Selective Modulation of Aryl Hydrocarbon Receptor by Coptisine in MAFLD DOI Creative Commons
Xiliang Zhu,

Qi Liu,

Zhaoyun Cheng

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

Abstract Background: Metabolic-associated fatty liver disease (MAFLD) is a multifaceted condition driven by disrupted lipid metabolism and chronic inflammation, influenced genetic, environmental, dietary factors. The Aryl Hydrocarbon Receptor (AHR) has emerged as critical regulator in this context, mediating responses to various environmental signals. dual role of AHR MAFLD complex, with some ligands exacerbating damage while others confer protective effects, suggesting that AHR’s impact may be highly context-dependent. Methods: This study analyzed single-cell RNA sequencing (scRNA-seq) data explore the metabolic transcriptional heterogeneity hepatocyte subpopulations high-sucrose, high-fat diet (HSDFD)-induced model. Virtual screening identified potential AHR-targeting compounds, leading selection CPT for further study. efficacy was evaluated through vivo vitro assays, including Cellular Thermal Shift Assay (CETSA), Drug Affinity Responsive Target Stability (DARTS), Western blotting, immunohistochemistry (IHC), immunofluorescence, Bodipy staining. These methods were employed elucidate molecular interactions between its ligands, assess CPT’s on accumulation AHR-mediated activity. Results: Our findings reveal significant alterations subpopulation dynamics under HSDFD conditions, such Rasd1(hi), Galnt17(hi), Lpin1(-) displaying enhanced Transcriptional regulation analysis reorganization M1 regulon module, differential activity across subpopulations. Notably, potent compound, effectively reducing restoring CYP1A1 expression models. Structural dynamic analyses demonstrated induces specific conformational changes AHR, environment favors oxidative stress management. Conclusion: highlights complex underscores therapeutic modulating mitigate dysregulation. provide valuable insights developing targeted therapies leverage AHR/CYP1A1 pathway treat MAFLD.

Language: Английский

Microplastics: An emerging environmental risk factor for gut microbiota dysbiosis and cancer development? DOI Creative Commons
Sheik Aliya, Munirah Alhammadi,

S Ilangovan

et al.

Environmental Chemistry and Ecotoxicology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Resinacein S, a novel triterpenoid from functional mushroom Ganoderma resinaceum, curbs obesity by regulating thermogenesis and energy metabolism DOI
Gang Wei, Feng‐Jie Shen, Jun‐Li Liu

et al.

Journal of Food Science, Journal Year: 2025, Volume and Issue: 90(4)

Published: April 1, 2025

Abstract Ganoderma mushrooms are popularly used as dietary supplements to promote health around the world. However, their potential applications for prevention and treatment of obesity needs be further investigated. In this study, we isolated a novel triterpenoid from resinaceum , Resinacein S (Res S), determined its absolute configuration. We reported that Res significantly inhibited high‐fat HF diet‐induced body weight gain though increased thermogenesis energy metabolism. Specifically, with promoted brown adipose tissue activation browning inguinal white tissue, improving whole‐body glucose lipid homeostasis. Mechanistically, induced expression thermogenic genes related protein, example, uncoupling protein 1 mitochondrial biogenesis in cell‐autonomous manner by activating AMPK‐PGC1α signaling pathway. These findings identify therapeutic alternative setting increasingly high prevalence. Highlights S) exhibited potent anti‐obesity effects diet‐fed mice; tissue; stimulated UCP1 enhanced function; adipocyte activity through axis.

Language: Английский

Citations

0
Exploring the Micro- and Nanoplastics–Diabetes Nexus: Shattered Barriers, Toxic Links, and Methodological Horizons DOI

V.C. Shruti,

Gurusamy Kutralam-Muniasamy, Fermín Pérez‐Guevara

et al.

Environmental Pollution, Journal Year: 2025, Volume and Issue: 375, P. 126319 - 126319

Published: April 26, 2025

Language: Английский

Citations

0
Metabolic reprogramming shapes the immune microenvironment in pancreatic adenocarcinoma: prognostic implications and therapeutic targets DOI Creative Commons
Weihua Song,

Yabin Yu,

Shuai Wang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 21, 2025

Introduction Pancreatic adenocarcinoma (PAAD) is characterized by a profoundly immunosuppressive tumor microenvironment (TME) that limits the efficacy of immunotherapy. Emerging evidence suggests tumor-specific metabolic reprogramming may drive disease progression and shape immune landscape in PAAD. Methods We integrated multi-omics data from TCGA, GEO, ICGC to identify key metabolism-related genes (MRGs) influence cell infiltration, progression, patient survival. Based on nine pivotal MRGs (including ANLN, PKMYT1, HMGA1), we developed validated novel metabolic-prognostic index (MPI). Functional enrichment analyses were conducted elucidate pathways associated with different MPI risk groups. In vitro experiments drug sensitivity performed confirm oncogenic role selected explore their therapeutic implications. Results The effectively stratified patients into high- low-risk High-MPI scores correlated poor overall survival, elevated mutation burden (TMB), an TME, evidenced reduced CD8⁺ T-cell infiltration increased expression checkpoints (PD-L1, TGF-β). revealed glycolysis folate biosynthesis as dominant high-MPI groups, whereas fatty acid metabolism prevailed low-MPI Experimental validation underscored ANLN promoting epithelial-mesenchymal transition (EMT) evasion via NF-κB signaling. knockdown significantly glycolytic activity, migration, evasion. Drug indicated resistance gemcitabine but afatinib patients. Although TIDE analysis predicted checkpoint inhibitor (ICI) tumors, subset showed favorable responses anti-PD-L1 therapy. Discussion These findings provide comprehensive framework for understanding how shapes PAAD’s TME affects treatment outcomes. By accurately stratifying patients, serves promising tool guide decisions, including targeted therapy selection immunotherapy prediction, ultimately offering potential more personalized management

Language: Английский

Citations

0
Unraveling the connection between Hashimoto’s Thyroiditis and non-alcoholic fatty liver disease: exploring the role of CD4+central memory T cells through integrated genetic approaches DOI

Dairui Li,

Zeji Zhang,

Cheng Zhang

et al.

Endocrine, Journal Year: 2024, Volume and Issue: 85(2), P. 751 - 765

Published: Feb. 24, 2024

Language: Английский

Citations

2
Identification of cell differentiation trajectory-related gene signature to reveal the prognostic significance and immune landscape in prostate cancer based on multiomics analysis DOI Creative Commons

Liangxue Sun,

Zhouting Tuo,

Xin Chen

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(6), P. e27628 - e27628

Published: March 1, 2024

BackgroundIn the context of prostate cancer (PCa), occurrence biochemical recurrence (BCR) stands out as a pivotal factor significantly impacting prognosis, potentially leading to metastasis and mortality. However, early detection BCR poses substantial challenge for PCa patients. There is an urgent need pinpoint hub genes that can serve predictive indicators in patients.MethodsOur primary goal was identify cell differentiation trajectory-related gene signature patients by pseudo-time trajectory analysis. We further explored functional enrichment overlapped marker probed clinically relevant modules BCR-related using Weighted Gene Co-expression Network Analysis (WGCNA) Key predicting recurrence-free survival were meticulously identified through univariate multivariate Cox regression analyses. Subsequently, these utilized construct prognostic signature, expression, efficacy, putative functions, immunological landscape which thoroughly validated. Additionally, we employed immunohistochemistry (IHC) western blotting assay quantify expression PYCR1 clinical samples.ResultsOur single-cell RNA (scRNA) sequencing analysis unveiled three subgroups characterized distinct trajectories, associated with groups extracted from These successfully classified sample into two molecular subtypes, demonstrating robust correlation characteristics survival. Through WGCNA Lasso analysis, four (KLK3, CD38, FASN, PYCR1) risk profile linked BCR. Notably, high-risk patient group exhibited elevated levels B naive, Macrophage M0, M2 infiltration, while low-risk displayed higher T cells CD4 memory activated monocyte infiltration. Furthermore, IHC assays confirmed heightened tissues.ConclusionThis study leveraged genetic variability microenvironment uncover crucial findings present novel perspectives tailoring treatment strategies on individualized basis.

Language: Английский

Citations

2
Toxicological Effects of Ingested Microplastics on Human Health DOI
Daniel A. Ayejoto, Johnbosco C. Egbueri, Leonard N. Onuba

et al.

Emerging contaminants and associated treatment technologies, Journal Year: 2024, Volume and Issue: unknown, P. 427 - 461

Published: Jan. 1, 2024

Language: Английский

Citations

2
Is liver fibrosis a risk factor for gynecological cancers? DOI Open Access
Amedeo Lonardo

Metabolism and Target Organ Damage, Journal Year: 2024, Volume and Issue: 4(1)

Published: Feb. 22, 2024

A recent study by Crudele et al. reported on the association between surrogate indices of liver fibrosis and risk gynecological cancers among dysmetabolic women. To put this in context, notions regarding sex dimorphism nonalcoholic fatty disease (NAFLD) are discussed. Additionally, meta-analytic reviews extrahepatic reviewed. Next, I discuss relationship metabolic dysfunction-associated (MAFLD) with cancers, notably including breast female reproductive systems humans. The pathomechanisms potentially accounting for include genetics, deregulated hormones, chronic subclinical inflammatory state, milieu, oxidative stress, gut dysbiosis, environmental pollution, altered immune surveillance.

Language: Английский

Citations

1
Distinct roles of CD244 expression in cancer diagnosis and prognosis: A pan-cancer analysis DOI Creative Commons
Zhenzhen Deng, Yuanhong Liu, Haiyan Zhou

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28928 - e28928

Published: March 30, 2024

The abnormal expression of tumor associated genes in pan-cancer is closely related to the clinicopathological features distinct cancer types. Thus, identifying role specific needed for developing effective anti-cancer strategies. However, function CD244 has not been fully understood. In this study, we explored profile across 33 types based on Cancer Genome Atlas project, Gene Expression Omnibus database, and other bioinformatics tools. We found down-regulated levels seven up-regulated two subsequently relationship between survival rate expression, positive patients with adrenocortical carcinoma (ACC), head neck squamous cell (HNSC), skin cutaneous melanoma (SKCM), uterine corpus endometrial (UCEC). further investigated association tumor-infiltrating immune cells, discovered their correlation different tumors. that level was higher normal samples than UCEC samples, positively CD8+ T cells infiltrating. mutation status, promoter methylation, CD244-related molecules signaling pathways were also employed study potential initiation progression. Our offers a comprehensive overview human tumors, revealing as prognostic biomarker immunotherapeutic target cancers.

Language: Английский

Citations

1
The size-dependence and reversibility of polystyrene nanoplastics-induced hepatic pyroptosis in mice through TXNIP/NLRP3/GSDMD pathway DOI

Yanyang Lu,

Weizhen Hua,

Lu Lu

et al.

Toxicology Research, Journal Year: 2024, Volume and Issue: 13(4)

Published: July 1, 2024

As emerging environmental contaminants, nanoplastics (NPs) are progressively accumulating in terrestrial and aquatic ecosystems worldwide, posing a potential threat to human health. The liver is considered as one of the primary organs targeted by NPs accumulation living organisms. However, there remains large knowledge gap concerning NPs-induced hepatotoxicity. In this study, we examined impact chronic exposure environmentally relevant doses polystyrene (PS) on hepatic pyroptosis mice. results demonstrated that both particle sizes PS-NPs (100 nm 500 nm) significantly triggered mouse liver, evidenced upregulation GSDMD-N protein levels; moreover, pyroptotic effect induced 100 was more pronounced compared PS-NPs. Mechanistically, resulted an TXNIP expression, thereby activating NLRP3 inflammasome subsequently inducing inflammatory responses pyroptosis. Notably, following termination subsequent recovery period 50 days, PS-NPs-mediated inflammation via TXNIP/NLRP3 pathway were effectively ameliorated, even returning levels close baseline. Collectively, our findings provide novel evidence for size-dependence reversibility through TXNIP/NLRP3/GSDMD vivo.

Language: Английский

Citations

1