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AIMS AND BACKGROUND: Matrix metalloproteinase-7 (MMP-7) and Syndecan-1 (SDC1) are involved in multiple functions during tumorigenesis. We aimed to evaluate the diagnostic and prognostic performance of these serum proteins, as potential biomarkers, in patients with pancreatic ductal adenocarcinoma (PDAC) and benign pancreatic cysts. METHODS: In this case-control study, patients with newly diagnosed PDAC (N = 121) were compared with the benign cyst (N = 66) and healthy control (N = 48) groups. Serum MMP-7 and SDC1 were measured by ELISA. The diagnostic accuracy of their levels for diagnosing PDAC and pancreatic cysts was computed, and their association with survival outcomes was evaluated. RESULTS: MMP-7 median serum levels were significantly elevated in the PDAC (7.3 ng/mL) and cyst groups (3.7 ng/mL) compared with controls (2.9 ng/mL) (p < 0.001 and 0.02, respectively), and also between the PDAC and cyst groups (p < 0.001), while SDC1 median serum levels were significantly elevated in PDAC (43.3 ng/mL) compared with either cysts (30.1 ng/mL, p < 0.001) or controls (31.2 ng/mL, p < 0.001). The receiver operating characteristic curve analysis area under the curve in PDAC versus controls was 0.90 and 0.78 for MMP-7 and SDC1, respectively, while it was 1.0 for the combination of the two and CA 19-9 (p < 0.001). The combination of the three biomarkers had a perfect sensitivity (100%). CONCLUSIONS: Due to its high sensitivity, this biomarker panel has the potential to rule out PDAC in suspected cases.

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BACKGROUND: Endothelial glycocalyx (EG) degradation occurs in septic humans and EG products can be used as biomarkers of endothelial injury. Information about EG biomarkers and their association with disease severity is lacking in hospitalized foals. OBJECTIVES: Measure serum syndecan-1 (SDC-1), heparan sulfate (HS), angiopoietin-2 (ANG-2), aldosterone (ALD), and plasma atrial natriuretic peptide (ANP) concentrations and to determine their association with disease severity and death in hospitalized foals. ANIMALS: Ninety foals ≤3 days old. METHODS: Prospective, multicenter, longitudinal study. Foals were categorized into hospitalized (n = 74; 55 septic; 19 sick nonseptic) and 16 healthy foals. Serum ([SDC-1], [HS], [ANG-2], [ALD]) and plasma (ANP) were measured over 72 hours using immunoassays. RESULTS: Serum ([SDC-1], [HS], [ANG-2], [ALD]) and plasma (ANP) were significantly higher in hospitalized and septic than healthy foals (P < .05). Serum (ANG-2) and plasma (ANP) were significantly higher in hospitalized nonsurvivors than in survivors (P < .05). On admission, hospitalized foals with serum (HS) > 58.7 ng/mL had higher odds of nonsurvival (odds ratio [OR] = 6.1; 95% confidence interval [CI] = 1.02-36.7). Plasma (ANP) >11.5 pg/mL was associated with the likelihood of nonsurvival in hospitalized foals (OR = 7.2; 95% CI = 1.4-37.4; P < .05). Septic foals with serum (ANG-2) >1018 pg/mL on admission had higher odds of nonsurvival (OR = 6.5; 95% CI =1.2-36.6; P < .05). CONCLUSION AND CLINICAL IMPORTANCE: Critical illness in newborn foals is associated with EG degradation and injury, and these biomarkers are related to the severity of disease on admission and the outcome of sick foals.

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OBJECTIVES: This study investigated whether serum syndecan1 at diagnosis reflects activity at diagnosis and predicts poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: The study included 79 patients with AAV from the cohort of Korean patients diagnosed with AAV. AAV-specific indices, including the Birmingham vasculitis activity score (BVAS), five-factor score (FFS), 36-item short-form survey (SF-36) physical and mental component summary (PCS and MCS), and vasculitis damage index (VDI), were assessed. Laboratory data including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also collected. The highest tertile and upper half of the BVAS were tentatively defined as having high AAV activity. Serum syndecan1 levels were measured in sera stored at diagnosis. RESULTS: Serum syndecan1 at diagnosis was significantly correlated with AAV activity and functional status, as assessed by BVAS, FFS, SF-36 PCS, MCS, and acute-phase reactants, including ESR and CRP. Patients with serum syndecan1 ≥ 76.1 ng/mL at diagnosis, and those with serum syndecan1 ≥ 60.0 ng/mL at diagnosis showed significantly higher risks for the highest tertile and the upper half of BVAS at diagnosis than those without, respectively. Patients with serum syndecan1 ≥ 120.1 ng/mL at diagnosis had a significantly higher risk for all-cause mortality during follow-up than those without, and further, exhibited a significantly lower cumulative patients' survival rate than those without. CONCLUSION: Serum syndecan1 at diagnosis may not only reflect AAV activity at diagnosis but may also be associated with all-cause mortality during follow-up.

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Introduction: The administration of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) in the treatment of acute ischemic stroke (AIS) has been a subject of debate, and its potential benefits remain uncertain. This retrospective study aimed to investigate the effect of preoperative IVT on glycocalyx damage in patients with cerebral ischemia-reperfusion injury (IRI). Methods: A cohort of 106 patients with acute large vessel occlusion in the anterior circulation treated with mechanical thrombectomy was enrolled. The levels of the glycocalyx damage marker, syndecan-1, were measured in the peripheral blood of these patients to assess glycocalyx damage during IRI, and clinical outcomes were compared between patients receiving MT alone vs. combined IVT and MT. Results: The study results indicate that thrombolytic drugs have a significant impact on syndecan-1 levels in the blood. Compared to patients who underwent direct MT, those who received preoperative IVT had significantly lower levels of syndecan-1 in their blood. Although preoperative IVT did not alter the final clinical outcomes, the levels of syndecan-1 shedding reflect the extent of damage to the endothelial glycocalyx. Discussion: This suggests that using thrombolytic drugs before mechanical thrombectomy may reduce endothelial glycocalyx damage in patients with ischemia-reperfusion injury. These findings provide indirect clinical evidence supporting the preoperative use of intravenous thrombolysis in such patients.

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BACKGROUND: Spermatogonial stem cells (SSCs) are essential for the maintenance and initiation of male spermatogenesis. Despite the advances in understanding SSC biology in mouse models, the mechanisms underlying human SSC development remain elusive. RESULTS: Here, we analyzed the signaling pathways involved in SSC regulation by testicular somatic cells using single-cell sequencing data (GEO datasets: GSE149512 and GSE112013) and identified that Leydig cells communicate with SSCs through pleiotrophin (PTN) and its receptor syndecan-2 (SDC2). Immunofluorescence, STRING prediction, and protein immunoprecipitation assays confirmed the interaction between PTN and SDC2 in spermatogonia, but their co-localization was observed only in approximately 50% of the cells. The knockdown of SDC2 in human SSC lines impaired cell proliferation, DNA synthesis, and the expression of PLZF, a key marker for SSC self-renewal. Transcriptome analysis revealed that SDC2 knockdown downregulated the expression of GFRA1, a crucial factor for SSC proliferation and self-renewal, and inhibited the HIF-1 signaling pathway. Exogenous PTN rescued the proliferation and GFRA1 expression in SDC2 knockdown SSC lines. In addition, we found downregulation of PTN and SDC2 as well as altered localization in non-obstructive azoospermia (NOA) patients, suggesting that downregulation of PTN and SDC2 may be associated with impaired spermatogenesis. CONCLUSIONS: Our results uncover a novel mechanism of human SSC regulation by the testicular microenvironment and suggest a potential therapeutic target for male infertility.

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In Sjögren's disease (SjD), the salivary glandular epithelial cells can induce the chemotaxis of B cells by secreting B-cell chemokines such as C-X-C motif chemokine ligand 13 (CXCL13). Syndecan-1 (SDC-1) is a major transmembrane heparan sulfate proteoglycan (HSPG) predominantly expressed on epithelial cells that binds to and regulates heparan sulfate (HS)-binding molecules, including chemokines. We aimed to determine whether SDC-1 plays a role in the pathogenesis of SjD by acting on the binding of HS to B-cell chemokines. To assess changes in glandular inflammation and SDC-1 concentrations in the submandibular gland (SMG) and blood, female NOD/ShiLtJ and sex- and age-matched C57BL/10 mice were used. In the SMG of NOD/ShiLtJ mice, inflammatory responses were identified at 8 weeks of age, but increased SDC-1 concentrations in the SMG and blood were observed at 6 weeks of age, when inflammation had not yet started. As the inflammation of the SMG worsened, the SDC-1 concentrations in the SMG and blood increased. The expression of the CXCL13 and its receptor C-X-C chemokine receptor type 5 (CXCR5) began to increase in the SMG at 6 weeks of age and continued until 12 weeks of age. Immunofluorescence staining in SMG tissue and normal murine mammary gland cells confirmed the co-localization of SDC-1 and CXCL13, and SDC-1 formed a complex with CXCL13 in an immunoprecipitation assay. Furthermore, NOD/ShiLtJ mice were treated with 5 mg/kg HS intraperitoneally thrice per week for 6-10 weeks of age, and the therapeutic effects in the SMG were assessed at the end of 10 weeks of age. NOD/ShiLtJ mice treated with HS showed attenuated salivary gland inflammation with reduced B-cell infiltration, germinal center formation and CXCR5 expression. These findings suggest that SDC-1 plays a pivotal role in the pathogenesis of SjD by binding to CXCL13 through the HS chain.

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BACKGROUND: The development of acute kidney injury (AKI) post-cardiac surgery significantly increases patient morbidity and healthcare costs. Prior researches have established Syndecan-1 (SDC-1) as a potential biomarker for endothelial injury and subsequent acute kidney injury development. This study assessed whether postoperative SDC-1 levels could further predict AKI requiring kidney replacement therapy (AKI-KRT) and AKI progression. METHODS: In this prospective study, 122 adult cardiac surgery patients, who underwent valve or coronary artery bypass grafting (CABG) or a combination thereof and developed AKI within 48 h post-operation from May to September 2021, were monitored for the progression to stage 2-3 AKI or the need for KRT. We analyzed the predictive value of postoperative serum SDC-1 levels in relation to multiple endpoints. RESULTS: In the study population, 110 patients (90.2%) underwent cardiopulmonary bypass, of which thirty received CABG or combined surgery. Fifteen patients (12.3%) required KRT, and thirty-eight (31.1%) developed progressive AKI, underscoring the severe AKI incidence. Multivariate logistic regression indicated that elevated SDC-1 levels were independent risk factors for progressive AKI (OR = 1.006) and AKI-KRT (OR = 1.011). The AUROC for SDC-1 levels in predicting AKI-KRT and AKI progression was 0.892 and 0.73, respectively, outperforming the inflammatory cytokines. Linear regression revealed a positive correlation between SDC-1 levels and both hospital (ß = 0.014, p = 0.022) and ICU stays (ß = 0.013, p < 0.001). CONCLUSION: Elevated postoperative SDC-1 levels significantly predict AKI progression and AKI-KRT in patients following cardiac surgery. The study's findings support incorporating SDC-1 level monitoring into post-surgical care to improve early detection and intervention for severe AKI.

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BACKGROUND: Endothelial cellular senescence is emerging as a key mechanism of age-related vascular dysfunction. Disruption of the endothelium glycocalyx and shedding of the syndecan (SDC) ectodomains have been associated with several age-related diseases. Although SDC4 is highly expressed in endothelial cells, its levels and shedding in senescent endothelial cells and vascular endothelial dysfunction associated with aging are still unknown. METHODS: To assess whether SDC4 expression was affected by inflammatory conditions, we evaluated its levels in young human umbilical vein endothelial cells (HUVECs) treated with TNF-α at a concentration of 50 ng/mL for 24 h and in cells undergoing replicative senescence. Plasma levels of SDC4 were evaluated in two previously recruited cohorts of (i) subjects with type 2 diabetes (T2D, n = 110) followed for a median of 16.8 years and age- and gender-matched healthy subjects (n = 100), and (ii) middle-aged subjects with mild-to-moderate dyslipidemia. Binomial logistic regression was used to assess whether SDC4 levels could be prognostic for major adverse cardiovascular events (MACE). RESULTS: In the in vitro study, we showed that HUVECs, when exposed to TNF-α or undergoing replicative senescence, exhibited elevated expression levels of SDC4 and matrix metallopeptidase 9 (MMP-9), as well as increased shedding of SDC4 into the extracellular microenvironment, in comparison to actively proliferating young HUVECs. Analysis of human samples revealed that patients with T2D without complications exhibited higher SDC4 levels compared to healthy controls and those with T2D vascular complications. In particular, patients with a history of major adverse cardiovascular events (MACE) had lower SDC4 levels. The longitudinal evaluation revealed that higher SDC4 levels predict the onset of new MACE during a 16.8-year follow-up. In the second cohort, no significant association was observed between SDC4 and endothelial dysfunction, assessed by flow-mediated dilation (FMD) or nitric oxide metabolites. SDC4 levels correlated positively with C-reactive protein (CRP) in both cohorts and with PAI-1 in the cohort of patients with T2D. CONCLUSION: Overall, we conclude that the shedding of SDC4 from endothelial cells increases under acute (TNF-α treatment) and chronic (senescence) inflammatory conditions and that increased circulating SDC4 levels are associated with systemic inflammation in pathological aging.

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The aim of this study was to review the roles of endothelial cells in normal tissue function and to show how COVID-19 disease impacts on endothelial cell properties that lead to much of its associated symptomatology. This places the endothelial cell as a prominent cell type to target therapeutically in the treatment of this disorder. Advances in glycosaminoglycan analytical techniques and functional glycomics have improved glycosaminoglycan mimetics development, providing agents that can more appropriately target various aspects of the behaviour of the endothelial cell in-situ and have also provided polymers with potential to prevent viral infection. Thus, promising approaches are being developed to combat COVID-19 disease and the plethora of symptoms this disease produces. Glycosaminoglycan mimetics that improve endothelial glycocalyx boundary functions have promising properties in the prevention of viral infection, improve endothelial cell function and have disease-modifying potential. Endothelial cell integrity, forming tight junctions in cerebral cell populations in the blood-brain barrier, prevents the exposure of the central nervous system to circulating toxins and harmful chemicals, which may contribute to the troublesome brain fogging phenomena reported in cognitive processing in long COVID disease.

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BACKGROUND: Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix. OBJECTIVE: This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA). METHODS: Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin-1ß (rrIL-1ß) and SDC4 small interfering RNA (si-SDC4). Anti-SDC4 ectodomain-specific antibodies or IgG were intra-articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4-cKO) and Sdc4flox/flox mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col-II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays. RESULTS: SDC4 expression was evidently increased in MIA-model animals compared to control groups. rrIL-1ß stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col-II. These effects were reversed by si-SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col-II and ACAN, and a decrease in SDC4, MMP13 and cleaved-CASP3-positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition. CONCLUSIONS: SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA.

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INTRODUCTION: Syndecan (SDC)-1 is a transmembrane heparan sulfate proteoglycan and is a major component of endothelial glycocalyx (EG). This study aimed to investigate the association of serum SDC-1 concentration as a marker of EG degradation with albuminuria in type 2 diabetes. METHODS: We included 370 patients with type 2 diabetes and 219 individuals with no diabetes. The individuals with estimate glomerular filtration rate <30 mL/min/1.73 m2 were excluded. RESULTS: Serum SDC-1 concentration was higher in type 2 diabetes than in no diabetes. The presence of diabetes was independently associated with log [SDC-1] in multivariate analysis. In type 2 diabetes, serum SDC-1 concentration was correlated with log [urinary albumin-to-creatinine ratio (ACR)]. Moreover, log [SDC-1] was an independent determinant of log [ACR] after adjustment for known risk factors of albuminuria. CONCLUSIONS: Serum SDC-1 concentration was higher in patients with type 2 diabetes compared to individuals with no diabetes and an independent determinant of ACR. This study implicates the role of the EG degradation in albuminuria in type 2 diabetes.

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Aims: Cardiovascular disease remains a major global health concern, with atherosclerosis (AS) being a significant contributor. Vulnerable plaques play a critical role in acute cardiovascular events. Syndecan-1 (SDC-1), a vital membrane proteoglycan in the vascular endothelial glycocalyx, is believed to be associated with plaque progression. However, its precise relationship with severity and vulnerability of atherosclerotic plaque remains unclear. This study aimed to investigate SDC-1 expression and its potential correlation with plaque vulnerability in ApoE-/- atherosclerosis mouse model. Methods and results: Eight-week-old mice were induced into the AS model using a high-fat diet (HFD) and/or partial ligation of the left common carotid artery (PLCA), with a chow diet (CD) control group. After 16 weeks, plaques in the aortic root showed the following order: HFD + PLCA group > HFD group > CD + PLCA group > CD group. Immunohistochemistry revealed heightened accumulation of lipid/foam cells and CD68-labeled macrophages in the plaques, elevated vascular endothelial growth factor (VEGF), and matrix Metalloproteinase-9 (MMP-9) in the HFD + PLCA group's plaques, along with reduced collagen and α-SMA-labeled smooth muscle cells, resulting in the highest vulnerability index value. Immunohistofluorescence analysis of frozen plaque sections showed significantly higher SDC-1 expression in the AS mice group compared to the CD group, both positively correlated with plaque vulnerability. Serum analysis demonstrated elevated levels of SDC1, sphingosine 1-phosphate (S1P), and VEGF-A in the AS mice, all positively correlated with plaque vulnerability. Multivariate analysis identified SDC1 as an independent predictor of plaque vulnerability. Conclusion: This study enhances our understanding of plaque vulnerability mechanisms and presents SDC1 as a potential biomarker for atherosclerosis. These findings underscore the importance of addressing modifiable risk factors, such as diet and hemodynamics and suggest the utility of serum SDC1 as a valuable clinical marker. Ultimately, these insights may lead to more effective strategies in combating cardiovascular diseases and improving patient outcomes.

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INTRODUCTION: Cognitive decline is prevalent in maintenance hemodialysis patients. The blood-brain barrier has been implicated in cognitive decline. In this prospective cohort study, we investigated the associations between endothelium-related biomarkers and steeper cognitive decline in this population. METHODS: Cognitive function was assessed using the Portuguese-adapted Cambridge Cognitive Examination (CAMCOG) with items of the Mini-Mental State Examination (MMSE). Endothelium-related biomarkers included syndecan-1, ICAM-1, VCAM-1 and angiopoietin-2 (AGPT2). Patients were followed up for 4 years, and cognitive assessments were repeated. Multinomial regression analyses were performed to evaluate associations between biomarkers and cognitive decline. RESULTS: A total of 216 patients completed the test battery at baseline. After 4 years, 102 patients had follow-up data. There was a significant decrease in cognitive function according to the CAMCOG and MMSE scores: a change of -0.39 (95% CI -0.27 to -0.51) and -0.51 (95% CI -0.27 to -0.76) standard deviation (SD) of the baseline scores. Additionally, executive function but not memory significantly decreased. Syndecan-1 level was independently associated with steeper cognitive decline; each increase in the SD of the syndecan-1 level was associated with a decrease in the CAMCOG of 0.20 (95% CI 0.07-0.33) SD from baseline. Syndecan-1 was associated with a steeper decline in MMSE score (ß 0.54, 95% CI 0.28-0.81) and executive function (ß 0.17, 95% CI 0.02-0.32). Syndecan-1 predicted severe cognitive impairment with an area under the curve for receiver operating characteristic curves of 0.75 (95% CI 0.64-0.83). CONCLUSION: Our findings highlight the potential of syndecan-1, a biomarker of endothelium glycocalyx derangement, as a predictor of steeper cognitive decline in prevalent hemodialysis patients.

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Hemorrhagic shock and subsequent resuscitation can cause significant dysregulation of critical systems, including the vascular endothelium. Following hemorrhage, the endothelial lining (glycocalyx) can shed, causing release of glycocalyx components, endothelial activation, and systemic inflammation. A canine model of hemorrhagic shock was used to evaluate five resuscitation fluids, including Lactated Ringers+Hetastarch, Whole Blood (WB), Fresh Frozen Plasma+packed Red Blood Cells (FFP+pRBC), and two hemoglobin-based oxygen carrier (HBOC) fluids, for their impact on glycocalyx shedding. Under anesthesia, purpose-bred adult canines were instrumented and subjected to a controlled hemorrhage with blood being drawn until a mean arterial pressure of <50 mmHg was reached or 40 % of the estimated blood volume was removed. Canines were left in shock for 45 mins before being resuscitated with one of the resuscitation fluids over 30 mins. Following resuscitation, the dogs were monitored up to 2 weeks. Following an additional 3-4 weeks for washout, the canines repeated the protocol, undergoing each resuscitation fluid individually. Blood samples were collected during each round at various timepoints for serum isolation, which was used for detection of glycocalyx biomarker. Comparison of baseline and post-hemorrhage alone showed a significant reduction in serum protein (p<0.0001), heparan sulfate (p<0.001), and syndecan-1 (p<0.0001) concentrations, and a significant increase in hyaluronan (p<0.0001) concentration. Intercomparisons of resuscitation fluids indicated minimal differences in glycocalyx markers over time. Comparisons within each fluid showed dynamic responses in glycocalyx biomarkers over time. Relative to individual baselines, syndecan-1 was significantly reduced after resuscitation in most cases (p<0.0001), excluding WB and FFP+pRBC. In all cases, VE-cadherin was significantly elevated at 24 hr compared to baseline (p<0.001). Hyaluronan was significantly elevated by 3 hr in all cases (p<0.01), except for HBOC fluids. Total glycosaminoglycans were significantly reduced only at 3 hr (p<0.001) for non-HBOC fluids. Similarly, heparan sulfate was significantly reduced with all fluids between resuscitation and 24 hr (p<0.01), except WB. The temporal changes in canine glycocalyx biomarkers were atypical of hemorrhage response in other species. This suggests that the hemorrhage lacked severity and/or typical glycocalyx biomarkers do not reflect the canine endothelium compared to other species. Further research is needed to characterize the canine endothelium and the response to resuscitation fluids.

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This study aims to explore the impact of metabolites from three vaginal bacteria on the expression of Syndecan 1 (SDC-1). Human cervical epithelial cells (HcerEpic) were separately incubated with the cell-free supernatants of Lactobacillus crispatus (LCS group), Gardnerella vaginalis (GVS group), and Atopobium vaginalis (AVS group). LCS showed a proliferative effect on HcerEpic, with the most significant effect observed at a concentration of 30 % (P < 0.001). GVS and AVS exhibited some cytotoxicity, with significant growth inhibitory effects observed at concentrations of 30 % and 40 % (P < 0.01). Therefore, subsequent experiments were conducted using 30 % LCS, 40 % GVS, and 40 % AVS. In terms of cellular morphology, compared to the Control group, the LCS group showed more frequent fusion of cell sheets, with no obvious changes in the morphology of individual cells. In the GVS and AVS groups, some individual cells became round and smaller, with reduced protrusions and even a small amount of floating cells. The metabolic products of the three vaginal bacteria significantly upregulated the expression of IL-1ß, IL-6, and TNF-α in HcerEpic (P < 0.05). In the GVS and AVS groups, the level of SDC-1 on the surface of HcerEpic was significantly decreased (P < 0.01), while the concentration of SDC-1 in the cell culture supernatant was significantly increased (P < 0.0001). Additionally, the level of SDC-1 mRNA was significantly downregulated (P < 0.01). In the LCS group, no significant changes were observed in SDC-1 protein and mRNA expression (P > 0.05). LCS promotes HcerEpic proliferation, without significant impact on SDC-1 expression and shedding. This provides molecular evidence for LCS as a protective factor against human papillomavirus infection in the cervix. Metabolites of GV and AV inhibit HcerEpic proliferation, induce cytokine secretion, suppress SDC-1 transcription and expression, and promote SDC-1 shedding.

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Objective: To obtain insight into the molecular process implicated in venous malformations (VMs) and identify potential targets for treatment of VMs, this study profiled the gene expression pattern in VMs, investigated alterations of syndecan-1 (SDC1) expression in VMs, and tested the hypothesis that aberrant SDC1 expression triggers abnormal angiogenesis and VM development. Methods: Microarray analysis was performed to identify differentially expressed genes (DEGs) on a transcriptome-wide level in VMs and conjunctive normal. Gene Ontology molecular functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out to establish enhancement of biological signaling pathways involved in VMs. Among the DEGs, we focused on SDC1, which is involved in matrix remodeling, cell proliferation and invasion, and angiogenesis. SDC1 expression in VMs was verified by qRT-PCR, western blotting, and immunohistochemistry. Loss-of-function of SDC1 was achieved in human umbilical vein endothelial cells (HUVECs) by siRNA to investigate the roles of SDC1 in cell migration, invasion, and angiogenesis. Results: Compared with control tissue, the transcriptome study identified 274 upregulated DEGs and 3 downregulated DEGs. The transcript and protein levels of SDC1 were significantly decreased in VMs compared with normal tissue. Inhibition of SDC1 enhanced HUVEC migration, invasion, and angiogenesis. Conclusion: Our genome-wide microarray analysis suggests the involvement of numerous genes in VMs. Among them, SDC1 plays a substantial role in the process of angiogenesis and development of VMs. SDC1 may represent a potential target for a molecular therapy for VMs.

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Background: The relationship between serum glycoprotein syndecan-1 and disease activity in rheumatoid arthritis (RA) is still unknown. This study aimed to evaluate whether serum syndecan-1 concentrations are associated with moderate/severe disease activity. Methods: Study Design: This was a cross-sectional study. Seventy-five adult women with RA were classified into (a) moderate/severe RA based on the disease activity score, using the erythrocyte sedimentation rate (DAS28-ESR ≥ 3.2, n = 50), and (b) RA in remission (DAS28-ESR < 2.6, n = 25). Twenty-five healthy women were taken as the reference group. Syndecan-1 levels were determined using enzyme-linked immunosorbent assay (ELISA). High values of serum syndecan-1 levels (≥24 ng/mL) were used to identify the utility values of this biomarker. Results: The patients with RA had higher levels of syndecan-1 than the controls (p < 0.001). RA patients with active disease had higher syndecan-1 levels than RA patients in remission (57.6 vs. 23.5 ng/mL, respectively; p = 0.002). High syndecan-1 concentrations demonstrated the following utility values for identifying disease activity: sensitivity, 84% (95%CI: 71-93); specificity, 52% (95%CI: 31-72); positive predictive value, 78% (95%CI: 70-84); and negative predictive value, 62% (95%CI: 44-77). Conclusions: High syndecan-1 levels have good sensitivity and positive predictive value for identifying disease activity; however, their specificity is limited. Future prospective studies are needed to assess whether syndecan-1 levels can predict treatment failure in RA.

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BACKGROUND: The association of plasma biomarkers and clinical outcomes in ARDS resulting from SARS-CoV-2 infection predate the evidence-based use of immunomodulators. RESEARCH QUESTION: Which plasma biomarkers are associated with clinical outcomes in patients with ARDS resulting from SARS-CoV-2 infection treated routinely with immunomodulators? STUDY DESIGN AND METHODS: We collected plasma from patients with ARDS resulting from SARS-CoV-2 infection within 24 h of admission to the ICU between December 2020 and March 2021 (N = 69). We associated 16 total biomarkers of inflammation (eg, IL-6), coagulation (eg, D-dimer), epithelial injury (eg, surfactant protein D), and endothelial injury (eg, angiopoietin-2) with the primary outcome of in-hospital mortality and secondary outcome of ventilatory ratio (at baseline and day 3). RESULTS: Thirty patients (43.5%) died within 60 days. All patients received corticosteroids and 6% also received tocilizumab. Compared with survivors, nonsurvivors demonstrated a higher baseline modified Sequential Organ Failure Assessment score (median, 8.5 [interquartile range (IQR), 7-9] vs 7 [IQR, 5-8]); P = .004), lower Pao2 to Fio2 ratio (median, 153 [IQR, 118-182] vs 184 [IQR, 142-247]; P = .04), and higher ventilatory ratio (median, 2.0 [IQR, 1.9-2.3] vs 1.5 [IQR, 1.4-1.9]; P < .001). No difference was found in inflammatory, coagulation, or epithelial biomarkers between groups. Nonsurvivors showed higher median neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) levels (median, 8.4 ng/mL [IQR, 7.0-11.2 ng/mL] vs 6.9 ng/mL [IQR, 5.5-8.0 ng/mL]; P = .0025), von Willebrand factor domain A2 levels (8.7 ng/mL [IQR, 7.9-9.7 ng/mL] vs 6.5 ng/mL [IQR, 5.7-8.7 ng/mL]; P = .007), angiopoietin-2 levels (9.0 ng/mL [IQR, 7.9-14.1 ng/mL] vs 7.0 ng/mL [IQR, 5.6-10.6 ng/mL]; P = .01), and syndecan-1 levels (15.9 ng/mL [IQR, 14.5-17.5 ng/mL] vs 12.6 ng/mL [IQR, 10.5-16.1 ng/mL]; P = .01). Only NEDD9 level met the adjusted threshold for significance (P < .003). Plasma NEDD9 level was associated with 60-day mortality (adjusted OR, 9.7; 95% CI, 1.6-60.4; P = .015). Syndecan-1 level correlated with both baseline (ρ = 0.4; P = .001) and day 3 ventilatory ratio (ρ = 0.5; P < .001). INTERPRETATION: Biomarkers of inflammation, coagulation, and epithelial injury were not associated with clinical outcomes in a small cohort of patients with ARDS uniformly treated with immunomodulators. However, endothelial biomarkers, including plasma NEDD9, were associated with 60-day mortality.

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Cell surface receptors play crucial roles in cellular responses to extracellular ligands, helping to modulate the functions of a cell based on information coming from outside the cell. Syndecan refers to a family of cell adhesion receptors that regulate both extracellular and cytosolic events. Alteration of syndecan expression disrupts regulatory mechanisms in a cell type-specific fashion, often leading to serious diseases, notably cancer. Given the multifaceted functions and distinct tissue distributions of syndecan, it will be important to unravel the gene-level intricacies of syndecan expression and thereby further understand its involvement in various carcinogenic processes. Although accumulating evidence indicates that the protein expression patterns of syndecan family members are significantly altered in cancer cells, the underlying gene-level mechanisms remain largely unknown. This review endeavors to explore syndecan gene expression levels across different cancer types by scrutinizing extensive cancer genome datasets using tools such as cBioPortal. Our analysis unveils that somatic mutations in SDC genes are rare occurrences, whereas copy number alterations are frequently observed across diverse cancers, particularly in SDC2 and SDC4. Notably, amplifications of SDC2 and SDC4 correlate with heightened metastatic potential and dismal prognosis. This underscores the recurrent nature of SDC2 and SDC4 amplifications during carcinogenesis and sheds light on their role in promoting cancer activity through augmented protein expression. The identification of these amplifications not only enriches our understanding of carcinogenic mechanisms but also hints at the potential therapeutic avenue of targeting SDC2 and SDC4 to curb cancer cell proliferation and metastasis.

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The endothelial glycocalyx is damaged in postcardiac arrest syndrome (PCAS), but the prognostic value is unknown. We aimed to observe the expression and prognostic value of glycocalyx shedding products, including syndecan-1 (SDC-1), hyaluronan (HA), and heparan sulfate (HS) in PCAS. Data on clinical and 28-day outcomes of seventy-one consecutive patients with out-of-hospital cardiac arrest (OHCA) after the return of spontaneous circulation (ROSC) were collected. SDC-1, HA, and HS were measured on days 0, 1, and 3 after ROSC. Thirty healthy individuals were controls. Glycocalyx shedding was observed in human umbilical vein endothelial cells (HUVECs) stimulated during hypoxia and reoxygenation in vitro. Within 4 h of ROSC, SDC-1 and HA levels, significantly increased. In the 28-day non-survivors, HA levels showed a gradual upward trend, SDC-1 remained at a high level, and HS levels first increased, then decreased. Kaplan-Meier curves and binary logistic regression analysis showed the prognostic value of SDC-1 levels on days 0, 1, and 3, HA levels on days 1 and 3, and HS levels on day 1. Only HS levels on day 1 showed a prognostic value for 28-day neurological outcomes. SDC-1 and HA levels were positively correlated with the no-flow time. In vitro, HUVECs showed shedding of SDC-1 and HS during a prolonged duration of hypoxia. After ROSC, SDC-1, HA, and HS levels may predict the 28-day survival after PCAS, and HS levels are associated with functional outcomes.

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