Green salad intake is associated with improved oral cancer survival and lower soluble CD44 levels

Deficiencies in fruit and vegetable intake have been associated with oral cancer (oral cavity and oropharyngeal). Salivary rinses contain measurable biomarkers including soluble CD44 (solCD44) and total protein, which are known markers of oral cancer risk. This study investigates the effect of nutritional factors on solCD44 and protein levels to evaluate oral cancer risk and survival. We evaluated solCD44 and protein levels from 150 patients with oral and oropharyngeal squamous cell carcinoma and 150 frequency-matched controls. We subsequently characterized the effect of food group consumption and these biomarkers on progression-free survival (PFS) and overall survival (OS). Patients reported eating fewer servings of salad (p = 0.015), while controls reported eating fewer servings of potatoes (p \u3c 0.001). Oral cancer patients who consumed at least one serving per week of green salad were found to have significantly lower CD44 levels than those who ate salad less frequently (mean of log2[solCD44]1.73 versus 2.25, p = 0.014). Patients who consumed at least one serving per week of “salad or other vegetables” had significantly longer PFS (median 43.5 versus 9.1 months, p = 0.003, adjusted hazard ratio (HR) = 0.39 p = 0.014) and OS (median 83.6 versus 10 months, p = 0.008, adjusted HR = 0.04 p = 0.029). These findings suggest that dietary factors, namely greater green salad and vegetable intake, may be associated with lower CD44 levels and better prognosis in oral cancer patients

Decreased Levels of Soluble CD44 in a High-Risk Population following a Smoking Cessation Program

Tobacco is a risk factor of head and neck cancer (HNC) and smoking cessation alone may reduce HNC risk by 70%. Soluble CD44 (solCD44), a cell surface receptor linked to cell proliferation and migration, and total protein (TP) levels can detect early HNC. This study aims to determine whether salivary solCD44 and TP levels in oral rinses change following a smoking cessation program. 150 smokers provided oral rinse samples at baseline and at a 12-month follow-up after participation in a smoking cessation program. Assays to measure levels of solCD44, TP, and cotinine, a metabolite used as a biomarker of tobacco exposure, were completed. A paired-samples t-test was used to determine whether there was a statistically significant ( \u3c 0.05) mean difference in biomarker levels before and after the program. Baseline and at 12-month follow-up data were available for 88 subjects, 21 of whom quit smoking entirely. Mean levels of solCD44 significantly decreased by 0.412 ng/mL from baseline to the 12-month follow-up, = 0.010. There was no significant difference in mean TP levels, = 0.975. Mean cotinine levels decreased significantly by 74.7 ng/mL, = 0.035. This is the first work demonstrating an association between smoking cessation and decreased solCD44 levels in oral rinses. Decreased expression of the tumorigenic CD44 may be one mechanism by which smoking cessation lowers cancer risk

Decreased levels of soluble cd44 in a high-risk population following a smoking cessation program

Tobacco is a risk factor of head and neck cancer (HNC) and smoking cessation alone may reduce HNC risk by 70%. Soluble CD44 (solCD44), a cell surface receptor linked to cell proliferation and migration, and total protein (TP) levels can detect early HNC. This study aims to determine whether salivary solCD44 and TP levels in oral rinses change following a smoking cessation program. 150 smokers provided oral rinse samples at baseline and at a 12-month follow-up after participation in a smoking cessation program. Assays to measure levels of solCD44, TP, and cotinine, a metabolite used as a biomarker of tobacco exposure, were completed. A paired-samples t-test was used to determine whether there was a statistically significant (p \u3c 0.05) mean difference in biomarker levels before and after the program. Baseline and at 12-month follow-up data were available for 88 subjects, 21 of whom quit smoking entirely. Mean levels of solCD44 significantly decreased by 0.412 ng/mL from baseline to the 12-month follow-up, p = 0.010. There was no significant difference in mean TP levels, p = 0.975. Mean cotinine levels decreased significantly by 74.7 ng/mL, p = 0.035. This is the first work demonstrating an association between smoking cessation and decreased solCD44 levels in oral rinses. Decreased expression of the tumorigenic CD44 may be one mechanism by which smoking cessation lowers cancer risk

Mechanisms of Thermal Adaptation Revealed From the Genomes of the Antarctic Archaea Methanogenium frigidum and Methanococcoides burtonii

We generated draft genome sequences for two cold-adapted Archaea, Methanogenium frigidum and Methanococcoides burtonii, to identify genotypic characteristics that distinguish them from Archaea with a higher optimal growth temperature (OGT). Comparative genomics revealed trends in amino acid and tRNA composition, and structural features of proteins. Proteins from the cold-adapted Archaea are characterized by a higher content of noncharged polar amino acids, particularly Gin and Thr and a lower content of hydrophobic amino acids, particularly Leu. Sequence data from nine methanogen genomes (OGT 15degrees-98degreesC) were used to generate IIII modeled protein structures. Analysis of the models from the cold-adapted Archaea showed a strong tendency in the solvent-accessible area for more Gin, Thr, and hydrophobic residues and fewer charged residues. A cold shock domain (CSD) protein (CspA homolog) was identified in M. frigidum, two hypothetical proteins with CSD-folds in M. burtonii, and a unique winged helix DNA-binding domain protein in M. burtonii. This suggests that these types of nucleic acid binding proteins have a critical role in cold-adapted Archaea. Structural analysis of tRNA sequences from the Archaea indicated that GC content is the major factor influencing tRNA stability in hyperthermophiles, but not in the psychrophiles, mesophiles or moderate thermophiles. Below an OGT of 60degreesC, the GC content in tRNA was largely unchanged, indicating that any requirement for flexibility of tRNA in psychrophiles is mediated by other means. This is the first time that comparisons have been performed with genome data from Archaea spanning the growth temperature extremes. from psychrophiles to hyperthermophile

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

Siderophore-based detection of Fe(iii) and microbial pathogens

Siderophores are low-molecular-weight iron chelators that are produced and exported by bacteria, fungi and plants during periods of nutrient deprivation. The structures, biosynthetic logic, and coordination chemistry of these molecules have fascinated chemists for decades. Studies of such fundamental phenomena guide the use of siderophores and siderophore conjugates in a variety of medicinal applications that include iron-chelation therapies and drug delivery. Sensing applications constitute another important facet of siderophore-based technologies. The high affinities of siderophores for both ferric ions and siderophore receptors, proteins expressed on the cell surface that are required for ferric siderophore import, indicate that these small molecules may be employed for the selective capture of metal ions, proteins, and live bacteria. This minireview summaries progress in methods that utilize native bacterial and fungal siderophore scaffolds for the detection of Fe(III) or microbial pathogens.Massachusetts Institute of Technology. Dept. of Chemistr

Effective early detection of oral cancer using a simple and inexpensive point of care device in oral rinses

Introduction: Head and neck cancer remains a challenging disease that is increasing in incidence with the majority of patients diagnosed at an advanced stage where 5-year survival is approximately 50%. Current approaches including oral-brush biopsies, fluorescence-based technologies,  and salivary molecular profiling have demonstrated some success; however, cost, ease of use, and accuracy remain limiting factors. Areas covered: This is a profile of a novel, easy to use oral rinse point-of-care (POC) test to aid in the diagnosis of oral and oropharyngeal cancer. Background science related to the challenge of oral and oropharyngeal cancer and natural history of diagnostic aids for this disease are provided. Results of studies performed for validation of a POC and laboratory test are also discussed. Expert commentary: The POC test has been validated through a case : control clinical study and a prospective European trial, using version 1.0 (v1.0), which have demonstrated consistent performance including a > 90% negative predictive value, with a sensitivity of 80%. The assay was designed to identify malignant lesions in the oral cavity and oropharynx by improving upon standard clinical assessment