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In this Cell Science at a Glance article and the accompanying poster, we briefly summarize the history of the discovery of TRPs, their unique features, recent advances in the understanding of TRP activation mechanisms, the structural basis of TRP Ca2+ selectivity and ligand binding, as well as potential roles in mammalian physiology and pathology.In the native vasculature, flowing blood produces a frictional force on vessel walls that directly effects endothelial cell phenotype and function. In the arterial system, the vasculature's local geometry directly influences variations in flow profiles and shear stress magnitudes. Straight arterial sections with pulsatile shear stress have been shown to promote an athero-protective endothelial phenotype. Conversely, areas with a more complex geometry, such as arterial bifurcations and branch points with disturbed flow patterns and a lower, oscillatory shear stress, typically lead to endothelial dysfunction and the pathogenesis of cardiovascular diseases. Many studies have investigated the regulation of endothelial responses to various shear stress environments. Importantly, the accurate in vitro simulation of in vivo hemodynamics is critical to the deeper understanding of mechano-transduction through the proper use and design of flow chamber devices. In this review, we describe several flow chamber apparatuses and their fluid mechanics design parameters, including parallel plate flow chambers, cone-and plate devices, and microfluidic devices. In addition, chamber-specific design criteria and relevant equations are defined in detail for the accurate simulation of shear stress environments to study endothelial cell responses.The G allele of FOXO3 gene (Single nucleotide polymorphism - SNP; rs2802292) is strongly associated with human longevity. However, knowledge of the effect of FOXO3 in older populations, men or women, with heart disease is limited. This cross-sectional study in Japan included 1836 older adults in the 70 and 80-year-old groups. DNA samples isolated from buffy coat samples of peripheral blood were used to genotype FOXO3 (rs2802292). Self-reports were used to obtain heart disease data according to physician diagnosis. Multiple logistic regression was used to test the association by adjusting for the traditional risk factor of heart disease. The prevalence of heart disease in women FOXO3 G allele carriers was higher than non-carriers (16.7 vs. 11.6%, p=.022). The prevalence of coronary heart disease was lower for FOXO3 G carriers in the 70-year-old group for both sexes (men 9.3 vs. 4.3%, p=.042, and women 10 vs. 9%, p=.079, respectively). The G allele was negatively associated with heart disease after adjusting for diabetes, hypertension, dyslipidemia, and smoking in men (odds ratio (OR)= 0.70, 95%confidence intervals (CI), 0.49-0.99, p=.046), although the association was weaker after full adjustment. In contrast, women carriers of the FOXO3 G allele showed a positive association with heart disease after total adjustment (OR= 1.49, 95%CI, 1.00-2.21, p=.049). In conclusion, the longevity associated G allele of FOXO3 was observed to have contrasting associations with heart disease prevalence according to sex in older Japanese. To further confirm this association, a longitudinal study and a large sample size will be required.Exosomes derived from human umbilical cord mesenchymal stem cells (hUMSC-Ex) play important roles in immune and inflammation diseases. However, the role of hUMSC-Ex in atherosclerosis has not been elucidated. In this study, the isolated exosomes were identified by transmission electron microscopy and nanoparticle tracking analysis. Exosome marker protein levels were increased in the hUMSC-Ex compared with those in hUMSC suspension, indicating that exosomes were successfully isolated from hUMSCs. Furthermore, eosinophils were treated with oxidized low-density lipoprotein (ox-LDL) to construct inflammation model and then incubated with hUMSC-Ex derived from hUMSCs which were transfected with miR-100-5p mimic or miR-100-5p inhibitor. We found that hUMSC-Ex increased miR-100-5p expression, inhibited cell migration, promoted cell apoptosis, and reduced inflammatory cytokine levels in ox-LDL-treated eosinophils, and miR-100-5p overexpression in hUMSCs enhanced these effects, while miR-100-5p inhibition reversed these effects. read more Moreover, frizzled 5 (FZD5) was a target gene of miR-100-5p. FZD5 overexpression reversed the inhibitory effects of hUMSC-Ex-miR-100-5p on cell progression and inflammation in eosinophils. Additionally, hUMSC-Ex-miR-100-5p decreased the expression of cyclin D1 and β-catenin proteins. Wnt/β-catenin pathway activator BML-284 effectively reversed the effects of hUMSC-Ex-miR-100-5p on cell progression and inflammation in eosinophils. ApoE-/- mice were fed with high-fat diet to construct an atherosclerosis mice model, and hUMSC-Ex was injected into mice. HUMSC-Ex reduced atherosclerotic plaque area and inflammation response in atherosclerosis mice. This study demonstrates that hUMSC-Ex-miR-100-5p inhibits cell progression and inflammatory response in eosinophils via the FZD5/Wnt/β-catenin pathway, thereby alleviating atherosclerosis progression.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severe chronic illness which reduces the quality of life. A potential role of neuroendocrine autoimmune dysfunction has been hypothesized.
To investigate the occurrence of anti-pituitary (APA) and anti-hypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunctions in ME/CSF patients.
This is a case-control study conducted in University Hospital setting (Stanford, Naples). Thirty women with ME/CSF (Group 1) diagnosed according to Fukuda, Canadian, and IOM criteria, at Stanford University, were enrolled and compared with 25 age-matched healthy controls.
APA and AHA were detected by immunofluorescence; moreover, we investigated hormonal secretions of anterior pituitary and respective target glands and plasma and urinary osmolality. Both APA and AHA titers were assessed and the prevalence of pituitary hormone deficiencies was also investigated.
Patients in Group 1 showed a high prevalence of AHA (33%) and APA (56%) and a significant lower levels of ACTH/cortisol, and GH peak/IGF1 vs controls (all AHA/APA negative).
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