Diagnostic value of integrin alpha3, beta4, and beta5 gene expression levels for the clinical outcome of tongue squamous cell carcinoma

BACKGROUND: The objective of the current study was to identify biomarkers that reflect the clinical course of squamous cell carcinoma of the tongue (TSCC). METHODS: TSCC tissue samples from 66 patients were subjected to gene expression analysis by real-time polymerase chain reaction. Eleven integrin family genes and 14 genes used for normalization, including housekeeping genes and genes that encode desmosomal, cytoskeletal, and extracellular matrix molecules, were considered. Multivariate statistical analysis was performed on 154 expression ratios of integrin genes with clinical parameters. RESULTS: In principal-component analysis, the first principal component was related to the outcome of death, and the second principal component mainly reflected the tendency for cervical lymph node (LN) metastasis. The former axis consisted of the variance of the integrin beta4 gene (ITGB4) and ITGB5 expression levels, and the latter axis agreed with the expression level of the integrin alpha3 gene (ITGA3). Multivariate logistic regression analysis with cervical LN metastasis as the response variable concordantly identified ITGA3/junction plakoglobin gene (JUP) expression (P=.02) and ITGB5/paxillin gene (PXN) expression (P=.04) as significant factors. Only ITGB4/JUP expression was identified as a significant factor in terms of the outcome of death (P<.00049) by a Cox proportional hazards model. The group with high ITGB4/JUP levels exhibited a significantly high death rate on a Kaplan-Meier curve (P<.0001; Wilcoxon and log-rank tests). CONCLUSIONS: The expression levels of ITGA3, ITGB4, and ITGB5 with functional normalization by desmosomal or cytoskeletal molecule genes were selected as candidate biomarkers for cervical LN metastasis or for the outcome of death in TSCC.     

Effects of fluoride on membrane permeability and brush border enzymes of rat intestine in situ

The effect of different concentrations of sodium fluoride (12, 24, 48 and 96 mM), instilled into the ligated intestine of anaesthetized rats for 30 min, on intestinal permeability and some brush border enzymes was investigated. A concentration-dependent change in permeability was observed; there was an increase in the volume of luminal fluid and altered net transport of Na+ and K K+ ions. The change in permeability was accompanied by increased protein, sialic acid and nucleic acid accumulation in the luminal fluid. A striking loss of brush border alkaline phosphatase (41%) sucrase (59%) and gamma-glutamyl transpeptidase (73%) activities was observed at 96 mM fluoride with a corresponding increase in the activity of these enzymes in luminal fluid, while 12 mM fluoride did not produce any significant effect. This loss was probably not due to an inhibition of the enzymes by fluoride since in vitro experiments did not produce any such effect over a range of NaF concentrations (0-32 mM) except on alkaline phosphatase activity at the 32 mM NaF concentration. The studies, therefore, suggest that the loss of brush-border enzyme activities observed in situ was most probably due to membrane damage caused by the high fluoride concentration.     

2,1-Benzothiazine – (quinolin/thiophen)yl hydrazone frameworks as new monoamine oxidase inhibitory agents; synthesis,in vitro and in silico investigation

Two series of new 2,1-benzothiazine derivatives have been synthesized by condensation of 4-hydrazono-1-methyl-3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxide (5) with 2-chloroquinoline-3-carbaldehydes and acetylthiophenes to acquire new heteroaryl ethylidenes 7(a–f) and 9(a–k) in excellent yields. After characterization by FTIR, ¹H NMR, ¹³C NMR and elemental analyses, the newly synthesized analogues were investigated against monoamine oxidase enzymes (MAO A and MAO B). The titled compounds exhibited activity in the lower micromolar range among which 9e was the most potent compound against MAO A with IC₅₀ of 1.04 ± 0.01 μM whereas 9h proved to be the most potent derivative against MAO B with an IC₅₀ value of 1.03 ± 0.17 μM. Furthermore, in vitro results were further endorsed by molecular docking studies to determine the interaction between the potent compounds and the enzyme active site. These newly synthesized compounds represent promising hits for the development of safer and potent lead molecules for therapeutic use against depression and other neurological diseases.

Two series of new 2,1-benzothiazine-heteroaryl ethylidene derivatives 7(a–f) and 9(a–k) have been synthesized in excellent yields and tested against MAOs.     

Effect of fluoride on uptake of D-glucose by isolated epithelial cells of rat intestine

Inhibition on uptake of D-glucose by isolated intestinal epithelial cells (IIEC) was observed when the fluoride concentration ranged between 0.25 and 5 mM. Active transport was almost completely inhibited at 5 mM. When CaCl2 was added to fluoride, the inhibitory effect on glucose uptake was abolished. Preincubation of IIEC with different concentrations of fluoride (2.5-5.0 mM) for different intervals of time (2-20 min) at different pH levels (6.2-7.8) and temperatures (0-37 degrees C) revealed that the conditions which led to higher uptake of fluoride by IIEC produced maximum inhibition. The degree of inhibition was not appreciably altered by a change in glucose concentrations. A concentration-dependent effect of fluoride on lactic acid and carbon dioxide production by IIEC was also observed.     

Optical imaging with a high-resolution microendoscope to identify sinonasal pathology

Objectives

High-resolution microendoscopy (HRME) is an optical imaging modality that allows real time imaging of epithelial tissue and structural changes within. We hypothesize that HRME, using proflavine, a contrast agent that preferentially stains cell nuclei and allows detection of cellular morphologic changes, can distinguish sinonasal pathology from uninvolved mucosa, potentially enabling real-time surgical margin differentiation.