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

Qi Liu,

Zhaoyun Cheng

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 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.

Язык: Английский

Microplastics in human skeletal tissues: Presence, distribution and health implications DOI Creative Commons

Qiaoyi Yang,

Peng Ye, Xiaodong Wu

и другие.

Environment International, Год журнала: 2025, Номер 196, С. 109316 - 109316

Опубликована: Фев. 1, 2025

Although microplastics have been detected in human blood, placenta and other tissues. In this study, for the first time, we characterized presence variation of microplastic deposition patterns three skeletal tissues, namely bone, cartilage, intervertebral discs. Forty fragments were observed 24 samples from disc, ranging 25.44 to 407.39 μm diameter. The abundance disc (61.1 ± 44.2 particles/g) was higher than those bone (22.9 15.7 cartilage tissue (26.4 17.6 particles/g). average sizes discs (159.5 103.8 μm) (138.86 105.67 larger that (87.5 30.7 μm). most frequently identified polymers polypropylene (35 %), ethylene vinyl acetate copolymer (30 polystyrene (20 %). vivo experiment suggested invaded through blood circulation after 4 weeks exposure. Serum levels tumor necrosis factor-α (TNF-α), Type Ⅰ procollagen amino-terminal peptide (PINP), tartrate-resistant acid phosphatase-5b (TRACP-5b) elevated compared with control group (p < 0.05). Our study suggests invade supply, causing distinct accumulation these regions. Microplastic invasion can affect health by influencing expression inflammatory morphogenetic cytokines. These findings provide insights into investigating impact on health.

Язык: Английский

Процитировано

4
Detection and quantification of microplastics in various types of human tumor tissues DOI Creative Commons
Jun Zhao, Haibo Zhang, Lei Shi

и другие.

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 283, С. 116818 - 116818

Опубликована: Июль 30, 2024

Microplastics (MPs) have been detected in various human tissues. However, whether MPs can accumulate within tumors and how they affect the tumor immune microenvironment (TIME) therapeutic responses remains unclear. This study aimed to determine presence of their potential effects on TIME. Sixty-one samples were collected for analysis. The was qualitatively quantitatively assessed using pyrolysis-gas chromatography-mass spectrometry. 26 examined. Three types identified: polystyrene, polyvinyl chloride, polyethylene. In lung, gastric, colorectal, cervical tumors, MP detection rates 80 %, 40 50 17 % (7.1-545.9 ng/g), respectively. 70 pancreatic (18.4-427.1 ng/g) but not esophageal tumors. cancer, MP-infiltrated TIME exhibited a reduction CD8

Язык: Английский

Процитировано

13
Impact of microplastics and nanoplastics on liver health: Current understanding and future research directions DOI Creative Commons
Chun‐Cheng Chiang, Hsuan Yeh, Ruei-Feng Shiu

и другие.

World Journal of Gastroenterology, Год журнала: 2024, Номер 30(9), С. 1011 - 1017

Опубликована: Март 5, 2024

With continuous population and economic growth in the 21

Язык: Английский

Процитировано

7
An evaluation of a hepatotoxicity risk induced by the microplastic polymethyl methacrylate (PMMA) using HepG2/THP-1 co-culture model DOI Creative Commons
Tuğçe Boran, Özge Sultan Zengin, Zehra Şeker

и другие.

Environmental Science and Pollution Research, Год журнала: 2024, Номер 31(20), С. 28890 - 28904

Опубликована: Апрель 2, 2024

Abstract Inappropriate disposal of plastic wastes and their durability in nature cause uncontrolled accumulation land/marine ecosystems, also causing destructive effects by bioaccumulating along the food chain. Microplastics may chronic inflammation relation to permanent structures, especially through oxidative stress cytotoxic cellular damage, which could increase risk cancer development. The microplastics liver is a major concern, therefore, identification mechanisms hepatotoxic great importance. Polymethyl methacrylate (PMMA) widely used thermoplastic. It has been determined that PMMA disrupts lipid metabolism various aquatic organisms causes reproductive developmental toxicity. PMMA-induced humans have not yet clarified. In our study, toxic (in range 3–10 μm) on human were investigated using HepG2/THP-1 macrophage co-culture model, sensitive immune-mediated injury model. Cellular uptake micro-sized cells was done transmission electron microscopy. Determination its cell viability inflammatory response, stress, with gene protein expression levels play role mechanism pathways underlying investigated. results concluded inflammation, disruptions should be focus attention as important hepatotoxicity. Our points out potential adverse health, supports literature information subject.

Язык: Английский

Процитировано

7
Links between fecal microplastics and parameters related to metabolic dysfunction-associated steatotic liver disease (MASLD) in humans: An exploratory study DOI Creative Commons
Katherine J. P. Schwenger,

Yasaman Ghorbani,

Sharvika Bharatselvam

и другие.

The Science of The Total Environment, Год журнала: 2024, Номер 953, С. 176153 - 176153

Опубликована: Сен. 10, 2024

Язык: Английский

Процитировано

5
Effects of microplastics on the immune system: How much should we worry? DOI Creative Commons
Claudia Vanetti,

Martina Broggiato,

Stefania Pezzana

и другие.

Immunology Letters, Год журнала: 2025, Номер 272, С. 106976 - 106976

Опубликована: Фев. 1, 2025

Plastics are everywhere. It is widely recognized that they represent a global problem, the extent of which yet to be defined. Humans broadly exposed plastics, whose effects and consequences poorly characterized so far. The main route exposure via alimentary respiratory intake. pollutions may come from both: water food contamination itself, their packaging. smaller sizes (i.e. microplastics <150 µm - MPs) considered most pervasive living organisms and, therefore, potentially harmful. As humans occupy one apex positions chain, we bioaccumulation biomagnification MPs. In fact, MPs commonly found in human stools blood. However, there no data available on ability accumulate produce detrimental biological systems. Even though plastics pollution studied mammals, including humans, appear have inflammatory effects, rather concerning as many etiologies disease based pro-inflammatory status.

Язык: Английский

Процитировано

0
Microplastics in our diet: A growing concern for human health DOI
Ramon Bocker, Eric Keven Silva

The Science of The Total Environment, Год журнала: 2025, Номер 968, С. 178882 - 178882

Опубликована: Фев. 22, 2025

Язык: Английский

Процитировано

0
Overview of the hazardous impacts of metabolism-disrupting chemicals on the progression of fatty liver diseases DOI Creative Commons

G.-H. An,

Jinyeop Song, Wei Ying

и другие.

Molecular & Cellular Toxicology, Год журнала: 2025, Номер 21(2), С. 387 - 397

Опубликована: Фев. 27, 2025

Given the global increase in obesity, metabolic dysfunction-associated steatotic liver disease (MASLD) is a major health concern. Because primary organ for xenobiotic metabolism, impact of environmental stressors on homeostasis and MASLD has garnered significant interest over past few decades. The concept metabolism-disrupting chemicals (MDCs) been introduced to underscore importance factors homeostasis. Recent epidemiological biological studies suggest causal link between exposure MDCs prevalence progression MASLD. This review aims introduce emerging their representative toxic mechanisms. In particular, this focuses broadening understanding impacts or steatohepatitis (MASH) progression. research highlighted contaminants, such as heavy metals, microplastics, pesticides, have potential influence hepatic metabolism aggravate MASLD/MASH These not only directly affect lipid hepatocytes but also other cell types, immune cells stellate cells, well gut-liver axis. Collectively, these findings contribute establishing well-defined adverse outcome pathway identify novel therapeutic options diseases associated with pollutants.

Язык: Английский

Процитировано

0
Biological Effects of Micro-/Nano-Plastics in Macrophages DOI Creative Commons
Massimiliano G. Bianchi, Lavinia Casati,

Giulia Sauro

и другие.

Nanomaterials, Год журнала: 2025, Номер 15(5), С. 394 - 394

Опубликована: Март 4, 2025

The environmental impact of plastics is worsened by their inadequate end-of-life disposal, leading to the ubiquitous presence micro- (MPs) and nanosized (NPs) plastic particles. MPs NPs are thus widely present in water air inevitably enter food chain, with inhalation ingestion as main exposure routes for humans. Many recent studies have demonstrated that gain access several body compartments, where they taken up cells, increase production reactive oxygen species, lead inflammatory changes. In most tissues, resident macrophages engage first approach foreign materials, this interaction largely affects subsequent fate material possible pathological outcomes. On other hand, organizers controllers both responses tissue repair. Here, we aim summarize available information on NPs. Particular attention will be devoted consequences macrophage viability functions, well implications pathology.

Язык: Английский

Процитировано

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

Yabin Yu,

Shuai Wang

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 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

Язык: Английский

Процитировано

0