Poor oral health and inflammatory, haemostatic and cardiac biomarkers in older age: Results from two studies in the UK and USA.

BACKGROUND: We examined the association of objective and subjective oral health markers with inflammatory, haemostatic and cardiac biomarkers in older age. METHODS: Cross-sectional analyses were based on the British Regional Heart Study (BRHS) comprising British men aged 71-92 years (n=2147), and the Health, Aging and Body Composition (HABC) Study comprising American men and women aged 71-80 years (n=3075). Oral health markers included periodontal disease, tooth count, dry mouth. Inflammatory biomarkers included C-reactive protein (CRP), interleukin-6 (IL-6) in both studies, and tissue plasminogen activator (t-PA), von Willebrand Factor (vWF), fibrin D-dimer, high sensitivity Troponin T (hsTnT) and N-terminal pro-brain natriuretic peptide (NTproBNP) only in the BRHS. RESULTS: In both studies, tooth loss, was associated with the top tertile of CRP - odds ratios (95%CI) are 1.31 (1.02-1.68) in BRHS; and 1.40 (1.13-1.75) in the HABC Study, after adjusting for confounders. In the HABC Study, cumulative (≥3) oral health problems were associated with higher levels of CRP (OR (95%CI) =1.42 (1.01-1.99)). In the BRHS, complete and partial tooth loss were associated with haemostatic factors, in particular with the top tertile of fibrin D-dimer (OR (95%CI) = 1.64 (1.16-2.30) and 1.37 (1.05-1.77) respectively). Tooth loss and periodontal disease were associated with increased levels of hsTnT. CONCLUSIONS: Poor oral health in older age, particularly tooth loss, was consistently associated with some inflammatory, haemostatic and cardiac biomarkers. Prospective studies and intervention trials could help understand better if poor oral health is causally linked to inflammatory, haemostatic and cardiac biomarkers

The CS1 segment of fibronectin is involved in human OSCC pathogenesis by mediating OSCC cell spreading, migration, and invasion

<p>Abstract</p> <p>Background</p> <p>The alternatively spliced V region or type III connecting segment III (IIICS) of fibronectin is important in early development, wound healing, and tumorigenesis, however, its role in oral cancer has not been fully investigated. Thus, we investigated the role of CS-1, a key site within the CSIII region of fibronectin, in human oral squamous cell carcinoma (OSCC).</p> <p>Methods</p> <p>To determine the expression of CS-1 in human normal and oral SCC tissue specimens immunohistochemical analyses were performed. The expression of CS1 was then associated with clinicopathological factors. To investigate the role of CS-1 in regulating OSCC cell spreading, migration and invasion, OSCC cells were assayed for spreading and migration in the presence of a CS-1 peptide or a CS-1 blocking peptide, and for invasion using Matrigel supplemented with these peptides. In addition, integrin α4siRNA or a focal adhesion kinase (FAK) anti-sense oligonucleotide was transfected into OSCC cells to examine the mechanistic role of integrin α4 or FAK in CS1-mediated cell spreading and migration, respectively.</p> <p>Results</p> <p>CS-1 expression levels were significantly higher in OSCC tissues compared to normal tissues (p < 0.05). Also, although, high levels of CS-1 expression were present in all OSCC tissue samples, low-grade tumors stained more intensely than high grade tumors. OSCC cell lines also expressed higher levels of CS-1 protein compared to normal human primary oral keratinocytes. There was no significant difference in total fibronectin expression between normal and OSCC tissues and cells. Inclusion of CS-1 in the in vitro assays enhanced OSCC cell spreading, migration and invasion, whereas the CS1 blocking peptide inhibited these processes. Suppression of integrin α4 significantly inhibited the CS1-mediated cell spreading. Furthermore, this migration was mediated by focal adhesion kinase (FAK), since FAK suppression significantly blocked the CS1-induced cell migration.</p> <p>Conclusion</p> <p>These data indicate that the CS-1 site of fibronectin is involved in oral cancer pathogenesis and in regulating OSCC cell spreading, migration and invasion.</p

ANK, a Host Cytoplasmic Receptor for the Tobacco mosaic virus Cell-to-Cell Movement Protein, Facilitates Intercellular Transport through Plasmodesmata

Plasmodesma (PD) is a channel structure that spans the cell wall and provides symplastic connection between adjacent cells. Various macromolecules are known to be transported through PD in a highly regulated manner, and plant viruses utilize their movement proteins (MPs) to gate the PD to spread cell-to-cell. The mechanism by which MP modifies PD to enable intercelluar traffic remains obscure, due to the lack of knowledge about the host factors that mediate the process. Here, we describe the functional interaction between Tobacco mosaic virus (TMV) MP and a plant factor, an ankyrin repeat containing protein (ANK), during the viral cell-to-cell movement. We utilized a reverse genetics approach to gain insight into the possible involvement of ANK in viral movement. To this end, ANK overexpressor and suppressor lines were generated, and the movement of MP was tested. MP movement was facilitated in the ANK-overexpressing plants, and reduced in the ANK-suppressing plants, demonstrating that ANK is a host factor that facilitates MP cell-to-cell movement. Also, the TMV local infection was largely delayed in the ANK-suppressing lines, while enhanced in the ANK-overexpressing lines, showing that ANK is crucially involved in the infection process. Importantly, MP interacted with ANK at PD. Finally, simultaneous expression of MP and ANK markedly decreased the PD levels of callose, β-1,3-glucan, which is known to act as a molecular sphincter for PD. Thus, the MP-ANK interaction results in the downregulation of callose and increased cell-to-cell movement of the viral protein. These findings suggest that ANK represents a host cellular receptor exploited by MP to aid viral movement by gating PD through relaxation of their callose sphincters

ADAM 17‐mediated CD 44 cleavage promotes orasphere formation or stemness and tumorigenesis in HNSCC

CD 44, an extracellular matrix ( ECM ) receptor, has been described as a cancer stem cell marker in multiple cancers, including head and neck squamous cell carcinoma ( HNSCC ). HNSCC orasphere formation or stemness was characterized by cleavage of CD 44, and thus we hypothesized that this proteolytic processing may be critical to stemness and tumorigenesis. We tested this hypothesis by examining the mechanisms that regulate this process in vitro and in vivo, and by exploring its clinical relevance in human specimens. Sphere assays have been used to evaluate stemness in vitro. Spheres comprised of HNSCC cells or oraspheres and an oral cancer mouse model were used to examine the significance of CD 44 cleavage using stable suppression and inhibition approaches. These mechanisms were also examined in HNSCC specimens. Oraspheres exhibited increased levels of CD 44 cleavage compared to their adherent counterparts. Given that disintegrin and metalloproteinase domain‐containing protein 17 (ADAM17) is a major matrix metalloproteinase known to cleave CD 44, we chemically inhibited and stably suppressed ADAM 17 expression in HNSCC cells and found that these treatments blocked CD 44 cleavage and abrogated orasphere formation. Furthermore, stable suppression of ADAM 17 in HNSCC cells also diminished tumorigenesis in an oral cancer mouse model. Consistently, stable suppression of CD 44 in HNSCC cells abrogated orasphere formation and inhibited tumorigenesis in vivo. The clinical relevance of these findings was confirmed in matched primary and metastatic human HNSCC specimens, which exhibited increased levels of ADAM 17 expression and concomitant CD 44 cleavage compared to controls. CD 44 cleavage by ADAM 17 is critical to orasphere formation or stemness and HNSCC tumorigenesis. Our data demonstrate, for the first time that CD44 cleavage by ADAM17 is a critical determinant of orasphere formation or stemness and tumorigenesis in oral cancer. Our data support the concept that therapeutics that target CD44 cleavage mechanisms within the stem cell compartment can impair stemness and thus hold promise for treating aggressive oral cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101782/1/cam4147.pd

Metabolomics of head and neck cancer: A mini-review

© 2016 Shin, Kamarajan, Fenno, Rickard and Kapila.Metabolomics is used in systems biology to enhance the understanding of complex disease processes, such as cancer. Head and neck cancer (HNC) is an epithelial malignancy that arises in the upper aerodigest

Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC1.

Nisin, a bacteriocin and commonly used food preservative, may serve as a novel potential therapeutic for treating head and neck squamous cell carcinoma (HNSCC), as it induces preferential apoptosis, cell cycle arrest, and reduces cell proliferation in HNS

Metabolomics of head and neck cancer: A mini-review

© 2016 Shin, Kamarajan, Fenno, Rickard and Kapila.Metabolomics is used in systems biology to enhance the understanding of complex disease processes, such as cancer. Head and neck cancer (HNC) is an epithelial malignancy that arises in the upper aerodigest

Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC1.

Nisin, a bacteriocin and commonly used food preservative, may serve as a novel potential therapeutic for treating head and neck squamous cell carcinoma (HNSCC), as it induces preferential apoptosis, cell cycle arrest, and reduces cell proliferation in HNS

ADAM17-mediated CD44 cleavage promotes orasphere formation or stemness and tumorigenesis in HNSCC.

CD44, an extracellular matrix (ECM) receptor, has been described as a cancer stem cell marker in multiple cancers, including head and neck squamous cell carcinoma (HNSCC). HNSCC orasphere formation or stemness was characterized by cleavage of CD44, and th

Antimicrobial nisin acts against saliva derived multi-species biofilms without cytotoxicity to human oral cells.

Nisin is a lantibiotic widely used for the preservation of food and beverages. Recently, investigators have reported that nisin may have clinical applications for treating bacterial infections. The aim of this study was to investigate the effects of ultr