SCUBE1 Promotes Gestational Diabetes Mellitus: A Bioinformatics and Experimental Investigation.

Gestational diabetes mellitus (GDM) is one of the most common metabolic diseases in pregnant women, posing significant risks to the life and health of both mothers and fetuses. With improving living standards, the incidence of GDM is increasing rapidly. Therefore, understanding the underlying mechanism of GDM is of paramount importance. We downloaded two datasets from the Gene Expression Omnibus (GEO) database, containing sequencing data specifically related to "gestational diabetes" and "placenta". By merging these two datasets, a mRNA expression dataset was obtained and subjected to bioinformatics analyses. To screen out corresponding genes, differential analysis and weighted correlation network analysis (WGCNA) were carried out. Lasso, support vector machine and random forest analyses were subsequently performed for identifying key genes from the differentially expressed genes (DEGs) jointly screened out through differential analysis and WGCNA. Afterwards, immunoinfiltration and correlation analysis were performed to screen immune cells that play a role in disease progression and explore the correlation between the screened key genes and immune cells, after which Western Blot, quantitative real-time polymerase chain reaction, Immunohistochemistry, methyl thiazolyl tetrazolium, flow cytometry, scratch and Transwell assays were, respectively, performed for verification. For further verification, we found that the expression levels of MAP6D1 and SCUBE1 in embryonic tissues of GDM patients was higher compared to those of healthy pregnant women, which was consistent with the results of bioinformatics analysis. Consequently, SCUBE1 was selected for follow-up experiment. In order to explore the role of SCUBE1 in the development of GDM, we treated the trophoblastic cells HTR-8/SVneo with high glucose, and on this basis downregulated the expression of SCUBE1. Through further analysis, we observed that SCUBE1 had a role in reducing cell activity, migration and invasion, and promoting cell apoptosis. In summary, SCUBE1 promotes the development of GDM by increasing cell apoptosis and reducing cell activity, migration, and invasion.

SCUBE1 promotes pulmonary artery smooth muscle cell proliferation and migration in acute pulmonary embolism by modulating BMP7.

Objectives: After an episode of acute pulmonary embolism (APE), activated platelets have the ability to release various bioactive factors that can stimulate both proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). SCUBE1 has been previously reported to engage in platelet-platelet interactions, potentially contributing to the activation of platelets in early onset thrombi. The purpose of this study was to examine the alterations in SCUBE1 expression in PASMCs after APE, as well as understand the mechanism behind these changes. Methods: The platelet-rich plasma samples of both APE patients and healthy individuals were collected. A hyperproliferative model of PASMCs was established by using platelet-derived growth factor (PDGF) as a stimulator and various assays were used to investigate how SCUBE1-mediated BMP7 can regulate PDGF-induced PASMC proliferation and migration. Results: Elevated level of SCUBE1 were observed in platelet-rich plasma from patients with APE and in PASMCs induced by PDGF. SCUBE1 interference ameliorated PDGF-driven cell proliferation and migration, and also downregulated PCNA expression. Additionally, mechanistic studies demonstrated that SCUBE1 could directly bind to bone morphogenetic protein 7 (BMP7) and enhance BMP7 expression, which completely abolished the impact of SCUBE1 silencing on proliferation and migration ability of PASMCs after PDGF treatment. Conclusion: In the PDGF-induced proliferation of PASMCs, the expression of SCUBE1 and BMP7 was upregulated. Silencing of SCUBE1 impeded PDGF-induced proliferation and migration of PASMCs by restraining BMP7.

Could signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 be a therapeutic target in the pathogenesis of preeclampsia?

SUMMARY OBJECTIVE: Determination of biomolecules that play a role in the etiopathogenesis of preeclampsia and their application as therapeutic targets may increase surveillance in this patient group. The aim of this study was to investigate the relationship between signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1, a marker of endothelial dysfunction and platelet activation, and the development of preeclampsia. METHODS: In this observational cross-sectional study conducted between April 2021 and December 2022, 73 consecutive pregnant women with preeclampsia and 73 healthy pregnant women were included. Blood samples were taken from all patients with preeclampsia to measure signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 levels at the time of hospitalization. Excluded from the study were pregnant women with certain medical conditions or treatments, and the signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 levels of the groups were compared according to the development of preeclampsia. RESULTS: Signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 levels were significantly higher in the preeclampsia group than in the controls (p<0.001). In multivariate analysis, signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 was determined as an independent predictor for preeclampsia (OR: 1.678, 95%CI 1.424-1.979, p<0.001). Receiver operating characteristic curve analysis showed that the best cutoff value of signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 at 3.25 ng/mL predicted the development of preeclampsia with 71% sensitivity and 68% specificity (area under the curve, 0.739; 95% confidence ınterval (95%CI), 0.681-0.798, p<0.001). CONCLUSION: Signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 is significantly elevated in pregnant women with preeclampsia compared with healthy controls.

Can signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) be used as an indicator of endothelial dysfunction in acromegaly patients?

PURPOSE: Acromegaly is closely related to increased oxidative stress and endothelial dysfunction (ED). This study aimed to evaluate, for the first time in the literature, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and endothelial nitric oxide synthase e(NOS) levels in the setting of acromegaly. METHOD: A total of 56 acromegaly patients and a control group composed of 30 healthy volunteers were included in this study. In the postoperative follow-up, patients were grouped as active or in-remission according to their GH and IGF-1 levels in oral glucose stimulation test (OGST). After detailed physical examination of acromegaly patients and the control subjects, 8-hour fasting blood samples were collected to evaluate biochemical parameters including lipid profile, anterior pituitary hormones, and SCUBE-1 and e(NOS) levels. RESULTS: Inactive and active acromegaly was noted in 78.6% and 21.4% of patients, respectively. The median (min-max) SCUBE-1 levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (1.6(0.4-2.4) and 1.8(1.1-2.5) vs. 0.4(0.2-1.0) ng/mL, respectively, p < 0.001 for each). The median (min-max) e(NOS) levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (132.7 (26.8-602.9) and 137.3 (69.7-488.7) vs. 83.9 (16.4-218.7) pg/mL, p = 0.018 and p = 0.048, respectively). We have also detected positive correlations of e(NOS) with leukocyte (r = 0.307, p = 0.021) and neutrophil counts (r = 0.309, p = 0.021). CONCLUSION: Our study revealed for the first time in literature that SCUBE-1 levels, being a novel marker for ED, were significantly higher in acromegaly patients than in control subjects. When supported with clinical studies, SCUBE-1can be used as an early indicator of endothelial damage in acromegaly patients.

The diagnostic potential of plasma SCUBE-1 concentration for pulmonary embolism: A pilot study.

INTRODUCTION: This study aimed to investigate the potential application of plasma signal peptide-complement C1r/C1s, Uegf and Bmp1-epidermal growth factor domain-containing protein 1 (SCUBE-1) as a biomarker in the diagnosis of pulmonary embolism (PE). METHODS: This cross-sectional study enrolled 177 patients who underwent PE diagnostic test and 87 healthy controls. The results of CT pulmonary angiogram (CTPA) were used as reference standards for PE diagnosis. The levels of SCUBE-1 and D-dimer in participants' plasma were detected with enzyme-linked immunosorbent assay and compared among patients with confirmed PE, suspicious PE and healthy controls. The diagnostic values were analysed using receiver operating characteristic (ROC) curve analysis. In addition, differences in plasma SCUBE-1 levels were compared among patients with different risk stratifications. RESULTS: The plasma SCUBE-1 concentration levels in patients with CTPA confirmed PE (14.28 ± 7.74 ng/ml) was significantly higher than those in the suspicious patients (11.11 ± 4.48 ng/ml) and in healthy control (4.40 ± 3.23 ng/ml) (P < 0.01). ROC curve analysis showed that at the cut-off of 7.789 ng/ml, SCUBE-1 has significant diagnostic value in differentiating PE patients from healthy control (AUC = 0.919, sensitivity = 81.25%, specificity = 92.13%), and the performance is more accurate than D-dimer (cut-off 273.4 ng/ml, AUC = 0.648, sensitivity = 65.75%, specificity = 67.42%). The combination of D-dimer with SCUBE-1 did not further improve the diagnostic value. However, SCUBE-1 did not show significant diagnostic value in identifying PE among suspicious patients There was no significant difference in SCUBE-1 level among different risk groups (P > 0.05). CONCLUSION: We believe that SCUBE-1 could be a potential coagulation-related marker for the diagnosis of PE.

Diagnostic value of serum signal peptide-CUB-EGF-like domain-containing protein 1 levels in patients with acute appendicitis

SUMMARY OBJECTIVE: Acute appendicitis is one of the most common surgical causes of an acute abdomen among patients admitted to the emergency room due to abdominal pain. The clinical diagnosis of acute appendicitis is usually difficult and is made by evaluating the clinical, laboratory, and radiological findings together. The aim of this study was to investigate the diagnostic potential of signal peptide-CUB-EGF-like domain-containing protein 1 as a biomarker for acute appendicitis. METHODS: A total of 67 adult patients without any comorbidities who presented to the emergency department with abdominal pain and were clinically diagnosed with acute appendicitis were included in the case group. The patients included in the study were classified into the negative appendectomy group and the acute appendicitis group according to their histopathological final diagnosis. In addition, 48 healthy volunteers without comorbidities were included in the control group. Signal peptide-CUB-EGF-like domain-containing protein 1 levels of patients and the control group were measured. RESULTS: According to postoperative histopathological examinations of the patients, 7 (10.4%) patients were diagnosed with negative appendectomy, and 60 (89.6%) patients were diagnosed with acute appendicitis. Signal peptide-CUB-EGF-like domain-containing protein 1 levels were higher in the patients with acute appendicitis than in negative appendectomy patients (p=0.012). Signal peptide-CUB-EGF-like domain-containing protein 1 levels were also higher in the case group compared to the control group (p=0.001). CONCLUSION: The admission signal peptide-CUB-EGF-like domain-containing protein 1 level was significantly higher in adults with acute appendicitis. The SCUBE1 level is a novel but promising biomarker that aids in the diagnosis of acute appendicitis.

An evaluation of the change in serum SCUBE-1 levels with CPAP treatment in patients with severe obstructive sleep apnea.

OBJECTIVE: Signal peptide CUB-EGF domain-containing protein 1 (SCUBE-1) is a cell surface protein, wherein inflammation causes an increase in serum. The aim of this study was to compare serum SCUBE-1 levels in OSA patients and to investigate the serum SCUBE-1 change with CPAP treatment. METHODS: Blood samples were obtained from 61 severe OSA patients and from 25 control subjects evaluated as simple snorers. The 61 patients with severe OSA were treated with CPAP therapy and were recalled for follow up after 1 year. Evaluation was made after 1 year of CPAP therapy. RESULTS: Serum SCUBE-1 values were significantly higher in patients with severe OSA. The SCUBE-1 values significantly decreased after treatment with CPAP. CONCLUSION: Serum SCUBE-1 values in OSA patients showed a significant reduction in SCUBE-1 levels following 1 year of CPAP treatment.

CAFs-derived SCUBE1 promotes malignancy and stemness through the Shh/Gli1 pathway in hepatocellular carcinoma.

BACKGROUND: The tumour microenvironment and cirrhotic liver are excellent sources of cancer-associated fibroblasts (CAFs), which participate in carcinogenesis. Thus, it is important to clarify the crosstalk between CAFs and HCC cells and the related mechanism in regulating carcinogenesis. METHODS: Human hepatocellular carcinoma (HCC) tissues and matched adjacent normal tissues were obtained from HCC patients. Immunohistochemistry, Western blotting (WB) and RT-qPCR were performed to detect the expression of SCUBE1. The roles of SCUBE1 in inducing stemness features in HCC cells were explored and investigated in vitro and in vivo. Student's t tests or Mann-Whitney U tests were used to compare continuous variables, while chi-square tests or Fisher's exact tests were used to compare categorical variables between two groups. RESULTS: SCUBE1 was confirmed to be highly expressed in CAFs in HCC and had a strong connection with stemness and a poor prognosis. In addition, CAFs were found to secrete SCUBE1 to enhance the malignancy of HCC cells and increase the proportion of CD133-positive cells. Silencing SCUBE1 expression had the opposite effect. The Shh pathway was activated by SCUBE1 stimulation. Inhibition of cyclopamine partially reversed the stimulating effect of SCUBE1 both in vivo and in vitro. Moreover, based on the RT-qPCR, ELISA and WB results, a high SCUBE1 expression level was found in HCC tissue and serum. CONCLUSION: This study revealed that CAFs-derived SCUBE1 can enhance the malignancy and stemness of HCC cells through the Shh pathway. This study aims to provide new perspectives for future HCC studies and provide new strategies for HCC treatment.

SCUBE1 is associated with thrombotic complications, disease severity, and in-hospital mortality in COVID-19 patients.

INTRODUCTION: COVID-19 disease, which has recently become an important cause of mortality and morbidity all over the world, is remarkably associated with thrombotic complications. Although many factors are responsible for these increased thrombotic complications in COVID-19 disease, its relationship with a marker that increases the risk of thrombosis such as Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) has not yet been clarified. This is the first study to examine the potential diagnostic and prognostic value of SCUBE1 levels in patients with COVID-19. In this study, we aimed to clarify the relationship between the increased risk of thrombosis and SCUBE1 in the course of COVID-19 disease. MATERIALS AND METHODS: 553 patients with COVID-19 and 553 healthy controls were compared in terms of SCUBE1 levels. Additionally, patients with COVID-19 were divided into two groups according to their SCUBE1 levels and compared in terms of severity of disease, thrombotic complications and in-hospital mortality. RESULTS: SCUBE1 levels were significantly higher in patients with COVID-19 compared to the control group (p < 0.001). Plasma SCUBE1 levels were significantly higher in patients with severe disease and thrombotic complications, those with mild to moderate disease, and those without thrombotic complications (p < 0.001, for both). In addition, SCUBE1 was found to be an independent predictor of in-hospital mortality (p < 0.001). CONCLUSIONS: SCUBE1 may be one of the major determinants of thrombotic complications, which is an increased cause of mortality and morbidity in COVID-19 patients so inhibition of this peptide may be among the therapeutic targets in patients with COVID-19.

The Diagnostic Value of ischemia-modified albumin (IMA) and signal peptide-CUB-EGF domain-containing protein-1 (SCUBE-1) in an Experimental Model of Strangulated Mechanical Bowel Obstruction.

BACKGROUND: Mechanical bowel obstruction (MBO) is one of the principal pathologies requiring emergency surgery and a significant worldwide cause of morbidity. The identification of patients in whom bowel obstruction resolves spontaneously is important in terms of preventing unnecessary surgical interventions and future potential adhesions. The decision-making process is difficult in patients presenting without classic examination findings. METHODS: 36 female Sprague-Dawley rats randomly divided into six experimental groups. In Group 1, 3 and 5, laparotomy was performed, with blood and tissue specimens being collected after 1, 2 and 6 h, respectively. In Group 2, 4 and 6, the ileum segment was ligated following laparotomy, and blood and tissue specimens were collected after 1, 2 and 6 h, respectively. The ileum specimens were examined macroscopically, after which 1-cm sections were taken and examined in terms of histopathological changes. IMA and SCUBE-1 levels were determined for each group, and macro- and microscopic tissue examination findings were compared between the groups. RESULTS: Comparison within the groups exposed to waiting times of 1 h (groups 1 and 2), 2 h (groups 3 and 4) and 6 h (groups 5 and 6) revealed higher mean IMA and SCUBE-1 levels in rats undergoing ligation together with incision (groups 2, 4, and 6) compared to those undergoing laparotomy only (groups 1, 3, and 5). Correlation analysis was applied to determine the relationship between total scores obtained from histopathological examination and IMA and SCUBE-1 values. The analysis revealed strong, significant and positive correlation between histopathological examination scores and IMA (r=0.643, p=0.000) and SCUBE-1 (r=0.509, p=0.002) values. CONCLUSION: The study findings showed that both IMA and SCUBE-1 values increased in a strangulated MBO model in rats. We think that IMA and SCUBE-1 values can be used as a markers of damage in the early period in strangulated MBO, and that the patient's surgery requirement can thus be determined in the early period.

Can we use serum SCUBE 1 levels as a biomarker in obstructive sleep apnea hypopnea syndrome?

OBJECTIVE: To examine the SCUBE1 level, a biomarker in vascular biology that could determine the prognosis of cardiovascular events during OSA treatment. METHODS: In total, 129 patients were included in the study. Thirty were diagnosed with simple snoring and 99 with OSA. RESULTS: In males, significant correlation was determined between SCUBE1 non-REM AHI, hypopnea index, total apnea index, mean SO2, minimum SO2, and < 90% saturation duration. CONCLUSION: Serum SCUBE1 levels increased more in male patients with severe OSA compared to other OSA levels, and high serum SCUBE1 levels were found to be associated with lower oxygen levels in OSA patients. The SCUBE1 biomarker can correlate with severe OSA in males. There was a statistically significant difference between OSA groups in terms of SCUBE1 score for male patients (p = 0.002) but not for females (p = 0.498). It is important that future SCUBE1 studies evaluate males vs. females.

Pericardial SCUBE1 levels may help predict postoperative results in patients operated on for coronary artery bypass graft surgery.

INTRODUCTION: Signal peptide-CUB epidermal growth factorlike domain-containing protein (SCUBE1) is a newly described, secretable and measurable cellular surface protein associated with atherosclerotic lesions in humans, which may be involved in hypertension and cardiovascular pathologies. We aimed to detect normal SCUBE1 levels in pericardial fluid and investigate the effects of SCUBE1 values on postoperative outcomes after coronary artery bypass surgery. METHODS: Between February 2016 and March 2017, 184 consecutive patients were included in the study. Group 1 consisted of patients with unstable angina pectoris, group 2 of patients with non-ST-elevation myocardial infarction, group 3 of patients with ST-elevation myocardial infarction, and group 4 consisted of patients operated on due to non-coronary reasons. Pericardial fluid and arterial blood SCUBE1 values, demographic variables and postoperative results were noted and compared. RESULTS: Normal SCUBE1 level in pericardial fluid was 0.049 ± 0.061 ng/ml. Arterial SCUBE1 levels of smokers were higher. Pericardial SCUBE1 levels were higher in patients requiring postoperative intra-aortic balloon pump support and patients needing peri-operative temporary cardiac pacing. High pericardial SCUBE1 values did not correlate with postoperative stroke, prolonged intensive care unit stay and mortality. CONCLUSIONS: High levels of pericardial SCUBE1 may help us predict the need for postoperative intra-aortic balloon pump support and the need for temporary cardiac pacing, however they were not helpful in predicting prolonged intensive care unit stay and early postoperative mortality.

SCUBE1 Controls BMPR2-Relevant Pulmonary Endothelial Function: Implications for Diagnostic Marker Development in Pulmonary Arterial Hypertension.

Utilizing publicly available ribonucleic acid sequencing data, we identified SCUBE1 as a BMPR2-related gene differentially expressed between induced pluripotent stem cell-endothelial cells derived from pulmonary arterial hypertension (PAH) patients carrying pathogenic BMPR2 mutations and control patients without mutations. Endothelial SCUBE1 expression was decreased by known triggers of PAH, and its down-regulation recapitulated known BMPR2-associated endothelial pathophenotypes in vitro. Meanwhile, SCUBE1 concentrations were reduced in plasma obtained from PAH rodent models and patients with PAH, whereas plasma concentrations were tightly correlated with hemodynamic markers of disease severity. Taken together, these data implicate SCUBE1 as a novel contributor to PAH pathogenesis with potential therapeutic, diagnostic, and prognostic applications.

Evaluation of SCUBE-1 levels as a placental dysfunction marker at gestational diabetes mellitus.

Objective: To evaluate the alteration of plasma levels of signal peptide-CUB-EGF domain-containing protein (SCUBE)-1 as a marker of endothelial dysfunction and vascular injury in gestational diabetes mellitus (GDM) in comparison to healthy pregnant controls.Methods: A prospective study conducted at an antenatal outpatient clinic of a University hospital. Fifty pregnancies with GDM and thirty healthy pregnancies as controls were enrolled in the study.Results: There was no statistically significant difference between the groups in terms of age, gravidity, weight and BMI from pre-pregnancy until delivery, total weight gain, fetal weight and other hematological and biochemical parameters. SCUBE-1 levels were significantly higher in GDM patients (p = .007).Conclusions: Hyperglycemia predisposes to endothelial injury and vascular remodeling at GDM, and therefore, SCUBE-1 could be a predictor of vascular injury during pregnancy. Our study is the first to illustrate increased SCUBE-1 levels in GDM as a marker of placental endothelial dysfunction.

De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder with a genetic risk component, yet identification of high-confidence risk genes has been challenging. In recent years, risk gene discovery in other complex psychiatric disorders has been achieved by studying rare de novo (DN) coding variants. METHODS: We performed whole-exome sequencing in 222 OCD parent-child trios (184 trios after quality control), comparing DN variant frequencies with 777 previously sequenced unaffected trios. We estimated the contribution of DN mutations to OCD risk and the number of genes involved. Finally, we looked for gene enrichment in other datasets and canonical pathways. RESULTS: DN likely gene disrupting and predicted damaging missense variants are enriched in OCD probands (rate ratio, 1.52; p = .0005) and contribute to risk. We identified 2 high-confidence risk genes, each containing 2 DN damaging variants in unrelated probands: CHD8 and SCUBE1. We estimate that 34% of DN damaging variants in OCD contribute to risk and that DN damaging variants in approximately 335 genes contribute to risk in 22% of OCD cases. Furthermore, genes harboring DN damaging variants in OCD are enriched for those reported in neurodevelopmental disorders, particularly Tourette's disorder and autism spectrum disorder. An exploratory network analysis reveals significant functional connectivity and enrichment in canonical pathways, biological processes, and disease networks. CONCLUSIONS: Our findings show a pathway toward systematic gene discovery in OCD via identification of DN damaging variants. Sequencing larger cohorts of OCD parent-child trios will reveal more OCD risk genes and will provide needed insights into underlying disease biology.

Serum SCUBE-1 levels in patients with diabetic retinopathy.

PURPOSE: Signal peptide-CUB-Epidermal growth factor-like domain-containing protein 1 (SCUBE-1) is a protein expressed on the cell surface of endothelial cells and platelets. We aimed to determine the alterations in SCUBE-1 levels in patients at different stages of diabetic retinopathy (DR). MATERIALS AND METHODS: Participants were grouped into 4 regarding the presence and stage of diabetic retinopathy as follows: control group (n 32), patients without DR (n 39), patients with background DR (n 42) and patients with proliferative DR (n 55). Age, gender, duration of diabetes, fasting blood glucose levels, serum hemoglobin A1c (HbA1c), SCUBE-1 and malondialdehyde (MDA) levels of the patients were recorded. Central macular thickness and central macular volume were recorded and compared between groups. RESULTS: Totally 136 patients with diabetes mellitus and 32 control cases were included in the study. There is a significant increase in SCUBE-1 and MDA levels with an advance in DR. In correlation analysis, there was only a significant correlation present between serum SCUBE-1 and MDA levels (p 0.001) but not with other parameters. CONCLUSION: For the first time in literature, we determined a significant increase in SCUBE-1 levels in patients with DR. Moreover, with an advance in DR, SCUBE-1 levels were also increasing.

Influence of circadian blood pressure alterations on serum SCUBE-1 and soluble CD40 ligand levels in patients with essential hypertension.

BACKGROUND: Dipper and non-dipper hypertension are different clinical forms of essential hypertension. In this study, the effect of circadian blood pressure changes on serum SCUBE-1 and soluble CD40 ligand (sCD40L) levels was investigated in patients with hypertension. METHODS: A total of 100 participants aged 23-89 years were included in the study. Patients with essential hypertension were followed up by ambulatory blood pressure measurement. RESULTS: Serum SCUBE1 levels were significantly higher in the non-dipper group than in the normal group (P < 0.001). Dipper and non-dipper patients had significantly higher serum sCD40L levels when compared to the normal group (P = 0.048 and P = 0.035, respectively). We also found a positive correlation between SCUBE1, sCD40L levels and 24-hour mean systolic blood pressure levels (r: 0.232, p: 0.034 and r: 0.241, p: 0.027, respectively). CONCLUSION: Serum SCUBE1 and sCD40L levels were higher in hypertensive patients than normal participants. Serum SCUBE1 levels were higher in patients with non-dipper compared to other participants.

The value of plasma SCUBE1 and oxidative stress parameters in the early diagnosis of acute ovarian torsion.

AIM: The purpose of our study was to determine the diagnostic value of plasma SCUBE1, malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant status (TAS) investigated on the 4th hour of ovarian torsion, and at the same time to determine the relation between these markers and histopathological damage occurring in the ovary. MATERIALS AND METHODS: Sixteen rats were included, eight in the torsion group and eight in the control group. The right ovaries of the rats in the torsion group were rotated clockwise 720 degrees, after which they were fixed and attached to the abdominal wall. The abdominal walls of the control group rats were opened for 1 min and then closed. Relaparotomy was performed 4 h after surgery in both groups, blood specimens were collected for biochemical analyses, and the right ovaries were surgically extracted. RESULTS: No statistically significant difference was determined in the control and torsion groups' plasma SCUBE1, SOD and TAS values (p = 0.987, p = 0.33, and p = 0.244, respectively). Torsion group plasma MDA values were significantly higher than those of the control group (p = 0.039). At histopathological evaluation, histological score, apoptotic index and Caspase-3 index values of the torsion group were significantly higher compared to the control group. CONCLUSION: Plasma SCUBE1 is not useful in the early diagnosis of ovarian torsion. Similarly, use of the oxidative stress markers SOD and TAS does not appear useful in early diagnosis, although MDA may be considered for that purpose (Tab. 2, Fig. 3, Ref. 23).

Upregulation of SCUBE1 in Dengue Virus Infection.

BACKGROUND: Dengue is a major communicable disease in tropical areas, with an increasing prevalence every year. Thrombocytopenia is one of the commonly used laboratory parameters for predicting the severity of the disease. It is detected on day 6 or day 7 after the febrile stage, and its presence indicates that the disease has become potentially fatal. Therefore, it is necessary to identify a marker for the early recognition of dengue virus infection during the febrile stage before the detection of thrombocytopenia on day 6 to prevent severe disease outcomes. Signal peptide-CUB- (complement C1r/C1s)-EGF (epidermal growth factor)-like domain-containing protein 1 (SCUBE1) is secreted in activated platelets under inflammatory conditions and enhances platelet-platelet adhesion and agglutination. This gene was first identified in human vascular endothelium, but its biological role in platelets remains unknown. AIM: This study aims to identify SCUBE1 expression during the febrile stage of dengue virus infection and examine the correlation of its expression with thrombocytopenia occurrence on day 6. MATERIAL AND METHODS: Blood samples were collected from 17 patients infected with dengue virus on day-3 fever and from 16 healthy controls who met the inclusion and exclusion criteria for dengue virus infection according to the World Health Organization (WHO) classification for dengue virus infection. All samples were subjected to SCUBE1 gene analysis using real-time reverse transcription quantitative PCR (RT-PCR). RESULTS: The results showed that upregulation of SCUBE1 gene in infected patients (8.9 ± 3.1-fold) compared to that in healthy controls, indicating SCUBE1 involvement in dengue virus infection. Furthermore, we analysed the laboratory parameters of infected patients on day 3 and day 6, when thrombocytopenia is usually detected. Platelet count was found to be significantly decreased from day 3 until day 6 in the infected patients. Unfortunately, our results showed no correlation between SCUBE1 expression in the febrile stage and the occurrence of thrombocytopenia on day 6. CONCLUSION: The conclusion of this study is SCUBE1 might play a role in dengue virus infection but does not correlate with thrombocytopenia on day-6 fever.