Endothelial Cell-specific Molecule-1 Levels Research Articles

Endothelial cell-specific molecule 1 is regulated separately in follicular and serum compartments of PCOS patients: a pilot study.

The aim of our study is to detect endothelial cell-specific molecule 1 (ESM-1) levels in the serum and follicular fluids (FF) of patients undergoing IVF/ICSI for PCOS. The presence of ESM-1 traffic between the serum and follicular compartment was analyzed. A total of 50 patients, including 25 infertile patients diagnosed with PCOS according to the Revised Rotterdam criteria, and 25 patients in infertility follow-up for reasons other than PCOS, were included in the pilot study. Patients in the control group were required to have no clinical and laboratory findings of PCOS. Non-PCOS controls were selected from patients diagnosed with a male factor or unexplained infertility, and a homogeneous group was formed. Patients in PCOS and control groups were matched in terms of age and BMI. IVF/ICSI was started with antagonist protocol in both groups. Follicular fluids obtained on the day of egg collection were centrifuged, put into RNAlater, frozen, and stored until the day of analysis. Endothelial cell-specific Molecule 1 levels were measured in follicular fluid and serum samples of PCOS patients by enzyme-linked immunosorbent assay (ELISA) using the Human ESM-1 kit. Serum ESM-1 levels of the PCOS group were significantly lower than FF-ESM1 levels (668.6±189.2 vs. 979.0±233.9 ng/L, p<0.02). FF-ESM1 levels of the control group were significantly higher than serum ESM1 levels (639.3±206.4 ng/L vs. 503.2±102.4 ng/L, p<0.01). Serum ESM1 levels of the PCOS group were significantly higher than the control group (668.6±189.2 ng/L vs. 503.2±102.4 ng/L, p<0.01). Similarly, FF-ESM1 levels of the PCOS group were significantly higher than the control group (979.0±233.9 ng/L vs. 639.3±206.4 ng/L, p<0.01). There was no significant correlation between serum and FF-ESM1 levels. A positive and significant correlation was found between FF-ESM1 and serum LH levels in PCOS (r=0.655, p<0.02). Similarly, a positive and significant correlation was found between FF-ESM1 and serum testosterone levels in PCOS (r=0.470, p<0.03). Moreover, a positive and significant correlation was detected between FF-ESM-1, AFC, MII, and total oocyte counts in PCOS. Serum and FF-ESM-1 are regulated independently of each other in PCOS patients. ESM-1 may play a role in ovulatory dysfunction due to PCOS.

475-P: Intermittent Hypoxia Increased the Expression of Intercellular Adhesion Molecule-1 and Endothelial Cell–Specific Molecule-1 in Vascular Endothelial Cells via the Downregulation of MicroRNA-181a1

Sleep apnea syndrome (SAS), which is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]), is a risk factor for vascular dysfunction, as well as hypertension, and insulin resistance/Type 2 diabetes. We have reported correlations between IH and insulin resistance/Type 2 diabetes, and hypertension. However, the question of why vascular dysfunction is induced by IH has remained unanswered. Here, we investigated the effects of IH on the expression of endothelial inflammatory transcripts such as intercellular adhesion molecule-1 (ICAM-1), interleukin (IL)-8, C-C motif chemokine ligand 5 (CCL5), endothelial nitric oxide synthase (NOS3), vascular cell adhesion molecule-1 (VCAM-1), endothelial cell specific molecule 1 (ESM1), and endothelin-1 (EDN-1) using an in vitro IH system. Human and mouse vascular endothelial cells (HUEhT-1 and UV2) were exposed to IH or normoxia for 24 hours. Real-time RT-PCR revealed that IH significantly increased the mRNA levels of ICAM-1 and ESM1 in both HUEhT-1 (P=0.0436 and P=0.0145, respectively) and UV2 cells (P&amp;lt;0.0001 and P=0.0422, respectively). ELISA showed that ICAM-1 and ESM1 were significantly increased (P=0.0105 and P&amp;lt;0.0001, respectively) in the UV2 cell medium by IH. Reporter assays revealed that the promoter activities of ICAM-1 and ESM1 were not increased by IH. The microRNA (miR)-181a1 level of IH-treated cells was significantly decreased relative to that of normoxia-treated cells (P=0.0374). The IH-induced upregulation of ICAM-1 and ESM1 was abolished by the introduction of miR-181a1 mimic, indicating that IH stress increased levels of ICAM-1 and ESM1 via the inhibition of miR-181a1-mediated mRNA degradation, leading SAS patients to develop atherosclerosis. Disclosure S.Takasawa: None. M.Makino: None. A.Yamauchi: None. S.Sakuramoto-tsuchida: None. Y.Takeda: None. T.Uchiyama: None. R.Shobatake: None.

Serum E-selectin and endothelial cell-specific Molecule-1 levels among people living with HIV on long term ART in Uganda: a pilot cross-sectional study

BackgroundProlonged exposure to HIV and anti-retroviral therapy (ART) has been linked with endothelial cell activation which subsequently predisposes people living with HIV (PLWH) to cardiovascular diseases. Serum biomarkers of endothelial cell activation such as E-Selectin and endothelial cell-specific molecule-1 (ESM-1) could aid in early detection of PLWH at a risk of cardiovascular diseases. However, there is a paucity of data on these biomarkers like E-selectin and endothelial cell-specific molecule-1 (ESM-1) among PLWH on long term ART (≥ 10 years) in Uganda. The aim of this study is to determine the serum levels of these biomarkers in this population.MethodsThis was a cross-sectional study where we randomly sampled 73 stored serum samples of PLWH who were enrolled in the Infectious Diseases Institute (IDI) ART long term (ALT cohort). We measured serum levels of E-selectin and ESM-1 by ELISA. Data was summarized using median and interquartile range. Inferential statistics were performed to determine predictors of elevated levels of E-selectin.ResultsOf the 73 samples analyzed, 38 (52.1%) were from female participants. The mean age was 54 ± 9.0 years. Twenty participants (27.4%) had a history of smoking while 52 (71.2%) had a history of alcohol intake. Twenty-five (34.3%) of the participants were overweight whereas 4 (5.6%) were obese. Fifty-four (74%) had an undetectable viral load (≤ 0 copies/ml) and the mean duration of ART at the time of sampling (2014/2015) was 10.4 ± 0.4 years. While serum levels of ESM-1 were not detectable in any of our samples, the median E-selectin levels was 147.6 μm/L ranging from 8.44 μm/L and 1,979.36 μm/L. Sixty-seven participants (91.8%) had elevated levels of E-selectin (> 39 μm/L). CD4 count > 500 cells/µl compared to lower counts was a predictor of elevated levels of E-Selectin (adjusted Odd Ratio 12.5, 95% CI (1.03 — 149.95, p < 0.05).ConclusionsThe majority (91.8%) of PLWH on long term ART had elevated levels of E-selectin. Having high CD4 count (> 500 cells/µl) was predictive of elevated levels of E-Selectin. Future work should longitudinally assess the trend of levels of E-selectin and ESM-1 while assessing for cardiovascular diseases endpoint.

Combination of Maternal Serum ESM-1 and PLGF with Uterine Artery Doppler PI for Predicting Preeclampsia.

This study aimed to determine whether the combination of pregnancy-associated endothelial cell-specific molecule 1 (ESM-1), the placental growth factor (PLGF) in the first- and second-trimester maternal serum, and the uterine artery Doppler pulsatility index (PI) in the second trimester can predict preeclampsia (PE). The serum levels of ESM-1 and PLGF in 33 severe preeclampsia (SPE) patients, 18 mild preeclampsia patients (MPE), and 60 age-matched normal controls (CON) were measured. The Doppler ultrasonography was performed, and the artery pulsatility index (PI) was calculated for the same subjects. The 2nd PLGF level was significantly lower and the 2nd PI was higher than those in the MPE group. Combining the 2nd PLGF with the 2nd PI yielded an AUC of 0.819 (83.33% sensitivity and 70.00% specificity). In the SPE group, the 1st ESM-1 level and the 2nd PLGF level were significantly lower, and the 2nd ESM-1 level and the 2nd PI were significantly higher in the SPE group. The combination of the 1st ESM-1, the 2nd PLGF, and the 2nd PI yielded an AUC of 0.912 (72.73% sensitivity and 95.00% specificity). The 1st ESM-1 and the 2nd PLGF levels and the 2nd PI were associated with PE. The combination of serum biomarkers and the PI improved the screening efficiency of the PE prediction, especially for SPE.

Validation of ESM1 Related to Ovarian Cancer and the Biological Function and Prognostic Significance.

Background: Ovarian cancer (OC), a serious gynecological malignant disease, remains an enormous challenge in early diagnosis and medical treatment. Based on the GEO and TCGA databases in R language, endothelial cell-specific molecule 1 (ESM1) was confirmed separately with the bioinformatic analysis tool. ESM1 has been demonstrated to be upregulated in multiple cancer types, but the oncogenic mechanism by which ESM1 promotes OC is still largely unknown. Methods: In this study, we used WGCNA and random survival forest variable screening to filter 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 the ESM1 level and clinical data of OC patients was further confirmed, including FIGO stage, lymph node metastasis, and recurrence. The role of ESM1 in OC development was explored by several functional experiments in vivo and in vitro. Then, the molecular mechanisms of ESM1 were further elucidated by bioinformatic end experimental analysis. Results: ESM1 was significantly upregulated in OC and was positively correlated with PFS but negatively correlated with OS. ESM1 knockdown inhibited cell proliferation, apoptosis escape, the cell cycle, angiogenesis, migration and invasion in multiple experiments. Moreover, GSVA found that ESM1 was associated with the Akt pathway, and our results supported this 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.

Association between Endothelial Cell-Specific Molecule 1 and Galectin-3 in Patients with ST-Segment Elevation Myocardial Infarction: A Pilot Study.

The biomarkers galectin-3 (Gal-3) and endothelial cell-specific molecule 1 (ESM-1) reflect endothelial function and inflammation. As a consequence, they play an important role in both the diagnosis and characterization of ST-segment elevation myocardial infarction (STEMI). However, no prior study has explored the association between ESM-1 and Gal-3 in STEMI patients. This study is aimed at determining the ESM-1 and Gal-3 levels in the serum of STEMI patients and then exploring the correlation between the levels of these two biomarkers and their clinical significance in STEMI patients. The participants were divided into two groups: the ST group comprised 35 hospitalized STEMI patients while the control group comprised 24 people with normal coronary arteries. In all the patients, venous blood was taken from the middle of the antecubital fossa. The serum ESM-1 and Gal-3 concentrations were determined using an enzyme-linked immunosorbent assay. The results revealed that the ESM-1 and Gal-3 levels in the STEMI patients were 1.6 and 2.8 times higher, respectively, when compared with the controls (P < 0.001). Moreover, the ESM-1 and Gal-3 levels exhibited a positive linear correlation (r = 0.758, P < 0.001) in the acute STEMI patients. In conclusion, the ESM-1 and Gal-3 levels were found to be significantly elevated and correlated in the STEMI patients. Thus, combining these two biomarkers of endothelial dysfunction and inflammation might be useful for the diagnosis and assessment of STEMI.

Arctigenin Attenuates Vascular Inflammation Induced by High Salt through TMEM16A/ESM1/VCAM-1 Pathway.

Salt-sensitive hypertension is closely related to inflammation, but the mechanism is barely known. Transmembrane member 16A (TMEM16A) is the Ca2+-activated chloride channel in epithelial cells, smooth muscle cells, and sensory neurons. It can promote inflammatory responses by increasing proinflammatory cytokine release. Here, we identified a positive role of TMEM16A in vascular inflammation. The expression of TMEM16A was increased in high-salt-stimulated vascular smooth muscle cells (VSMCs), whereas inhibiting TMEM16A or silencing TMEM16A with small interfering RNA (siRNA) can abolish this effect in vitro or in vivo. Transcriptome analysis of VSMCs revealed some differential downstream genes of TMEM16A related to inflammation, such as endothelial cell-specific molecule 1 (ESM1) and CXC chemokine ligand 16 (CXCL16). Overexpression of TMEM16A in VSMCs was accompanied by high levels of ESM1, CXCL16, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1). We treated VSMCs cultured with high salt and arctigenin (ARC), T16Ainh-A01 (T16), and TMEM16A siRNA (siTMEM16A), leading to greatly decreased ESM1, CXCL16, VCAM-1, and ICAM-1. Beyond that, silencing ESM1, the expression of VCAM-1 and ICAM-1, and CXCL16 was attenuated. In conclusion, our results outlined a signaling scheme that increased TMEM16 protein upregulated ESM1, which possibly activated the CXCL16 pathway and increased VCAM-1 and ICAM-1 expression, which drives VSMC inflammation. Beyond that, arctigenin, as a natural inhibitor of TMEM16A, can reduce the systolic blood pressure (SBP) of salt-sensitive hypertension mice and alleviate vascular inflammation.

Increasing circulating ESM-1 and adhesion molecules are associated with earlystage atherosclerosis in OSA patients:A cross-sectional study

BackgroundThere are increasing evidences for a direct relationship between the vascular system and obstructive sleep apnea (OSA). The aim of this study was to investigate the relationship between circulating endothelial cell specific molecule-1 (ESM-1), adhesion molecules and subclinical atherosclerosis in patients with OSA. MethodsThis was a cross-sectional study in which 161 patients with OSA and 56 controls were recruited. Demographic data, biochemical and polysomnography parameters were collected. We used a powerful high-throughput Multiplex Immunobead Assay technique to simultaneously test plasm levels of ESM-1, P-selectin, E-selectin, L-selectin, inter-cellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Carotid intima-media thickness (CIMT) were measured as parameters of vascular endothelial dysfunction and early atherosclerosis. ResultsIncreasing circulating levels of ESM-1, P-selectin, E-selectin, L-selectin, ICAM-1 and VCAM-1 were found increased in patients with OSA (all P < 0.001). Furthermore, OSA patients exhibited increased CIMT than controls (P < 0.05). Multivariate linear analysis indicated that elevated ESM-1, P-Selectin, E-selectin, and L-selectin levels were associated with AHI (all P < 0.05). Moreover, multivariate analysis showed that increasing ESM-1, VCAM-1, P-Selectin, and L-selectin were significantly associated with thick CIMT in OSA patients (all P < 0.05). ConclusionsIncreased circulating ESM-1 and adhesion molecules associated with thick CIMT in OSA, which is a marker of subclinical atherosclerosis. Strict attention to monitor circulating ESM-1 and adhesion molecules is necessary for early detection of subclinical atherosclerosis in OSA patients.

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.

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

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.

The Relationship Between the Level of Serum ESM-1 and Lp-PLA2 in Patients With Acute ST-Segment Elevation Myocardial Infarction.

Acute ST‐segment elevation myocardial infarction (STEMI) is the most lethal coronary heart disease with vascular endothelium dysfunction and inflammation in the disease development process. Endothelial cell‐specific molecule 1 (ESM‐1) and lipoprotein‐associated phospholipase A2 (Lp‐PLA2) are important for the diagnosis and characterization of STEMI. To date, no studies have reported the correlation between ESM‐1 and Lp‐PLA2 levels in patients with STEMI, which may be an important predictor of the fatal disease. To measure the level of serum ESM‐1 and Lp‐PLA2, and to evaluate the relationship and the clinical significance of these two biomarkers in patients with acute STEMI, 37 inpatients with acute STEMI were sequentially enrolled in the research group and 24 study objects with normal coronary artery function were included in the control group. The measurement of the relative parameters was done by enzyme‐linked immunosorbent assay using blood samples taken from the median cubital vein while the inpatients were enrolled. The levels of serum SEM‐1 and Lp‐PLA2 were significantly higher in patients with acute STEMI than in study objects with normal coronary artery function (P < 0.05). A significant correlation of serum SEM‐1 and Lp‐PLA2 was observed, leading to close linearity (r 2 = 0.8131, P < 0.0001). In conclusion, the endothelium dysfunction factor ESM‐1 and inflammatory factor Lp‐PLA2 are significantly higher and correlated in patients with acute STEMI. These two factors could be novel and effective biomarkers for acute STEMI diagnosis and evaluation.

Determination the Role of Endothelial Cell-Specific Molecule-1(ESM-1) in Childhood Bronchial Asthma

Background Endothelial Cell-Specific Molecule-1 (ESM-1) is a 50 kDa soluble proteoglycan that is produced mainly the vascular endothelial cells of the kidney and lung. It is produced by the effects of proangiogenic and pro-inflammatory cytokines, and it indicates activation and dysfunction of the vascular endothelium. We aimed to detect the role of ESM-1 in children with asthma. Materials and Methods This study is a prospective cross sectional study and include 50 child (32 with mild persistent, 18 with moderate persistent asthma (patients) and 30 healthy children served as controls, both groups were selected from outpatient pulmonology clinic and inpatient pediatric department at children hospital, Minia University, Egypt, from 2016 to 2018; and were subjected to: detailed clinical examination, lung function test, complete blood picture and measurement of level of ESM-1 in serum. Results Level of ESM-1 was increased in asthmatic children compared to the controls (p=0.001). Also, the level of ESM-1 in children suffering from moderate persistent asthma was markedly higher than those with mild persistent asthma (p=0.001). In addition, ESM-1 level was positively correlated with eosinophil counts (r=0.79, p=0.01), but had negative correlation with lung functions FEV1 and PEFR (r=- 0.89, - 0.84, p=0.001). Conclusion ESM-1 level was increased in asthmatic children suggesting that it may have a role in asthma, furthermore, it was associated with decreased lung function indicating that it is considered as an indicator of severe asthma.

Placental Growth Factor and Endothelial Cell-Specific Molecule 1 Levels in Discordant and Concordant Twins and Their Effects on Fetal Growth

Objective: We explored whether fetal twin growth was related to the levels of placental growth factor (PGF) and endothelial cell-specific molecule 1 (ESM-1) and sought correlations between cord blood PGF and ESM1 levels and birth weight discordance. Methods: This was a prospective study. We evaluated 79 pairs of twins, thus 158 infants. Twenty-nine (37%) twins were naturally conceived; the remaining 50 (63%) resulted from assisted reproduction. Results: Nine (11%) sets of twins were monochorionic. Eighteen of the 79 twin sets (22%) were discordant. We found a positive correlation between PGF and ESM-1 levels (r = 0.51, p = 0.001) and between discordance and PGF level (r = 0.430, p = 0.001). Conclusion: The growth discordance may not be attributable to the different PGF levels, but the difference in PGF level may be a consequence.

Serum Level of Endothelial Cell-Specific Molecule -1 (ESM -1) as a New Potential Biomarker for Rheumatoid Arthritis Disease Activity

Background:Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by destruction of the joint cartilage and bone. Endothelial dysfunction (ED) in RA may be related to disease activity. Our objective is to explore serum levels of endothelial cell-specific molecule-1 (ESM-1) as a biomarker for RA disease activity.Methods:A cross-sectional study was carried out and included 83 adult patients with RA, in addition to 20 healthy subjects (age and sex-matched) as a control group. Based on Disease Activity Score in 28 joints (DAS-28), the patient's group was subdivided into four subgroups(remission, mild, moderate and severe disease activity state). The demographic &amp; clinical data, BMI, DAS-28 and Serological assessment [Erythrocyte Sedimentation Rate (ESR), CRP, Rheumatoid Factor (RF) and Anti-Citrullinated Peptide Antibody (ACPA)] were recorded. ESM-1was assayed for all participants.Results:Serum levels of ESM1 were significantly higher in the patient group than the control group (P&lt; 0.0001). ESM-1 serum levels were significantly higher in patients with severe disease activity subgroup compared with patients with remission and mild disease activity subgroups (P&lt; 0.0001). ESM-1 was positively and significantly correlated with DAS-28 score, The Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Larsen score (P= 0.002, 0.0001 &amp; 0.0001 respectively).Conclusion:ESM-1 could be a biomarker for RA disease activity.

Plasma levels of endothelial cell-specific molecule-1 and pentraxin-3 in idiopathic sudden sensorineural hearing loss.

To evaluate the plasma levels of endothelial cell-specific molecule-1 (ESM-1) and pentraxin-3 (PTX-3) in patients with idiopathic sudden sensorineural hearing loss, and to compare the pre- and post-treatment levels in patients responsive and non-responsive to therapy. The study included 108 subjects: 51 with idiopathic sudden sensorineural hearing loss and 57 controls. For ESM-1 and PTX-3 analyses, blood samples were collected before and three months after treatment initiation in the idiopathic sudden sensorineural hearing loss group and once for the control group. Treatment response was evaluated three months after therapy initiation with pure tone audiometry, and the patients were divided into two groups: responsive and non-responsive to treatment. Serum ESM-1 levels were significantly higher in the idiopathic sudden sensorineural hearing loss group than the control group, whereas the difference was not significant for PTX-3. In the responsive and non-responsive groups, ESM-1 and PTX-3 levels were not statistically different before and after treatment. To our knowledge, this is the first study investigating plasma ESM-1 and PTX-3 levels in idiopathic sudden sensorineural hearing loss. Increased plasma ESM-1 levels may confirm endothelial dysfunction involvement in idiopathic sudden sensorineural hearing loss pathogenesis, which could be associated with vascular impairment.

Changes in endothelial cell specific molecule 1 plasma levels during preeclamptic pregnancies compared to healthy pregnancies.

We aimed to assess the levels of endothelial cell specific molecule 1 (ESM-1) during pregnancy and preeclampsia. Plasma and placental samples were collected from women with a control pregnancy, early- or late-onset preeclamptic women and non-pregnant women (experiment 1). Plasma samples were collected between weeks 12 and birth from pregnant women at high risk for developing preeclampsia (experiment 2). ESM-1 plasma levels were measured by ELISA and in the placenta mRNA and protein were detected by immunohistochemistry and qPCR. In the first experiment we observed lower concentrations of ESM-1 in pregnant women as compared to non-pregnant women and higher concentrations during early- and late-onset preeclampsia as compared to control pregnancies of the same gestational age. Early- and late-onset preeclamptic pregnancies were not different from their subsequent controls in ESM-1 mRNA or protein levels in placental tissue. The second experiment showed that in women who had an control pregnancy, plasma ESM-1 levels were decreased as compared to non-pregnant women, from week 16 ± 2 until the end of pregnancy and returned to non-pregnant levels postpartum. In women who developed early- or late-onset preeclampsia, plasma ESM-1 was also decreased as compared to non-pregnant women from week 20 ± 2 until week 28 ± 2 of pregnancy. Then ESM-1 levels increased and were no longer different from levels in non-pregnant women on weeks 32 and 36. Plasma ESM-1 levels are decreased during pregnancy and increased in early- and late-onset preeclampsia. The source of ESM-1 is probably not the placenta, but most likely maternal endothelial cells.

Comparison of the Effects of Ticagrelor and Clopidogrel on Inflammatory Factors, Vascular Endothelium Functions and Short-Term Prognosis in Patients with Acute ST-Segment Elevation Myocardial Infarction Undergoing Emergency Percutaneous Coronary Intervention: a Pilot Study

Background/Aims: Acute ST-segment elevation of myocardial infarction (STEMI) is the most severe type of acute coronary syndrome (ACS). Particular attention has been focused on studying the pathogenesis of STEMI, and how to prevent thrombosis, reduce inflammatory reaction, stabilize plaques and improve vascular endothelial functions to preserve the survived myocardium. This study aimed to compare the anti-inflammatory endothelium-protective effects, clinical prognosis, and relevant bleeding risks of ticagrelor versus clopidogrel in patients with STEMI who underwent urgent percutaneous coronary intervention (PCI) and provide certain experimental evidence and a theoretical basis for the selection of safe and effective drugs and their proper dosage, thereby further guiding clinical medication. Methods: We sequentially enrolled 193 patients (104 males and 89 females) admitted to hospital due to acute STEMI. These patients underwent urgent PCI between December 2013 and May 2015 and met the inclusion criteria. They were assigned (1: 1) into two groups according to different treatments, 97 patients in the ticagrelor group (treatment group), and 96 patients in the clopidogrel group (control group). Levels of hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and endothelial cell-specific molecule 1 (ESM-1) taken at admission and 24 h, 4 days, and 7 days after administration, as well as the correlation between the levels of IL-6, hs-CRP, and ESM-1, were determined in the two groups. At the same time, the effects of treatment with ticagrelor and clopidogrel on the efficacy endpoint events (ischemic and safety) were explored. Results: No statistically significant difference was found in the levels of hs-CRP, IL-6, or ESM-1 at admission between the two groups (P> 0.05); Their levels were significantly elevated 24 h after administration, with statistical differences between two groups (P< 0.05). Furthermore, a downward trend with statistically significant differences was found on Day 4 and Day 7 (P< 0.05); ESM-1 levels increased along with increases of hs-CRP and IL-6 levels, indicating ESM-1 was positively correlated with hs-CRP (r=0.523, P< 0.001) and IL-6 (r=0.431, P< 0.001); and the occurrence rates of ischemic endpoint events at 30 days were lower in the treatment group than in the control group. The occurrence of safety endpoint events was higher than in the control group; however, no statistically significant difference was found (P> 0.05). Conclusions: Compared with clopidogrel, ticagrelor appears to rapidly reduce the prevalence of inflammatory reactions and stabilize the functions of vascular endothelium to improve the stability of atherosclerotic plaque and decrease the occurrence rate of thrombosis as well as ischemic outcome events without any obvious increase in the risk of bleeding in patients with acute STEMI receiving urgent PCI. This renders it a potential drug for clinical practice. At the same time, measurement of ESM-1, a new biological marker for vascular endothelial function disorder, could possibly become a simple, effective, and practical new method for clinical evaluation of risk stratification of patients with acute STEMI at admission.

Protective Effects of Chymostatin on Paraquat-Induced Acute Lung Injury in Mice.

This study aims to evaluate the role of chymostatin in paraquat-induced acute lung injury. Institute of Cancer Research mice were randomly distributed into the NS, DMSO, chymostatin, paraquat or chymostatin treatment groups. Six mice from each group were intraperitoneally injected with chloral hydrate at 0, 1, 2, 4, 8, 12, 24 and 48h after treatment administration. Blood samples were collected through cardiac puncture. Lung tissues were stained with haematoxylin and eosin for the observation of lung histology. The degree of pulmonary oedema was determined on the basis of lung wet-to-dry ratio (W/D). The serum activity of cathepsin G was determined through substrate fluorescence assay. The serum levels of endothelial cell-specific molecule-1 (endocan), tumour necrosis factor-a (TNF-a), interleukin-1β (IL-1β), IL-6 and high-mobility group box protein 1 (HMGB1) were determined through enzyme-linked immunosorbent assay. The expression levels of endocan and nuclear NF-κBp65 in the lung were quantified through Western blot. Chymostatin alleviated the pathological changes associated with acute alveolitis in mice; decreased the lung W/D ratio, the activity of cathepsin G and the serum concentrations of TNF-a, IL-1β, IL-6 and HMGB1; and increased the serum concentration of endocan. Western blot results revealed that chymostatin up-regulated endocan expression and down-regulated nuclear NF-κBp65 expression in the lung. Chymostatin reversed the inflammatory effects of paraquat-induced lung injury by inhibiting cathepsin G activity to up-regulate endocan expression and indirectly inhibit NF-κBp65 activity.