Liver diseases: epidemiology, causes, trends and predictions

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 4, 2025

Abstract As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles metabolism, detoxification, immune response. Various factors including viruses, alcohol, metabolites, toxins, other pathogenic agents can compromise function, leading to acute or chronic injury that may progress end-stage diseases. While sharing common features, diseases exhibit distinct pathophysiological, clinical, therapeutic profiles. Currently, contribute approximately 2 million deaths globally each year, imposing significant economic social burdens worldwide. However, there no cure for many kinds of diseases, partly due lack thorough understanding development these Therefore, this review provides comprehensive examination epidemiology characteristics covering spectrum from conditions manifestations. We also highlight multifaceted mechanisms underlying initiation progression spanning molecular cellular levels networks. Additionally, offers updates on innovative diagnostic techniques, current treatments, potential targets presently under clinical evaluation. Recent advances pathogenesis hold critical implications translational value novel strategies.

Language: Английский

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Treating myocardial infarction via a nano-ultrasonic contrast agent-mediated high-efficiency drug delivery system targeting macrophages

Science Advances, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 3, 2025

Following myocardial infarction (MI), the accumulation of CD86-positive macrophages in ischemic injury zone leads to secondary damage. Precise pharmacological intervention targeting this process remains challenging. This study engineered a nanotherapeutic delivery system with macrophage-specific and ultrasound-responsive release capabilities. A folic acid (FA)–modified gene/drug system, assembled from DOTAP, DSPE-PEG2000-FA, cholesterol, perfluorohexane (PFH)—termed FA-PNBs—was developed codeliver small interfering RNA STAT1 (siSTAT1) small-molecule nitro-oleic (OA-NO 2 ) into macrophages. Upon irradiation low-intensity focused ultrasound, FA-PNBs siSTAT1 OA-NO at zone. The results demonstrated system’s precise efficient combined modulation optimizes immune microenvironment infarcted region, alleviates ventricular remodeling, preserves cardiac function, holds promise for clinical strategies after MI.

Language: Английский

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Cardiomyocyte LGR6 alleviates ferroptosis in diabetic cardiomyopathy via regulating mitochondrial biogenesis

Metabolism, Journal Year: 2024, Volume and Issue: 159, P. 155979 - 155979

Published: July 20, 2024

Language: Английский

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Mechanism of TGIF1 on glycolipid metabolism disorders in mice with type 2 diabetes

BMJ Open Diabetes Research & Care, Journal Year: 2025, Volume and Issue: 13(1), P. e004509 - e004509

Published: Jan. 1, 2025

Introduction Type 2 diabetes (T2D) is a chronic condition characterized by high levels of blood glucose resulting from the inefficiency insulin. This study aims to explore mechanism TGFB-induced factor homeobox 1 (TGIF1) in glycolipid metabolism mice with T2D. Research design and methods Mice T2D were induced high-fat diet low-dose streptozotocin (STZ) injection. After TGIF1 was overexpressed T2D, weight monitored. The fasting plasma glucose, serum insulin, triglycerides, total cholesterol, low-density lipoprotein high-density cholesterol measured. Staining assays performed observe liver tissue pathology lipid accumulation. Liver function oxidative stress Palmitic acid (PA)-induced primary hepatocytes used establish cell models. cells, viability, cellular uptake consumption, intracellular glycogen content detected. expression TGIF1, miR-106b-5p, early growth response (EGR2) detected their binding relationships analyzed. Combined experiments conducted validate mechanism. Results downregulated overexpression reduced hyperglycemia hyperlipidemia, improved insulin resistance, increased content, attenuated accumulation disorders enriched on miR-106b-5p promoter promoted expression. inhibited EGR2 inhibition or partially reversed alleviative effect disorders. Conclusion reduces through miR-106b-5p/EGR2 axis.

Language: Английский

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Complex regulation of cardiac fibrosis: insights from immune cells and signaling pathways

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 28, 2025

Cardiac fibrosis is a physiological process that involves the formation of scar tissue in heart response to injury or damage. This initially protective measure characterized by enhanced fibroblasts, which are responsible for producing extracellular matrix proteins provide structural support heart. However, when becomes excessive, it can lead adverse outcomes, including increasing stiffness and impaired cardiac function, ultimately result failure with poor prognosis. While fibroblasts primary cells involved fibrosis, immune have also been found play vital role its progression. Recent research has shown exert multifaceted effects besides regulation inflammatory response. Advanced techniques such as single-cell sequencing multiomics provided insights into specific subsets complex process. Targeted immunotherapy against gaining traction potential treatment option, but still unclear how achieve this whether distinct different roles. To better understand essential examine classical signaling pathways closely related formation. We focused on unique properties diverse their intercommunications. Therefore, review will delve plasticity heterogeneity roles propose facilitate development anti-fibrosis therapeutic strategies.

Language: Английский

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Inhalable cardiac targeting peptide modified nanomedicine prevents pressure overload heart failure in male mice

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 18, 2024

Abstract Heart failure causes considerable morbidity and mortality worldwide. Clinically applied drugs for the treatment of heart are still severely limited by poor delivery efficiency to off-target consumption. Inspired high inhaled drugs, we present an inhalable cardiac-targeting peptide (CTP)-modified calcium phosphate (CaP) nanoparticle TP-10, a selective inhibitor PDE10A. The CTP modification significantly promotes cardiomyocyte fibroblast targeting during pathological state in male mice. TP-10 is subsequently released from TP-10@CaP-CTP effectively attenuates cardiac remodelling improved function. In view these results, low dosage (2.5 mg/kg/2 days) medication exerted good therapeutic effects without causing severe lung injury after long-term treatment. addition, mechanism underlying amelioration investigated, results reveal that this system on cardiomyocytes fibroblasts mainly mediated through cAMP/AMPK cGMP/PKG signalling pathways. By demonstrating capacity verifying biosafety CaP nanoparticles lung, work provides perspective exploring myocardium-targeted therapy presents promising clinical strategy management failure.

Language: Английский

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Fibroblast-specific TGF-β signaling mediates cardiac dysfunction, fibrosis, and hypertrophy in obese diabetic mice

Cardiovascular Research, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 7, 2024

Abstract Aims Transforming growth factor (TGF)-β is up-regulated in the diabetic myocardium and may mediate fibroblast activation. We aimed at examining role of TGF-β-induced activation pathogenesis cardiomyopathy. Methods results generated lean obese db/db mice with fibroblast-specific loss TbR2, Type 2 receptor-mediating signaling through all three TGF-β isoforms, Smad3 disruption. Systolic diastolic function, myocardial fibrosis, hypertrophy were assessed. Transcriptomic studies vitro experiments used to dissect mechanisms Fibroblast-specific TbR2 attenuated systolic dysfunction mice. The protective effects associated fibrosis reduced cardiomyocyte hypertrophy, suggesting that addition their fibrous tissue deposition, TGF-β-stimulated fibroblasts also exert paracrine actions on cardiomyocytes. phenocopied Db/db had increased expression genes oxidative response (such as Fmo2, encoding flavin-containing monooxygenase 2), matricellular Thbs4 Fbln2), Lox (encoding lysyl oxidase). Ingenuity pathway analysis (IPA) predicted neurohumoral mediators, cytokines, factors AGT, TGFB1, TNF) serve important upstream regulators transcriptomic profile mouse fibroblasts. IPA scRNA-seq data identified p53, MYC, PDGF-BB, EGFR, WNT3A/CTNNB1 underlying hearts. Comparison transcriptome from fl/fl controls [encoding thrombospondin-4 (TSP-4), a marker activated fibroblasts] candidate diabetes-induced fibrogenic mediator. However, showed no significant activating or intracellular TSP-4 cardiac Conclusion TGF-β/Smad3 mediates ventricular diabetes.

Language: Английский

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The Impact of Natriuretic Peptides on Heart Development, Homeostasis, and Disease

Cells, Journal Year: 2024, Volume and Issue: 13(11), P. 931 - 931

Published: May 28, 2024

During mammalian heart development, the clustered genes encoding peptide hormones, Natriuretic Peptide A (NPPA; ANP) and B (NPPB; BNP), are transcriptionally co-regulated co-expressed predominately in atrial ventricular trabecular cardiomyocytes. After birth, expression of NPPA a natural antisense transcript NPPA-AS1 becomes restricted to Both NPPB induced by cardiac stress serve as markers for cardiovascular dysfunction or injury. gene products extensively used diagnostic prognostic biomarkers various disorders. Membrane-localized guanylyl cyclase receptors on many cell types throughout body mediate signaling natriuretic ligands through generation intracellular cGMP, which interacts with modulates activity cGMP-activated kinase other enzymes ion channels. The system plays fundamental role cardio-renal homeostasis, its potent diuretic vasodilatory effects provide compensatory mechanisms pathophysiological conditions failure. In addition, both peptides, but also CNP, have important intracardiac actions during development homeostasis independent systemic functions. Exploration functions may new leads therapeutic utility peptide-mediated diseases rhythm Here, we review recent insights into regulation disease.

Language: Английский

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The mechanisms and therapeutic potential of clopidogrel in mitigating diabetic cardiomyopathy in db/db mice

iScience, Journal Year: 2024, Volume and Issue: 27(3), P. 109134 - 109134

Published: Feb. 6, 2024

Highlights•Clopidogrel alleviates diabetes-induced cardiac hypertrophy and dysfunction in mice•Clopidogrel treatment effectively blocks TGF-β1/Smad3/P2RY12 pathway db/db mice•P2RY12 might be an effective target for the of diabetic cardiomyopathy•Clopidogrel protects against oxidative damage by induction Nrf2 pathwaySummaryClopidogrel has been shown to play a protective role nephropathy. However, whether clopidogrel exerts effect cardiomyopathy (DCM) is unknown. Three-month-old male mice were administered daily at doses 5, 10, 20 mg/kg gavage 5 months. Here, we showed that attenuated inhibiting fibrosis, inflammatory responses, stress mice. Diabetes-induced fibrosis was inhibited via blockade inhibition macrophage infiltration The effects mediated signaling pathway. Taken together, our findings provide strong evidence promising agent DCM alleviating dysfunction. P2RY12 DCM.Graphical abstract

Language: Английский

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Ferroptosis in diabetic cardiomyopathy: Advances in cardiac fibroblast-cardiomyocyte interactions

Heliyon, Journal Year: 2024, Volume and Issue: 10(15), P. e35219 - e35219

Published: July 28, 2024

Diabetic cardiomyopathy (DCM) is a common complication of diabetes, and its pathogenesis remains elusive. Ferroptosis, process dependent on iron-mediated cell death, plays crucial role in DCM via disrupted iron metabolism, lipid peroxidation, weakened antioxidant defenses. Hyperglycemia, oxidative stress, inflammation may exacerbate ferroptosis diabetes. This review emphasizes the interaction between cardiac fibroblasts cardiomyocytes DCM, influencing occurrence. By exploring modulation for potential therapeutic targets, this article offers fresh perspective treatment. The study systematically covers interplay, mechanisms, targeted drugs linked to development.

Language: Английский

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