Int J Biol Macromol
January 2025
Human calcitonin (hCT) is a peptide hormone that regulates calcium homeostasis, but its abnormal aggregation can disrupt physiological functions and increase the risk of medullary thyroid carcinoma. To elucidate the mechanisms underlying hCT aggregation, we investigated the self-assembly dynamics of hCT segments (hCT, hCT, and hCT) and the folding and dimerization of full-length hCT through microsecond atomistic discrete molecular dynamics (DMD) simulations. Our results revealed that hCT and hCT predominantly existed as isolated monomers with transient small-sized oligomers, indicating weak aggregation tendencies.
View Article and Find Full Text PDFAortic aneurysm is a life-threatening disease caused by progressive dilation of the aorta and weakened aortic walls. Its pathogenesis involves an imbalance between connective tissue repair and degradation. CD34 cells comprise a heterogeneous population that exhibits stem cell and progenitor cell properties.
View Article and Find Full Text PDFEmerging evidence suggests that physiological C-terminal truncation of α-synuclein (αS) plays a critical role in regulating liquid-liquid phase separation and promoting amyloid aggregation, processes implicated in neurodegenerative diseases such as Parkinson's disease (PD). However, the molecular mechanisms through which C-terminal truncation influences αS conformation and modulates its aggregation remain poorly understood. In this study, we investigated the impact of C-terminal truncation on αS conformational dynamics by comparing full-length αS with truncated αS monomers using atomistic discrete molecular dynamics simulations.
View Article and Find Full Text PDFThe endothelial-mesenchymal transition (EndMT) is involved in the development of atherosclerosis (AS) and is a key process in vascular endothelial injury. Oxidative stress, inflammation, and apoptosis are common causes of EndMT, and EndMT progression can further accelerate the development of AS. The metabolite trimethylamine N-oxide (TMAO) is produced by the gut microbiome and is implicated in the development of several diseases, including diabetes and chronic kidney disease.
View Article and Find Full Text PDFColloids Surf B Biointerfaces
December 2024
Background: Major depressive disorder (MDD) plays a crucial role in the occurrence of heart failure (HF). This investigation was undertaken to explore the possible mechanism of MDD's involvement in HF pathogenesis and identify candidate biomarkers for the diagnosis of MDD with HF.
Methods: GWAS data for MDD and HF were collected, and Mendelian randomization (MR) analysis was performed to investigate the causal relationship between MDD and HF.
Background: Recent studies provide compelling evidence linking the gut microbiota to most cancers. Nevertheless, further research is required to establish a definitive causal relationship between the gut microbiota and malignant cardiac tumors.
Methods: The genome-wide association studies (GWAS) data on the human gut Microbiota, included in the IEU Open GWAS project, was initially collected by the MiBioGen consortium.
Background: The role of diet choline in atherosclerotic cardiovascular disease (ASCVD) is uncertain. Findings from animal experiments are contradictory while there is a lack of clinical investigations. This study aimed to investigate the association between choline intake and ASCVD based on individuals from the National Health and Nutrition Examination Survey (NHANES) database.
View Article and Find Full Text PDFHuman calcitonin (hCT) regulates calcium-phosphorus metabolism, but its amyloid aggregation disrupts physiological activity, increases thyroid carcinoma risk, and hampers its clinical use for bone-related diseases like osteoporosis and Paget's disease. Improving hCT with targeted modifications to mitigate amyloid formation while maintaining its function holds promise as a strategy. Understanding how each residue in hCT's amyloidogenic core affects its structure and aggregation dynamics is crucial for designing effective analogues.
View Article and Find Full Text PDFThe genetic information of plasma total-exosomes originating from tissues have already proven useful to assess the severity of coronary artery diseases (CAD). However, plasma total-exosomes include multiple sub-populations secreted by various tissues. Only analysing the genetic information of plasma total-exosomes is perturbed by exosomes derived from other organs except the heart.
View Article and Find Full Text PDFThe challenge posed by opioid overdose has become a significant concern for health systems due to the complexities associated with drug prohibition, widespread clinical use, and potential abuse. In response, healthcare professionals have primarily concentrated on mitigating the hallucinogenic and respiratory depressant consequences of opioid overdose to minimize associated risks. However, it is crucial to acknowledge that most opioids possess the capacity to prolong the QT interval, particularly in cases of overdose, thereby potentially resulting in severe ventricular arrhythmias and even sudden death if timely intervention is not implemented.
View Article and Find Full Text PDFChromatin regulators are indispensable upstream epigenetic regulators.The emergence and progression of atherosclerosis has been demonstrated to be influenced by smooth muscle-related chromatin regulators, such as ZEB2 and MAFF. However, specific chromatin regulators and their possible roles have not been clarified.
View Article and Find Full Text PDFGlioblastoma (GBM) is a primary brain malignancy with a dismal prognosis and remains incurable at present. In this study, macrophages (MΦ) were developed to carry nanoparticle albumin-bound paclitaxel (nab-PTX) to form nab-PTX/MΦ. The aim of this study is to use a GBM-on-a-chip to evaluate the anti-GBM effects of nab-PTX/MΦ.
View Article and Find Full Text PDFBackground And Aim: The relationship between appendicular lean mass (ALM) and most cardiovascular events has been established, but the direct association between ALM and atrial fibrillation (AF) remains uncertain.
Methods And Results: Herein, we identified 494 single-nucleotide polymorphisms (SNPs) strongly associated with ALM as instrumental variables (P < 5E-8) based on a genome-wide association study (GWAS) with 450,243 European participants. Then, we employed five Mendelian randomization (MR) analysis methods to investigate the causal relationship between ALM and AF.
The aggregation of medin forming aortic medial amyloid is linked to arterial wall degeneration and cerebrovascular dysfunction. Elevated levels of arteriolar medin are correlated with an increased presence of vascular amyloid-β (Aβ) aggregates, a hallmark of Alzheimer's disease (AD) and vascular dementia. The cross-interaction between medin and Aβ results in the formation of heterologous fibrils through co-aggregation and cross-seeding processes both in vitro and in vivo.
View Article and Find Full Text PDFAlzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative diseases with markedly different pathological features of β-amyloid (Aβ) plaques and α-synuclein (αS) Lewy bodies (LBs), respectively. However, clinical overlaps in symptoms and pathologies between AD and PD are commonly observed caused by the cross-interaction between Aβ and αS. To uncover the molecular mechanisms behind their overlapping symptoms and pathologies, we computationally investigated the impact of αS on an Aβ monomer and dimerization using atomistic discrete molecular dynamics simulations (DMD).
View Article and Find Full Text PDFPathological cardiac hypertrophy (CH) is featured by myocyte enlargement and cardiac malfunction. Multiple signaling pathways have been implicated in diverse pathological and physiological processes in CH. However, the function of LOC102549726/miR-760-3p network in CH remains unclear.
View Article and Find Full Text PDFMedin is a principal component of localized amyloid found in the vasculature of individuals over 50 years old. Its amyloid aggregation has been linked to endothelial dysfunction and vascular inflammation, contributing to the pathogenesis of various vascular diseases. Despite its significance, the structures of the medin monomer, oligomer, and fibril remain elusive, and the dynamic processes of medin aggregation are not fully understood.
View Article and Find Full Text PDFBackground: Long QT syndrome type 2 (LQT2) is caused by mutations in the /human ether-à-go-go-related gene (hERG). Some hERG genetic mutation-associated diseases are alleviated by hERG-specific drug chaperones (glycerol, dimethyl sulfoxide, trimethylamine N-oxide, thapsigargin), delayed rectifier K current (IKr) blockers methanesulfonanilide E4031, the antihistamine astemizole, or the prokinetic drug cisapride, and the anti-arrhythmic drug quinidine. Meanwhile, many and studies have reported the efficacy of 4-phenylbutyric acid (4-PBA) in diseases with inherited genetic mutations.
View Article and Find Full Text PDFBackground: Observational studies have suggested that immune-mediated inflammatory diseases (IMIDs) are associated with a higher risk of valvular heart disease (VHD). But the potential causal association is not clear. Therefore, we used Mendelian randomization (MR) analysis to assess the causal association of IMIDs with VHD risk.
View Article and Find Full Text PDFGlioblastoma (GBM) is the most malignant type of primary intracranial tumor with a median overall survival of only 14 months, a very poor prognosis and a recurrence rate of 90%. It is difficult to reflect the complex structure and function of the GBM microenvironment using traditional models. GBM-on-a-chip platforms can integrate biological or chemical functional units of a tumor into a chip, mimicking functions of GBM cells.
View Article and Find Full Text PDFBackground: Observational studies have suggested that irritability is associated with a higher risk of cardiovascular disease (CVD). However, the potential causal association is not clear. Therefore, we used Mendelian randomization (MR) analysis to assess the causal association of irritability with CVD risk.
View Article and Find Full Text PDFThe pathological aggregation of α-synuclein (αS) into amyloid fibrils is the hallmark of Parkinson's disease (PD). The self-assembly and membrane interactions of αS are mainly governed by the seven imperfect 11-residue repeats of the XKTKEGVXXXX motif around residues 1-95. However, the particular role of each repeat in αS fibrillization remains unclear.
View Article and Find Full Text PDFFront Cardiovasc Med
December 2022