• Have Fuentes posted an update 6 months ago

    Proton pump inhibitors (PPIs) are among the most prescribed medications. Previous epidemiological studies have presented contradictory results about PPIs and the risk of dementia. Our objective was to investigate the association between the use of PPIs and an increasing risk of incident AD or non-AD dementias. A community-based retrospective cohort study was conducted based on the data available from 1st January 2002 to 31st December 2015 in the Catalan health service (CatSalut) system. This cohort included all PPI users (N = 36,360) and non-users (N = 99,362). A lag window of 5 years was considered between the beginning of the PPI treatment and the diagnosis of dementia. PPI use was not associated with the risk of AD (adjusted odds ratio (OR) 1.06) (95% CI 0.93-1.21; p = 0.408). A weakly but significantly increased risk of non-AD dementias was observed among PPI users (adjusted OR 1.20, 95% CI 1.05-1.37; p = 0.007). A higher dose of PPIs was not associated with an increased risk of either AD or non-AD dementias (OR 1.20; 95% CI 0.91-1.61 and OR 0.95; 95% CI 0.74-1.22, respectively). Regarding the number of PPIs used, we observed an increased risk of AD (OR 1.47; 95% CI 1.18-1.83) and non-AD dementias (OR 1.38; 95% CI 1.12-1.70) in users of two types of PPIs compared with those who used only one type. We did not find a higher incidence of AD among PPI users, but a weak increase in the risk of non-AD dementias among PPI users was observed.The aim of this study is to investigate the expression levels of genome-wide association studies (GWAS)-identified variants near Gasdermin-C (GSDMC) and its association with lumbar disc degeneration (LDD) in a Chinese population. In accordance with previously reported findings, our study involved the top 4 variants; rs6651255, rs7833174, rs4130415, and rs7816342. A total of 800 participants, 400 LDD patients and 400 controls were involved in the study. The LDD patients were divided into two mutually exclusive subgroups subgroup 1 lumbar disc herniation; subgroup 2 lumbar spinal stenosis. Genotyping were performed using TaqMan assay, and Enzyme-Linked Immunosorbent Assay (ELISA) used to measure the plasma GSDMC levels, while quantitative reverse-transcription (qRT)-PCR and immunohistochemistry (IHC) were used to evaluate the GSDMC expression levels. Among the studied variants, there were no statistically significant differences in allelic and genotypic frequencies between LDD patients and their controls (all P > 0.05). However, the subgroup analysis revealed a significant association between rs6651255 and rs7833174 in patients with lumbar spinal stenosis (subgroup 2). Furthermore, the max-statistic test revealed that the inheritance models of two variants of lumbar spinal stenosis were represented by the recessive model. The plasma and mRNA expression levels of GSDMC were significantly higher in patients with lumbar spinal stenosis compared with the control group (P  less then  0.05). Furthermore, the CC genotypes of rs6651255 and rs7833174 were significantly associated with increased plasma expression levels of GSDMC in patients with lumbar spinal stenosis (P  less then  0.01). Two GWAS-identified variants (rs6651255 and rs7833174) near GSDMC were associated with a predisposition to lumbar spinal stenosis. GSDMC protein and mRNA expression levels may have prognostic qualities as biomarkers for the existence, occurrence or development of lumbar spinal stenosis.The use of plant growth promoting bacteria (PGPB) as biostimulants favors the increase of crop productivity and the improvement of yield quality. The main objective of the present study was to investigate the effect of the PGPB biostimulants (Azotobacter chroococcum, Bacillus subtilis, Bacillus megatherium and their mixes) and the application method (foliar and soil) on the growth, the physiology, the yield and the quality of maize. The obtained results showed that A. chroococcum treatment increased the chlorophyll content up to 6.1%, the photosynthetic rate up to 18.4% and the transpiration rate up to 34.3%. The highest maize yields were performed by the treatments B. megatherium (244.67 g) and the mix of A. chroococcum and B. subtilis (11) (243.67 g) when applied on the soil. The Soil application of the PGPB resulted in increased yield of maize from 5.5 to 13.4% compared to control treatment. Concerning quality characteristics, B. subtilis treatment increased total solids content in harvested maize seeds by 92%, as well as crude fiber content by 46% compared to control. The results confirmed that the use of PGPB could contribute as a new cultivation practice for sustainable growth, productivity and quality of grain crops.The disruption of the protective intestinal barrier-the ‘leaky gut’-is a common complication of the inflammatory bowel disease. JAK Inhibitor I price There is limited data on the mechanisms of the intestinal barrier disruption upon low-grade inflammation characteristic of patients with inflammatory bowel disease in clinical remission. Thus, animal models that recapitulate the complexity of chronic intestinal inflammation in vivo are of particular interest. In this study, we used Mucin-2 (Muc2) knockout mice predisposed to colitis to study intestinal barrier upon chronic inflammation. We used 4-kDa FITC-Dextran assay and transmission electron microscopy to demonstrate the increased intestinal permeability and morphological defects in intercellular junctions in Muc2 knockout mice. Confocal microscopy revealed the disruption of the apical F-actin cytoskeleton and delocalization of tight junction protein Claudin-3 from the membrane. We further demonstrate mitochondrial damage, impaired oxygen consumption and the reduction of the intestinal ATP content in Muc2 knockout mice. Finally, we show that chemically induced mitochondrial uncoupling in the wild type mice mimics the intestinal barrier disruption in vivo and causes partial loss of F-actin and membrane localization of Claudin-3. We propose that mitochondrial damage and metabolic shifts during chronic inflammation contribute to the leaky gut syndrome in Muc2 knockout animal model of colitis.

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