The role of novel adipokines and adipose-derived extracellular vesicles (ADEVs): Connections and interactions in liver diseases

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 222, P. 116104 - 116104

Published: Feb. 29, 2024

Adipose tissues (AT) are an important endocrine organ that secretes various functional adipokines, peptides, non-coding RNAs, and acts on AT themselves or other distant organs through autocrine, paracrine, manners. An accumulating body of evidence has suggested many adipokines play role in liver metabolism. Besides the traditional such as adiponectin leptin, novel have recently been identified to regulatory effects liver. Additionally, can produce extracellular vesicles (EVs) act peripheral tissues. However, under pathological conditions, obesity diabetes, dysregulation is associated with changes AT, which may cause diseases. In this review, we focus newly discovered EVs secreted by highlight their actions context obesity, nonalcoholic fatty diseases (NAFLD), some Clarifying action adipose tissue-derived would help identify therapeutic targets biomarkers for metabolic

Language: Английский

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Single-cell and spatially resolved transcriptomics for liver biology

Hepatology, Journal Year: 2023, Volume and Issue: 80(3), P. 698 - 720

Published: April 1, 2023

Single-cell transcriptomics enables the identification of rare cell types and inference state transitions, whereas spatially resolved allows quantification cells genes in context tissues. The recent progress these new technologies is improving our understanding landscape its roles diseases. Here, we review key biological insights into liver homeostasis, development, regeneration, chronic disease, cancer obtained from single-cell transcriptomics. We highlight atlas that characterizes comprehensive cellular composition; diversity function; spatial architecture such as zonation, communication, proximity; identity conversion cell-specific alterations are associated with pathology; therapeutic targets. further discuss outstanding challenges, advanced experimental technologies, computational methods help to address challenges.

Language: Английский

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Neuregulin4 Acts on Hypothalamic ErBb4 to Excite Oxytocin Neurons and Preserve Metabolic Homeostasis

Advanced Science, Journal Year: 2023, Volume and Issue: 10(16)

Published: April 14, 2023

Neuregulin 4 (Nrg4) is an adipose tissue-enriched secreted factor that modulates glucose and lipid metabolism. Nrg4 closely associated with obesity preserves diet-induced metabolic disorders. However, the specific mechanisms via which regulates homeostasis remain incompletely understood. Here, this work finds receptor, ErbB4, highly expressed in hypothalamus, phosphorylation of hypothalamic ErbB4 reduced (DIO) mice. Peripheral can act on blood circulation excite neurons paraventricular nucleus hypothalamus (PVN). Central administration recombinant protein (rNrg4) reduces related disorders by influencing energy expenditure intake. Overexpression PVN protects against obesity, whereas its knock down oxytocin (Oxt) neuron accelerates obesity. Furthermore, Nrg4-ErbB4 signaling excites Oxt release, ablation considerably attenuates effect balance. These data suggest a key target Nrg4, partially explains multifaceted roles

Language: Английский

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Tumor-associated macrophages in anti-PD-1/PD-L1 immunotherapy for hepatocellular carcinoma: recent research progress

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: June 18, 2024

Hepatocellular carcinoma (HCC) is one of the cancers that seriously threaten human health. Immunotherapy serves as mainstay treatment for HCC patients by targeting programmed cell death protein 1/programmed 1 ligand (PD-1/PD-L1) axis. However, effectiveness anti-PD-1/PD-L1 limited when becomes drug-resistant. Tumor-associated macrophages (TAMs) are an important factor in negative regulation PD-1 antibody targeted therapy tumor microenvironment (TME). Therefore, emerging direction cancer immunotherapy research HCC, it crucial to elucidate correlations and mechanisms between TAMs PD-1/PD-L1-mediated immune tolerance. This paper summarizes effects on pathogenesis progression their impact immunotherapy, further explores current potential therapeutic strategies target including eliminating TME, inhibiting recruitment tumors functionally repolarizing M2-TAMs (tumor-supportive) M1-TAMs (antitumor type).

Language: Английский

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TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 21, 2025

Abstract Background Triggering receptor expressed on myeloid cells 2 (TREM2), a surface predominantly cells, is major hub gene in pathology-induced immune signaling. However, its function hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the role of TREM2 tumor microenvironment context HCC progression. Methods was experimentally induced wild-type (WT) and Trem2 -deficient ( −/− ) mice, clinical sample analysis vitro studies macrophages were conducted. treated with conditioned medium from WT or macrophages, their malignant phenotypes underlying mechanisms analyzed. Results deficiency reduced liver burden orthotopic subcutaneous models by altering CD8 + T cell infiltration. presented increased chemokine secretion. TGF-β1 found be positively correlated expression HCC, TGF-β blockade reversed induction. On other hand, associated glycolysis PKM2 cells; this association may related secretion IL-1β, which enhances cells. Conclusions These results reveal that play driving progression suppressing infiltration promoting glycolysis, providing new therapeutic target for HCC.

Language: Английский

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