The dynamics of gene expression changes in a mouse model of oral tumorigenesis may help refine prevention and treatment strategies in patients with oral cancer.

A better understanding of the dynamics of molecular changes occurring during the early stages of oral tumorigenesis may help refine prevention and treatment strategies. We generated genome-wide expression profiles of microdissected normal mucosa, hyperplasia, dysplasia and tumors derived from the 4-NQO mouse model of oral tumorigenesis. Genes differentially expressed between tumor and normal mucosa defined the "tumor gene set" (TGS), including 4 non-overlapping gene subsets that characterize the dynamics of gene expression changes through different stages of disease progression. The majority of gene expression changes occurred early or progressively. The relevance of these mouse gene sets to human disease was tested in multiple datasets including the TCGA and the Genomics of Drug Sensitivity in Cancer project. The TGS was able to discriminate oral squamous cell carcinoma (OSCC) from normal oral mucosa in 3 independent datasets. The OSCC samples enriched in the mouse TGS displayed high frequency of CASP8 mutations, 11q13.3 amplifications and low frequency of PIK3CA mutations. Early changes observed in the 4-NQO model were associated with a trend toward a shorter oral cancer-free survival in patients with oral preneoplasia that was not seen in multivariate analysis. Progressive changes observed in the 4-NQO model were associated with an increased sensitivity to 4 different MEK inhibitors in a panel of 51 squamous cell carcinoma cell lines of the areodigestive tract. In conclusion, the dynamics of molecular changes in the 4-NQO model reveal that MEK inhibition may be relevant to prevention and treatment of a specific molecularly-defined subgroup of OSCC

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Preparation of Magnetic Surface Ion-Imprinted Polymer Based on Functionalized Fe₃O₄ for Fast and Selective Adsorption of Cobalt Ions from Water

A novel cobalt ion-imprinted polymer (Co(II)-MIIP) based on magnetic Fe3O4 nanoparticles was prepared by using Co(II) as the template ion, and bis(2-methacryloxyethyl) phosphate and glycylglycine as dual functional monomers. The fabricated material was analyzed by Fourier transform infrared spectroscopy, thermogravimetric analysis, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, Brunauer–Emmett–Teller, X-ray diffraction, and vibrating sample magnetometer. The adsorption experiments with Co(II)-MIIP, found that the maximum adsorption capacity could reach 33.4 mg·g−1, while that of the non-imprinted polymer (Co(II)-NIP) was found to reach 15.7 mg·g−1. The adsorption equilibriums of Co(II)-MIIP and Co(II)-NIP was established within 20 min and 30 min, respectively. The adsorption process could be suitably described by the Langmuir isotherm model and the pseudo-second-order kinetics model. In binary mixtures of Co(II)/Fe(II), Co(II)/Cu(II), Co(II)/Mg(II), Co(II)/Zn(II), and Co(II)/Ni(II), the relative selectivity coefficients of Co(II)-MIIP toward Co(II)-NIP were 5.25, 4.05, 6.06, 11.81, and 4.48, respectively. The regeneration experiments indicated that through six adsorption–desorption cycles, the adsorption capacity of Co(II)-MIIP remained nearly 90%

Stereoselective reduction of 1-O-isopropyloxygenipin enhances its neuroprotective activity in neuronal cells from apoptosis induced by sodium nitroprusside

Genipin is a Chinese herbal medicine with both neuroprotective and neuritogenic activity. Because of its unstable nature, efforts have been to develop more stable genipin derivatives with improved biological activities. Among the new compounds reported in the literature, (1R)-isopropyloxygenipin (IPRG001) is a more stable but less active compound compared with the parent, genipin. Here, two new IPRG001 derivatives generated by stereoselective reduction of the C=C double bond were synthesized. The 1R and 1S isomers of (4aS,7S,7aS)-methyl-7-(hydroxymethyl)-1-isopropoxy-1,4a,5, 6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate (CHR20 and CHR21) were shown to be very stable both in high-glucose cell culture medium and in mice serum at 37 °C. Evaluation using an MTT assay and Hoechst staining showed that CHR20 and CHR21 promote the survival of rat adrenal pheochromocytoma (PC12) and retinal neuronal (RGC-5) cells from injury induced by sodium nitroprusside (SNP). The neuroprotective effects of CHR20 and CHR21 were greater than both isomers of IPRG001, the parent compounds. These results indicate that reduction of 1-O-isopropyloxygenipin enhances its neuroprotective activity without affecting its stability. Remastering Chinese herbal medicine: Genipin is known to have neuroprotective activity but problematic stability under physiological conditions. Isomeric derivatives of isopropyloxygenipin, a synthetic genipin analogue, were synthesized by stereoselective reduction of the C =C double bond and found to exhibit improved neuroprotective activity and stability over the parent compounds

Strategies for identification of somatic variants using the Ion Torrent deep targeted sequencing platform

Abstract Background ‘Next-generation’ (NGS) sequencing has wide application in medical genetics, including the detection of somatic variation in cancer. The Ion Torrent-based (IONT) platform is among NGS technologies employed in clinical, research and diagnostic settings. However, identifying mutations from IONT deep sequencing with high confidence has remained a challenge. We compared various computational variant-calling methods to derive a variant identification pipeline that may improve the molecular diagnostic and research utility of IONT. Results Using IONT, we surveyed variants from the 409-gene Comprehensive Cancer Panel in whole-section tumors, intra-tumoral biopsies and matched normal samples obtained from frozen tissues and blood from four early-stage non-small cell lung cancer (NSCLC) patients. We used MuTect, Varscan2, IONT’s proprietary Ion Reporter, and a simple subtraction we called “Poor Man’s Caller.” Together these produced calls at 637 loci across all samples. Visual validation of 434 called variants was performed, and performance of the methods assessed individually and in combination. Of the subset of inspected putative variant calls (n=223) in genomic regions that were not intronic or intergenic, 68 variants (30%) were deemed valid after visual inspection. Among the individual methods, the Ion Reporter method offered perhaps the most reasonable tradeoffs. Ion Reporter captured 83% of all discovered variants; 50% of its variants were visually validated. Aggregating results from multiple packages offered varied improvements in performance. Conclusions Overall, Ion Reporter offered the most attractive performance among the individual callers. This study suggests combined strategies to maximize sensitivity and positive predictive value in variant calling using IONT deep sequencing

Long-term trend and interannual variability of precipitation-use efficiency in Eurasian grasslands

International audienc

Isolation of first row transition metal-carboxylate zwitterions

10.1039/c5ra05564dRSC Advances55342978-4298