Evidence map›Paper›PMID 41629945›Full record

ArticleJournal of translational medicine2026

In vitro evidence and integrative bioinformatics identify the SGLT2-PPARγ axis as a target against polyethylene microplastic-driven metabolic reprogramming in colorectal cancer cells.

Isabella Donisi, Celestino Sardu, Antonino Colloca, Anna Balestrieri, Vitale Del Vecchio, Raffaele Marfella, Giuseppe Campanile, Nunzia D'Onofrio, Maria Luisa Balestrieri

Registry-linked trialAbstract read
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In one paragraph

Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07580326 (Plastic Accumulation in Residual Brain Tissues From Hemorrhagic Events), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07580326 active not recruitingnot on this map

Plastic Accumulation in Residual Brain Tissues From Hemorrhagic Events: Neurological Outcomes and Pathogenetic Evidence (PARTENOPE Study)

TypeobservationalSponsorUniversity of Campania Luigi VanvitelliRan2024 to 2026Enrolled150ConditionsIntracerebral Hemorrhage, Brain HematomaArmsObservational Analysis
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Isabella DonisiDepartment of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138, Naples, Italy.
Celestino SarduDepartment of Advanced Clinical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia, 80138, Naples, Italy.
Antonino CollocaDepartment of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138, Naples, Italy.
Anna BalestrieriFood Safety Department, Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055, Portici, Italy.
Vitale Del VecchioDepartment of Experimental Medicine, University of Campania Luigi Vanvitelli, Via Luciano Armanni 5, 80138, Naples, Italy.
Raffaele MarfellaDepartment of Advanced Clinical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia, 80138, Naples, Italy.
Giuseppe CampanileDepartment of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137, Naples, Italy.
Nunzia D'OnofrioDepartment of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138, Naples, Italy. nunzia.donofrio@unicampania.it.
Maria Luisa BalestrieriDepartment of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138, Naples, Italy.

Funding

Ministero della Salute IZS ME 09/22Ministero dello Sviluppo Economico F/310110/04/X56Ministero dell'Università e della Ricerca 2022KH87XSMinistero dell'Università e della Ricerca P2022SZE5Y
6 · The paper itself

Abstract

backgroundMicroplastics have emerged as a growing burden to human health, with increasing evidence linking chronic exposure to adverse outcomes including inflammation, metabolic disruption, and carcinogenesis. Microplastics can be internalized by colorectal cancer (CRC) cells and influence cancer-related processes including metastasis, chemoresistance, oxidative stress, and cellular metabolism. However, the molecular mechanism underlying microplastic effects on CRC progression and metabolism remain poorly understood.

methodsHT-29 and HCT 116 CRC cells were exposed to polyethylene (PE) microplastics (10 µg/mL) up to 72 h. Cell viability was assessed using the CCK-8 assay, and metabolic and tumorigenic features were evaluated through enzyme-linked immunosorbent (ELISA) assays and XF HS Seahorse Bioanalyzer. The modulatory effects of SGLT2 inhibitor canagliflozin (iSGLT2), γ-butyrobetaine (γBB) and L-carnitine (Cnt) on PE-induced alterations was investigated with immunoblotting, flow cytometric and bioinformatic analyses.

resultsPE exposure enhanced proliferation (p < 0.001), inflammation, angiogenesis and invasive potential. PE also increased cellular bioenergetics, marked by heightened glycolysis and mitochondrial respiration (p < 0.05). At molecular level, upregulation of SIRT1 (p < 0.05), and SGLT2 protein expression (p < 0.05) were observed. iSGLT2 counteracted the effects of PE, by reducing cell proliferation, inflammation, mitochondrial respiration, and glycolysis (p < 0.001), while promoting lipid peroxidation and ferroptotic cell death (p < 0.001), highlighting the potential to target metabolic vulnerability of CRC cells. Similarly, PE, γBB and Cnt (PE + γBB + Cnt) ameliorated the onco-metabolic changes induced by PE and triggered ferroptotic cell death. Bioinformatic analysis identified PPARγ as a common target of CRC and iSGLT2 and was modulated by both canagliflozin and γBB + Cnt, suggesting a shared molecular mechanism.

conclusionResults unveil the adverse effects of PE on CRC progression underscoring a dynamic interplay between environmental pollutants, metabolic regulators and dietary bioactive modulators. This evidence lay the groundwork for future studies on integrative approaches aimed at mitigating the effects of microplastic pollution on CRC.

Indexed as

Colorectal NeoplasmsComputational BiologyMetabolic ReprogrammingMicroplasticsPPAR gammaSignal TransductionSodium-Glucose Transporter 2Cell Line, TumorCell ProliferationCell SurvivalHCT116 CellsHT29 CellsHumansMicroplasticsPPAR gammaSLC5A2 protein, humanSodium-Glucose Transporter 2Colorectal cancerPolyethylene-microplasticQuaternary ammonium compoundsSGLT2 inhibitor

Identifiers

PMID41629945

What Socratic holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.