Kidney International Reports, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 1, 2025
Language: Английский
Circulation, Journal Year: 2024, Volume and Issue: 149(8)
Published: Jan. 24, 2024
BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, obesity) factors (cholesterol, blood pressure, glucose control, metabolic syndrome) that contribute health. AHA Disease Stroke Statistical Update presents latest data on a range major clinical circulatory disease conditions (including brain health, complications pregnancy, kidney congenital rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary cardiomyopathy, failure, valvular venous thromboembolism, peripheral artery disease) associated outcomes quality care, procedures, economic costs). METHODS: AHA, through its Epidemiology Prevention Statistics Committee, continuously monitors evaluates sources stroke United States globally provide current information available annual review published literature year before writing. 2024 is product full year’s worth effort 2023 by dedicated volunteer clinicians scientists, committed government professionals, staff members. strives further understand help heal problems inflicted structural racism, public crisis can significantly damage mental perpetuate disparities access education, income, housing, several other vital healthy lives. This edition includes additional global data, as well monitoring benefits population, an enhanced focus equity across key domains. RESULTS: Each chapters focuses different topic statistics. CONCLUSIONS: represents critical resource for lay public, policymakers, media clinicians, care administrators, researchers, advocates, others seeking best these conditions.
Language: Английский
Citations
882
Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)
Published: March 17, 2023
Abstract Chronic kidney disease (CKD) is estimated to affect 10–14% of global population. Kidney fibrosis, characterized by excessive extracellular matrix deposition leading scarring, a hallmark manifestation in different progressive CKD; However, at present no antifibrotic therapies against CKD exist. fibrosis identified tubule atrophy, interstitial chronic inflammation and fibrogenesis, glomerulosclerosis, vascular rarefaction. Fibrotic niche, where organ initiates, complex interplay between injured parenchyma (like tubular cells) multiple non-parenchymal cell lineages (immune mesenchymal located spatially within scarring areas. Although the mechanisms are complicated due kinds cells involved, with help single-cell technology, many key questions have been explored, such as what kind renal tubules profibrotic, myofibroblasts originate, which immune how communicate each other. In addition, genetics epigenetics deeper that regulate fibrosis. And reversible nature epigenetic changes including DNA methylation, RNA interference, chromatin remodeling, gives an opportunity stop or reverse therapeutic strategies. More marketed (e.g., RAS blockage, SGLT2 inhibitors) developed delay progression recent years. Furthermore, better understanding also favored discover biomarkers fibrotic injury. review, we update advances mechanism summarize novel treatment for CKD.
Language: Английский
Citations
260
Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(4)
Published: Feb. 14, 2023
Kidney disease is a major driver of mortality among patients with diabetes and diabetic kidney (DKD) responsible for close to half all chronic cases. DKD usually develops in genetically susceptible individual as result poor metabolic (glycemic) control. Molecular genetic studies indicate the key role podocytes endothelial cells driving albuminuria early diabetes. Proximal tubule changes show strong association glomerular filtration rate. Hyperglycemia represents cellular stress by altering metabolism imposing an excess workload requiring energy oxygen proximal cells. Changes induce adaptive hypertrophy reorganization actin cytoskeleton. Later, mitochondrial defects contribute increased oxidative activation inflammatory pathways, causing progressive function decline fibrosis. Blockade renin-angiotensin system or sodium-glucose cotransporter associated protection slowing decline. Newly identified molecular pathways could provide basis development much-needed novel therapeutics.
Language: Английский
Citations
172
Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(5), P. 735 - 759
Published: May 4, 2023
Language: Английский
Citations
106
Nature Genetics, Journal Year: 2023, Volume and Issue: 55(6), P. 995 - 1008
Published: June 1, 2023
Abstract The kidneys operate at the interface of plasma and urine by clearing molecular waste products while retaining valuable solutes. Genetic studies paired metabolomes may identify underlying processes. We conducted genome-wide 1,916 metabolites detected 1,299 significant associations. Associations with 40% implicated would have been missed studying alone. urine-specific findings that provide information about metabolite reabsorption in kidney, such as aquaporin (AQP)-7-mediated glycerol transport, different metabolomic footprints kidney-expressed proteins are consistent their localization function, including transporters NaDC3 ( SLC13A3 ) ASBT SLC10A2 ). Shared genetic determinants 7,073 metabolite–disease combinations represent a resource to better understand metabolic diseases revealed connections dipeptidase 1 circulating digestive enzymes hypertension. Extending metabolome beyond yields unique insights into processes body compartments.
Language: Английский
Citations
47
Cell, Journal Year: 2024, Volume and Issue: 187(15), P. 3789 - 3820
Published: July 1, 2024
Language: Английский
Citations
33
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Nov. 26, 2024
Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.
Language: Английский
Citations
24
Kidney International, Journal Year: 2024, Volume and Issue: 106(1), P. 24 - 34
Published: April 16, 2024
Kidney epithelial cells have very high energy requirements, which are largely met by fatty acid oxidation. Complex changes in lipid metabolism observed patients with kidney disease. Defects oxidation and increased uptake, especially the context of hyperlipidemia proteinuria, contribute to this excess build-up exacerbate disease development. Recent studies also highlighted role de novo lipogenesis fibrosis. The defect causes starvation. Increased synthesis, lower can cause toxic build-up, reactive oxygen species generation, mitochondrial damage. A better understanding these metabolic processes may open new treatment avenues for diseases targeting metabolism.
Language: Английский
Citations
20
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Jan. 10, 2024
There is a need to define regions of gene activation or repression that control human kidney cells in states health, injury, and repair understand the molecular pathogenesis disease design therapeutic strategies. Comprehensive integration expression with epigenetic features regulatory elements remains significant challenge. We measure dual single nucleus RNA chromatin accessibility, DNA methylation, H3K27ac, H3K4me1, H3K4me3, H3K27me3 histone modifications decipher landscape regulation reference adaptive injury states. establish spatially-anchored epigenomic atlas kidney's active, silent, accessible across genome. Using this atlas, we note distinct different epithelial cell types. A proximal tubule transcription factor network ELF3, KLF6, KLF10 regulates transition between health while thick ascending limb regulated by NR2F1. Further, combined perturbation distinguishes two tubular subtypes, one which manifested trajectory after knockout. This will serve as foundation facilitate targeted cell-specific therapeutics reprogramming networks.
Language: Английский
Citations
17
Science, Journal Year: 2025, Volume and Issue: 387(6734)
Published: Feb. 6, 2025
Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci. Ancestry-specific analysis indicated an attenuation newly signals on common variants European ancestry populations the power population diversity for further discoveries. We defined genotype effects allele-specific gene expression regulatory circuitries more than 700 human kidneys 237,000 cells. found 1363 coding disrupting 782 genes, with 601 genes also targeted by convergence 161 genes. Integrating 32 types information, present “Kidney Disease Genetic Scorecard” prioritizing potentially causal cell types, druggable targets kidney disease.
Language: Английский
Citations
2