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- Mi, JR, et al.
(författare)
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Mendelian randomization in blood metabolites identifies triglycerides and fatty acids saturation level as associated traits linked to pancreatitis risk
- 2022
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Ingår i: Frontiers in nutrition. - : Frontiers Media SA. - 2296-861X. ; 9, s. 1021942-
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Tidskriftsartikel (refereegranskat)abstract
- There is very limited evidence on the causal effects of blood metabolites on pancreatitis risks. To reveal the causal associations between plasma metabolites and pancreatitis risks, we performed two-sample Mendelian randomization (MR) and Bayesian model averaging (MR-BMA) analyses in European ancestry.MethodsThe summary-level statistics from two genome-wide association studies with 249 and 123 metabolic traits derived from two separate cohorts involving ~115,000 (UK Biobank) and ~25,000 individuals from European ancestry were used for the analyses. The summary statistics of four pancreatitis datasets from FinnGen R5 and two pancreatitis datasets from UK Biobank were exploited as the outcome. We first performed univariable MR analysis with different metabolic GWAS data on multiple pancreatitis datasets to demonstrate the association pattern among different metabolites categories. Next, we exploited the MR-BMA method to pinpoint the dominating factors on the increased risk of pancreatitis.ResultsIn the primary analysis with 249 traits, we found that plasma triglycerides were positively associated with pancreatitis risk. Intriguingly, a large number of traits associated with saturation or unsaturation of fatty acids also demonstrated causal associations. The replication study analyzing 123 metabolic traits suggested that bisallylic groups levels and omega-3 fatty acids were inversely correlated with pancreatitis risk. MR-BMA analyses indicated that the ratio of triglycerides to total lipid in various HDL particles played leading roles in pancreatitis susceptibility. In addition, the degree of unsaturation, the ratio of polyunsaturated fatty acids to monounsaturated fatty acids and the level of monounsaturated fatty acids showed causal associations with either decreased or increased pancreatitis susceptibility.ConclusionsOur MR study provided an atlas of causal associations of genetically predicted blood metabolites on pancreatitis, and offered genetic insights showing intervention in triglycerides and the supplementation of unsaturated fatty acids are potential strategies in the primary prevention of pancreatitis.
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- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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- Sbarra, AN, et al.
(författare)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Tidskriftsartikel (refereegranskat)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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- Yao, JT, et al.
(författare)
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Early modulation of macrophage ROS-PPARγ-NF-κB signalling by sonodynamic therapy attenuates neointimal hyperplasia in rabbits
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 11638-
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Tidskriftsartikel (refereegranskat)abstract
- Disruption of re-endothelialization and haemodynamic balance remains a critical side effect of drug-eluting stents (DES) for preventing intimal hyperplasia. Previously, we found that 5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) suppressed macrophage-mediated inflammation in atherosclerotic plaques. However, the effects on intimal hyperplasia and re-endothelialization remain unknown. In this study, 56 rabbits were randomly assigned to control, ultrasound, ALA and ALA-SDT groups, and each group was divided into two subgroups (n = 7) on day 3 after right femoral artery balloon denudation combined with a hypercholesterolemic diet. Histopathological analysis revealed that ALA-SDT enhanced macrophage apoptosis and ameliorated inflammation from day 1. ALA-SDT inhibited neointima formation without affecting re-endothelialization, increased blood perfusion, decreased the content of macrophages, proliferating smooth muscle cells (SMCs) and collagen but increased elastin by day 28. In vitro, ALA-SDT induced macrophage apoptosis and reduced TNF-α, IL-6 and IL-1β via the ROS-PPARγ-NF-κB signalling pathway, which indirectly inhibited human umbilical artery smooth muscle cell (HUASMC) proliferation, migration and IL-6 production. ALA-SDT effectively inhibits intimal hyperplasia without affecting re-endothelialization. Hence, its clinical application combined with bare-metal stent (BMS) implantation presents a potential strategy to decrease bleeding risk caused by prolonged dual-antiplatelet regimen after DES deployment.
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