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In this review we discuss the evidence implicating the MPC as an important, perhaps causal, mediator of heart failure progression.Ubiquitination is an essential post-translational modification that regulates most cellular processes. The assembly of ubiquitin into polymeric chains by E3 ubiquitin ligases underlies the pleiotropic functions ubiquitin chains regulate. Ubiquitin chains assembled via the N-terminal methionine, termed Met1-linked ubiquitin chains or linear ubiquitin chains, have emerged as essential signalling scaffolds that regulate pro-inflammatory responses, anti-viral interferon responses, cell death and xenophagy of bacterial pathogens downstream of innate immune receptors. Met1-linked ubiquitin chains are exclusively assembled by the linear ubiquitin chain assembly complex, LUBAC, and are disassembled by the deubiquitinases OTULIN and CYLD. Genetic defects that perturb the regulation of Met1-linked ubiquitin chains causes severe immune-related disorders, illustrating their potent signalling capacity. Here, we review the current knowledge about the cellular machinery that conjugates, recognises, and disassembles Met1-linked ubiquitin chains, and discuss the function of this unique posttranslational modification in regulating inflammation, cell death and immunity to pathogens.
Insulin resistance (IR) is a pathophysiological construct that derives a series of metabolic disturbances that promote cardiometabolic dysfunction. This study evaluated mediating and modifying effects of homeostatic model assessment-based IR (HOMA-IR) on the association between sugar-sweetened beverage (SSB) consumption and a constellation of adolescent cardiometabolic abnormalities.
Comprehensive data on sociodemographics, diet, physical activity, and anthropometric and biochemical parameters for 1454 adolescents were obtained from a large-scale representative study for adolescent metabolic syndrome (MetS) conducted in Taiwan. The original (HOMA1-IR) and updated nonlinear (HOMA2-IR) HOMA-IR indicators were used as IR biomarkers. Principal component (PC) analysis was employed to create reduced groups of variables and risk scores for retained PCs.
Higher SSB intake was associated with higher levels of HOMA1-IR and HOMA2-IR, and the two IR biomarkers were positively correlated with metabolic dysfunction cescents, and this association may be partly mediated by HOMA-IR levels. The adverse effects of HOMA-IR on bodyweight-associated cardiometabolic risk factors depend on the type of SSB consumption, with enhanced risks observed in the intake of high amounts of HFCS-containing SSBs.
We investigated the efficacy and safety of liraglutide 3 mg daily in combination with diet and exercise 2, 4, and 6 months after initiation in real-world settings in Korea.
People first using liraglutide starting in 2018 were recruited from ten sites in Korea. Body weight and body mass index (BMI) were measured after 2, 4, and 6 months and compared with baseline values.
The full cohort comprised 769 participants 672 in the 2-month group, 427 in the 4-month group, and 219 in the 6-month group. The baseline mean ± standard deviation of BMI and body weight were 32.2 ± 5.1 kg/m
, and 87.5 ± 18.8 kg, respectively. Body weight and BMI decreased after initiation of liraglutide treatment -2.94 kg and -1.08 kg/m
at 2 months; -4.23 kg and -1.55 kg/m
at 4 months, and -5.14 kg and -1.89 kg/m
at 6 months (all P < 0.001). In the 6-month cohort, 52.5% and 18.3% of subjects lost ≥5% and ≥10% of body weight, respectively. After 6 months, systolic and diastolic blood pressure decreased significantly by 3.90 and 1.93 mmHg, respectively. In those with diabetes mellitus, HbA1c and fasting glucose levels decreased significantly by 1.14% and 27.8 mg/dl, respectively. Among all participants, 27.6% experienced adverse effects, including nausea (20.8%), vomiting (5.2%), diarrhoea (2.5%), and skin rash (3.6%). Documented reasons for discontinuation of treatment were lack of effect (4.4%), adverse events (4.3%), and high cost (3.1%).
In real-world settings in Korea, daily treatment with liraglutide 3 mg was associated with clinically meaningful weight loss without serious adverse events.
In real-world settings in Korea, daily treatment with liraglutide 3 mg was associated with clinically meaningful weight loss without serious adverse events.
To investigate (1) the association of four VDR polymorphisms (TaqI/rs731236, ApaI/rs7975232, FokI/rs10735810, and Bsml/rs1544410) with markers of adiposity and tissue-specific insulin resistance at baseline, after weight loss and weight maintenance; (2) the effect of the VDR polymorphisms in the SAT transcriptome in overweight/obese Caucasians of the DiOGenes cohort.
We included 553 adult obese individuals (mean BMI 34.8 kg/m
), men (n = 197) and women (n = 356) at baseline, following an 8-week weight loss intervention and 26 weeks weight maintenance. Genotyping was performed using an Illumina 660W-Quad SNP chip on the Illumina iScan Genotyping System. Tissue-specific IR was determined using Hepatic Insulin Resistance Index (HIRI), Muscle Insulin Sensitivity Index (MISI), and Adipose Tissue Insulin Resistance Index (Adipo-IR). Expression quantitative trait loci (eQTL) analysis was performed to determine the effect of SNPs on SAT gene expression.
None of the VDR polymorphisms were associated with HIRI oicating that putative mechanisms of action remain to be determined. Finally, VDR SNPs did not affect dietary intervention outcome in the present cohort.
Although excess visceral fat (VAT) is associated with numerous cardio-metabolic risk factors, measurement of this fat depot has historically been difficult. Recent dual X-ray absorptiometry approaches have provided an accessible estimate of VAT that has shown acceptable validity against gold standard methods. The aims of this study were to (i) evaluate DXA measured VAT as a predictor of elevated blood lipids and blood pressure and (ii) calculate thresholds associated with these cardio-metabolic risk factors.
The sample comprised 1482 adults (56.4% women) aged 18-66 years. Total body scans were performed using a GE Lunar Prodigy, and VAT analyses were enabled through Corescan software (v 16.0). Blood pressure and blood lipids were measured by standard procedures. JAK inhibitor Regression models assessed how VAT mass was associated with each cardio-metabolic risk factor compared to other body composition measures. Measures of sensitivity and specificity were used to determine age- and sex-specific cut points for VAT mass associated with high cardio-metabolic risk.
Homepage: https://www.selleckchem.com/JAK.html
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