Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 16, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty (NAFLD), is the most common disorder worldwide, with an estimated global prevalence of more than 31%. steatohepatitis (MASH), formerly (NASH), a progressive form MASLD characterized by hepatic steatosis, inflammation, and fibrosis. This review aims to provide comprehensive analysis extrahepatic manifestations MASH, focusing on chronic diseases related cardiovascular, muscular, renal systems. A systematic published studies literature was conducted summarize findings systemic impacts MASH. The focused association MASH metabolic comorbidities, cardiovascular mortality, sarcopenia, kidney disease. Mechanistic insights into concept lipotoxic inflammatory "spill over" from MASH-affected were also explored. are highly associated (50%-80%) other comorbidities such impaired insulin response, type 2 diabetes, dyslipidemia, hypertriglyceridemia, hypertension. Furthermore, 90% obese patients diabetes have Data suggest that in middle-aged individuals (especially those aged 45-54), independent risk factor for plays crucial role mediating pathological effects observed. Understanding multifaceted impact heart, muscle, early detection stratification. knowledge timely implementing management strategies addressing multi-organ involvement pathogenesis.

Language: Английский

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A multifunctional injectable hydrogel for boosted diabetic wound healing assisted by Quercetin-ZIF system

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 495, P. 153425 - 153425

Published: June 22, 2024

Language: Английский

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cSTAR analysis identifies endothelial cell cycle as a key regulator of flow-dependent artery remodeling

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

Published: Jan. 3, 2025

Fluid shear stress (FSS) from blood flow sensed by vascular endothelial cells (ECs) determines vessel behavior, but regulatory mechanisms are only partially understood. We used cell state transition assessment and regulation (cSTAR), a powerful computational method, to elucidate EC transcriptomic states under low (LSS), physiological (PSS), high (HSS), oscillatory (OSS) that induce inward remodeling, stabilization, outward or disease susceptibility, respectively. Combined with publicly available database on responses drug treatments, this approach inferred network controlling made several notable predictions. Particularly, inhibiting cycle–dependent kinase (CDK) 2 was predicted initiate remodeling promote atherogenesis. In vitro, PSS activated CDK2 induced late G 1 cycle arrest. mice, deletion of triggered artery pulmonary systemic hypertension, accelerated atherosclerosis. These results validate use cSTAR identify key determinants normal pathological remodeling.

Language: Английский

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Mechanisms of inflammatory microenvironment formation in cardiometabolic diseases: molecular and cellular perspectives

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 14, 2025

Cardiometabolic diseases (CMD) are leading causes of death and disability worldwide, with complex pathophysiological mechanisms in which inflammation plays a crucial role. This review aims to elucidate the molecular cellular within inflammatory microenvironment atherosclerosis, hypertension diabetic cardiomyopathy. In oxidized low-density lipoprotein (ox-LDL) pro-inflammatory cytokines such as Interleukin-6 (IL-6) Tumor Necrosis Factor-alpha (TNF-α) activate immune cells contributing foam cell formation arterial wall thickening. Hypertension involves activation renin-angiotensin system (RAS) alongside oxidative stress-induced endothelial dysfunction local mediated by T cells. cardiomyopathy, high-glucose environment leads accumulation advanced glycation end products (AGEs), activating Receptor for Advanced Glycation Endproducts (RAGE) triggering responses that further damage cardiac microvascular function. summary, different types metabolic cardiovascular diverse; understanding these deeply will aid developing more effective individualized treatment strategies.

Language: Английский

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Liver macrophages revisited: The expanding universe of versatile responses in a spatiotemporal context

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(7)

Published: July 1, 2024

The liver is a vital organ that continuously adapts to wide and dynamic diversity of self-antigens xenobiotics. This involves the active contribution immune cells, particularly by liver-resident macrophages, Kupffer cells (KCs), which exert variety central functions in homeostasis disease. As such, KCs interact with their microenvironment shape hepatic cellular landscape, control gut-derived signal integration, modulate metabolism. On injury, rapid recruitment bone marrow monocyte-derived macrophages alters this status quo and, when unrestrained, drastically compromises homeostasis, surveillance, tissue organization. Several factors determine functional roles these processes, such as ontogeny, activation/polarization profile importantly, spatial distribution within liver. Loss tolerance adaptability environment may result persistent inflammation, fibrosis, cirrhosis, tumorigenic niche promoting cancer. In review, we aim at providing most recent breakthroughs our understanding macrophage biology, spatiotemporal context, well on potential therapeutic interventions hold key tackling remaining clinical challenges varying etiologies hepatology.

Language: Английский

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Association Between Systemic Inflammatory Response Index and Cerebral Small Vessel Disease

Journal of Stroke and Cerebrovascular Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 108237 - 108237

Published: Jan. 1, 2025

This study aimed to explore the relationship between Systemic Inflammatory Response Index (SIRI) and Cerebral Small Vessel Disease (CSVD), focusing on its key imaging markers. We enrolled 344 patients admitted neurology department January 2022 September 2024, comprising 223 diagnosed with CSVD 121 without CSVD. Baseline characteristics were compared groups, multivariate logistic regression was performed assess impact of SIRI risk. Further, univariate analyses conducted examine markers, including White Matter Hyperintensity (WMH), lacunes, Perivascular Space (PVS), Recent Subcortical Infarct (RSSI). Significant differences observed non-CSVD groups in terms age, sex, history hypertension, diabetes, white blood cell count, neutrophil lymphocyte homocysteine levels, values. Multivariate analysis confirmed that elevated is independently associated an increased risk Additionally, higher values linked more severe features, moderate-to-severe WMH, presence RSSI. These findings demonstrate both occurrence severity markers such as suggests could serve a useful inflammatory marker for assessing progression.

Language: Английский

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Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammation

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 21, 2025

Aging significantly affects intercellular communication between vascular endothelial cells (ECs) and hematopoietic cells, leading to inflammation age-associated diseases. This study determined how senescent ECs communicate with monocytes, whether extracellular vesicles (EVs) released from affect monocyte functions, investigated the potential for epigallocatechin-3-gallate (EGCG), a flavonoid in green tea, reverse these effects. Human umbilical vein (HUVECs) were treated Etoposide (10 µM, 24 h) induce senescence, followed by EGCG (100 treatment evaluate its as senotherapeutic agent. The interaction monocytes was analyzed using co-culture system direct of EC-derived EVs. reduced senescence-associated phenotypes ECs, evidenced decreased (SA)-β-Gal activity reversal Etoposide-induced senescence markers. Monocytes co-cultured EGCG-treated showed pro-inflammatory responses compared those untreated ECs. Additionally, produced more EVs than non-senescent enhanced lipopolysaccharide (LPS)-induced activation whereas mitigated this activation, maintaining at normal levels. Our findings reveal that confers anti-senescent effects via modulation EC secretome (including EVs) capacity modify activation. These suggest could act agent reduce related aging.

Language: Английский

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The Interplay Between Immunity, Inflammation and Endothelial Dysfunction

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1708 - 1708

Published: Feb. 17, 2025

The endothelium is pivotal in multiple physiological processes, such as maintaining vascular homeostasis, metabolism, platelet function, and oxidative stress. Emerging evidence the past decade highlighted immunomodulatory function of endothelium, serving a link between innate, adaptive immunity inflammation. This review examines regulation immune-inflammatory axis by discusses immune functions, explores pathophysiological processes leading to endothelial dysfunction various metabolic disturbances, including hyperglycemia, obesity, hypertension, dyslipidaemia. final section focuses on novel, repurposed, emerging therapeutic targets that address dysfunction.

Language: Английский

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Retinal vasculitis after intravitreal aflibercept 8 mg for neovascular age-related macular degeneration

Japanese Journal of Ophthalmology, Journal Year: 2024, Volume and Issue: 68(5), P. 531 - 537

Published: Aug. 20, 2024

Abstract Purpose To evaluate short-term outcomes of intravitreal injection aflibercept 8 mg for neovascular age-related macular degeneration (nAMD). Study design Retrospective, interventional case series. Methods We retrospectively studied 35 eyes 34 consecutive patients with nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), and central choroidal (CCT) before 4 weeks after the initial dose mg. The rate achieving a dry macula incidence intraocular inflammation (IOI) at week were also determined. Results BCVA showed significant improvement, reductions in FT CCT (all P < 0.01), being achieved 20 (57.1%). However, 3 (8.6%) developed non-infectious IOI associated retinal vasculitis, an adverse event not reported previously. these was relatively mild treated posterior subtenon triamcinolone acetonide or without betamethasone eye drops, resulting amelioration any loss. Conclusions Intravitreal appears to be effective improving ameliorating exudative changes nAMD. special attention should given potential development vasculitis.

Language: Английский

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Associations between per- and polyfluoroalkyl chemicals and abdominal aortic calcification in middle-aged and older adults

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Per- and polyfluoroalkyl substances (PFAS) have infiltrated countless everyday products, raising concerns about potential effects on human health, specifically the cardiovascular system development of abdominal aortic calcification (AAC). However, our understanding this relationship is still limited. This study aims to investigate PFAS AAC using machine learning algorithms. Leveraging power (ML) technique, extreme gradient boosting (XGBoost), we assessed between exposure risk. We focused three compounds, perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic (PFHxS), perfluorononanoic (PFNA) through multiple logistic regression, restricted cubic spline (RCS), quantile g-computation (QGC) models. To get more insight into underlying mechanisms, mediation analyses are used mediating role fatty acids blood cell fractions in AAC. Our findings indicate that elevated serum levels PFHxS PFDeA associated with increased risk The QGC underscore overall positive association mixture risk, carrying greatest weight, followed by PFDeA. RCS reveal a dose-dependent increase concentration an inverted V-shape way. Moreover, age identified as primary factors contributing SHapley Additive exPlanation (SHAP) summary plot combined XGBoost technique. Although significantly change profile acids, do not find any roles them Despite strong associations hematological indicators, analysis does evidence these indicators mediate In summary, highlights detrimental impact health emphasizes need for further research understand mechanisms involved.

Language: Английский

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