Inhibition of Atrial Natriuretic Peptide Clearance Reduces Myocardial Fibrosis and Improves Cardiac Function in Diabetic Rats DOI Open Access

Jules Joel Bakhos,

Youakim Saliba,

Joelle Hajal

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 3, 2024

Abstract Background Natriuretic peptides (NP) exert pleotropic effects through the recruitment of cGMP-signaling pathways depending on their bioavailability which is regulated by clearance receptors and peptidases. Here, we tested hypothesis that increasing myocardial NP has a beneficial effect heart failure. We studied mutated NP, MANP, resistant to neprilysin in model diabetic cardiomyopathy characterized marked fibrosis. Methods as well sacubritril were delivered via osmotic mini-pumps high-fat/streptozotocin-induced type-2 (T2D) rats. Cardiac function was evaluated echocardiography. Myocardial remodeling histological approaches, collagen phenotype measurement cGMP tissue concentration. Live-cell biosensing conducted cultured rat cardiac fibroblasts investigate biological NPs. signaling pathway using various antibody arrays biochemicals assays fibroblasts. Results MANP exhibits superior efficacy than ANP reducing left ventricular dysfunction reduce fibrosis with less extracellular matrix deposition. In vitro , similarly generated activated PKG fibroblasts, attenuating SMAD activation, secretion cell proliferation. Nevertheless, vivo enhanced accumulation more potent activating cGMP/PKG inhibiting profibrotic pathway. Endopeptidase inhibition sacubitril also led reduced Conclusions major determinant peptide improving pump during cardiomyopathy. Clinical Perspective What Is New? Mutated atrial natriuretic (MANP) degradation outperforms wild-type diabetes While antifibrotic two isoforms involves cGMP-dependent fibroblast concentration importantly ANP. Sacubitril inhibits reduces activation function. Are Implications? crucial for mitigating failure general. holds potential new treatment modality management

Язык: Английский

Application and Progression of Single‐Cell RNA Sequencing in Diabetes Mellitus and Diabetes Complications DOI Creative Commons

Jiajing Hong,

Shiqi Lu,

Guohui Shan

и другие.

Journal of Diabetes Research, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Diabetes is a systemic metabolic disorder primarily caused by insulin deficiency and resistance, leading to chronic hyperglycemia. Prolonged diabetes can result in damage multiple organs, including the heart, brain, liver, muscles, adipose tissue, thereby causing various fatal complications such as diabetic retinopathy, cardiomyopathy, nephropathy. Single‐cell RNA sequencing (scRNA‐seq) has emerged valuable tool for investigating cell diversity pathogenesis of identifying potential therapeutic targets or complications. This review provides comprehensive overview recent applications scRNA‐seq diabetes‐related researches highlights novel biomarkers immunotherapy with cell‐type information its associated

Язык: Английский

Процитировано

0

Advances of research in diabetic cardiomyopathy: diagnosis and the emerging application of sequencing DOI Creative Commons
Qianqian He,

Zhizhen Lai,

Zidan Zhai

и другие.

Frontiers in Cardiovascular Medicine, Год журнала: 2025, Номер 11

Опубликована: Янв. 13, 2025

Diabetic cardiomyopathy (DCM) is one of the most prevalent and severe complications associated with diabetes mellitus (DM). The onset DCM insidious, symptoms being obvious only in late stage. Consequently, early diagnosis a formidable challenge which significantly influences treatment prognosis DCM. Thus, it becomes imperative to uncover innovative approaches facilitate prompt identification On traditional clinical side, we tend use serum biomarkers as well imaging common means diagnosing diseases because their convenience affordability. As delve deeper into mechanisms DCM, wide variety are becoming competitive diagnostic indicators. Meanwhile, application multiple techniques has also made efforts promote Besides, spurt sequencing technology possible give hints about disease from genome transcriptome, making less difficult, more sensitive, predictive. Overall, expected be superior choice plasma for detecting lesions at an earlier stage than imaging, its judicious utilization combined technologies will lead sensitive future. Therefore, this review meticulously consolidates progress various biomarkers, methods, realm diagnosis, aim furnishing novel theoretical foundation guide future research endeavors towards enhancing therapeutic landscape

Язык: Английский

Процитировано

0

Genome-wide chromatin accessibility and selective signals of meat rabbits reveal key Cis-regulatory elements and variants during postnatal development of skeletal muscles in rabbits DOI Creative Commons
Kun Du, Dai‐Hua Wang, Shenqiang Hu

и другие.

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Март 25, 2025

The development of skeletal muscles is intricately modulated by multiple genetic factors and significantly impacts the economic value meat rabbits. However, our knowledge epigenetics in rabbit remains largely unknown. In this study, we collected leg rabbits performed assays for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) to detect open across three developmental stages: birth (D1), weaning (D35), adulthood (D75). A total 126,959 accessible regions (ACRs) were identified samples, a broad increase decrease accessibility found from D1 D35 D75, respectively. Integrative analysis transcriptome data revealed ACRs that nearly closed at but highly D75 enriched muscle development. Cis-regulation further genes dominated enhancers mainly play roles neuron muscles. Moreover, detection selection signals footprinting transcription factor both base transversion (Chr13:12144967 A-> G) dynamics PRDM1 binding site might regulate ZSWIM5 during Our study provided category potential cis-regulatory elements understanding tissue level facilitate insights into growth regulation

Язык: Английский

Процитировано

0

Cardiac PDK4 promotes neutrophilic PFKL methylation and drives the innate immune response in diabetic myocardial infarction DOI Creative Commons

Yang Song,

Libo Yan,

Lang Chen

и другие.

Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107731 - 107731

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0

Knockout of B2M in combination with PD-L1 overexpression protects MSC-derived new islet β cells from graft rejection in the treatment of canine diabetes mellitus DOI Creative Commons
Pengxiu Dai, Yi Wu, Qingjie Du

и другие.

Stem Cell Research & Therapy, Год журнала: 2024, Номер 15(1)

Опубликована: Дек. 2, 2024

The immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these can be recognized cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect MSCs or, their in treatment diabetes other diseases. Solving this problem helpful for prolonging time that play role body clinical effect. In study, canine adipose-derived (ADSCs) were used as seed cells, gene editing technology was knock out B2M cooperate with overexpression PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics safety are not different from those normal ADSCs, have been obtained. GeADSCs reduced, escape ability enhanced, remain longer time. Using optimized induction program, efficiency differentiation into new islet β-cells increased, maturity increased. decreased, transplanted diabetic dogs (the graft site prevascularized implantation scaffold form vascularized pouch). number infiltrating content factors decreased at site. New β-cell transplantation, which low immunogenicity, reverse dogs, cell enhanced. This study provides method survival functional transplant recipients

Язык: Английский

Процитировано

0

Inhibition of Atrial Natriuretic Peptide Clearance Reduces Myocardial Fibrosis and Improves Cardiac Function in Diabetic Rats DOI Open Access

Jules Joel Bakhos,

Youakim Saliba,

Joelle Hajal

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 3, 2024

Abstract Background Natriuretic peptides (NP) exert pleotropic effects through the recruitment of cGMP-signaling pathways depending on their bioavailability which is regulated by clearance receptors and peptidases. Here, we tested hypothesis that increasing myocardial NP has a beneficial effect heart failure. We studied mutated NP, MANP, resistant to neprilysin in model diabetic cardiomyopathy characterized marked fibrosis. Methods as well sacubritril were delivered via osmotic mini-pumps high-fat/streptozotocin-induced type-2 (T2D) rats. Cardiac function was evaluated echocardiography. Myocardial remodeling histological approaches, collagen phenotype measurement cGMP tissue concentration. Live-cell biosensing conducted cultured rat cardiac fibroblasts investigate biological NPs. signaling pathway using various antibody arrays biochemicals assays fibroblasts. Results MANP exhibits superior efficacy than ANP reducing left ventricular dysfunction reduce fibrosis with less extracellular matrix deposition. In vitro , similarly generated activated PKG fibroblasts, attenuating SMAD activation, secretion cell proliferation. Nevertheless, vivo enhanced accumulation more potent activating cGMP/PKG inhibiting profibrotic pathway. Endopeptidase inhibition sacubitril also led reduced Conclusions major determinant peptide improving pump during cardiomyopathy. Clinical Perspective What Is New? Mutated atrial natriuretic (MANP) degradation outperforms wild-type diabetes While antifibrotic two isoforms involves cGMP-dependent fibroblast concentration importantly ANP. Sacubitril inhibits reduces activation function. Are Implications? crucial for mitigating failure general. holds potential new treatment modality management

Язык: Английский

Процитировано

0