Endothelial Cell-specific Molecule-1 Research Articles

Prognostic and Diagnostic Value of Endocan in Kidney Diseases.

Endocan, previously called endothelial cell-specific molecule-1, is a soluble proteoglycan that is predominantly expressed in vascular endothelial cells of the lungs and kidneys. It is upregulated by proinflammatory cytokines and plays a critical role in inflammatory, proliferative, and neovascularization processes. The utility of endocan as a biomarker in a wide spectrum of diseases is being increasingly acknowledged. In this review, we summarize the current evidence concerning the role of endocan in kidney diseases, with emphasis on its prognostic and diagnostic value. It seems that the determination of plasma endocan levels may provide useful prognostic information in many types of renal failure such as chronic kidney disease, IgA nephropathy, and diabetic nephropathy. Endocan could additionally improve the early diagnostic evaluation of acute kidney disease, chronic renal allograft injury, and acute rejection after kidney transplantation, thus contributing to endothelial cell injury monitoring in a timely manner.

Endocan: A Key Player of Cardiovascular Disease.

Endothelial dysfunction is considered to be an early change in atherosclerosis. Endocan, also known as endothelial cell specific molecule-1, is a soluble proteoglycan mainly secreted by endothelial cells. Inflammatory factors such as IL-1β and TNF-α can up regulate the expression of endocan and then affect the expression of cell adhesion molecules, such as ICAM-1 and VCAM-1, which play an important role in promoting leukocyte migration and inflammatory response. Elevated plasma levels of endocan may reflect endothelial activation and dysfunction, and is considered to be a potential immuno-inflammatory marker that may be related to cardiovascular disease. In the case of hypertension, diabetes, angina pectoris and acute myocardial infarction, the increase or decrease of serum endocan levels is of great significance. Here, we reviewed the current research on endocan, and emphasis its possible clinical value as a prognostic marker of cardiovascular disease. Endocan may be a useful biomarker for the prognosis of cardiovascular disease, but more research is needed on its mechanism of action.

Serum Expression of ESM-1, HMWA, and AGEs and Its Relationship with Disease Severity in Patients with Gestational Hypertension.

Objective The research is to investigate the expression and the relationship between serum endothelial cell-specific molecular molecule-1 (ESM-1), high molecular weight adiponectin (HMWA), and late glycosylation terminal product (AGEs) in patients with gestational hypertension. Methods 75 patients with pregnant hypertension who were treated in our hospital from June 2019 to June 2020 were selected as the case group, and 70 healthy pregnant women with pregnancy examination at the same period in our hospital were selected as the control group to analyze the changes in serum ESM-1, HMWA, and AGEs levels and the correlation with the degree of illness and their predictive value. Results Serum ESM-1 and AGEs were significantly higher in the case group than in the control group. Serum HMWA was significantly lower than that in the control group (P < 0.05). The gestational hypertensive serum ESM-1 and AGEs was significantly lower than in patients with mild preeclampsia and severe preeclampsia. Serum HMWA was significantly higher than in patients with mild preeclampsia and severe preeclampsia. Serum ESM-1 and AGEs of mild preeclampsia were significantly lower than in patients with severe preeclampsia. Serum HMWA was significantly higher than in patients with severe preeclampsia (P < 0.05). The result of correlation analysis shows a positive correlation between serum ESM-1 and AGEs (P < 0.05). A negative correlation was observed between HMWA and the degree of illness (P < 0.05). Conclusion Serum ESM-1, HMWA, and AGEs are abnormally expressed in gestational hypertension, are closely related to the degree of condition, and have important clinical significance for condition control.

Role of endothelial cell specific molecule-1 (endocan) and cardiac imaging in early detection of cardiac involvement in psoriatic patients with or without arthritis

Aim of the workMeasuring serum endocan level to determine its potential role in detecting subclinical cardiovascular involvement in psoriatic patients with or without arthritis. Patients and methodsThis work included 14 psoriatic arthritis (PsA) patients, 14 psoriasis only (PsO) patients, and 14 age and sex matched controls. The psoriasis area severity index was evaluated. Serum endocan level was measured, subclinical atherosclerosis was assessed using brachial artery flow-mediated vasodilation (FMD), and echocardiography: standard and tissue Doppler imaging (TDI) was performed. ResultsThe mean age of PsA patients was 38.3 ± 9.9 years and for PsO was 37.9 ± 8 years. They were 3 males and 11 females in both groups with a comparable psoriasis duration (11 ± 4.9 vs 8 ± 6.3 years; p = 0.17). PsA patients had significantly increased endocan level (618 ± 227.8 ng/L) compared to those with PsO or controls (359 ± 185.7 and 130.6 ± 38.2 ng/L respectively; p < 0.001). 4 (28.6%) PsA patients, 1 (7.1%) PsO patient and none of the controls had FMD abnormality. TDI revealed early diastolic mitral annular motion velocity (E') abnormality in 5 (35.7%) PsA patients. In PsA patients, endocan level was significantly elevated in patients with FMD or E' abnormality compared to those without (p = 0.01 and p = 0.001, respectively). Serum endocan significantly negatively correlated with FMD and E' in psoriatic patients. Serum endocan significantly detected FMD and E' abnormalities in psoriatic patients (p = 0.002 and p = 0.001, respectively). ConclusionSubclinical cardiovascular involvement was evident among psoriatic patients, particularly those with arthritis. Serum endocan is a promising endothelial biomarker for detecting subclinical atherosclerosis and preclinical cardiac dysfunction in psoriatic patients.

Total NT-proBNP, a novel biomarker related to recurrent atrial fibrillation

BackgroundNovel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown.ObjectivesTo test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons.MethodsA total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level.ResultsOver a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04–1.36], p = 0.026; NT-proBNP: HR:1.19[1.06–1.35], p = 0.016; Ang2: HR:1.07[0.95–1.20], p = 0.283; BMP10: HR:1.09[0.96–1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29–1.90], p < 0.001 1.63], p = 0.097).ConclusionsThe association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle.

EMS1/DLL4-Notch Signaling Axis Augments Cell Cycle-Mediated Tumorigenesis and Progress in Human Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignant neoplasm that is prone to local invasion and metastasis. Meanwhile, overexpressed endothelial cell-specific molecule 1 (ESM1) is closely related to tumorigenesis of multitudinous tumors. However, the prognosis value and biological function of ESM1 in ACC remains undefined. In the current essay, the assessment in human ACC samples and multiple public cancer databases suggested that ESM1 was significantly overexpressed in ACC patients. The abnormal expression of ESM1 was evidently correlated with dismal overall survival (OS) in ACC patients. Then, the gene-set enrichment analysis (GSEA) was applied to unravel that ESM1 was mostly involved in cell cycle and Notch4 signaling pathway. Furthermore, in vitro experiment, RNA interference of ESM1 was carried out to state that ESM1 augments CDK1 and p21-mediated G2/M-phase transition of mitosis, cell proliferation via DLL4-Notch signaling pathway in human ACC cell line, SW13 cells. Additionally, two possible or available therapeutic strategies, including immunotherapy and chemotherapy, have been further explored. Immune infiltration analysis highlighted that no significant difference was found in ACC patients between EMS1high and EMS1low group for immune checkpoint-related genes. In addition, the overexpression of ESM1 might trigger the accumulation of tumor mutation burden (TMB) during the cell cycle of DNA replication in ACC. The gene-drug interaction network then indicated that ESM1 inhibitors, such as cisplatin, might serve as potential drugs for the therapy of ACC. Collectively, the results asserted that ESM1 and related regulators might act as underlying prognostic biomarkers or novel therapeutic targets for ACC.

Diagnostic and Prognostic Value of Serum Endocan Levels in Patients With COVID-19.

We aimed to evaluate whether there was a relationship between endocan (human endothelial cell-specific molecule-1) levels and disease prognosis in patients who presented to the emergency department with coronavirus disease 2019 (COVID-19). A total of 60 patients with COVID-19 who were hospitalized from the emergency department to clinical wards and a control group consisting of healthy adult individuals (n = 28), were included in the study. The majority (93.3%) of the patients were discharged after recovery; 6.7% died. The median endocan value was 243.5 ng/mL in the patient group versus 201.5 ng/mL in the control group (P = .002). The median endocan level was 240.5 ng/mL in those discharged with recovery and 558 ng/mL in those who died (P = .001). There was no significant relationship in hospitalization duration, sex, tomography findings, and clinical outcomes. A 202 ng/mL serum endocan level had 86.7% sensitivity and 50% specificity for COVID-19. Serum endocan levels may be a useful biomarker both for the diagnosis of COVID-19 and to predict mortality.

Can we use endocan level to determine severity of pancreatitis?

Endothelial cell specific molecule-1 (ESM-1), also known as endocan, is a soluble proteoglycan secreted by human vascular endothelial cells. In some studies, it has been found that endocan have important effects on cell adhesion, inflammation and angiogenesis. In this study, we aimed to evaluate the endocan level in patients with pancreatitis and the availability of endocan level in determining the severity of the disease. A total of 42 patients with pancreatitis and 33 healthy individuals were included in the study. The serum endocan levels in patients were evaluated 1st and 3 th days after the symptom's onset. Current scoring systems and the relationship between the severity of the disease and endocan levels were evaluated. The endocan levels of the patients on day 1 are significantly correlated only with the APACHE II score (p=0.039 r=0.319), while the endocan values on day 3 are significantly correlated with the BISAP (bedside index of severity in acute pancreatitis) (p=0.013 r=0.380), APACHE II (Acute Physiology and Chronic Health Evaluation)(p<0.001; r=0.53) and Ranson (p=0.037 r=0.32) scores. The cutoff level of endocan (day 3) was calculated 92.2 pg/ml (83% sensitivity and 50% specificity; p=0.039 area under the curve 0.706) for severe pancreatitis when considering the patients with a score of 8 or higher in the APACHE II scoring system. Serum endocan level can be used as a marker of prognosis in patients with pancreatitis. However, studies involving large populations are needed on this matter.

The penile duplex ultrasound: How and when to perform it?

Because it is a superficial structure, the penis is ideally suited to ultrasound imaging. A number of disease processes, including Peyronie's disease, penile fractures and tumors, are clearly visualized with ultrasound. Baseline and dynamic assessment of cavernosal arterial changes after pharmaco-stimulation with alprostadil allows standardized diagnosis of arterial and venogenic causes of erectile dysfunction (ED). To illustrate how to correctly perform flaccid and dynamic penile duplex ultrasound (D-PDU) and in which patients to recommend it. An extensive search of the literature was carried out on Pubmed with the insertion of the following Medical Subjects Headings (MeSH) terms and keywords "penile color Doppler ultrasound" "peak systolic velocity" "end-diastolic velocity", "acceleration time", "resistance index". In our experience, arterial erectile dysfunction is identified after standardized intracavernous injection (ICI) of alprostadil (10mcg) when values of peak systolic velocity (PSV) are <35cm/s and, in the most severe forms, for values <25cm/s. Arterial insufficiency can also be identified by increased acceleration time (AT) values (>110ms) and/or by a lack of visualization of helicine arteries at power Doppler mode along with incomplete achievement of penile rigidity. The veno-occlusive incompetence is determined when end-diastolic velocity (EDV) values are >4.5-5cm/s or in the case of resistance index (RI) values <0.75. The assessment of additional surrogate markers of endothelial dysfunction, that is, intima-media thickness, mean platelet volume (MPV), endothelial progenitor cells (EPC), endothelial cell specific molecule-1(endocan) are also useful in assessing the patient's cardiovascular risk but are still considered investigational in the interpretation of D-PDU results. D-PDU scan after ICI with vasoactive drugs is a safe procedure and represents the gold standard for the diagnostics of penile pathologies and should be performed in men with ED not responding to oral conventional therapies and/or in those requiring accurate stratification of cardiovascular risk.

Targeting Endothelial Cell-Specific Molecule 1 Protein in Cancer: A Promising Therapeutic Approach.

Despite the dramatic advances in cancer research in the past few years, effective therapeutic strategies are urgently needed. Endothelial cell-specific molecule 1 (ESM-1), a soluble dermatan sulfate proteoglycan, also known as endocan, serves as a diagnostic and prognostic indicator due to its aberrant expression under pathological conditions, including cancer, sepsis, kidney diseases, and cardiovascular disease. Significantly, ESM-1 can promote cancer progression and metastasis through the regulation of tumor cell proliferation, migration, invasion, and drug resistant. In addition, ESM-1 is involved in the tumor microenvironment, containing inflammation, angiogenesis, and lymph angiogenesis. This article reviews the molecular and biological characteristics of ESM-1 in cancer, the underlying mechanisms, the currently clinical and pre-clinical applications, and potential therapeutic strategies. Herein, we propose that ESM-1 is a new therapeutic target for cancer therapy.

ESM1 promotes triple-negative breast cancer cell proliferation through activating AKT/NF-κB/Cyclin D1 pathway.

Triple-negative breast cancer (TNBC) is a subtype of invasive breast cancer that tests negative for PR, ER and excess HER2 protein. TNBC has a greater progression potential with poorer prognosis, compared with other types of breast cancer. Endothelial cell-specific molecule 1 (ESM1), also known as endocan, is overexpressed in various cancers including breast cancer and may play an important role in cancer progression. The online resource of The Cancer Genome Atlas (TCGA) was used for analyzing the expression alteration of ESM1 in breast cancer patient tissues. We examined the changes of various malignant behaviors of TNBC cell and in vivo tumor growth after inhibiting or overexpressing ESM1 in two human TNBC cell lines, MDA-MB-468 and MDA-MB-231. When ESM1 was knocked down or overexpressed in TNBC cell, AKT and p65 phosphorylation and Cyclin D1 expression were analyzed by western blotting. The ESM1-overexpressing TNBC cell was treated with MK-2206 and BAY-117082 at various concentrations. Our analyses show that ESM1 is overexpressed in TNBC cell lines as well as patient tissues, which is correlated to poor prognosis. Our results demonstrate that ESM1 knockdown decreases while overexpression of ESM1 increases in vitro proliferation, migration and invasion of TNBC cell and knockdown of ESM1 inhibits in vivo TNBC tumor growth. Our mechanistic study further discloses that ESM1 promotes the proliferation of TNBC cell through activating an Akt-dependent NF-κB/Cyclin D1 pathway. Our results demonstrate that ESM1 knockdown decreases while overexpression of ESM1 increases in vitro migration, proliferation and invasion of TNBC cell and knockdown of ESM1 inhibits in vivo tumor growth of TNBC in the xenograft mouse model. Our mechanistic study further discloses that ESM1 promotes the proliferation of TNBC cell through activating the Akt-dependent NF-κB/CyclinD1 pathway. Our findings expand the knowledge about the molecular mechanisms underlying TNBC progression and provide rationale for using ESM1 as a therapeutic target or prognostic marker for TNBC.

Increased Carotid Intima–Media Thickness and Endothelial Cell-Specific Molecule-1 (Endocan) Levels in Obese Children

Obesity in children appears to be associated with increased risk of cardiovascular and metabolic diseases later in life. Early development of insulin resistance (IR) may lead to endothelial dysfunction and increased carotid intima-media thickness (cIMT) even in childhood. We compared endothelial cell-specific molecule-1 (endocan) levels in pediatric obese patients with those in healthy controls to determine whether endocan could be used as a biological marker of complications caused by endothelial damage. In 80 obese pubertal children (44 males [M] and 36 females [F], mean age: 12.8 ± 2.5 years), anthropometric measurements, cIMT, endocan levels, and IR indices (homeostasis model assessment of insulin resistance [HOMA-IR]) were evaluated and compared with 80 healthy pubertal patients (42M/38F, mean age: 12.3 ± 3.2 years). High-resolution ultrasound was used to measure the cIMT. Obese children had higher levels of endocan compared with the controls (P < .001). Fasting insulin levels and HOMA-IR were also higher in obese children (P < .001 for both). In addition, obese children had an increased cIMT (P < .001). In obese children, there was a significant correlation between cIMT and HOMA-IR (β = -1.314, P = .002) and between cIMT and endocan (β = .483, P = .004). Measuring cIMT and endocan levels (noninvasive investigations) in obese children, together with early preventive measures, could significantly decrease morbidity and mortality in adulthood.

Validation of ESM1 Related to Ovarian Cancer and the Biological Function and Prognostic Significance by Bioinformatics Analysis and Experimental Verification

Background: Ovarian cancer (OC), a serious gynecological malignant disease, remains an enormous challenge in early diagnosis and medical treatment. Based on GEO and TCGA database by R language, Endothelial cell-specific molecule 1 (ESM1) were confirmed separately on the tool of bioinformatic analysis. ESM1 has been demonstrated that up-regulated in multiple cancer types, but the oncogenetic mechanism of ESM1 in promoting OC is still largely unknown. Methods: In the study, we used WGCNA network and Random survival forest variable screening to filtered out ESM1 in OC differentially expressed genes (DEGs). Next, we confirmed the mRNA and protein levels of ESM1 in OC samples via PCR and IHC. The correlation between ESM1 level and clinical data of OC patients were further confirmed, including FIGO stage, lymph node metastasis, and recurrence. The role of ESM1 in OC development were explored by several functional experimentations in vivo and in vitro. Then, the molecular mechanisms of ESM1 was further elucidated by bioinformatic end experimental analysis. Results: ESM1 was significantly up-regulated in OC, which positively with PFS but negatively with OS. ESM1 knockdown inhibited cell proliferation, apoptosis escaping, cell cycle, angiogenesis migration and invasion via multiple experiments. Moreover, GSVA analysis found that ESM1 was associated with the Akt pathway, and our results also supported the prediction. Conclusion: ESM1 was closely correlated with OC development and progression, and it could be considered a novel biomarker and therapeutic target for OC patients. Funding Statement: None. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study protocol was in line with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the research ethics committee of University of South China and the research ethics committee of Shenzhen University. Informed consent to participate in the study. was obtained from each patient that was recruited

Endocan (ESM-1) levels in gingival crevicular fluid correlate with ICAM-1 and LFA-1 in periodontitis.

Endocan, a 50 kDa soluble proteoglycan, also called endothelial cell-specific molecule-1 (ESM-1), is involved in many major cellular activities and has been reported to be overexpressed in inflammatory conditions. This study aims to determine ESM-1 levels in gingival crevicular fluid (GCF) samples from individuals with periodontitis to determine the correlation between the levels of lymphocyte-function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and clinical findings of periodontitis. This study enrolled 27 individuals diagnosed with Stage III-Grade C generalized periodontitis and 16 individuals as healthy controls. Bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were calculated. Enzyme-linked immunosorbent assay (ELISA) test was used for detecting the levels of ESM-1, ICAM-1, and LFA-1 in GCF samples. PPD, BOP, CAL, and GCF volumes were significantly increased in patients with periodontitis in comparison to the control group (p < 0.001). The total amount of ESM-1, ICAM-1, and LFA-1 levels in GCF were increased in the periodontitis group (p < 0.001). ESM-1 level correlated with PPD, BOP, and CAL (p < 0.05). ICAM-1 level correlated with BOP and CAL (p < 0.05). LFA-1 level correlated with PPD and CAL (p < 0.05). Our data indicate that ESM-1, ICAM-1, and LFA-1 levels are increased in GCF of patients with periodontitis. These molecules could be associated with the pathogenesis and progression of periodontal disease.

ESM1/HIF‑1α pathway modulates chronic intermittent hypoxia‑induced non‑small‑cell lung cancer proliferation, stemness and epithelial‑mesenchymal transition.

Obstructive sleep apnea (OSA) is a sleep‑related disorder characterized by chronic intermittent hypoxia (CIH). Previous studies have found that intermittent hypoxia promotes drug resistance, cell proliferation, migration and invasion in non‑small cell lung cancer (NSCLC). Endothelial cell‑specific molecule‑1 (ESM1) is a molecule shown to be overexpressed in several types of tumors. The purpose of this study was to investigate the correlation between CIH and ESM1 and their potential roles in the progression of NSCLC. Tumorspheres, cell viability and colony formation assays were used to evaluate cell proliferation. The expression levels of cancer stem cell (CSC) markers CD44, CD133, OCT4 and SOX2 were measured with western blotting and/or RT‑qPCR. Transwell assays were applied to assess cell migration and invasion. Changes in the expression levels of epithelial‑mesenchymal transition (EMT)‑associated proteins were also detected by western blotting. The results indicated that CIH enhanced lung cancer stem cell (LCSC) NSCLC progression by promoting stemness, drug resistance, cell proliferation, migration and invasion via the ESM1/HIF‑1α pathway. Unexpectedly, inhibition of ESM1 reversed the CIH‑involved negative effects on LCSCs and in a mouse model. ESM1 therefore appears to be crucial mediator of CIH‑mediated lung cancer progression.

Direct interaction of β-catenin with nuclear ESM1 supports stemness of metastatic prostate cancer.

Wnt/β-catenin signaling is frequently activated in advanced prostate cancer and contributes to therapy resistance and metastasis. However, activating mutations in the Wnt/β-catenin pathway are not common in prostate cancer, suggesting alternative regulations may exist. Here, we report that the expression of endothelial cell-specific molecule 1 (ESM1), a secretory proteoglycan, is positively associated with prostate cancer stemness and progression by promoting Wnt/β-catenin signaling. Elevated ESM1 expression correlates with poor overall survival and metastasis. Accumulation of nuclear ESM1, instead of cytosolic or secretory ESM1, supports prostate cancer stemness by interacting with the ARM domain of β-catenin to stabilize β-catenin-TCF4 complex and facilitate the transactivation of Wnt/β-catenin signaling targets. Accordingly, activated β-catenin in turn mediates the nuclear entry of ESM1. Our results establish the significance of mislocalized ESM1 in driving metastasis in prostate cancer by coordinating the Wnt/β-catenin pathway, with implications for its potential use as a diagnostic or prognostic biomarker and as a candidate therapeutic target in prostate cancer.

Decreased expression of endothelial cell specific molecule-1 in lung tissue in emphysematous mice and stable COPD patients.

Objective(s):Apoptosis of pulmonary alveolar septal cells is a pathogenesis characteristic of chronic obstructive pulmonary disease (COPD). Endothelial cell specific molecule-1 (ESM-1) plays an important role in apoptosis of cells. Here, we aimed to determine whether ESM-1 can involve in cell apoptosis in emphysematous mice and stable COPD patients. The sample size of patients was small, so two separate models were studied.Materials and Methods:At day 0, 11, and 22, murine were injected IP with 0.3 ml of PBS/Cigarette smoke extract, and euthanized at day 28. Lung tissues from 20 stable COPD patients and 12 Controls were evaluated. Serum was obtained from 25 stable COPD patients and 12 healthy Controls. Pulmonary function, pathology, pulmonary apoptosis index (AI), expression of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and ESM-1 in lung tissue, and concentration of ESM-1 in serum were tested. Results:Protein expression of ESM-1, VEGF and HGF were decreased significantly in emphysematous mice (P<0.05), while AI was increased (P<0.05). Correlation analysis indicated that association between AI and ESM-1 was negative (P<0.01), VEGF and ESM-1 was positive (P<0.01), and HGF and ESM-1 was positive (P<0.01). In stable COPD patients, we proved that ESM-1, VEGF and HGF were decreased significantly, while AI was increased (P<0.05). Correlation between AI and ESM-1 was negative (P<0.01), VEGF and ESM-1 was positive (P<0.01), and HGF and ESM-1 was positive (P<0.01). Conclusion:ESM-1 expression decreased and AI increased in emphysematous mice and stable COPD patients. Findings suggested that ESM-1 may be involved in anti-apoptotic therapy of COPD.

Maternal serum endothelial cell-specific molecule-1 level and its correlation with severity of early-onset preeclampsia

Preeclampsia (PE), the primary pathology of which is endothelial cell (EC) dysfunction, has long-lasting effects such as cardiovascular disease. Therefore, it was decided to investigate the maternal serum concentrations of EC-specific molecule-1 in patients with early-onset preeclampsia (E-PE). This study was conducted on 33 pregnant women with E-PE and 35 healthy pregnant women matched for gestational age. EC-specific molecule-1 level was measured using a commercially available enzyme-linked immunosorbent assay kit. The mean EC-specific molecule-1 concentrations were not significantly different between the groups (651.7 ± 632.2 pg/mL vs. 425.9 ± 263.0 pg/mL, p=.056). Among women with E-PE, the median EC-specific molecule-1 concentration did not differ significantly by disease severity (p=.115). EC-specific molecule-1 is not involved in the pathogenesis of E-PE. However, some studies in the literature report that EC-specific molecule-1 concentrations increased during the diagnosis of PE. Therefore, well-designed studies with a large sample are needed in cases of E-PE. Impact Statement What is already known on this subject? There is an increased risk of cardiovascular disease (CVD) in early-onset preeclampsia (E-PE) which is linked with endothelial dysfunction. Endothelial cell (EC)-specific molecule-1 stands out as an important marker in EC dysfunction related conditions such as preeclampsia. What the results of this study add? This study showed that EC-specific molecule-1 is not associated with the CVDs risk linked with endothelial dysfunction in E-PE. Additionally, there was also no significant relationship was detected between the severity of E-PE and EC-specific molecule-1 concentrations. What the implications are of these findings for clinical practice and/or further research? Endothelial cell-specific molecule-1 is not involved in the pathogenesis of E-PE. Moreover, advantageous and easy-to-measure markers are needed in larger sample studies to better understand the aetiology of E-PE.

Pan-cancer analysis identifies ESM1 as a novel oncogene for esophageal cancer.

Recent studies highlight the crucial role of endothelial cell-specific molecule 1 (ESM1) in the development of multiple cancer types. However, its aberrant expression and prognostic value in human pan-cancer have largely not been described. In this study, we used The Cancer Genome Atlas (TCGA) analysis databases to explore the expression level and prognostic significance of ESM1 in 33 types of human cancer. ESM1 was shown to be over-expressed in 12 cancer types, including BLCA, BRCA, COAD, CHOL, ESCA, HNSC, KIRC, KICH, LIHC, STAD, THCA, and UCEC. The expression of ESM1 was significantly correlated with the overall survival (OS) of patients in CESC, ESCA, KIRC, and KIRP. In addition, high ESM1 level indicated poor disease-free survival (DFS) of patients with ACC, ESCA, PRAD, LIHC, KIRP, and UCS. Through comparative analysis, we discovered that ESM1 was dramatically up-regulated in esophageal cancer (ESCA) and associated with worse patient OS and DFS. The elevation of ESM1 in ESCA was confirmed by the datasets from Cancer RNA-Seq Nexus (CRN) and Gene Expression Omnibus (GEO). Based on Gene Set Enrichment Analysis (GSEA), we analyzed the co-expressed genes of ESM1 in ESCA, and found that ESM1 was closely implicated in cell proliferation and migration and the regulation of Janus kinase (JAK) signaling pathway. Functionally, knockdown of ESM1 significantly suppressed cell proliferation and migration, and decreased the protein level of JAK1. Taken together, our results suggest for the first time that ESM1 functions as an oncogene and may be a clinical biomarker and/or therapeutic target in ESCA.

Serum biomarkers of endothelial glycocalyx injury in canine parvoviral infection

Canine parvoviral enteritis (PVE) is one of the most common diseases in young dogs. A range of diseases and inflammatory conditions can cause endothelial glycocalyx (eGCX) disruption, therefore, this study aimed to determine the presence of eGCX damage in dogs with PVE using serum biomarkers of eGCX, and to evaluate their prognostic importance among survivor and non-survivor dogs. Twenty dogs diagnosed with PVE and 10 healthy dogs of both sexes, mixed-breed, and under 6 months of age were included in the study. Clinical examination, blood gas analysis, and complete blood cell counts of the dogs were performed. To detect the eGCX injury, serum endothelial cell-specific molecule-1 (ESM-1), syndecan-1 (SDC-1), angiopoietin-2 (Ang-2), and heparan sulfate (HS) levels were measured. Results showed that at the time of admission serum levels of ESM-1 were higher in dogs with PVE compared to that of the healthy dogs. Dogs with PVE were further assigned into two groups: survivors (n:10) and non-survivors (n:10). The ESM-1 had high sensitivity and specificity to differentiate between survivor and non-survivor dogs with values of 100% and 67%, respectively, with at an optimum cut-off point of ≥460 pg/mL. We concluded that higher levels of ESM-1 in dogs with PVE may indicate eGCX injury when compared to healthy dogs. Also, the high levels of serum ESM-1 in non-survivor dogs suggest that serum ESM-1 may carry some prognostic usefulness for predicting mortality in dogs with PVE.