigmented features across different BCC anatomical locations. However, the comprehensive correlation analysis predominantly found a lack of significant associations between dermatoscopic appearances and expressions of the targeted immunohistochemical markers, with the notable exception of a correlation between observed hemorrhage and the Melan-A marker. Conclusions: The lack of significant correlations between dermatoscopic features and immunohistochemical marker expressions in BCC suggests that the biological behavior and angiogenic, melanocytic, and lymphangiogenic activities within BCC lesions may be influenced by factors beyond those assessed in this study. Despite the exploratory nature of these findings, they underscore the complexity of BCC biology and highlight the need for further research incorporating additional markers and advanced imaging techniques. [ABSTRACT FROM AUTHOR]

Voice abuse, chronic cough, laryngeal surgery, and tracheal intubation may lead to injury and subsequent repair/remodeling in the vocal fold mucosa. Periostin is known to be involved in airway remodeling and is also associated with various otolaryngological diseases. D-β -aspartic acid is the major isomer of D-aspartic acid found in tissues of elderly individuals. In ischemic heart disease, increased CD31 expression has been observed around cardiomyocytes during remodeling, and endothelial proliferation has been reported at these sites. In this study, we investigated the expression and role of CD31, CD34, D-β -aspartic acid, and periostin in the formation of laryngeal granulation tissue. This retrospective study involved five patients who underwent surgical treatment for laryngeal granulation tissue. The expressions of CD31, CD34, D-β -aspartic acid, and periostin in surgical samples were investigated by immunohistochemistry. Histologically, the specimens showed inflammatory cell infiltration, fibrin exudation, fibrosis, and neovascularization, but no tumor cells. No stratified squamous epithelial covering was observed. The expression of periostin and D-β -aspartic acid was also observed in the specimens. CD31-positive cells (endothelial cells) and CD34-positive cells (progenitors of endothelial cells) were observed in the specimens. Our results indicate that the overexpression of CD31, CD34, D-β -aspartic acid, and periostin may play a role in the pathogenesis of laryngeal granulation tissue, and we speculate that D-β -aspartic acid and periostin could serve as novel biomarkers and therapeutic targets for laryngeal granulation tissue. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Prevention & Treatment For Stomatological Diseases is the property of Journal of Prevention & Treatment For Stomatological Diseases Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Congenital diaphragmatic hernia (CDH) is a complex congenital disorder, characterized by pulmonary hypertension (PH) and hypoplasia. PH secondary to CDH (CDH-PH) features devastating morbidity and mortality (25–30%) among neonates. An unmet need is determining mechanisms triggering CDH-PH to save infants. Prior data suggest abnormal remodeling of the pulmonary vascular extracellular matrix (ECM), presumed to be driven by endothelial-to-mesenchymal transition (EndoMT), hinders postnatal vasodilation and limits anti-PH therapy in CDH. There are limited data on the role of EndoMT in CDH-PH. Methods: The purpose of the study was to investigate how EndoMT contributes to CDH-PH by identifying cells undergoing EndoMT noted by alpha smooth muscle actin (α-SMA) expression in human umbilical vein endothelial cells (HUVECs) and lung tissue obtained from murine pups using the nitrofen model. N = 8 CDH, N = 8 control HUVECs were stained for α-SMA and CD31 after being exposed for 24 h to TGFB, a known EndoMT promoter. N = 8 nitrofen, N = 8 control murine pup lungs were also stained for α-SMA and CD31. α-SMA and CD31 expression was quantified in HUVECs and murine tissue using Fiji imaging software and normalized to the total number of cells per slide noted by DAPI staining. Results: CDH HUVECs demonstrated a 1.1-fold increase in α-SMA expression (p = 0.02). The murine model did not show statistical significance between nitrofen and control pup lungs; however, there was a 0.4-fold increase in α-SMA expression with a 0.8-fold decrease in CD31 expression in the nitrofen pup lungs when compared to controls. Conclusion: These results suggest that EndoMT could potentially play a role in the ECM remodeling seen in CDH-PH. [ABSTRACT FROM AUTHOR]

Objectives: Tumor hypoxia and angiogenesis have been implicated in therapeutic resistance of head and neck squamous cell carcinomas (HNSCCs). Immunohistochemical evaluation of hypoxia-inducible factor-1 alpha (HIF-1 α), a hypoxia transcription factor, and vascular endothelial growth factor (VEGF), a hypoxia-responsive pro-angiogenic factor, can be exploited for prognostication and guiding treatment intensification or de-escalation decisions in HNSCC patients. The purpose of the study is to evaluate the immunohistochemical expression patterns of HIF-1 α and VEGF and the microvessel density (MVD) for angiogenesis in HNSCC and assess their pathological significance and prognostic role. Materials and Methods: In this cross-sectional study, immunohistochemical expression of HIF-1 α , VEGF, and MVD through Cluster of Differentiation (CD31) was evaluated in paraffin-embedded tumor resection tissue of 44 patients with HNSCC. Associations among HIF-1 α , VEGF, and MVD with clinicopathological variables were assessed. Statistical Analysis: For assessment of association between HIF-1α, VEGF and MVD by CD 31 immunohistochemical markers and other clinicopathological variables Pearson's chi-square test and Fisher's exact tests were used. Analysis of survival was done using Kaplan-Meier statistics. Also, the univariate and multivariate analysis were performed using the Cox proportional hazard regression model for the calculation of hazard ratios. Results: Nuclear expression of HIF-1 α showed significant association with MVD (P = 0.007) and cytoplasmic expression of HIF-1 α with histologic grade (P = 0.03). Overexpression of HIF-1 α was more frequent in T3/T4 stage. In addition to cytoplasmic staining, VEGF showed a unique nuclear expression pattern in four cases of advanced disease with nodal metastasis. Logistic regression analysis showed tumors with nuclear overexpression of HIF-1 α to have increased MVD (P = 0.05), and tumors with higher MVD to have a presence of lymphovascular invasion (P = 0.014). Multivariate analysis showed HIF-1 α nuclear overexpression to be significantly associated with decreased survival of patients (P = 0.05). Conclusions: Immunohistochemical overexpression of HIF-1 α and MVD quantification can serve as cost-effective tools for prognostication and treatment modification of HNSCC patients in resourcelimited settings. [ABSTRACT FROM AUTHOR]

Synovitis is characterized by a distinctmetabolic profile featuring the accumulation of lactate, a byproduct of cellular metabolism within inflamed joints. This study reveals that the activation of the CD31 signal by lactate instigates a metabolic shift, specifically initiating endothelial cell autophagy. This adaptive process plays a pivotal role in fulfilling the augmented energy and biomolecule demands associated with the formation of new blood vessels in the synovium of Rheumatoid Arthritis (RA). Additionally, the amino acid substitutions in the CD31 cytoplasmic tail at the Y663F and Y686F sites of the immunoreceptor tyrosine-based inhibitory motifs (ITIM) alleviate RA. Mechanistically, this results in the downregulation of glycolysis and autophagy pathways. These findings significantly advance our understanding of potential therapeutic strategies for modulating these processes in synovitis and, potentially, other autoimmune diseases.

BackgroundBasal Cell Carcinoma (BCC) is the most common form of skin cancer, characterized by its low metastatic potential yet considerable diversity in clinical and dermatoscopic presentation. Advances in dermatoscopy have significantly improved the early detection of BCC, revealing specific patterns that guide diagnosis and management. Parallelly, immunohistochemical markers have been explored for their potential to elucidate the underlying tumor biology and prognosis, with particular focus on angiogenesis, melanocytic activity, and lymphangiogenesis.ObjectiveThis study aims to investigate the correlations between dermatoscopic features and the immunohistochemical expressions of CD34, CD31, Melan-A, and D2-40 in BCC, through a comprehensive analysis of 100 cases We sought to determine whether visual dermatoscopic patterns correlate with the molecular characteristics defined by immunohistochemical staining, potentially enhancing diagnostic accuracy.MethodsA total of 100 cases of clinically and histopathologically confirmed BCC were prospectively analyzed, employing standard dermatoscopic techniques for lesion evaluation and immunohistochemical staining for CD34, CD31, Melan-A, and D2-40 to assess tumor angiogenic potential, melanocytic activity, and lymphangiogenesis. The study was conducted with adherence to ethical standards and informed consent from all participants.ResultsDermatoscopic examination revealed a variety of vascular patterns and pigmented features across different BCC anatomical locations. However, the comprehensive correlation analysis predominantly found a lack of significant associations between dermatoscopic appearances and expressions of the targeted immunohistochemical markers, with the notable exception of a correlation between observed hemorrhage and the Melan-A marker.ConclusionsThe lack of significant correlations between dermatoscopic features and immunohistochemical marker expressions in BCC suggests that the biological behavior and angiogenic, melanocytic, and lymphangiogenic activities within BCC lesions may be influenced by factors beyond those assessed in this study. Despite the exploratory nature of these findings, they underscore the complexity of BCC biology and highlight the need for further research incorporating additional markers and advanced imaging techniques.

Study Design. Basic science study using a hemisection spinal cord injury (SCI) model. Objective. We sought to assess the effect of blocking osteopontin (OPN) upregulation on motor function recovery and pain behavior after SCI and to further investigate the possible downstream target of OPN in the injured spinal cord. Summary of Background Data. OPN is a noncollagenous extracellular matrix protein widely expressed across different tissues. Its expression substantially increases following SCI. A previous study suggested that this protein might contribute to locomotor function recovery after SCI. However, its neuroprotective potential was not fully explored, nor were the underlying mechanisms. Materials and Methods. We constructed a SCI mouse model and analyzed the expression of OPN at different time points and the particular cell distribution in the injured spinal cord. Then, we blocked OPN upregulation with lentivirus-delivering siRNA targeting OPN specifically and examined its effect on motor function impairment and neuropathic pain after SCI. The underlying mechanisms were explored in the OPN-knockdown mice model and cultured vascular endothelial cells. Results. The proteome study revealed that OPN was the most dramatically increased protein following SCI. OPN in the spinal cord was significantly increased three weeks after SCI. Suppressing OPN upregulation through siRNA exacerbated motor function impairment and neuropathic pain. In addition, SCI resulted in an increase in vascular endothelial growth factor (VEGF), AKT phosphorylation, and angiogenesis within the spinal cord, all of which were curbed by OPN reduction. Similarly, OPN knockdown suppressed VEGF expression, AKT phosphorylation, cell migration, invasion, and angiogenesis in cultured vascular endothelial cells. Conclusion. OPN demonstrates a protective influence against motor function impairment and neuropathic pain following SCI. This phenomenon may result from the proangiogenetic effect of OPN, possibly due to activation of the VEGF and/or AKT pathways. [ABSTRACT FROM AUTHOR]

Pseudomyogenic hemangioendothelioma (PHE) is an uncommon mesenchymal neoplasm of intermediate malignant potential showing endothelial differentiation. Around 20 cases of primary osseous PHE have been reported to date. A 16-year-old boy presented with complaints of pain in his right leg. Imaging revealed multifocal intramedullary and cortical-based lytic lesions involving long and small bones. Microscopic examination revealed plump, spindled cells arranged in fascicles and admixed “epithelioid” and “rhabdoid” cells sans vasoformative areas. By immunohistochemistry, the lesional cells were reactive for AE1/AE3, CD31, Erg, Fli1, and SMA, while immunonegative for CD34, myogenin, and S100. Nuclear expression of the INI1/SMARCB1 protein was retained. PHE is a rare entity, more so as a primary osseous lesion; therefore, awareness of the presence of this entity in the bone is the key to making a diagnosis. We discuss its clinicopathological features, differential diagnosis, and an attempt a short review of the literature.

Introduction: Primary pleural epithelial angiosarcoma (EAS) is an extremely rare tumor with no specific clinical symptoms. Clinical data on primary pleural EAS are limited, and misdiagnosis often occurs. Case Presentation: The present study reports the case of a 31-year-old patient diagnosed with primary pleural EAS with lung and bone metastases. The patient presented with persistent right chest pain for 5 months and dyspnea for 2 months. Chest computed tomography (CT) scan revealed right hydropneumothorax, diffuse thickening of the right pleura, passive atelectasis, and scattered nodules in the left lung. A medical thoracoscopic pleural biopsy revealed a vasogenic tumor. To further confirm the diagnosis, positron emission tomography/CT (PET/CT) examination was recommended to determine the biopsy site after multidisciplinary discussion. Increased 18F-FDG uptake in the right pleura and hypermetabolic nodules in the right chest wall, first lumbar vertebrae, second sacral vertebrae, and bilateral iliac crest was detected via PET/CT. CT-guided chest wall and lung biopsies were performed. Immunohistochemistry of specific markers was performed according to remote consultation with a pathologist, and tumor cells with strong positive expression of CD31, CD34, and ETS-related genes led to the final diagnosis of primary pleural EAS. Conclusion: Primary pleural EAS should be considered for hydropneumothorax of an unknown cause. PET/CT can accurately locate the lesion. The pathological examination is the basis for primary pleural EAS diagnosis. Moreover, multidisciplinary discussion and remote expert consultation can improve the diagnosis rate of primary pleural EAS.

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular neoplasm with an intermediate pattern of malignancy between benign neoplasms and angiosarcomas. Only 46 cases of intracranial localization of primary EHE in adults have been published.Case report: A 47-year-old male patient developed pronounced speech disorder of sensory and amnestic aphasia type, right-sided pyramidal hemiparesis within 3–4 days. Magnetic resonance imaging revealed a delimited left sided brain islet neoplasm with signs of hemorrhage and small perifocal edema. Intraoperatively, the neoplasm was represented by a conglomerate of pathologic vessels, with involvement of the terminal branches of the M2 segment of the middle cerebral artery, which prevented radical resection of the neoplasm. Based on histopathological and immunohistochemistry analysis of the neoplasm (positive expression of CD31, CD34, proliferative activity index Ki-67 10%) the morphologic diagnosis of EHE was established. 3 months after surgery, continued growth of the residual part of the neoplasm was noted. Temozolomide chemotherapy was clinically ineffective. The patient died due to the development of dislocation syndrome after 9 months.Discussion. The malignant characteristics of EHE include invasive growth, recurrence, and metastasis, which is more common in intracranial localization of the neoplasm. If EHE is suspected, radical surgical removal of the neoplasm should be sought.

Objective: to study the applicability of the neutrophil-to-lymphocyte ratio (NLR) for monitoring recipient status and for possible minimization of maintenance immunosuppression in the long-term period after liver transplantation (LT).Materials and methods. Blood samples of 19 recipients with satisfactory graft function were examined by flow cytofluorometry at various time periods after LT using hematopoietic stem cell markers CD133, their CD31 derivatives, and alpha-fetoprotein (AFP), compared with the conventional NLR.Results. The use of NLR equivalents with CD133 and CD31 to assess liver transplant status is due to their high representation in liver tissue. Their values change in the long-term posttransplant period (from 1.5 to 6–7 years following LT) ≈20-fold and in different directions, but only when measuring their commissural to the liver cell fractions bearing the AFP marker.Conclusion. In contrast to the conventional NLR, maintenance of the lowest level of CD31 AFP, an NLR «equivalent», achieved at 1.5 years after LT, can be considered a criterion for the success of immunosuppressive therapy in the long-term post-LT period. The developed technique can be used to decide on whether to reduce or discontinue medication-assisted prophylaxis of graft rejection.

Trichinellosis is one of the global food-borne parasitic diseases that can cause severe tissue damage. The traditionally used drugs for the treatment of trichinellosis have limited efficacy against the encysted larvae in the muscular phase of the disease. Therefore, this study aimed to evaluate the role of atorvastatin and mesenchymal stem cells combined with ivermectin against different phases of Trichinella in experimentally infected mice. A total of 120 male Swiss albino mice were divided into two major groups (n = 60 of each), intestinal and muscular phases. Then, each group was subdivided into 10 subgroups (n = 6); non-infected control, infected non-treated control, infected ivermectin treated, infected atorvastatin treated, infected mesenchymal stem cells treated, infected combined ivermectin and atorvastatin treated, infected combined mesenchymal stem cells and ivermectin treated, infected combined mesenchymal stem cells and atorvastatin treated, infected combined mesenchymal stem cells and a full dose of (ivermectin and atorvastatin) treated, and infected combined mesenchymal stem cells and half dose of (ivermectin and atorvastatin) treated. Mice were sacrificed at days 5 and 35 post-infection for the intestinal and muscular phases, respectively. The assessment was performed through many parameters, including counting the adult intestinal worms and muscular encysted larvae, besides histopathological examination of the underlying tissues. Moreover, a biochemical assay for the inflammatory and oxidative stress marker levels was conducted. In addition, levels of immunohistochemical CD31 and VEGF gene expression as markers of angiogenesis during the muscular phase were investigated. The combined mesenchymal stem cells and atorvastatin added to ivermectin showed the highest significant reduction in adult worms and encysted larvae counts, the most noticeable improvement of the histopathological changes, the most potent anti-inflammatory (lowest level of IL-17) and anti-angiogenic (lowest expression of CD31 and VEGF) activities, and also revealed the highly effective one to relieve the oxidative stress (lowest level of SOD, GSH, and lipid peroxidase enzymes). These observed outcomes indicate that adding mesenchymal stem cells and atorvastatin to ivermectin synergistically potentiates its therapeutic efficacy and provides a promising candidate against trichinellosis. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii causes a global parasitic disease. Therapeutic options for eradicating toxoplasmosis are limited. In this study, ZnO and Mg-doped ZnO NPs were prepared, and their structural and morphological chrematistics were investigated. The XRD pattern revealed that Mg-doped ZnO NPs have weak crystallinity and a small crystallite size. FTIR and XPS analyses confirmed the integration of Mg ions into the ZnO framework, producing the high-purity Mg-doped ZnO nanocomposite. TEM micrographs determined the particle size of un-doped ZnO in the range of 29 nm, reduced to 23 nm with Mg2+ replacements. ZnO and Mg-doped ZnO NPs significantly decreased the number of brain cysts (p < 0.05) by 29.30% and 35.08%, respectively, compared to the infected untreated group. The administration of ZnO and Mg-doped ZnO NPs revealed a marked histopathological improvement in the brain, liver, and spleen. Furthermore, ZnO and Mg-doped ZnO NPs reduced P53 expression in the cerebral tissue while inducing CD31 expression, which indicated a protective effect against the infection-induced apoptosis and the restoration of balance between free radicals and antioxidant defense activity. In conclusion, the study proved these nanoparticles have antiparasitic, antiapoptotic, and angiogenetic effects. Being nontoxic compounds, these nanoparticles could be promising adjuvants in treating chronic toxoplasmosis. [ABSTRACT FROM AUTHOR]

Introduction: Primary pleural epithelial angiosarcoma (EAS) is an extremely rare tumor with no specific clinical symptoms. Clinical data on primary pleural EAS are limited, and misdiagnosis often occurs. Case Presentation: The present study reports the case of a 31-year-old patient diagnosed with primary pleural EAS with lung and bone metastases. The patient presented with persistent right chest pain for 5 months and dyspnea for 2 months. Chest computed tomography (CT) scan revealed right hydropneumothorax, diffuse thickening of the right pleura, passive atelectasis, and scattered nodules in the left lung. A medical thoracoscopic pleural biopsy revealed a vasogenic tumor. To further confirm the diagnosis, positron emission tomography/CT (PET/CT) examination was recommended to determine the biopsy site after multidisciplinary discussion. Increased 18F-FDG uptake in the right pleura and hypermetabolic nodules in the right chest wall, first lumbar vertebrae, second sacral vertebrae, and bilateral iliac crest was detected via PET/CT. CT-guided chest wall and lung biopsies were performed. Immunohistochemistry of specific markers was performed according to remote consultation with a pathologist, and tumor cells with strong positive expression of CD31, CD34, and ETS-related genes led to the final diagnosis of primary pleural EAS. Conclusion: Primary pleural EAS should be considered for hydropneumothorax of an unknown cause. PET/CT can accurately locate the lesion. The pathological examination is the basis for primary pleural EAS diagnosis. Moreover, multidisciplinary discussion and remote expert consultation can improve the diagnosis rate of primary pleural EAS. [ABSTRACT FROM AUTHOR]

Background: Due to the close association of CD31 marker positivity and tumor microvessel density, the relationship between this marker and the pathophysiological behavior of the tumor, such as the ability to invade the surrounding tissues and organ damage, is also quite probable. Objectives: We aimed at evaluating the association of CD3l expression with the likelihood of microvascular invasion and other abnormal histopathological findings in patients with colorectal cancer. Methods: In our cross-sectional study, the pathology numbers of 50 samples that were diagnosed with colorectal cancer in their pathology report during 202l and 2022 were identified by searching our hospital information system. Immunohistochemical staining (IHC) using CD31 monoclonal antibody was performed for assessing CD31 positivity. Results: CD31 positivity was found in 34.0% of cases, 35.5% in colon masses, and 31.6% in rectal masses. The patients with positive CD31 had significantly higher tumor grades (P< 0.045). The prevalence rate of vascular invasion was significantly higher in patients with positive CD31 compared to those with negative CD31 states (47.1% versus 12.1%, P = 0.006). Also, the rate of lymph node involvement in the groups with positive and negative CD31 was 58.8% and 24.2%, respectively, indicating a significant difference (P = 0.016). In multivariable logistic regression models, CD31 positivity was shown to be associated with the risk for vascular invasion (OR = 6.211, P = 0.020) and lymph node involvement (OR= 6.535, P = 0.011). Conclusions: CD31 positivity in patients with colorectal cancer can effectively predict invasive behavior of the tumor including vascular invasion, lymph node involvement, and high tumor grades. [ABSTRACT FROM AUTHOR]

In order to demonstrate the intricate interconnection of pulmonary lymphatic vessels, blood vessels, and nerve fibers, the rat lung was selected as the target and sliced at the thickness of 100 μm for multiply immunofluorescence staining with lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), alpha smooth muscle actin (α-SMA), phalloidin, cluster of differentiation 31 (CD31), and protein gene product 9.5 (PGP9.5) antibodies. Taking the advantages of the thicker tissue section and confocal microscopy, the labeled pulmonary lymphatic vessels, blood vessels, and nerve fibers were demonstrated in rather longer distance, which was more convenient to reconstruct a three-dimensional (3D) view for analyzing their spatial correlation in detail. It was clear that LYVE-1+ lymphatic vessels were widely distributed in pulmonary lobules and closely to the lobar bronchus. Through 3D reconstruction, it was also demonstrated that LYVE-1+ lymphatic vessels ran parallel to or around the α-SMA+ venules, phalloidin+ arterioles and CD31+ capillaries, with PGP9.5+ nerve fibers traversing alongside or wrapping around them, forming a lymphatic, vascular and neural network in the lung. By this study, we provide a detailed histological view to highlight the spatial correlation of pulmonary lymphatic, vascular and neural network, which may help us for insight into the functional role of this network under the physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

Background and purpose: The definitive role of mast cells and angiogenesis in the pathogenesis of Peripheral giant cell granuloma (PGCG) of the oral cavity is not yet fully understood. The aim of this study was to evaluate the mast cell counts (MCs) and microvascular density (MVD) and investigating the relationship between them and PGCG of the oral cavity. Materials and methods: In this descriptive-analytic study, 50 samples were selected from the archieve of oral pathology department in dental school at Zahedan University of Medical Sciences using census. The samples included 40 PGCG and 10 normal oral tissues that were stained by immunohistochemistry (CD31 antibody) and toluidine blue to identify MVD and MCs, respectively. Data were analyzed using T-test, Pearson correlation test in SPSS V.21. Results: The mean number of mast cells was 38.51±36.43 in PGCG and 14±3.21 in normal tissues indicating significant difference between the two groups (P= 0.041). Findings showed a significant difference in MVD between PGCG group (93.34±64.43) and normal tissues (41.9±16.7) (P=0.017). MVD and MCs below the epithelium were found to be higher compared with those in deeper area of connective tissue. No correlation was found between the MCs and MVD (r=0.003, P=0.982). Conclusion: In the present study, mast cells count and microvascular density were higher in PGCG than normal tissue which could explain the role of mast cells and the subsequent process of angiogenesis in the pathogenesis of this reactive lesion of the oral cavity, but no correlation was found between the mast cells count and microvascular density.

Age estimation of wounds in veterinary forensic investigations is based on the presence and amount of granulation tissue. However, accurate age assessment is challenging and new time-dependent markers are warranted to support and improve the current procedure. The objective of this study was to evaluate the expression of CD31-positive blood vessels and α-smooth muscle action (α-SMA)-positive myofibroblasts in granulation tissue in order to evaluate their value as markers for porcine wound age estimation in a veterinary forensic context. Immunohistochemical expression of CD31 and α-SMA in 14 experimental porcine skin wounds of different ages (4, 6, 8, 10, 18, 27 and 35 days) and 11 forensic porcine wound specimens (of unknown age) were evaluated. CD31-positive blood vessels and α-SMA-positive myofibroblasts were present in the granulation tissue in the experimental wounds at all time points. A significant decrease in the mean blood vessel counts was found in wounds aged 18, 27 and 35 days compared with wounds aged 6 days (P < 0.001), when assessing both the superficial and deep part of the wound bed. α-SMA expression was lower at 27 and 35 days post wounding compared with 6–18 days post wounding. Combined assessment of three parameters (mean blood vessel counts in the superficial and deep wound beds and α-SMA expression) could approximately specify the age of the wounds as either 6–18 days or ≥27 days. In two of the forensic cases a combination of the three parameters yielded results that were similar to the experimental wounds, indicating a wound age of 6–18 days or ≥27 days, respectively. In the remaining forensic cases a combination of the three parameters did not show the same expression pattern as in the experimental wounds. The results indicate that in some forensic cases the application of CD31 and α- SMA markers appeared to support the current procedure for porcine wound age estimation, but this must be combined with pathological characteristics. [ABSTRACT FROM AUTHOR]

Wound healing is a complex and meticulously orchestrated process involving multiple phases and cellular interactions. This narrative review explores the intricate mechanisms behind wound healing, emphasizing the significance of cellular processes and molecular factors. The phases of wound healing are discussed, focusing on the roles of immune cells, growth factors, and extracellular matrix components. Cellular shape alterations driven by cytoskeletal modulation and the influence of the 'Formin' protein family are highlighted for their impact on wound healing processes. This review delves into the use of absorbable meshes in wound repair, discussing their categories and applications in different surgical scenarios. Interleukins (IL-2 and IL-6), CD31, CD34, platelet rich plasma (PRP), and adipose tissue-derived mesenchymal stem cells (ADSCs) are discussed in their respective roles in wound healing. The interactions between these factors and their potential synergies with absorbable meshes are explored, shedding light on how these combinations might enhance the healing process. Recent advances and challenges in the field are also presented, including insights into mesh integration, biocompatibility, infection prevention, and postoperative complications. This review underscores the importance of patient-specific factors and surgical techniques in optimizing mesh placement and healing outcomes. As wound healing remains a dynamic field, this narrative review provides a comprehensive overview of the current understanding and potential avenues for future research and clinical applications. [ABSTRACT FROM AUTHOR]

Introduction: Optic nerves development begins throughout pregnancy and continues after birth. Aging entails gradual degeneration of the structure and the number of the optic nerve axons. Aim of the Work: This research was designed to clarify the prenatal and postnatal development of the optic nerve in the albino rat and the age-related changes in its axons. Material and Methods: Forty-five albino rats were used. The animals were divided into Prenatal group (Group I) and Postnatal group (Group II). In Group I, ten adult males were put with ten females for mating. Pregnant females were sacrificed at different times of gestation and five embryos were extracted for each subgroup; subgroup IA (aged 7 days of gestation), subgroup IB (aged 14 days of gestation) and subgroup IC (aged 21 days of gestation). In Group II, twenty-five albino rats of different ages were divided into five subgroups; Subgroup IIA (aged one month), Subgroup IIB (aged 3 months), Subgroup IIC (aged 9 months), Subgroup IID (aged 18 months) and Subgroup IIE (aged 24 months). The optic nerves of all subgroups were prepared for histological, immunohistochemical examination. Statistical analysis of immune-positive percentage area and the number of optic nerve axons were performed. Results: Optic nerve was first formed in rat embryos aged 21 days of gestation. It’s formed of the axons of retinal ganglion cells. Aging causes apparent deterioration of the optic nerve structure with a highly significant increase in CD31 immunopositive cells percentage area. Ultra-structurally, the number of optic nerve axons significantly decreased. Conclusion: This study provides histological description of development of the optic nerve in the albino rat across different prenatal and postnatal ages. The aging is associated with degeneration, neovascularization and reduction of optic nerve axons which could explain why most elderly have vision loss with varying extent. [ABSTRACT FROM AUTHOR]

Hepatic epithelioid hemangioendothelioma (HEHE) is an extremely uncommon tumor of the liver. It typically lacks recognizable clinical signs and is diagnosed with the aid of imaging and histopathology combined with immunohistochemical analysis. We discuss the case of a 40-year-old woman with HEHE. The aim of this case report and literature review is to increase doctors’ knowledge of HEHE and reduce the incidence of missed clinical diagnoses.

Abstract Background Hypoxia is a key driver of fibrosis and is associated with capillary rarefaction in humans. Objectives Characterize capillary rarefaction in cats with chronic kidney disease (CKD). Animals Archival kidney tissue from 58 cats with CKD, 20 unaffected cats. Methods Cross‐sectional study of paraffin‐embedded kidney tissue utilizing CD31 immunohistochemistry to highlight vascular structures. Consecutive high‐power fields from the cortex (10) and corticomedullary junction (5) were digitally photographed. An observer counted and colored the capillary area. Image analysis was used to determine the capillary number, average capillary size, and average percent capillary area in the cortex and corticomedullary junction. Histologic scoring was performed by a pathologist masked to clinical data. Results Percent capillary area (cortex) was significantly lower in CKD (median 3.2, range, 0.8‐5.6) compared to unaffected cats (4.4, 1.8‐7.0; P =

Although bone marrow mesenchymal stem cells (BMSCs) might have therapeutic potency in ischemic stroke, the benefits are limited. The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor (VEGF) on behavioral defects in a rat model of transient cerebral ischemia, which was induced by middle cerebral artery occlusion. VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke. We found that compared with the stroke-only group and the vehicle- and BMSCs-control groups, the VEGF-BMSCs treated animals displayed the largest benefits, as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke. Additionally, VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier, increased the regeneration of blood vessels in the region of ischemic penumbra, and reducedneuronal degeneration surrounding the infarct core. Further mechanistic studies showed that among all transplant groups, VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor. These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.

Ovarian cancer is the fifth leading cause of cancer‐related deaths in women and the most lethal gynecologic cancer. It is curable when discovered at an early stage, but usually remains asymptomatic until advanced stages. It is crucial to diagnose the disease before it metastasizes to distant organs for optimal patient management. Conventional transvaginal ultrasound imaging offers limited sensitivity and specificity in the ovarian cancer detection. With molecularly targeted ligands addressing targets, such as kinase insert domain receptor (KDR), attached to contrast microbubbles, ultrasound molecular imaging (USMI) can be used to detect, characterize and monitor ovarian cancer at a molecular level. In this article, the authors propose a standardized protocol is proposed for the accurate correlation between in‐ vivo transvaginal KDR‐targeted USMI and ex vivo histology and immunohistochemistry in clinical translational studies. The detailed procedures of in vivo USMI and ex vivo immunohistochemistry are described for four molecular markers, CD31 and KDR with a focus on how to enable the accurate correlation between in vivo imaging findings and ex vivo expression of the molecular markers, even if not the entire tumor could can be imaged by USMI, which is not an uncommon scenario in clinical translational studies. This work aims to enhance the workflow and the accuracy of characterization of ovarian masses on transvaginal USMI using histology and immunohistochemistry as reference standards, which involves sonographers, radiologists, surgeons, and pathologists in a highly collaborative research effort of USMI in cancer. [ABSTRACT FROM AUTHOR]

Back pain (BP) due to degenerative disc disease (DDD) is a severe, often disabling condition. The aim of this study was to determine the association between the expression level of proinflammatory cytokines (IL-1β, IL-6, and IL-17), angiogenesis markers (VEGF-A and CD31) in intervertebral disc (IVD) tissue and IVD degeneration in young people with discogenic BP. In patients who underwent discectomy for a disc herniation, a clinical examination, magnetic resonance imaging of the lumbar spine, histological and immunohistochemical analyses of these factors in IVD were performed in comparison with the parameters of healthy group samples (controls). Histology image analysis of IVD fragments of the DDD group detected zones of inflammatory infiltration, combined with vascularization, the presence of granulation tissue and clusters of chondrocytes in the tissue of nucleus pulposus (NP). Statistically significant increased expression of IL-1β, IL-6, IL-17, VEGF-A and CD31 was evident in the samples of the DDD group compared with the controls, that showed a strong correlation with the histological disc degeneration stage. Our results denote an immunoinflammatory potential of chondrocytes and demonstrates their altered morphogenetic properties, also NP cells may trigger the angiogenesis. [ABSTRACT FROM AUTHOR]

Several studies have shown that an abnormal vascular-immunity link could increase Alzheimer's disease (AD) risk; however, the mechanism is unclear. CD31, also named platelet endothelial cell adhesion molecule (PECAM), is a surface membrane protein of both endothelial and immune cells and plays important roles in the interaction between the vascular and immune systems. In this review, we focus on research regarding CD31 biological actions in the pathological process that may contribute to AD based on the following rationales. First, endothelial, leukocyte and soluble forms of CD31 play multi-roles in regulating transendothelial migration, increasing blood–brain barrier (BBB) permeability and resulting in neuroinflammation. Second, CD31 expressed by endothelial and immune cells dynamically modulates numbers of signaling pathways, including Src family kinases, selected G proteins, and β-catenin which in turn affect cell-matrix and cell–cell attachment, activation, permeability, survival, and ultimately neuronal cell injury. In endothelia and immune cells, these diverse CD31-mediated pathways act as a critical regulator in the immunity-endothelia-brain axis, thereby mediating AD pathogenesis in ApoE4 carriers, which is the major genetic risk factor for AD. This evidence suggests a novel mechanism and potential drug target for CD31 in the background of genetic vulnerabilities and peripheral inflammation for AD development and progression. [ABSTRACT FROM AUTHOR]

In porcine placenta, abnormal development of the placental vasculature leads to placental insufficiency. The aim of this study was to determine the mRNA expression of angiogenic growth factors and to determine the vascular characteristics in placenta at day 40 of pig gestation. Samples were collected from maternal‐chorioallantoic interface (n = 21) for the measurement of mRNA expression of VEGFA, ANGPT1, ANGPT2, FGF2 and its receptors KDR, TEK, FGFR1IIIc, FGFR2IIIb respectively, and for immunohistochemistry analysis of CD31 and VEGFA. Immunohistochemical analysis of CD31 and VEGFA, morphometric measurement of blood vessels, high‐resolution light microscopy and transmission electron microscopy were performed. Capillary area density, number of blood vessels and capillary area were significantly higher on the maternal side than on the fetal side (p <.05). The ultrastructural finding of blood vessels demonstrates close contact with the trophoblastic epithelium. The relative mRNA expression of VEGFA and its receptor KDR was higher compared with the other angiogenic genes. In conclusion, a high mRNA expression of VEGFA and its receptor KDR added to the immunohistochemical results suggest a potential role of these genes in this pathway associated with an increase in the density of the capillary area on the maternal side and a reduction in the hemotrophic diffusion distance at the interface for nutrient exchange. [ABSTRACT FROM AUTHOR]

Effective neutrophil migration to sites of inflammation is crucial for host immunity. A coordinated cascade of steps allows intravascular leukocytes to counteract the shear stress, transmigrate through the endothelial layer, and move toward the extravascular, static environment. Those events are tightly orchestrated by integrins, but, while the molecular mechanisms leading to their activation have been characterized, the regulatory pathways promoting their detachment remain elusive. In light of this, it has long been known that platelet-endothelial cell adhesion molecule (Pecam1, also known as CD31) deficiency blocks leukocyte transmigration at the level of the outer vessel wall, yet the associated cellular defects are controversial. In this study, we combined an unbiased proteomic study with in vitro and in vivo single-cell tracking in mice to study the dynamics and role of CD31 during neutrophil migration. We found that CD31 localizes to the uropod of migrating neutrophils along with closed β2-integrin and is required for essential neutrophil actin/integrin polarization. Accordingly, the uropod of Pecam1-/- neutrophils is unable to detach from the extracellular matrix, while antagonizing integrin binding to extracellular matrix components rescues this in vivo migratory defect. Conversely, we showed that sustaining CD31 co-signaling actively favors uropod detachment and effective migration of extravasated neutrophils to sites of inflammation in vivo. Altogether, our results suggest that CD31 acts as a molecular rheostat controlling integrin-mediated adhesion at the uropod of egressed neutrophils, thereby triggering their detachment from the outer vessel wall to reach the inflammatory sites.

Objective To unravel the possible mechanism of the role of recombinant human high mobility group box 1 (rhHMGB1) protein in regulating the angiogenesis of endothelial cells. Methods Endothelial cells were divided into the control group, bone marrow mesenchymal stem cells (MSC) supernatant group and rhHMGB1 group. The proliferation and survival of endothelial cells were detected by cell counting kit(CCK)-8 assay. The relative expression levels of vascular endothelial growth factor (VEGF), Yes-associated protein (YAP), CD31 and hypoxia inducible factor (HIF)-1α proteins were determined by Western blot. The relative expression levels of VEGF, YAP, CD31 and HIF-1α messenger RNA (mRNA) were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). The migration ability of endothelial cells was assessed by Transwell chamber test. The localization of YAP was detected by immunofluorescence staining. Results Compared with the control group, the migration rate of endothelial cells was increased in the rhHMGB1 group (P<0.05), and the cell migration rate was enhanced over time. Compared with the control group, the relative expression levels of VEGF and p-YAP proteins were up-regulated in the MSC supernatant group, and the differences were statistically significant (both P<0.05). Compared with the control group, the relative expression levels of VEGF and HIF-1α proteins, VEGF and CD31 mRNA and YAP and p-YAP proteins were up-regulated, and YAP/p-YAP ratio was increased in the rhHMGB1 group, and the differences were statistically significant (all P<0.05). Compared with the MSC supernatant group, the relative expression levels of CD31 mRNA and YAP protein were up-regulated, and the YAP/p-YAP ratio was increased in the rhHMGB1 group, and the differences were statistically significant (all P<0.05). Conclusions Exogenous high-concentration rhHMGB1 may promote the migration ability of endothelial cells and upregulate the expression levels of angiogenesis-related proteins by regulating the recruitment of YAP to the nucleus. [ABSTRACT FROM AUTHOR]

Background & Objective: Lymphovascular tumoral invasion is a typical histopathological feature of gastric carcinomas and supports the recognition of highrisk patients for the recurrence. We aimed to study CD31 expression in diverse subtypes of gastric carcinomas and to show its association with the histopathologic findings of the carcinoma to assess the prognosis. Methods: This cross-sectional study was conducted on 40 established patients with gastric adenocarcinoma from radical gastrectomy. The patients were classified according to the pathology assessments. Tumoral tissues were assessed by immunohistochemical staining for CD31 expression. Malignant behavior was estimated by histopathological evaluations. Results: CD31 positivity was described in 23 (57.5%) of all evaluated patients. In assessment of CD31 expression and tumor features presented, no significant association between the CD31 expression and patients' age, sex, tumor site, size, grade and stage, subtypes of carcinoma, perineural invasion, and also lymphovascular invasion, was found. (P>0.05). Conclusion: Lymphovascular invasion may make valuable additional evidence and may be useful to detect gastric carcinoma patients at high risk for recurrence, who could be candidates for more supplementary therapies. However, in our study, CD31 expression did not show any association with the aggressive histopathologic features of this tumor. [ABSTRACT FROM AUTHOR]

Background: Sjögren's syndrome (SS) is an autoimmune disease hallmarked by infiltration and destruction of exocrine glands. Currently, there is no therapy that warrants full recovery of the affected tissues. Umbilical cord-derived multipotent stromal cells, microincapsulated in an endotoxin-free alginate gel (CpS-hUCMS), were shown to modulate the inflammatory activity of PBMCs in SS patients in vitro, through release of soluble factors (TGFb1, IDO1, IL6, PGE2, VEGF). These observations led us to set up the present study, aimed at defining the in vitro effects of CpS-hUCMS on pro- and anti-inflammatory lymphocyte subsets involved in the pathogenesis of SS. Methods and results: Peripheral blood mononuclear cells (PBMCs) upon collection from SS patients and matched healthy donors, were placed in coculture with CpS-hUCMS for five days. Cellular proliferation and T-(Tang, Treg) and B-(Breg, CD19+) lymphocyte subsets were studied by flow cytometry, while Multiplex, Real-Time PCR, and Western Blotting techniques were employed for the analysis of transcriptome and secretome. IFNg pre-treated hUCMS were assessed with a viability assay and Western Blotting analysis before co-culture. After five days co-culture, CpS-hUCMS induced multiple effects on PBMCs, with special regard to decrease of lymphocyte proliferation, increase of regulatory B cells and induction of an angiogenic T cell population with high expression of the surface marker CD31, that had never been described before in the literature. Conclusion: We preliminarily showed that CpS-hUCMS can influence multiple pro- and anti-inflammatory pathways that are deranged in SS. In particular, Breg raised and a new Tang phenothype CD3+CD31HCD184+ emerged. These results may considerably expand our knowledge on multipotent stromal cell properties and may open new therapeutic avenues for the management of this disease, by designing ad hoc clinical studies. [ABSTRACT FROM AUTHOR]

Background: Hypoxia is a key driver of fibrosis and is associated with capillary rarefaction in humans. Objectives: Characterize capillary rarefaction in cats with chronic kidney disease (CKD). Animals: Archival kidney tissue from 58 cats with CKD, 20 unaffected cats. Methods: Cross‐sectional study of paraffin‐embedded kidney tissue utilizing CD31 immunohistochemistry to highlight vascular structures. Consecutive high‐power fields from the cortex (10) and corticomedullary junction (5) were digitally photographed. An observer counted and colored the capillary area. Image analysis was used to determine the capillary number, average capillary size, and average percent capillary area in the cortex and corticomedullary junction. Histologic scoring was performed by a pathologist masked to clinical data. Results: Percent capillary area (cortex) was significantly lower in CKD (median 3.2, range, 0.8‐5.6) compared to unaffected cats (4.4, 1.8‐7.0; P = <.001) and was negatively correlated with serum creatinine concentrations (r = −.36, P =.0013), glomerulosclerosis (r = −0.39, P = <.001), inflammation (r = −.30, P =.009), and fibrosis (r = −.30, P =.007). Capillary size (cortex) was significantly lower in CKD cats (2591 pixels, 1184‐7289) compared to unaffected cats (4523 pixels, 1801‐7618; P = <.001) and was negatively correlated with serum creatinine concentrations (r = −.40, P = <.001), glomerulosclerosis (r = −.44, P <.001), inflammation (r = −.42, P = <.001), and fibrosis (r = −.38, P = <.001). Conclusions and Clinical Importance: Capillary rarefaction (decrease in capillary size and percent capillary area) is present in kidneys of cats with CKD and is positively correlated with renal dysfunction and histopathologic lesions. [ABSTRACT FROM AUTHOR]

Liver cancer is characterized by hypervascularization. Anti-angiogenic agents may normalize the tumor vasculature and improve the efficacy of other treatments. The present study aims to investigate the anti-angiogenic effect of Plasmodium infection in a mouse model of implanted liver cancer cells. HepG2 cells were injected into the left liver lobe of nude mice as a model of in situ hepatic tumorigenesis. Plasmodium yoelii parasitized erythrocytes were administered in the animal model of liver cancer to introduce Plasmodium infection. The tumor growth and microvascular density were determined in the presence or absence of Plasmodium infection. The expression levels of hypoxia-inducible factor 1α (HIF-1α) and angiogenesis-related factors were evaluated using western blotting and reverse transcription-quantitative PCR analysis. The results demonstrated that Plasmodium infection suppressed tumor growth and vascularization in the mouse model of implanted HepG2 cells. Plasmodium parasites reduced the expression of pro-angiogenic factors (vascular endothelial growth factor A and angiopoietin 2), matrix metalloproteinases [(MMP)2 and MMP9] and inflammatory cytokines [tumor necrosis factor α, interleukin 6 (IL)-6) and IL-1β] in both hepatic and tumor tissues. HIF-1α was downregulated in both hepatic and tumor tissues upon Plasmodium infection, and HIF-1α overexpression rescued angiogenesis and tumor growth under the condition of Plasmodium infection. In conclusion, the results of the present study demonstrated the anti-angiogenic and anti-tumorigenic effects of Plasmodium infection on liver cancer through downregulating HIF-1α expression, indicating that Plasmodium parasites could be developed as an intervention strategy to restrain neo-angiogenesis in liver cancer. [ABSTRACT FROM AUTHOR]

Angiosarcomas are malignant neoplasms arising from endothelial cells. Cutaneous angiosarcoma is the most common form, typically occurring in the setting of chronic lymphedema or previous radiation. The head and neck are the most common locations for cutaneous angiosarcoma, with rare occurrence on the trunk and extremities. Herein, we present a case of angiosarcoma on the lower extremity in an elderly man. This 71-year-old man presented with a two-year history of red-yellow discoloration of the left lower leg with subsequent development of black nodules over the past several months prior to presentation. He denied any itching, bleeding, or ulceration. Past medical history included diabetes, hypertension, and non-melanoma skin cancer. Physical examination showed erythematous, violaceous, non-blanchable papules with yellow atrophic regions and overlying black crusted nodules and plaques. Biopsies were taken and the patient was diagnosed with angiosarcoma and referred to a tertiary care center for further evaluation.

IntrodcutionAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary.MethodsWe assessed the ability of anti-CD31-ORI-NPs to penetrate endothelial cell barriers and specifically accumulate in lung tissues using an animal model. We also compared the efficacy of anti-CD31-ORI-NPs to that of free oridonin in ameliorating acute lung injury and evaluated the cytotoxicity of both treatments on endothelial cells.ResultsCompared to free ORI, the amount of anti-CD31-ORI-NPs accumulated in lung tissues increase at least three times. Accordingly, anti-CD31-ORI-NPs improve the efficacy three times on suppressing IL-6 and TNF-a secretion, ROS production, eventually ameliorating acute lung injury in animal model. Importantly, anti-CD31-ORI-NPs significantly decrease the cytotoxicity at least two times than free oridonin on endothelial cells.DiscussionOur results from this study will not only offer a novel therapeutic strategy with high efficacy and low toxicity, but also provide the rational design of nanomaterials of a potential drug for acute lung injury therapy.

BackgroundSjögren’s syndrome (SS) is an autoimmune disease hallmarked by infiltration and destruction of exocrine glands. Currently, there is no therapy that warrants full recovery of the affected tissues. Umbilical cord-derived multipotent stromal cells, microincapsulated in an endotoxin-free alginate gel (CpS-hUCMS), were shown to modulate the inflammatory activity of PBMCs in SS patients in vitro, through release of soluble factors (TGFβ1, IDO1, IL6, PGE2, VEGF). These observations led us to set up the present study, aimed at defining the in vitro effects of CpS-hUCMS on pro- and anti-inflammatory lymphocyte subsets involved in the pathogenesis of SS.Methods and resultsPeripheral blood mononuclear cells (PBMCs) upon collection from SS patients and matched healthy donors, were placed in co-culture with CpS-hUCMS for five days. Cellular proliferation and T- (Tang, Treg) and B- (Breg, CD19+) lymphocyte subsets were studied by flow cytometry, while Multiplex, Real-Time PCR, and Western Blotting techniques were employed for the analysis of transcriptome and secretome. IFNγ pre-treated hUCMS were assessed with a viability assay and Western Blotting analysis before co-culture. After five days co-culture, CpS-hUCMS induced multiple effects on PBMCs, with special regard to decrease of lymphocyte proliferation, increase of regulatory B cells and induction of an angiogenic T cell population with high expression of the surface marker CD31, that had never been described before in the literature.ConclusionWe preliminarily showed that CpS-hUCMS can influence multiple pro- and anti-inflammatory pathways that are deranged in SS. In particular, Breg raised and a new Tang phenothype CD3+CD31HCD184+ emerged. These results may considerably expand our knowledge on multipotent stromal cell properties and may open new therapeutic avenues for the management of this disease, by designing ad hoc clinical studies.