Plasma Tenascin-C: a prognostic biomarker in heart failure with preserved ejection fraction
BIOMARKERS
Authors: Kanagala, Prathap; Arnold, Jayanth R.; Khan, Jamal N.; Singh, Anvesha; Gulsin, Gaurav S.; Chan, Daniel C. S.; Cheng, Adrian S. H.; Yang, Jing; Li, Zhuyin; Gupta, Pankaj; Squire, Iain B.; McCann, Gerry P.; Ng, Leong L.
Abstract
Introduction Tenascin-C is a marker of interstitial fibrosis. We assessed whether plasma Tenascin-C differed between heart failure with preserved ejection fraction (HFpEF) and asymptomatic controls and related to clinical outcomes. Materials and Methods Prospective, observational study of 172 age- and sex-matched subjects (HFpEFn = 130; controlsn = 42, age 73 +/- 9, males 50%) who underwent phenotyping with 20 plasma biomarkers, echocardiography, cardiac MRI and 6-minute-walk-testing. The primary endpoint was the composite of all-cause death/HF hospitalisation. Results Tenascin-C was higher in HFpEF compared to controls (13.7 [10.8-17.3] vs (11.1 [8.9-12.9] ng/ml,p < 0.0001). Tenascin-C correlated positively with markers of clinical severity (NYHA, E/E', BNP) and plasma biomarkers reflecting interstitial fibrosis (ST-2, Galectin-3, GDF-15, TIMP-1, TIMP-4, MMP-2, MMP-3, MMP-7, MMP-8), cardiomyocyte stress (BNP, NTpro-ANP), inflammation (MPO, hs-CRP, TNFR-1, IL6) and renal dysfunction (urea, cystatin-C, NGAL);p < 0.05 for all. During follow-up (median 1428 days), there were 61 composite events (21 deaths, 40 HF hospitalizations). In multivariable Cox regression analysis, Tenascin-C (adjusted hazard ratio [HR] 1.755, 95% confidence interval [CI] 1.305-2.360;p < 0.0001) and indexed extracellular volume (HR 1.465, CI 1.019-2.106;p = 0.039) were independently associated with adverse outcomes. Conclusions In HFpEF, plasma Tenascin-C is higher compared to age- and sex-matched controls and a strong predictor of adverse outcomes.
Screening of Health-Associated Oral Bacteria for Anticancer Propertiesin vitro
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
Authors: Baraniya, Divyashri; Jain, Vinay; Lucarelli, Ronald; Tam, Vincent; Vanderveer, Lisa; Puri, Sumant; Yang, Maobin; Al-hebshi, Nezar Noor
Abstract
While extensive literature exists about the role of oral bacterial pathogens likePorphyromonas gingivalisandFusobacterium nucleatumin oral squamous cell carcinoma (OSCC), the role of health-associated species has been largely unexplored. In this study, we assessed the effect ofStreptococcus mitis, Rothia mucilaginosa, Neisseria flavescens, Haemophilus parainfluenzae, Lautropia mirabilis, andVeillonella parvulaon proliferation and expression of marker genes (IL-6, TNF-alpha, MMP3, CD36, CCD1, and NANOG) in OSCC cell lines CAL27, SCC25, and SCC4.Porphyromonas gingivaliswas included as a pathogenic control. Both bacterial lysates (3 concentrations) and live cells (3 MOIs) were tested.S. mitis, H. parainfluenzae, andN. flavescensresulted in substantial, dose-dependent reduction of proliferation, which was found to be mediated by H(2)O(2)for the former and intracellular infection in the latter two species. However, onlyH. parainfluenzaeshowed differential antiproliferative effect against the cancer cell lines vs. the normal control (TIGKs). In the gene expression assays, the health-associated species mostly downregulated CD36, a gene that plays an important role in tumor growth and metastasis, whileP. gingivalisupregulated it. IL6 and TNF expression, on the other hand, was upregulated by almost all species, particularly the Gram-negatives includingP. gingivalis. The effect on other genes was less evident and varied significantly by cell line. This exploratory study is the first insight into how health-associated bacteria may interact with OSCC. Further studies to explore whether the observed effects may have implications for the prevention or treatment of oral cancer are warranted.