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- Structural Determinants of the Prion Protein N-Terminus and Its Adducts with Copper Ions. [Review]
- IJInt J Mol Sci 2018 Dec 20; 20(1)
- The N-terminus of the prion protein is a large intrinsically disordered region encompassing approximately 125 amino acids. In this paper, we review its structural and functional properties, with a pa…
The N-terminus of the prion protein is a large intrinsically disordered region encompassing approximately 125 amino acids. In this paper, we review its structural and functional properties, with a particular emphasis on its binding to copper ions. The latter is exploited by the region's conformational flexibility to yield a variety of biological functions. Disease-linked mutations and proteolytic processing of the protein can impact its copper-binding properties, with important structural and functional implications, both in health and disease progression.
- Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial. [Randomized Controlled Trial]
- JAMAJAMA 2018 12 11; 320(22):2325-2334
- CONCLUSIONS: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these.
- Intestinal Phosphorus Absorption in Chronic Kidney Disease. [Review]
- NNutrients 2018 Sep 23; 10(10)
- Chronic kidney disease (CKD) affects approximately 10% of adults worldwide. Dysregulation of phosphorus homeostasis which occurs in CKD leads to development of CKD-Mineral Bone Disorder (CKD-MBD) and…
Chronic kidney disease (CKD) affects approximately 10% of adults worldwide. Dysregulation of phosphorus homeostasis which occurs in CKD leads to development of CKD-Mineral Bone Disorder (CKD-MBD) and contributes to increased morbidity and mortality in these patients. Phosphorus is regulated by multiple hormones (parathyroid hormone (PTH), 1,25-dihyxdroxyvitamin D (1,25D), and fibroblast growth factor 23 (FGF23)) and tissues (kidney, intestine, parathyroid glands, and bone) to maintain homeostasis. In health, the kidneys are the major site of regulation for phosphorus homeostasis. However, as kidney function declines, the ability of the kidneys to adequately excrete phosphorus is reduced. The hormonal changes that occur with CKD would suggest that the intestine should compensate for impaired renal phosphorus excretion by reducing fractional intestinal phosphorus absorption. However, limited studies in CKD animal models and patients with CKD suggest that there may be a break in this homeostatic response where the intestine fails to compensate. As many existing therapies for phosphate management in CKD are aimed at reducing absolute intestinal phosphorus absorption, better understanding of the factors that influence fractional and absolute absorption, the mechanism by which intestinal phosphate absorption occurs, and how CKD modifies these is a much-needed area of study.
- Vitamin D in Cardiovascular Disease. [Review]
- VIn Vivo 2018 Sep-Oct; 32(5):977-981
- Cardiovascular disease is the prevalent cause of morbidity and mortality in the world, affecting many millions of individuals every year. Atherosclerosis, a chronic inflammatory condition that involv…
Cardiovascular disease is the prevalent cause of morbidity and mortality in the world, affecting many millions of individuals every year. Atherosclerosis, a chronic inflammatory condition that involves different cell types, several cytokines and adhesion molecules, is the underlying cause of cardiovascular disease. Vitamin D is known to control skeletal patho/physiology, regulating calcium and phosphorus and bone remodeling along with other calcium-regulating hormones. However, several active metabolites of vitamin D can exert both direct action, mainly via vitamin D3 receptor trans-activation and indirect actions on several other tissues by an endocrine, autocrine and paracrine manners. With regard to cardiovascular disease, vitamin D deficiency has been associated with activation of the pro-inflammatory mechanism, promoting atherogenesis. There are several large-scale clinical studies, as well as meta-analyses that support this finding. However, it is still unclear whether the plasma 25-hydroxyvitamin D level can be used as a biomarker for future cardiovascular disease. Herein we review the studies reporting a causative role for vitamin D in cardiovascular disease.
- Vitamin D status and functional parameters: A cross-sectional study in an older population. [Journal Article]
- PlosPLoS One 2018; 13(8):e0201840
- The present study aims to clarify the association of vitamin D status with functionality, measured through gait speed and hand grip strength, in a sample of older adults, considering sex-specific cha…
The present study aims to clarify the association of vitamin D status with functionality, measured through gait speed and hand grip strength, in a sample of older adults, considering sex-specific characteristics and the potential confounding effect of lifestyle factors, disease, skin phenotype, season of blood collection and vitamin D supplementation. The Nutrition UP 65 cross-sectional study was conducted in a population-based sample of 1,425 older adults ≥ 65 years old. Serum levels of 25-hydroxyvitamin D were quantified through electrochemiluminescence immunoassay. Multinomial logistic regressions were carried out using quartiles of gait speed and of hand grip strength as dependent variables. Participants at risk of vitamin D inadequacy (30.0-49.9 nmol/L) and deficiency (< 30.0 nmol/L) presented higher adjusted odds ratio of the lowest values of gait speed and hand grip strength than those with adequate vitamin D levels (≥ 50.0 nmol/L). These associations were strongest among men at risk of vitamin D deficiency [adjusted odds ratio for the lowest quartile of gait speed = 3.24; 95% CI: 1.56-6.73 and for the lowest quartile of hand grip strength = 3.28; 95% CI: 1.47-7.31] than in women at risk of vitamin D deficiency [adjusted odds ratio for the lowest quartile of gait speed = 2.72; 95% CI: 1.37-5.41 and for the lowest quartile of hand grip strength = 1.56; 95% CI: 0.81-3.00]. In conclusion, in older adults, particularly in men, the risk of vitamin D deficiency was directly associated with the lowest values of gait speed and of hand grip strength. However, randomized controlled trials are needed to overcome the possibility of reverse causation and residual confounding. Present results emphasise the need for strategies to promote the reduction of the high prevalence of low vitamin D status among the Portuguese older adult population.
- Ultraviolet Irradiation of Skin Alters the Faecal Microbiome Independently of Vitamin D in Mice. [Journal Article]
- NNutrients 2018 Aug 11; 10(8)
- Reduced sunlight exposure has been associated with an increased incidence of Crohn's disease and ulcerative colitis. The effect of ultraviolet radiation (UVR) on the faecal microbiome and susceptibil…
Reduced sunlight exposure has been associated with an increased incidence of Crohn's disease and ulcerative colitis. The effect of ultraviolet radiation (UVR) on the faecal microbiome and susceptibility to colitis has not been explored. C57Bl/6 female mice were fed three different vitamin D-containing diets for 24 days before half of the mice in each group were UV-irradiated (1 kJ/m²) for each of four days, followed by twice-weekly irradiation of shaved dorsal skin for 35 days. Faecal DNA was extracted and high-throughput sequencing of the 16S RNA gene performed. UV irradiation of skin was associated with a significant change in the beta-diversity of faeces compared to nonirradiated mice, independently of vitamin D. Specifically, members of phylum Firmicutes, including Coprococcus, were enriched, whereas members of phylum Bacteroidetes, such as Bacteroidales, were depleted. Expression of colonic CYP27B1 increased by four-fold and IL1β decreased by five-fold, suggesting a UVR-induced anti-inflammatory effect. UV-irradiated mice, however, were not protected against colitis induced by dextran sodium sulfate (DSS), although distinct faecal microbiome differences were documented post-DSS between UV-irradiated and nonirradiated mice. Thus, skin exposure to UVR alters the faecal microbiome, and further investigations to explore the implications of this in health and disease are warranted.
- Assays for NAD+-Dependent Reactions and NAD+ Metabolites. [Journal Article]
- MMMethods Mol Biol 2018; 1813:77-90
- Nicotinamide adenine dinucleotide (NAD+) is an essential redox cofactor and signaling molecule that controls the activity of enzymes involved in metabolism, DNA repair, and cellular survival, such as…
Nicotinamide adenine dinucleotide (NAD+) is an essential redox cofactor and signaling molecule that controls the activity of enzymes involved in metabolism, DNA repair, and cellular survival, such as the PARPs, CD38, and the sirtuins. Here, we describe three methods for measuring the activity of these enzymes: the etheno-NAD+ assay measures NAD+ hydrolase activity using an NAD+ analog to produce a fluorescent product that is measured in real time; the PNC1 assay converts a native product of NAD+ hydrolysis, nicotinamide, into a quantitative fluorescent readout; and liquid chromatography tandem mass spectrometry (LC-MS/MS) is used to characterize the entire NAD+ metabolome in a sample. These methods will enable new insights into the roles that NAD+ and the enzymes that utilize it play in health and disease.
- Vitamin B3 in Health and Disease: Toward the Second Century of Discovery. [Review]
- MMMethods Mol Biol 2018; 1813:3-8
- This introductory chapter briefly reviews the history, chemistry, and biochemistry of NAD (the term NAD as it is used here refers to both oxidized and reduced forms of the molecule) consuming ADP-rib…
This introductory chapter briefly reviews the history, chemistry, and biochemistry of NAD (the term NAD as it is used here refers to both oxidized and reduced forms of the molecule) consuming ADP-ribose transfer enzymes as components of the involvement of vitamin B3 in health and disease.
- Vitamin E status and its determinants in patients with cystic fibrosis. [Journal Article]
- AMAdv Med Sci 2018; 63(2):341-346
- CONCLUSIONS: Vitamin E deficiency in cystic fibrosis patients is rather rare nowadays. Excessive vitamin E levels seem to be more frequent. Vitamin E status wasn't documented to be strictly related to clinical determinants. Beyond vitamin E supplementation, exocrine pancreatic function and CFTR gene mutations may have had an impact on the vitamin E body resources in cystic fibrosis patients.
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- Sorafenib for Advanced Hepatocellular Carcinoma: A Real-Life Experience. [Journal Article]
- DDDig Dis 2018; 36(5):377-384
- CONCLUSIONS: In this real-life study, SOR significantly increased the survival rate by 1 year in patients with advanced HCC regardless of BCLC staging and CP score. Second-line therapy would be indicated in 21.6% of cases.