Neurodegenerative diseases are a common cause of morbidity and mortality worldwide with oxidative stress, inflammation and protein aggregation represent the main underlying mechanisms that ultimately lead to cell death. Ethanol has shown strong neurodegenerative consequences in experimental animal brains. Statins are a class of lipid-lowering drugs with many pleotropic effects. Therefore, the aim of the present study was to explore the modulatory effect of simvastatin (10 mg/kg/day) before and after the development of neurodegeneration (for 55 and 25 days, respectively) on redox state, caspase-3 expression, p-protein kinase B (p-Akt) and brain derived neurotrophic factor (BDNF) in ethanol (15% ethanol solution for 55 day) induced neurodegeneration. Seventy female Albino Swiss mice were included and randomly divided into 5 groups control (c) group; ethanol (E) group; (ES) group treated with simvastatin from the first day of ethanol intake; (E+S) group treated with simvastatin after neurodegeneration development; and simvastatin (S) group.  https://www.selleckchem.com/products/FK-506-(Tacrolimus).html  Administration of simvastatin from the first day improved the biochemical changes, suppressed apoptosis, induced autophagy and neurogenesis. However, its administration after the development of neurodegeneration resulted in partial improvement. The histopathological findings confirmed the biochemical changes. In conclusion; simvastatin has a neuroprotective effect against the development of ethanol-induced neurodegeneration and its progression.The heart-brain axis (HBA) recapitulates all the circuits that regulate bidirectional flow of communication between heart and brain. Several mechanisms may underlie the interdependent relationship involving heterogeneous tissues at rest and during specific target organ injury such as myocardial infarction, heart failure, arrhythmia, stroke, mood disorders, or dementia. In-depth translational studies of the HBA dysfunction under single-organ injury should include both male and female animals to develop sex- and gender-oriented prevention, diagnosis, and treatment strategies. Indeed, sex and gender are determining factors as females and males exhibit significant differences in terms of susceptibility to risk factors, age of onset, severity of symptoms, and outcome. Despite most studies having focused on the male population, we have conducted a careful appraisal of the literature investigating HBA in females. In particular, we have (i) analyzed sex-related heart and brain illnesses, (ii) recapitulated the most significant studies simultaneously conducted on cardio- and cerebro-vascular systems in female populations, and (iii) hypothesized future perspectives for the development of a gender-based approach to HBA dysfunction. Although sex- and gender-oriented research is at its infancy, the impact of sex on HBA dysfunction is opening unexpected new avenues for managing the health of female subjects exposed to risk of lifestyle multi-organ disease.We earlier showed that angiotensin (Ang) II-induced overexpression of Giα proteins contributes to the hyperproliferation of vascular smooth muscle cells (VSMC). In addition, the implication of the JAK2/STAT3 pathway in Ang II-induced hyperproliferation of VSMC has also been reported. However, the role of the JAK2/STAT3 pathway in Ang II-induced overexpression of Giα proteins and hyperproliferation of VSMC remains unexplored. In the present study, we show that inhibition or knockdown of the JAK2/STAT3 pathway by a specific inhibitor "cucurbitacin I" (CuI) or siRNAs attenuated Ang II-induced overexpression of Giα proteins and hyperproliferation of VSMC. In addition, the enhanced expression of cell cycle proteins induced by Ang II was also attenuated by CuI. Furthermore, Ang II-induced enhanced production of the superoxide anion (O2-), H2O2, and NADPH oxidase activity, as well as the enhanced expression of NADPH oxidase subunits implicated in enhanced expression of Giα proteins and hyperproliferation, were also attenuated by inhibition of the JAK2/STAT3 pathway. On the other hand, Ang II-induced inhibition and augmentation of the levels of nitric oxide and peroxynitrite, respectively, in VSMC were restored to control levels by CuI. In summary, our results demonstrate that Ang II through the JAK2/STAT3 pathway increases nitroxidative stress, which contributes to the overexpression of Giα proteins and cell cycle proteins and the hyperproliferation of VSMC.
  Brazil has a rapidly aging population, yet little is known about the occurrence of functional dependence in the rural older adult population. The objective of this study was to estimate the prevalence of functional dependence and its associated factors among community-dwelling older adults in the rural area of the municipality of Rio Grande, Rio Grande do Sul state, Brazil.
 
  This was a cross-sectional, population-based study. A systematic random sampling of households was used. Eighty percent of households in the rural area were selected, which included 1131 older adults. The outcome analyzed in this study was functional dependence. This was measured by and data were collected using the Katz Index for Activities of Daily Living (ADL) and Lawton and Brody's Scale for Instrumental Activities of Daily Living (IADL). Descriptive analysis was used to estimate the prevalence of functional dependence in ADL and IADL and to describe the sample. Crude and adjusted analysis was performed by Poisson regression with rural populations is necessary for the planning and developing actions, especially in the routine of primary care, which promote health and prevent or postpone the decline in functional capacity.A bioinert surface has been designed by simple coating with cholesterol end-modified poly(ethylene glycol), Chol-U-Pr-mPEG, using a cholesterol anchor. A poly(propylene) (PP) surface was immersed into the Chol-U-Pr-mPEG aqueous solution, where control mPEGs without cholesterol were not suitable for the design of bioinert surfaces. The resulting surfaces coated with Chol-U-Pr-mPEG above and below its critical micelle concentration were swollen and less swollen, respectively. Chol-U-Pr-mPEG with a molecular weight of 2000, Chol-U-Pr-mPEG (2k), formed a swollen layer with a thickness of 10-15 nm and adhered to the PP surface with an estimated Kd value of 4.4×10-7 M. The resulting Chol-U-Pr-mPEG (2k)-coated surface with the swollen layer suppressed the adsorption of γ-globulin proteins and the adhesion of platelets in plasma. Although the PP surface coated with Chol-U-Pr-mPEG with a molecular weight of 5000, Chol-U-Pr-mPEG (5k), also suppressed the adsorption of γ-globulin proteins, the Chol-U-Pr-mPEG (5k)-coated PP surface did not suppress the adhesion of the platelets in plasma despite the existence of a swollen layer with a thickness of 20-25 nm.