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Exploring the role of extracellular matrix proteins to develop biomarkers of plaque vulnerability and outcome.
Holm Nielsen, S, Jonasson, L, Kalogeropoulos, K, Karsdal, MA, Reese-Petersen, AL, Auf dem Keller, U, Genovese, F, Nilsson, J, Goncalves, I
Journal of internal medicine. 2020;(5):493-513
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Abstract
Cardiovascular disease (CVD) is the most common cause of death in industrialized countries. One underlying cause is atherosclerosis, which is a systemic disease characterized by plaques of retained lipids, inflammatory cells, apoptotic cells, calcium and extracellular matrix (ECM) proteins in the arterial wall. The biologic composition of an atherosclerotic plaque determines whether the plaque is more or less vulnerable, that is prone to rupture or erosion. Here, the ECM and tissue repair play an important role in plaque stability, vulnerability and progression. This review will focus on ECM remodelling in atherosclerotic plaques, with focus on how ECM biomarkers might predict plaque vulnerability and outcome.
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Obesity: a Ghost at the Feast of the Sustainable Development Goals.
Lobstein, T, Cooper, K
Current obesity reports. 2020;(4):470-478
Abstract
PURPOSE OF REVIEW Despite its rapidly rising global prevalence, obesity is not featured in any of the Sustainable Development Goals (SDGs). This review highlights the multiple points at which obesity is affected by the Goals. RECENT FINDINGS At least 14 out of the 17 thematic SDG targets play a role in driving the obesity epidemic, including health, food, education, water quality, land and ocean quality, urbanisation and employment. Although the SDGs recognise the need to reduce 'malnutrition in all its forms', the Goals underplay the role of urbanisation and unregulated markets on dietary health. Furthermore, adherence to the SDGs may be weak and compromised by conflicted interests. Nonetheless, governments have shown that they can, when pressed, respond to health challenges, and we anticipate how the rise in the numbers of people experiencing excess bodyweight may itself lead to greater demand for collective responsibility to ensure our environments are fully health-creating.
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Sexual hormones regulate the redox status and mitochondrial function in the brain. Pathological implications.
Torrens-Mas, M, Pons, DG, Sastre-Serra, J, Oliver, J, Roca, P
Redox biology. 2020;:101505
Abstract
Compared to other organs, the brain is especially exposed to oxidative stress. In general, brains from young females tend to present lower oxidative damage in comparison to their male counterparts. This has been attributed to higher antioxidant defenses and a better mitochondrial function in females, which has been linked to neuroprotection in this group. However, these differences usually disappear with aging, and the incidence of brain pathologies increases in aged females. Sexual hormones, which suffer a decrease with normal aging, have been proposed as the key factors involved in these gender differences. Here, we provide an overview of redox status and mitochondrial function regulation by sexual hormones and their influence in normal brain aging. Furthermore, we discuss how sexual hormones, as well as phytoestrogens, may play an important role in the development and progression of several brain pathologies, including neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, stroke or brain cancer.
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Effects of improved complementary feeding and improved water, sanitation and hygiene on early child development among HIV-exposed children: substudy of a cluster randomised trial in rural Zimbabwe.
Chandna, J, Ntozini, R, Evans, C, Kandawasvika, G, Chasekwa, B, Majo, F, Mutasa, K, Tavengwa, N, Mutasa, B, Mbuya, M, et al
BMJ global health. 2020;(1):e001718
Abstract
INTRODUCTION HIV-exposed uninfected children may be at risk of poor neurodevelopment. We aimed to test the impact of improved infant and young child feeding (IYCF) and improved water, sanitation and hygiene (WASH) on early child development (ECD) outcomes. METHODS Sanitation Hygiene Infant Nutrition Efficacy was a cluster randomised 2×2 factorial trial in rural Zimbabwe ClinicalTrials.gov NCT01824940). Pregnant women were eligible if they lived in study clusters allocated to standard-of-care (SOC; 52 clusters); IYCF (20 g small-quantity lipid-based nutrient supplement/day from 6 to 18 months, complementary feeding counselling; 53 clusters); WASH (pit latrine, 2 hand-washing stations, liquid soap, chlorine, play space, hygiene counselling; 53 clusters) or IYCF +WASH (53 clusters). Participants and fieldworkers were not blinded. ECD was assessed at 24 months using the Malawi Developmental Assessment Tool (MDAT; assessing motor, cognitive, language and social skills); MacArthur Bates Communication Development Inventory (assessing vocabulary and grammar); A-not-B test (assessing object permanence) and a self-control task. Intention-to-treat analyses were stratified by maternal HIV status. RESULTS Compared with SOC, children randomised to combined IYCF +WASH had higher total MDAT scores (mean difference +4.6; 95% CI 1.9 to 7.2) and MacArthur Bates vocabulary scores (+8.5 words; 95% CI 3.7 to 13.3), but there was no evidence of effects from IYCF or WASH alone. There was no evidence that that any intervention impacted object permanence or self-control. CONCLUSIONS Combining IYCF and WASH interventions significantly improved motor, language and cognitive development in HIV-exposed children. TRIAL REGISTRATION NUMBER NCT01824940.
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Transcriptome Profile of Yeast Strain Used for Biological Wine Aging Revealed Dynamic Changes of Gene Expression in Course of Flor Development.
Mardanov, AV, Eldarov, MA, Beletsky, AV, Tanashchuk, TN, Kishkovskaya, SA, Ravin, NV
Frontiers in microbiology. 2020;:538
Abstract
Flor strains of Saccharomyces cerevisiae are principal microbial agents responsible for biological wine aging used for production of sherry-like wines. The flor yeast velum formed on the surface of fortified fermented must is a major adaptive and technological characteristic of flor yeasts that helps them to withstanding stressful winemaking conditions and ensures specific biochemical and sensory oxidative alterations typical for sherry wines. We have applied RNAseq technology for transcriptome analysis of an industrial flor yeast strain at different steps of velum development over 71 days under experimental winemaking conditions. Velum growth and maturation was accompanied by accumulation of aldehydes and acetales. We have identified 1490 differentially expressed genes including 816 genes upregulated and 674 downregulated more than 2-fold at mature biofilm stage as compared to the early biofilm. Distinct expression patterns of genes involved in carbon and nitrogen metabolism, respiration, cell cycle, DNA repair, cell adhesion, response to various stresses were observed. Many genes involved in response to different stresses, oxidative carbon metabolism, high affinity transport of sugars, glycerol utilization, sulfur metabolism, protein quality control and recycling, cell wall biogenesis, apoptosis were induced at the mature biofilm stage. Strong upregulation was observed for FLO11 flocculin while expression of other flocculins remained unaltered or moderately downregulated. Downregulated genes included those for proteins involved in glycolysis, transportation of ions, metals, aminoacids, sugars, indicating repression of some major transport and metabolic process at the mature biofilm stage. Presented results are important for in-depth understanding of cell response elicited by velum formation and sherry wine manufacturing conditions, and for the comprehension of relevant regulatory mechanisms. Such knowledge may help to better understand the molecular mechanisms that flor yeasts use to adapt to winemaking environments, establish the functions of previously uncharacterized genes, improve the technology of sherry- wine production, and find target genes for strain improvement.
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Impact of antidiabetic agents on dementia risk: A Bayesian network meta-analysis.
Zhou, JB, Tang, X, Han, M, Yang, J, Simó, R
Metabolism: clinical and experimental. 2020;:154265
Abstract
BACKGROUND Dementia is more prevalent among people with type 2 diabetes, but little is known regarding the influence of antidiabetic agents on this association. OBJECTIVE This study assessed the impact of various antidiabetic agents on the risk of dementia among patients with Type 2 diabetes mellitus. METHODS Relevant studies were retrieved from the PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases. Nine antidiabetic agents were included in the search. Data were pooled via network meta-analysis and meta-analysis. RESULTS Nine studies were selected for the network meta-analysis with 530,355 individuals and 17 studies for the meta-analysis with 1,258,879 individuals. The analysis excluded glucagon-like peptide 1 (GLP-1) analogs and sodium-dependent glucose transporter 2 (SGLT-2) inhibitors due to the absence of relevant data. The use of dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, thiazolidinedione, and sulfonylurea was associated with a decreased risk of dementia in comparison to no treatment with antidiabetic agents (hazard ratio [HR] for DPP-4 inhibitors, 0.54; 95% confidence interval [CI], 0.38-0.74, HR for metformin, 0.75; 95% CI, 0.63-0.86; HR for sulfonylurea, 0.85; 95%CI, 0.73-0.98 and HR for thiazolidinedione, 0.70; 95% CI, 0.55-0.89, respectively). However, the node-splitting analysis showed the inconsistency of direct and indirect estimates in sulfonylurea (P = 0.042). DPP-4 inhibitors, metformin, thiazolidinedione, and sulfonylurea exhibited a significant impact on the risk of dementia in diabetics compared with insulin (HR, 0.35; 95%CI, 0.20-0.59, HR, 0.48; 95% CI, 0.30-0.77, HR, 0.45; 95% CI, 0.29-0.73 and HR, 0.55; 95% CI, 0.34-0.88, respectively). DPP-4 inhibitors also exhibited a protective effect on the risk of Alzheimer's dementia compared with the no treatment with antidiabetic agents (HR, 0.48; 95% CI, 0.25-0.92). The meta-analysis demonstrated a protective effect of using metformin and DPP-4 inhibitors on the risk of dementia (HR, 0.86; 95% CI, 0.74-1.00 and HR, 0.65; 95% CI, 0.55-0.76, respectively). Further analysis showed insulin was associated with an increased risk of Alzheimer's dementia (HR, 1.60; 95% CI, 1.13-2.26). Only two case-control studies mentioned GLP-1 analogs and SGLT-2 inhibitors, and the pooled ORs showed no evidence of an association with dementia (GLP-1 analogs: 0.71; 95% CI, 0.46-1.10 and SGLT-2 inhibitors: 0.74; 95% CI, 0.47-1.15). CONCLUSION This analysis indicated that patients with type 2 diabetes under treatment with DPP-4 inhibitors presented with the lowest risk of dementia, followed by those treated with metformin and thiazolidinedione, while treatment with insulin was associated with the highest risk. For the increasing focus on the protective effect on dementia, further specific clinical studies are needed to evaluate the impact of GLP-1 analogs and SGLT-2 inhibitors on the risk of dementia.
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Review article: the emerging role of genetics in precision medicine for patients with non-alcoholic steatohepatitis.
Carlsson, B, Lindén, D, Brolén, G, Liljeblad, M, Bjursell, M, Romeo, S, Loomba, R
Alimentary pharmacology & therapeutics. 2020;(12):1305-1320
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Abstract
BACKGROUND Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) characterised by liver fat accumulation, inflammation and progressive fibrosis. Emerging data indicate that genetic susceptibility increases risks of NAFLD, NASH and NASH-related cirrhosis. AIMS To review NASH genetics and discuss the potential for precision medicine approaches to treatment. METHOD PubMed search and inclusion of relevant literature. RESULTS Single-nucleotide polymorphisms in PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13 are clearly associated with NASH development or progression. These genetic variants are common and have moderate-to-large effect sizes for development of NAFLD, NASH and hepatocellular carcinoma (HCC). The genes play roles in lipid remodelling in lipid droplets, hepatic very low-density lipoprotein (VLDL) secretion and de novo lipogenesis. The PNPLA3 I148M variant (rs738409) has large effects, with approximately twofold increased odds of NAFLD and threefold increased odds of NASH and HCC per allele. Obesity interacts with PNPLA3 I148M to elevate liver fat content and increase rates of NASH. Although the isoleucine-to-methionine substitution at amino acid position 148 of the PNPLA3 enzyme inactivates its lipid remodelling activity, the effect of PNPLA3 I148M results from trans-repression of another lipase (ATGL/PNPLA2) by sequestration of a shared cofactor (CGI-58/ABHD5), leading to decreased hepatic lipolysis and VLDL secretion. In homozygous Pnpla3 I148M knock-in rodent models of NAFLD, targeted PNPLA3 mRNA knockdown reduces hepatic steatosis, inflammation and fibrosis. CONCLUSION The emerging genetic and molecular understanding of NASH paves the way for novel interventions, including precision medicines that can modulate the activity of specific genes associated with NASH.
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Glutaredoxins and iron-sulfur protein biogenesis at the interface of redox biology and iron metabolism.
Mühlenhoff, U, Braymer, JJ, Christ, S, Rietzschel, N, Uzarska, MA, Weiler, BD, Lill, R
Biological chemistry. 2020;(12):1407-1428
Abstract
The physiological roles of the intracellular iron and redox regulatory systems are intimately linked. Iron is an essential trace element for most organisms, yet elevated cellular iron levels are a potent generator and amplifier of reactive oxygen species and redox stress. Proteins binding iron or iron-sulfur (Fe/S) clusters, are particularly sensitive to oxidative damage and require protection from the cellular oxidative stress protection systems. In addition, key components of these systems, most prominently glutathione and monothiol glutaredoxins are involved in the biogenesis of cellular Fe/S proteins. In this review, we address the biochemical role of glutathione and glutaredoxins in cellular Fe/S protein assembly in eukaryotic cells. We also summarize the recent developments in the role of cytosolic glutaredoxins in iron metabolism, in particular the regulation of fungal iron homeostasis. Finally, we discuss recent insights into the interplay of the cellular thiol redox balance and oxygen with that of Fe/S protein biogenesis in eukaryotes.
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Lack of Efficacy of the Neutropenic Diet in Decreasing Infections among Cancer Patients: A Systematic Review.
Ramamoorthy, V, Rubens, M, Appunni, S, Saxena, A, McGranaghan, P, Veledar, E, Viamonte-Ros, A, Shehadeh, N, Kaiser, A, Kotecha, R
Nutrition and cancer. 2020;(7):1125-1134
Abstract
The objective of this systematic review is to evaluate the existing evidence supporting the effectiveness of the neutropenic diet in decreasing infection and mortality among cancer patients. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Scopus for relevant articles published from database inception until March 2019. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed for this review. Individual studies were evaluated using the Oxford Center for Evidence-Based Medicine guidelines. A total of 473 articles were identified and 11 articles were selected after assessing eligibility. Our review showed that the neutropenic diet does not decrease infection rates or mortality among cancer patients. Currently, there is no uniform definition for the neutropenic diet across different institutions. For example, some institutions follow general food safety practices while others avoid foods that increase exposure to microbes and bacteria, and some follow both. Given these differences in practice regarding what constitutes a neutropenic diet, it is advisable that safe food handling and preparation practices recommended by the Food and Drug Administration be uniformly followed for neutropenic patients.
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Childhood obesity, cardiovascular and liver health: a growing epidemic with age.
Faienza, MF, Chiarito, M, Molina-Molina, E, Shanmugam, H, Lammert, F, Krawczyk, M, D'Amato, G, Portincasa, P
World journal of pediatrics : WJP. 2020;(5):438-445
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Abstract
BACKGROUND The frequency of childhood obesity has increased over the last 3 decades, and the trend constitutes a worrisome epidemic worldwide. With the raising obesity risk, key aspects to consider are accurate body mass index classification, as well as metabolic and cardiovascular, and hepatic consequences. DATA SOURCES The authors performed a systematic literature search in PubMed and EMBASE, using selected key words (obesity, childhood, cardiovascular, liver health). In particular, they focused their search on papers evaluating the impact of obesity on cardiovascular and liver health. RESULTS We evaluated the current literature dealing with the impact of excessive body fat accumulation in childhood and across adulthood, as a predisposing factor to cardiovascular and hepatic alterations. We also evaluated the impact of physical and dietary behaviors starting from childhood on cardio-metabolic consequences. CONCLUSIONS The epidemic of obesity and obesity-related comorbidities worldwide raises concerns about the impact of early abnormalities during childhood and adolescence. Two key abnormalities in this context include cardiovascular diseases, and nonalcoholic fatty liver disease. Appropriate metabolic screenings and associated comorbidities should start as early as possible in obese children and adolescents. Nevertheless, improving dietary intake and increasing physical activity performance are to date the best therapeutic tools in children to weaken the onset of obesity, cardiovascular diseases, and diabetes risk during adulthood.