Background: The extracellular matrix (ECM) glycoprotein changes are associated with the pathogenesis and complications of atherosclerosis, leading to acute coronary syndrome (ACS). Tenascin-C (TNC), an ECM protein, has been implemented in the pathogenesis, diagnosis, and prognosis of patients with cardiovascular disease. Aim: The study aimed to compare the genetic variants of the TNC gene (rs13321, rs2104772, and rs12347433) between South Indians with ACS and healthy participants. Materials and Methods: This case-control study recruited 150 ACS patients as cases and 150 healthy participants as controls. TNC genotyping was performed using TaqMan 5\'-exonuclease allele discrimination assay. Serum TNC levels were measured by enzyme-linked immunosorbent assay. Results: Serum TNC levels were significantly higher in cases compared with controls. No significant difference was observed in allele and genotype frequencies of rs13321, rs2104772, and rs12347433 between cases and controls, which was confirmed by dominant, recessive, codominant, and homozygotic genetic models. The patients with heterozygous genotypes of rs13321, rs2104772, and rs12347433 had significantly lower serum TNC levels than patients with respective homozygous genotypes. Haplotype analyses revealed that the C-T-A haplotype in the block of rs13321-rs12347433-rs2104772 was associated with lower ACS risk (OR = 0.33, 95% CI: 0.15 - 0.75; p = 0.005). Also, the C-T-T and G-T-A haplotypes of the TNC gene were associated with higher and lower serum TNC levels, respectively. Conclusion: Our study demonstrated no genetic association between single nucleotide polymorphisms of the TNC gene and ACS risk; however, the C-T-A haplotype of the TNC gene might be associated with reduced ACS risk in South Indians.

OBJECTIVE: Tenascin-C (TNC) is an extracellular matrix glycoprotein closely associated with the progression of psychiatric disorders. The present study was performed to investigate the possible association between serum gonadal hormones and TNC levels in male patients with depressive disorder.
METHODS: We measured serum TNC levels by enzyme-linked immunosorbent assay. In addition, we investigated the influence of testosterone (T) and estradiol (E2) on TNC levels in primary neuronal cultures.
RESULTS: Patients with depression had lower levels of T, free tri-iodothyronine (FT3), thyroid-stimulating hormone (TSH), and the T/E2 ratio than healthy control patients. Levels of TNC and high-sensitivity C-reactive protein were significantly higher in patients than in healthy volunteers. Serum TNC concentrations were negatively associated with levels of E2 and T and with the T/E2 ratio. Levels of TNC, TSH, and FT3 and the T/E2 ratio were predictors of depression. Among men with depression, TNC was negatively associated with T levels and with the T/E2 ratio. Incubating pheochromocytoma 12 cells with the combination of T and E2 greatly decreased TNC levels in the culture medium.
CONCLUSIONS: Increased TNC levels may predict imbalance between T and E2 in patients with depression, and gonadal hormones may modulate TNC expression in vivo.

The purpose of this study was to compare the immunohistochemical expression of tenascin-C (Tn-C) regarding clinicopathological variables and its association with the clinical behavior of central giant cell lesions (CGCLs). Forty-eight paraffin-embedded samples of CGCLs were selected. Based on clinical and radiographic features, the lesions were classified as aggressive (A-CGCLs) and non-aggressive (NA-CGCLs) subtypes. Histological assessment included the microvessel count (MVC), multinucleated giant cell (MGC) count, and the proportion of tissue area involved by mononuclear stromal cells/interstitial fibrosis. Immunoreactivity, immunolocalization, and distribution patterns of Tn-C were studied immunohistochemically. The association between Tn-C expression and clinicopathological characteristics was analyzed separately and adjusted for confounders using logistic regression models. A significantly greater proportion of cases with moderate-to-intense, intracellular, and diffuse staining of Tn-C was observed in A-CGCLs. CGCLs with a size ≥3.3 cm, fast growth, cortical disruption, high MVC/MGC counts, and low interstitial fibrosis showed a significantly greater frequency of moderate-to-intense, intracellular, and diffuse staining. Logistic regression analysis indicated a strong/independent association of these three immunohistochemical parameters with the aggressiveness of lesions. These data appear to suggest a possible role for Tn-C in the etiopathogenesis of CGCLs of the jaws, where its upregulation might favor the destructive behavior of A-CGCLs.

UNASSIGNED: Elevated levels of tenascin-C are linked to increased risk and severity of major depressive disorder (MDD), while testosterone shows a protective effect. The present study explored associations between serum levels of tenascin-C and testosterone in Chinese men with MDD.
UNASSIGNED: Testosterone and tenascin-C levels were measured in sera of 412 men with MDD and 237 age- and sex-matched controls. Serum levels of thyroid hormone, lipids, and high-sensitivity C-reactive protein (hs-CRP) were also quantified. Potential associations were examined using covariance, subgroup analysis, and multivariate linear regression analyses.
UNASSIGNED: Significantly higher concentrations of tenascin-C were detected in sera of subjects with MDD than in controls. Among subjects with MDD, testosterone concentrations inversely correlated with tenascin-C levels. This relationship was observed when patients were stratified by age at onset; duration or severity of depression; or concentration of thyroid hormones, low- or high-density lipoprotein, or hs-CRP. The negative association remained even when the statistical model was adjusted for age, smoking status, alcohol use, and body mass index. Linear regression with bootstrap resampling confirmed that high tenascin-C levels inversely correlated with testosterone levels.
UNASSIGNED: In men with MDD, high tenascin-C concentrations correlate with testosterone deficiency. The combination of elevated tenascin-C and testosterone deficiency may be associated with MDD progression.

OBJECTIVE: Gastrointestinal symptoms are common in endometriosis, but the mechanisms behind these symptoms are yet poorly understood. Associations between endometriosis and irritable bowel syndrome (IBS), celiac disease, and various autoimmune diseases have been reported. These diseases express characteristic autoantibodies. The aim of the current study was to investigate autoantibodies against gonadotropin-releasing hormone 1 (GnRH1) and luteinizing hormone (LH) and their receptors, tenascin-C, matrix metalloproteinase-9, deamidated gliadin peptide, and tissue transglutaminase in a cohort of women with endometriosis, compared to controls and women with IBS or enteric dysmotility.
METHODS: One hundred seventy-two women with laparoscopy-verified endometriosis completed questionnaires regarding socio-demographics, lifestyle habits, medical history, and gastrointestinal symptoms, and sera were analyzed with ELISA for the abovementioned antibodies. Healthy female blood donors (N = 100) served as controls, and women with IBS or enteric dysmotility (N = 29) were used for comparison.
RESULTS: A non-significantly higher prevalence of IgM antibodies directed at tenascin-C (7.6% vs. 2.0%; p = 0.06) was the only observed difference in autoantibody levels in endometriosis compared to controls. Antibody presence was not associated with any clinical parameters. Patients with IBS or enteric dysmotility expressed higher levels of IgM antibodies against GnRH1 compared to both patients with endometriosis (p = 0.004) and healthy controls (p = 0.002), and higher levels of tenascin-C antibodies compared to healthy controls (17.2% vs. 2.0%; p = 0.006).
CONCLUSIONS: Women with endometriosis do not express higher prevalence of autoantibodies found to be characteristic in other patient groups with gastrointestinal symptoms.

Hepatitis C virus (HCV)-related cirrhosis, one of the most common etiologies of liver cirrhosis in the Western world, is a risk factor for hepatocellular carcinoma. To confirm and improve current effectiveness of screening and prognosis of patients with established cirrhosis, a credible, simple plasma biomarker is needed. Hepatic stellate cell activation, a pivotal event in cirrhosis development, results in increased secretion of extracellular matrix proteins, including tenascin-C (TnC). Herein, we tested TnC as a simple biomarker to identify cirrhotic patients with active HCV infection from those with HCV eradication.
A prospective study of subjects with HCV-related cirrhosis, stratified into two groups, HCV or virologic cure, was conducted. Plasma TnC expression was measured by ELISA and Western blots. TnC values were correlated with markers of liver injury and ROC analyses performed between groups.
The HCV cirrhotic cohort, consisting mostly of men (56%), Caucasians (76%), and genotype 1a or 1b (84%), was compared to healthy controls (HCs). Plasma TnC was significantly higher in HCV cirrhotic patients with active infection compared to HCs (P < 0.0001) and virologic cure (P < 0.0001). TnC concentrations in virologic cure subjects were not statistically different from HCs. TnC levels correlated with AST, platelets, MELD, APRI, FIB-4, and Child-Pugh score. TnC and AST together were significantly better indicators of cirrhosis in patients with active HCV infection than other markers tested.
TnC and AST provided the best model for discriminating HCV cirrhotics with active infection from HC and virologic cure cohorts over current liver injury markers, suggesting TnC as a potential indicator of ongoing hepatic injury and inflammation.

Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N\'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor.

OBJECTIVE: Ventricular noncompaction/hypertrabeculation (NC/HT) is a rare form of congenital cardiomyopathy. We aimed to investigate the presence of serum tenascin-C (TN-C) in adult patients with NC/HT and evaluate its value.
RESULTS: Serum TN-C levels were measured by ELISA in 50 NC/HT patients both with/without systolic dysfunction and in 23 normal controls. Systolic dysfunction was defined as ejection fraction (EF) ≤ 40. Mann-Whitney U-test and ROC curve analysis were done. Of 49 NC/HT patients, 24 (49%) patients had systolic dysfunction (mean age 36 ± 15) and 25 patients (51%) had normal systolic function (mean age 36 ± 17). The ages between groups were not different. The mean levels of serum TN-C in patients with or without systolic dysfunction were 26 ± 10 ng/mL and 26 ± 8 ng/mL respectively, compared to normal controls, 7 ± 2 ng/mL (P < 0.001). No significance was observed between 2 groups of NC/HT patients regarding TN-C levels (P = 0.8). The ROC curve analysis revealed that a TN-C value of 11.7 ng/mL identified patients with NC/HT with 100% sensitivity and specifity.
CONCLUSIONS: High serum TN-C levels are present in adult NC/HT cardiomyopathy even when left ventricular systolic function remains normal. Also, serum TN-C levels could be regarded as a candidate biomarker in the diagnosis of NC/HT which needs to be tested in larger prospective studies.

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