Disparate Molecular Properties of Two Hypertrophic Cardiomyopathy-Associated cMyBP-C Mutants Reveal Distinct Pathogenic Mechanisms Beyond Haploinsufficiency

Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1010 - 1010

Published: April 22, 2025

Background/Objectives: Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder marked by abnormal thickening of the left ventricular myocardium, often leading to arrhythmias and heart failure. Mutations in sarcomeric protein genes, particularly MYBPC3, which encodes myosin-binding C (cMyBP-C), are major contributors HCM pathogenesis. This study aims investigate structural functional effects two HCM-associated missense mutations, p.S236G p.E334K, located within C0–C2 domains cMyBP-C. Methods: Following silico analysis, bacterial expression system was applied, enabling discrete wild-type (cMyBP-CWT) mutant (cMyBP-CS236G cMyBP-CE334K) cMyBP-C proteins be expressed purified as recombinant proteins. Structural stability changes were assessed using circular dichroism (CD), differential scanning calorimetry (DSC), chemical denaturation assays. Functional impact on actin binding also evaluated vitro. Results: CD analysis revealed altered secondary structure both mutants compared protein. Thermal assays indicated increased cMyBP-CE334K mutant, suggesting that it exhibits more rigid conformation. rigidity corresponded with significant reduction actin-binding affinity relative Conclusions: Our findings demonstrate specific detrimental p.E334K mutation underscore importance understanding consequences mutations assist development targeted therapeutic strategies.

Language: Английский

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Advancing athletic assessment by integrating conventional methods with cutting-edge biomedical technologies for comprehensive performance, wellness, and longevity insights

Frontiers in Sports and Active Living, Journal Year: 2024, Volume and Issue: 5

Published: Jan. 8, 2024

In modern athlete assessment, the integration of conventional biochemical and ergophysiologic monitoring with innovative methods like telomere analysis, genotyping/phenotypic profiling, metabolomics has potential to offer a comprehensive understanding athletes' performance longevity. Telomeres provide insights into cellular functioning, aging, adaptation elucidate effects training on health. Genotype/phenotype analysis explores genetic variations associated athletic performance, injury predisposition, recovery needs, enabling personalization plans interventions. Metabolomics especially focusing low-molecular weight metabolites, reveal metabolic pathways responses exercise. Biochemical tests assess key biomarkers related energy metabolism, inflammation, recovery. Essential elements depict micronutrient status individual, which is critical for optimal performance. Echocardiography provides detailed cardiac structure function, while burnout testing evaluates psychological stress, fatigue, readiness By integrating this scientific battery, multidimensional health can be achieved, leading personalized interventions in training, nutrition, supplementation, prevention, mental wellness support. This scientifically rigorous approach hereby presented holds significant improving longevity through evidence-based, individualized interventions, contributing advances field sports optimization.

Language: Английский

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Genetic Markers of Cardiovascular Disease

Current Problems in Cardiology, Journal Year: 2024, Volume and Issue: 49(7), P. 102588 - 102588

Published: April 22, 2024

Language: Английский

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Synthesis and Biological Activity Evaluation of Novel Chalcone Analogues Containing a Methylxanthine Moiety and Their N-Acyl Pyrazoline Derivatives

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(49), P. 19343 - 19356

Published: Dec. 4, 2023

On the basis of structures natural methylxanthines and chalcone, a series novel chalcone analogues containing methylxanthine moiety, Ia–Ig, their N-acyl pyrazoline derivatives IIa–IIz IIaa–IIaf were synthesized identified through melting points, 1H NMR, 13C HRMS. The single crystal compound IId was obtained, which further illustrated structural characteristics methylxanthine-acylpyrazoline compounds. biological tests showed that some them displayed favorable insecticidal activities toward Plutella xylostella L. superior to caffeine while being comparable with insecticide triflumuron (e.g., Ic: LC50 = 16.8508 mg/L, IIf: 1.5721 against P. xylostella). Of these compounds, Ic, IIf, IIu could serve as leading for study. Some compounds good fungicidal Ig: EC50 14.74 μg/mL, Rhizoctonia cerealis; 7.06 Physalospora piricola; IIac: 5.37 8.19 Phytophthora capsici Sclerotinia sclerotiorum, respectively); Ig, IIa, IIr, IIs, IIv, IIac, IIaf be exploration. Furthermore, most tested exhibited apparent herbicidal Brassica campestris at concentration 100 μg/mL; among others, IIa best one both Echinochloa crusgalli deserves investigation. structure–activity relationships also summarized discussed in detail. contrast experiment results C-1 C-2 positive effect on activity enhancement from combination moiety N-dichloroacetyl phenylpyrazoline skeleton. In addition, two 3D-QSAR models predictive capability constructed based afford deep insight into bioactivity profiles This research provides useful guidance reference discovery development xanthine product-based pesticides.

Language: Английский

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The Current State of Knowledge Regarding the Genetic Predisposition to Sports and Its Health Implications in the Context of the Redox Balance, Especially Antioxidant Capacity

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 6915 - 6915

Published: June 24, 2024

The significance of physical activity in sports is self-evident. However, its importance becoming increasingly apparent the context public health. constant desire to improve health and performance suggests looking at genetic predispositions. knowledge genes related can be utilized initially training athletes assign them appropriate sport. In field medicine, this may more effectively prevention treatment cardiometabolic diseases. Physical exertion engages entire organism, a basic physiological level, organism's responses are primarily oxidant antioxidant reactions due intensified cellular respiration. Therefore, modifications involve body adjusting stresses, especially oxidative stress. consequence regular exercise an increase capacity. Among considered, those that promote processes dominate, as they associated with energy production during exercise. What missing, however, look other side coin, which, case, them. It has been demonstrated increased do not always result Nevertheless, it seems maintaining oxidant-antioxidant balance most important thing regard.

Language: Английский

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