Metabolism of hepatic stellate cells in chronic liver diseases: emerging molecular and therapeutic interventions

Theranostics, Год журнала: 2025, Номер 15(5), С. 1715 - 1740

Опубликована: Янв. 2, 2025

Chronic liver diseases, primarily metabolic dysfunction-associated steatotic disease (MASLD), and alcoholic (MetALD), viral hepatitis, can lead to fibrosis, cirrhosis, cancer. Hepatic stellate cell (HSC) activation plays a central role in the development of myofibroblasts fibrogenesis chronic diseases. However, HSC is influenced by complex microenvironments within liver, which are largely shaped interactions between HSCs various other types. Changes phenotypes mechanisms involve glucose, lipid, cholesterol metabolism, oxidative stress, unfolded protein response (UPR), autophagy, ferroptosis, senescence, nuclear receptors. Clinical interventions targeting these pathways have shown promising results addressing inflammation as well modulating glucose lipid metabolism stress responses. Therefore, comprehensive understanding presents opportunities for novel therapeutic approaches aimed at halting or even reversing

Язык: Английский

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Extracellular vesicle-mediated bidirectional communication between the liver and other organs: mechanistic exploration and prospects for clinical applications

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Март 8, 2025

The liver, functioning as an endocrine organ, secretes a variety of substances that influence the activities other body organs. Conversely, molecules generated by organs such bone, gut, and adipose tissue can also impact liver function. Accumulating evidence suggests bidirectional communication between However, research on how extracellular vesicles (EVs), which transport active molecular mediators, contribute to this interorgan is still in its nascent stages. EVs are capable transporting functional molecules, including lipids, nucleic acids, proteins, thereby affecting recipient cells across different at biological level. This review examines role facilitating cardiovascular system, pancreas, brain, lungs, kidneys, tissue. It explores their potential disease treatment highlights challenges understanding EV-mediated interactions. contribution mediator-carrying two-way remains area ongoing investigation. Future will provide more comprehensive theoretical foundation clarify precise mechanisms governing organs, pinpoint medical targets, expand application within realm precision medicine.

Язык: Английский

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Dietary Influences on Gut Microbiota and Their Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Nutrients, Год журнала: 2024, Номер 17(1), С. 143 - 143

Опубликована: Дек. 31, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major contributor to liver-related morbidity, cardiovascular disease, and metabolic complications. Lifestyle interventions, including diet exercise, are first line in treating MASLD. Dietary approaches such as the low-glycemic-index Mediterranean diet, ketogenic intermittent fasting, high fiber diets have demonstrated potential addressing dysfunction underlying this condition. The development progression of MASLD closely associated with taxonomic shifts gut microbial communities, relationship well-documented literature. Given importance primary treatment for MASLD, it important understand how microbiota their byproducts mediate favorable outcomes induced by healthy dietary patterns. Conversely, changes conferred unhealthy patterns Western may induce dysbiosis influence through promoting hepatic inflammation, up-regulating lipogenesis, dysregulating bile acid metabolism, increasing insulin resistance, causing oxidative damage hepatocytes. Although emerging evidence has identified links between microbiota, significant gaps remain understanding specific roles, metabolite pathways, host interactions, causal relationships. Therefore, review aims provide mechanistic insights into role microbiota-mediated processes analysis both contribution pathophysiology. By better elucidating interplay nutrients, processes, onset work identify new opportunities targeted interventions treat efficiently.

Язык: Английский

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Bacterial Nanovesicles as Interkingdom Signaling Moieties Mediating Pain Hypersensitivity

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

Gut dysbiosis contributes to multiple pathologies, yet the mechanisms of gut microbiota-mediated influence on systemic and distant responses remain largely elusive. This study aimed identify role nanosized bacterial extracellular vesicles (bEVs) in mediating allodynia, i.e., pain hypersensitivity, a diet-induced obesity (DIO) model. bEVs were enriched from feces lean (bEVLean) DIO (bEVDIO) mice by an approach combining ultracentrifugation immunoprecipitation then extensively analyzed for purity characteristics. Next, injected, either intraplantarly or intravenously, assess sensitivity. Fluorescence-labeled injected enema biodistribution. The effect bEV immune cells inflammation was array, immunophenotyping, microscopy, NF-κB activation, cellular uptake assays. Results showed that bEVDIO administration wild-type replicated allodynia phenotype observed both mechanical thermal stimuli. Importantly, this compromised TRPA1/TRPV1 double-knockout mice. Biodistribution analyses entry into circulation with subsequent localization at sites. Multiple revealed exposure incited inflammation, primarily through modulating innate system. inflammatory mechanism involved LPS surface, activating TLR2- TLR4-related pathways, as confirmed using TLR2 TLR4 inhibitors shaving surface proteins. Interestingly, enhanced contingent interactions involving proteins TLR2/TLR4 monocytes. These findings illuminate hitherto unexplored pivotal mediators linked dysbiosis.

Язык: Английский

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The liver’s dilemma: sensing real danger in a sea of PAMPs: the (arterial) sinusoidal segment theory

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 27, 2025

The liver is susceptible to viruses and bacterial infections, tumors, sterile tissue damage, but immunological danger recognition in the highly unconventional. When analyzing innate adaptive immunity organ, valid concepts that guide immune response periphery should be put aside. In liver, vascular anatomy a game changer, as about 80% of blood percolates organ arrives from hepatic portal vein, draining rich molecules intestinal flora. This 24/7 exposure high amounts pathogen-associated molecular pattern (PAMPs) results tolerance. dendritic, Kupffer (KC), sinusoidal endothelial cells (LSECs), even hepatocytes express PD-L1, T lymphocyte downregulatory molecule. Most Fas-L, IL-10, TGF-β, low levels co-stimulatory molecules, lack or have MHC-I and/or MHC-II expression. Moreover, other negative regulators such CTLA-4, IDO-1, prostaglandin E2 (PGE2) are regularly expressed. Then, how can real discerned recognized this sea PAMPs? an open question. Here, we hypothesize conventional occur specific minor arterial segments,. triad, where artery ramificates into stroma carries with no gut-derived PAMPs, there evolutive environmental pressure for immunosuppressive pathways, could occur. Therefore, segments recognize support immunity.

Язык: Английский

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Bacterial extracellular vesicles for gut microbiome-host communication and drug development

Acta Pharmaceutica Sinica B, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

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Extracellular Vesicles in Aging and Age‐Related Diseases. How Important Are They?

Advanced Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Abstract Extracellular vesicles (EVs), lipid bilayer‐bound particles secreted by cells, have attracted significant research attention for their roles in aging‐related disorders, including cardiovascular disease, metabolic dysfunction, cancer, and neurodegeneration. Research shows that EV cargo function are influenced factors age, disease state, exercise, nutrition sleep, they may modulate various aging‐associated processes such as stem cell renewal, nutrient sensing, senescence, mitochondrial function, insulin resistance. This perspective highlights, a general audience, selection of studies EVs aging age‐related diseases, diverse organ crosstalk. While current evidence indicates play multiple aging, there numerous challenges methodological limitations, heterogeneous reports cargo, limited reproducibility, apparent context‐dependent effects cargo. Together, this limits the interpretation these studies. is proposed act fine‐tuners cellular communication within broader secretome importance standardizing methods emphasized. Last, future directions suggested.

Язык: Английский

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Intestinal bacteria-derived extracellular vesicles in metabolic dysfunction-associated steatotic liver disease: from mechanisms to therapeutics

Molecules and Cells, Год журнала: 2025, Номер unknown, С. 100216 - 100216

Опубликована: Апрель 1, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive that affects the health of approximately one-third world's population. It primary cause end-stage disease, malignancy, and transplantation, resulting in great medical burden. No medications have yet been approved by US Food Drug Administration (FDA) for treating MASLD without inflammation or scarring. Therefore, development specific drugs to treat remains key task ongoing research objective. Extracellular vesicles (EVs) play an important role communication between organs, tissues, cells. Recent studies found intestinal microbiota are closely related pathogenesis progression MASLD. EVs produced bacteria (BEVs) indispensable this process. Thus, study provides new direction treatment. However, mechanism which BEVs affect unclear. investigated influence function Additionally, we focus on progress recent years, explain relationship from perspectives glucose lipid metabolism, immune responses, homeostasis. Finally, summarized potential therapeutic value other sources, such as adipocytes, immunocytes, stem cells, plants.

Язык: Английский

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Biogenesis mechanisms, regulatory strategies, and applications of bacterial extracellular vesicles

Critical Reviews in Biotechnology, Год журнала: 2025, Номер unknown, С. 1 - 17

Опубликована: Май 14, 2025

Bacterial extracellular vesicles (EVs) are produced by both Gram-negative and Gram-positive bacteria. These EVs composed of lipid bilayers various components derived from parent bacteria, including proteins, lipids, nucleic acids. Previous studies have indicated the significant role bacterial in interactions between bacteria hosts. Moreover, emerging as promising delivery vectors capable transporting drug molecules over long distances to tissues. Therefore, understanding biogenesis how regulate their production holds great importance for expanding applications. In this review, we provide an overview EVs, especially focusing on distinct mechanisms regulation Additionally, discuss methods cargos loading into well diverse applications vaccines, cancer therapy, delivery. We anticipate that review will advance field contributing enhancement existing emergence novel

Язык: Английский

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Reviewing the function of macrophages in liver diseases

Expert Review of Gastroenterology & Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Май 19, 2025

The liver is a central metabolic organ, but also hosting unique immune microenvironment to sustain homeostasis and proper defense measures against injury threats in healthy individuals. Liver macrophages, mostly represented by the tissue-resident Kupffer cells bone marrow- or monocyte-derived are intricately involved various aspects of disease, including tissue injury, inflammation, fibrogenesis repair mechanisms. We review recent findings on defining macrophage landscape their functions diseases with aim highlighting potential targets for therapeutic interventions. A comprehensive literature search PubMed Google Scholar was conducted identify relevant up date. macrophages orchestrate key homeostatic pathogenic processes liver. Thus, targeting represents an attractive strategy drug development, e.g. ameliorate steatohepatitis fibrosis. However, translation from fundamental research therapies remains challenging due versatile nature compartment. Recent major technical advances such as single-cell spatially-resolved omics approaches deepened our understanding biology at molecular level. Yet, further studies needed suitable, etiology- stage-dependent strategies treatment diseases.

Язык: Английский

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