A recurrent variant c.5126C>T in a Han-Chinese family with tuberous sclerosis complex.

Objective: To identify the disease-causing variant in a family with tuberous sclerosis complex (TSC).

Methods: This study including a Han-Chinese pedigree recruited from the Third Xiangya Hospital, Central South University, Changsha, Hunan, China was conducted between February, 2019 and January, 2023. Detailed clinical examinations were performed on the proband and other family members of a Han-Chinese family with TSC.

Dynamic map illuminates Hippo-cMyc module crosstalk driving cardiomyocyte proliferation.

Numerous regulators of cardiomyocyte (CM) proliferation have been identified, yet how they coordinate during cardiac development or regeneration is poorly understood. Here, we developed a computational model of the CM proliferation regulatory network to obtain key regulators and systems-level understanding. The model defines five modules (DNA replication, mitosis, cytokinesis, growth factor, Hippo pathway) and integrates them into a network of 72 nodes and 88 reactions that correctly predicts 73 of 78 (93.

The role of myocardial energy metabolism perturbations in diabetic cardiomyopathy: from the perspective of novel protein post-translational modifications.

Diabetic cardiomyopathy (DbCM), a significant chronic complication of diabetes, manifests as myocardial hypertrophy, fibrosis, and other pathological alterations that substantially impact cardiac function and elevate the risk of cardiovascular diseases and patient mortality. Myocardial energy metabolism disturbances in DbCM, encompassing glucose, fatty acid, ketone body and lactate metabolism, are crucial factors that contribute to the progression of DbCM. In recent years, novel protein post-translational modifications (PTMs) such as lactylation, β-hydroxybutyrylation, and succinylation have been demonstrated to be intimately associated with the myocardial energy metabolism process, and in conjunction with acetylation, they participate in the regulation of protein activity and gene expression activity in cardiomyocytes.

Interactions between DASH-style diet and ADIPOQ and ARL15 genes polymorphisms on blood pressure and central obesity in Iranian adults.

This study aimed to investigate the interactions between the Dietary approaches to stop hypertension (DASH) and the rs1501299 and rs6450176 SNPs in terms of cardiometabolic risk factors. This cross-sectional study was conducted on 387 adults (20-70 years old) residing in Yazd, Iran. The participants were selected from participants in the recruitment phase of the Yazd Health Study (YaHS) which is a population-based cohort of 9,962 adults.

A novel uORF regulates folliculin to promote cell growth and lysosomal biogenesis during cardiac stress.

Pathological cardiac remodeling is a maladaptive response that leads to changes in the size, structure, and function of the heart. These changes occur due to an acute or chronic stress on the heart and involve a complex interplay of hemodynamic, neurohormonal and molecular factors. As a critical regulator of cell growth, protein synthesis and autophagy mechanistic target of rapamycin complex 1 (mTORC1) is an important mediator of pathological cardiac remodeling.

A European Delphi Consensus on the Management of Abdominal Aortic Aneurysms in Patients with Heritable Aortic Diseases.

Objective: Abdominal aortic aneurysm (AAA) in a patient with an underlying heritable aortic disease (HAD) is rare, and evidence based recommendations for its management are lacking. This study aimed to generate a consensus from multidisciplinary specialists on the diagnosis, treatment, and surveillance of AAA associated with HAD and to define topics of interest for future research.

Methods: A Delphi consensus was designed involving European multidisciplinary specialists and reported using the ACcurate COnsensus Reporting Document (ACCORD) reporting guideline.

The 40S ribosomal subunit recycling complex modulates mitochondrial dynamics and endoplasmic reticulum - mitochondria tethering at mitochondrial fission/fusion hotspots.

The 40S ribosomal subunit recycling pathway is an integral link in the cellular quality control network, occurring after translational errors have been corrected by the ribosome-associated quality control (RQC) machinery. Despite our understanding of its role, the impact of translation quality control on cellular metabolism remains poorly understood. Here, we reveal a conserved role of the 40S ribosomal subunit recycling (USP10-G3BP1) complex in regulating mitochondrial dynamics and function.

Enhancing dementia prediction: A 19-year validation of the CAIDE risk score with insulin resistance and APOE ε4 integration in a population-based cohort.

Background: Dementia is a significant cause of disability and dependency. Persons with high dementia risk but intact cognition will benefit from preventive interventions.

Objectives: The aim was to validate dementia risk score Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) in a national population-based cohort with data on age, education, hypertension, obesity, hyperlipidemia and physical activity.

Clonal Haematopoiesis of Indeterminate potential and Cardiovascular diseases : A review.

Cardiovascular disease (CVD) is a major driver of mortality and declining health worldwide. Cardiovascular diseases (CVD) is the most common cause of morbidity and mortality globally. Although dyslipidemia, smoking, diabetes, hypertension and obesity are some well-known causes of CVD, the overlapping genetic pathways between other diseases and those affecting cardiovascular health have been overlooked.

TARGETING LUNG HEME IRON BY AEROSOL HEMOPEXIN ADMINSTRATION IN SICKLE CELL DISEASE PULMONARY HYPERTENSION.

Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH.

Pilot work of the 10K Chinese People Genomic Diversity Project along the Silk Road suggests a complex east-west admixture landscape and biological adaptations.

Genomic sources from China are underrepresented in the population-specific reference database. We performed whole-genome sequencing or genome-wide genotyping on 1,207 individuals from four linguistically diverse groups (1,081 Sinitic, 56 Mongolic, 40 Turkic, and 30 Tibeto-Burman people) living in North China included in the 10K Chinese People Genomic Diversity Project (10K_CPGDP) to characterize the genetic architecture and adaptative history of ethnic groups in the Silk Road Region of China. We observed a population split between Northwest Chinese minorities (NWCMs) and Han Chinese since the Upper Paleolithic and later Neolithic genetic differentiation within NWCMs.

The Formation and Features of Massive Vacuole Induced by Nutrient Deficiency in Human Embryonic Kidney Cells.

Background: Cellular vacuolization is a commonly observed phenomenon under physiological and pathological conditions. However, the mechanisms underlying vacuole formation remain largely unresolved.

Methods: LysoTracker Deep Red probes and Enhanced Green Fluorescent Protein-tagged light chain 3B (LC3B) plasmids were employed to differentiate the types of massive vacuoles.

The Impact of Modifiable Risk Factors on the Endothelial Cell Methylome and Cardiovascular Disease Development.

Cardiovascular disease (CVD) is the most prevalent cause of mortality and morbidity in the Western world. A common underlying hallmark of CVD is the plaque-associated arterial thickening, termed atherosclerosis. Although the molecular mechanisms underlying the aetiology of atherosclerosis remain unknown, it is clear that both its development and progression are associated with significant changes in the pattern of DNA methylation within the vascular cell wall.

Circulating neuropeptide Y dynamics and performance during exercise in heart failure patients with contemporary medical and device therapy.

High cardiac sympathetic drive and release of the sympathetic cotransmitter neuropeptide Y (NPY) are significant features of congestive heart failure (CHF), in which resting venous NPY levels are known to be associated with mortality. However, whether circulating NPY levels increase during exercise in CHF when they are already elevated is controversial. We sought to establish the dynamics of circulating NPY levels in CHF patients treated with contemporary medical therapy and devices in relationship to indices of performance linked to long-term prognosis.

Protective Role of Dietary Polyphenols in the Management and Treatment of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM), a serious metabolic disorder, is a worldwide health problem due to the alarming rise in prevalence and elevated morbidity and mortality. Chronic hyperglycemia, insulin resistance, and ineffective insulin effect and secretion are hallmarks of T2DM, leading to many serious secondary complications. These include, in particular, cardiovascular disorders, diabetic neuropathy, nephropathy and retinopathy, diabetic foot, osteoporosis, liver damage, susceptibility to infections and some cancers.

Role of miRNAs in Regulating Ascending Aortic Dilation in Bicuspid Aortic Valve Patients Operated for Aortic Stenosis.

Deregulation of micro-RNAs (miRNAs) may contribute to mechanisms of injury in the bicuspid aortic valve (BAV). Our objective was to investigate the expression of miRNAs in aortic tissue from patients who underwent aortic valve replacement for aortic stenosis and its relationship with aortic dilatation. The study included 78 patients, 40 with bicuspid aortic valve (BAV) and 38 with tricuspid aortic valve (TAV).

MicroRNA Expression Profile in Acute Ischemic Stroke.

Acute ischemic stroke with large vessel occlusion (LVO) continues to present a considerable challenge to global health, marked by substantial morbidity and mortality rates. Although definitive diagnostic markers exist in the form of neuroimaging, their expense, limited availability, and potential for diagnostic delay can often result in missed opportunities for life-saving interventions. Despite several past attempts, research efforts to date have been fraught with challenges likely due to multiple factors, such as the inclusion of diverse stroke types, variable onset intervals, differing pathobiologies, and a range of infarct sizes, all contributing to inconsistent circulating biomarker levels.

Homocysteine Metabolites, Endothelial Dysfunction, and Cardiovascular Disease.

Atherosclerosis is accompanied by inflammation that underlies cardiovascular disease (CVD) and its vascular manifestations, including acute stroke, myocardial infarction, and peripheral artery disease, the leading causes of morbidity/mortality worldwide. The monolayer of endothelial cells formed on the luminal surface of arteries and veins regulates vascular tone and permeability, which supports vascular homeostasis. Endothelial dysfunction, the first step in the development of atherosclerosis, is caused by mechanical and biochemical factors that disrupt vascular homeostasis and induce inflammation.

Fecal Microbiota Strongly Correlates with Tissue Microbiota Composition in Colorectal Cancer but Not in Non-Small Cell Lung Cancer.

Microbiota could be of interest in the diagnosis of colorectal and non-small cell lung cancer (CRC and NSCLC). However, how the microbial components of tissues and feces reflect each other remains unknown. In this work, our main objective is to discover the degree of correlation between the composition of the tissue microbiota and that of the feces of patients affected by CRC and NSCLC.

Acute Severe Hypoxia Decreases Mitochondrial Chain Complex II Respiration in Human Peripheral Blood Mononuclear Cells.

Peripheral blood mononuclear cells' (PBMCs) mitochondrial respiration is impaired and likely involved in myocardial injury and heart failure pathophysiology, but its response to acute and severe hypoxia, often associated with such diseases, is largely unknown in humans. We therefore determined the effects of acute hypoxia on PBMC mitochondrial respiration and ROS production in healthy volunteers exposed to controlled oxygen reduction, achieving an inspired oxygen fraction of 10.5%.

Missing Regulation Between Genetic Association and Transcriptional Abundance for Hypercholesterolemia Genes.

Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for cardiovascular disease, and it plays a causal role in the development of atherosclerosis. Genome-wide association studies (GWASs) have successfully identified hundreds of genetic variants associated with LDL-C. Most of these risk loci fall in non-coding regions of the genome, and it is unclear how these non-coding variants affect circulating lipid levels.

Incidence and Impact of Myocarditis in Genetic Cardiomyopathies: Inflammation as a Potential Therapeutic Target.

Background: Myocardial disease is an important component of the wide field of cardiovascular disease. However, the phenomenon of multiple myocardial diseases in a single patient remains understudied.

Aim: To investigate the prevalence and impact of myocarditis in patients with genetic cardiomyopathies and to evaluate the outcomes of myocarditis treatment in the context of cardiomyopathies.

Proteomic Profiling Towards a Better Understanding of Genetic Based Muscular Diseases: The Current Picture and a Look to the Future.

Proteomics accelerates diagnosis and research of muscular diseases by enabling the robust analysis of proteins relevant for the manifestation of neuromuscular diseases in the following aspects: (i) evaluation of the effect of genetic variants on the corresponding protein, (ii) prediction of the underlying genetic defect based on the proteomic signature of muscle biopsies, (iii) analysis of pathophysiologies underlying different entities of muscular diseases, key for the definition of new intervention concepts, and (iv) patient stratification according to biochemical fingerprints as well as (v) monitoring the success of therapeutic interventions. This review presents-also through exemplary case studies-the various advantages of mass proteomics in the investigation of genetic muscle diseases, discusses technical limitations, and provides an outlook on possible future application concepts. Hence, proteomics is an excellent large-scale analytical tool for the diagnostic workup of (hereditary) muscle diseases and warrants systematic profiling of underlying pathophysiological processes.

Visceral Adipose Tissue Inflammation and Vascular Complications in a Rat Model with Severe Dyslipidemia: Sex Differences and PAI-1 Tissue Involvement.

We investigated the sex-dependent effects of inflammatory responses in visceral adipose tissue (VAT) and perivascular adipose tissue (PVAT), as well as hematological status, in relation to cardiovascular disorders associated with prediabetes. Using male and female hereditary hypertriglyceridemic (HHTg) rats-a nonobese prediabetic model featuring dyslipidemia, hepatic steatosis, and insulin resistance-we found that HHTg females exhibited more pronounced hypertriglyceridemia than males, while HHTg males had higher non-fasting glucose levels. Additionally, HHTg females had higher platelet counts, larger platelet volumes, and lower antithrombin inhibitory activity.

Application Strategies of Super-Enhancer RNA in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are a leading cause of death worldwide, and new therapeutic strategies are urgently needed. In recent years, enhancer RNAs (eRNAs) have gradually attracted attention because they offer new directions for the treatment of CVDs. Super-enhancer RNAs (seRNAs) are a subset of non-coding RNAs that are transcribed from regions of the genome known as super enhancers, which are large clusters of enhancers with a high density of transcription factors and cofactors.