The Liver X Receptor Promotes Immune Homeostasis via Controlled Activation of the Innate Immune System in the Liver DOI Creative Commons
Hiroyuki Nakashima, Bradley M. Kearney, Manabu Kinoshita

и другие.

Biomolecules, Год журнала: 2024, Номер 15(1), С. 25 - 25

Опубликована: Дек. 28, 2024

The liver is an indispensable metabolic organ, responsible for accumulating and transporting various nutritional compounds in hepatocytes. However, the transport of these materials from energetically intensive task because they contain a considerable number hydrophobic components, including free cholesterol, require specialized transfer proteins to shuttle substances through aqueous phase. Liver X receptors (LXRs) induce expression cholesterol transporters macrophages derived apoptotic cells into extracellular space via high-density lipoproteins. Additionally, LXRs control innate immune two major mechanisms: upregulating phagocytic activity suppressing inflammatory reactions prevent aggressive activation cells. Therefore, primary role accelerate efferocytosis without provoking inflammation facilitate intracellular space. This mechanism makes system substantial contributor systemic control. Concomitantly, are important factors regulating defense mechanisms efficient regulation LXR activation, therefore, has great potential clinical applications treatment metabolic, infectious, autoimmune diseases. In this review, we discuss current understanding link between liver, along with prospects agonists.

Язык: Английский

Connecting the Dots: LncRNAs in the KRAS Pathway and Cancer DOI
Mudasir Maqbool, Md Sadique Hussain, Ajay Singh Bisht

и другие.

Pathology - Research and Practice, Год журнала: 2024, Номер 262, С. 155570 - 155570

Опубликована: Авг. 29, 2024

Язык: Английский

Процитировано

10
Mechanism of liver x receptor alpha in intestine, liver and adipose tissues in metabolic associated fatty liver disease DOI

Kaiwen Lei,

Runsheng Chen, Jian‐Xing Wu

и другие.

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 142275 - 142275

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
A Novel Rexinoid Agonist, UAB116, Decreases Metastatic Phenotype in Hepatoblastoma by Inhibiting the Wnt/β-Catenin Pathway via Upregulation of TRIM29 DOI Open Access
Swatika Butey, Morgan Brown, Janet R. Julson

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(9), С. 3933 - 3933

Опубликована: Апрель 22, 2025

Hepatoblastoma (HB) is the most common pediatric primary liver tumor. About 20% of affected children have pulmonary metastasis at presentation. Survival rates for these are dismal, not exceeding 25%. To study this subset patients, we sequenced a metastatic HB cell line, HLM_2, and identified downregulation Liver X Receptor (LXR)/Retinoid (RXR) pathway. LXR/RXRs function as transcriptional regulators that influence genes implicated in development, including Wnt/β-catenin signaling We assessed effects novel LXR/RXR agonist, UAB116, on HB, hypothesizing compound would affect governing pathway, decreasing phenotype HLM_2 cells. evaluated its viability, proliferation, stemness, clonogenicity, motility, performed RNA sequencing to differential gene regulation. Treatment with UAB116 72 h decreased invasion. an eight-fold increase TRIM29, known inhibit β-catenin, cells treated UAB116. Administration reduces invasiveness cells, potentially by upregulation modulator providing support further exploration agonism therapeutic strategy HB.

Язык: Английский

Процитировано

0
Intersecting Blood Cytokines With Cholesterol Parameters to Profile Patients With Advanced Solid Tumors Receiving Immune Checkpoint Inhibitors DOI
Giulia Mazzaschi, Fabiana Perrone, Giuseppe Maglietta

и другие.

Journal of Immunotherapy, Год журнала: 2024, Номер 47(9), С. 388 - 394

Опубликована: Июль 11, 2024

The study investigated the relationship between serum proinflammatory cytokine levels, cholesterol metabolism, and clinical outcome in cancer patients undergoing immune checkpoint inhibitors (ICIs). Peripheral blood was collected before therapy from ICI-treated advanced patients. We retrospectively assessed plasma total (TC), ABCA1- ABCG1-mediated efflux (CE), passive diffusion (PD), loading capacity (CLC), IL-6, IL-10, TNF-α. association parameters inflammatory cytokines their effect on overall survival (OS), progression-free (PFS), benefit (CB) ICIs were statistically assessed. Among 70 consecutively enrolled (nonsmall cell lung cancer: 94%; renal carcinoma: 6%), TC, CLC, PD resulted significantly higher IL-6 low IL-10 cases ( P <0.05), whereas ABCA1-mediated CE increased high =0.018). Uni- multivariable analysis revealed meaningfully longer OS PFS (HR 2.13 2.97, respectively) 3.17 2.62) groups. At univariate all cholesterol-related indices correlated with PFS, at multivariate only validated as a protection factor (OS, HR 0.75; 0.84). Finally, uni- showed significant inverse of CB ABCG1-CE (OR 0.62), 0.13) 0.10). In-depth characterization interplay metabolism immune-inflammatory might provide novel insights into complex among cancer, inflammation, lipids profile, response to immunotherapy.

Язык: Английский

Процитировано

1
Ergosterol and its Metabolites as Agonists of Liver X Receptor and Their Anticancer Potential in Colorectal Cancer DOI

Yogain Taank,

Navneet Agnihotri

Опубликована: Янв. 1, 2024

AbstractAberrant cholesterol homeostasis is a well-recognized hallmark of cancer and implicated in metastasis as well chemotherapeutic resistance, the two major causes associated mortality. Liver X receptors (LXRs) are key transcription factors that induce efflux via enhancing expression ABCA1 ABCG1. Therefore, comprehensive analysis several novel sterols namely ergosta-7,22,24(28)-trien-3β-ol (Erg1), ergosta-5,22,25-trien-3-ol (Erg2), ergosta-5,7,22,24(28)-tetraen-3β-ol (Erg3), ergosta-7,22-dien-3β-ol (Erg4) LXR agonists has been performed. Molecular docking studies have shown these possess higher binding affinities for LXRs compared to reference ligands (GW3965 T0901317) also formed critical activating interactions. dynamic simulations further confirmed complexes made significant stability. To assess extent activation, promoter was cloned into luciferase reporter plasmid transfected HCT116 cells. It observed treatment with Erg, Erg 2 Erg4 led activation an EC50 5.74µM 142.47µM respectively. Furthermore, increase mRNA target genes i.e. NR1H2, ABCA1, ABCG1 ApoE upon treatment. Flow cytometric revealed Cytotoxicity conducted on colorectal cell normal epithelial line showed selectively toxic towards Our findings suggests ergosterol activates LXRs, anticancer activity could be likely candidate manage aberrant homeostasis.

Язык: Английский

Процитировано

0
Ergosterol and its metabolites as agonists of Liver X receptor and their anticancer potential in colorectal cancer DOI

Yogain Taank,

Vinay Randhawa, Navneet Agnihotri

и другие.

The Journal of Steroid Biochemistry and Molecular Biology, Год журнала: 2024, Номер 243, С. 106572 - 106572

Опубликована: Июнь 21, 2024

Язык: Английский

Процитировано

0
The Liver X Receptor Promotes Immune Homeostasis via Controlled Activation of the Innate Immune System in the Liver DOI Creative Commons
Hiroyuki Nakashima, Bradley M. Kearney, Manabu Kinoshita

и другие.

Biomolecules, Год журнала: 2024, Номер 15(1), С. 25 - 25

Опубликована: Дек. 28, 2024

The liver is an indispensable metabolic organ, responsible for accumulating and transporting various nutritional compounds in hepatocytes. However, the transport of these materials from energetically intensive task because they contain a considerable number hydrophobic components, including free cholesterol, require specialized transfer proteins to shuttle substances through aqueous phase. Liver X receptors (LXRs) induce expression cholesterol transporters macrophages derived apoptotic cells into extracellular space via high-density lipoproteins. Additionally, LXRs control innate immune two major mechanisms: upregulating phagocytic activity suppressing inflammatory reactions prevent aggressive activation cells. Therefore, primary role accelerate efferocytosis without provoking inflammation facilitate intracellular space. This mechanism makes system substantial contributor systemic control. Concomitantly, are important factors regulating defense mechanisms efficient regulation LXR activation, therefore, has great potential clinical applications treatment metabolic, infectious, autoimmune diseases. In this review, we discuss current understanding link between liver, along with prospects agonists.

Язык: Английский

Процитировано

0