Villadsen Barry (drakedrug2)

This is the first in vivo study in which salivary gland dysfunction is associated with the ferroptosis in postmenopausal animal model. Increased lipid and iron deposition in normal submandibular gland tissues of postmenopausal women can suggest that the salivary gland dysfunction after menopause may be associated with the ferroptosis.Human evidence for the role of continuous antigenic stimulation from persistent latent infections in frailty is limited. #link# We conducted a nested case-control study (99 deceased and 43 survivors) of participants aged 55 and above in a longitudinal ageing cohort followed up from 2003 to 2017. Using blood samples and baseline data collected in 2003-2004, we examined the association of pathogenic load (PL) count of seropositivity to 10 microbes (viruses, bacteria and mycoplasma) with cumulated deficit-frailty index (CD-FI) and the physical frailty (PF) phenotype, and mortality. Controlling for age, sex, education, smoking and alcohol histories, high PL (7-9) versus low PL (3-6) was associated with an estimated increase of 0.035 points in the CD-FI (Cohen's D=0.035 / 0.086, or 0.41). was associated with 8.5 times odds of being physically frail (p=0.001), 2.8 times odds of being weak (p=0.010), 3.4 times odds of being slow (p=0.024), and mortality hazard ratio of 1.53 (p=0.046). There were no significant associations for specific pathogens, except marginal associations for Epstein-Barr virus and Chikungunya. Conclusion A high pathogenic load of latent infections was associated with increased risks of frailty and mortality.In this study, we studied the effect and possible mechanism of TGF-β1 on vascular calcification. We found that the serum levels of TGF-β1 and cycloxygenase-2 (COX-2) were significantly increased in patients with chronic kidney disease. Phosphate up regulated TGF-β1 in vascular smooth muscle cells (VSMCs). TGF-β1 decreased the markers of VSMCs, but increased osteogenic markers and calcification in aortic segments. The phosphate-induced osteogenic markers were reduced by the TGFβR I inhibitor (LY364947), which also attenuated the potential of phosphate to reduce VSMC markers in VSMCs. Both phosphate and TGF-β1 increased the protein level of β-catenin, which was partially mitigated by LY364947. TGF-β1 decreased sclerostin, and exogenous sclerostin decreased the mineralization induced by TGF-β1. LY364947 reduced the phosphate and TGF-β1 induced COX-2. Meanwhile, the effects of TGF-β1 on osteogenic markers, β-catenin, and sclerostin, were partially reversed by the COX-2 inhibitor. Mechanistically, we found that p-Smad2/3 and p-CREB were both enriched at the promoter regions of sclerostin and β-catenin. TGF-β1 and COX-2 were significantly elevated in serum and aorta of rats undergoing renal failure. Therapeutic administration of meloxicam effectively ameliorated the renal lesion. Our results suggested that COX-2 may mediate the effect of TGF-β1 on vascular calcification through down-regulating sclerostin in VMSCs.The purpose of this study was to identify a specific circular RNA and to investigate its regulatory mechanism in intervertebral disc degeneration (IDD). CircGLCE was selected after microarray analyses and was further analysed by RT-qPCR and FISH. CircGLCE was found to stably exist in the cytoplasm of nucleus pulposus (NP) cells. It was downregulated in IDD. After silencing CircGLCE, its function was assessed with RT-qPCR, immunofluorescence analysis and flow cytometry. Knockdown of CircGLCE promoted apoptosis and induced the expression of matrix-degrading enzymes in NP cells. CircGLCE served as a miR-587 sponge in NP cells. Inhibiting miR-587 counteracted the IDD-enhancing effect caused by silencing CircGLCE. STAP1 served as the miRNA target that mediated the functions of miR-587. In an IDD mouse model, the in vivo effects of overexpressing CircGLCE on IDD were confirmed by imaging techniques, TUNEL staining, FISH, western blo