American College of Toxicology (ACT)的动态

?? Idiosyncratic drug-induced liver injury (iDILI) is unpredictable. Our latest study published in Archives of Toxicology shows that individual-centric spheroid models can predict iDILI risk and identify mechanisms. ?? Findings reveal that troglitazone-mediated iDILI risk is linked to the suppression of IL-12 production by autologous macrophages and dendritic cells in specific individuals. Our proprietary cell educating technology offers a personalized strategy to mitigate iDILI risk. Read the full study in Archives of Toxicology. https://bit.ly/3TeWdQO ?? Confirm the safety of your drug and find out how to suppress iDILI risk with individual-centric spheroid models! ?? Meet our experts at EUROTOX Congress 2024 in Copenhagen (poster session #501 and #585) to discuss your project or business partnering. [email protected] www.predictcan.com #drugsafety #presicionmedicine #predictcan #alternativemodels #dili

Excited to share my latest publication in BMC Pharmacology & Toxicology! I'm thrilled to announce that our research article, "Nephroprotective role of resveratrol in renal ischemia-reperfusion injury: a preclinical study in Sprague-Dawley rats," has been published in BMC Pharmacology & Toxicology. In this study, we investigated the potential of resveratrol, a natural compound found in grapes and red wine, to protect kidneys from damage caused by ischemia-reperfusion injury (IRI). IRI occurs when blood flow to the kidneys is interrupted and restored, often leading to inflammation and oxidative stress. Our findings suggest that resveratrol may be a promising therapeutic option for preventing or treating renal IRI. By reducing inflammation, oxidative stress, and apoptosis (cell death), resveratrol helped preserve kidney function in our rat model. https://rdcu.be/d1TBm #nephrology #kidneyhealth #resveratrol #antioxidants #pharmacology #toxicology #research ?

We have a new App Note! We're excited to share a breakthrough in predictive gastrointestinal (GI) toxicity research, in collaboration with Promega Corporation . It showcases how our newest product, the OrganoReady? Colon Organoid, combined with functional multiplexed assays, helps address a critical gap in drug development—predicting drug-induced GI adverse events. Key highlights: ?? Ready-to-use 3D human colon organoid ?? Translatable model for drug screening ?? Predicts on-target & off-target toxicity with advanced assays Learn how to enhance your toxicology workflows and improve drug safety with this innovative gut model: https://lnkd.in/eXEFnxrr #Organoids #Toxicology #DrugDevelopment #GItoxicity #3DModels

The hit of excitement that follows the publication of a new scientific paper never gets old. So please let me share with you Mitologics’ latest article, published in Toxicological Sciences. My heartfelt thanks go to Bernard Fromenty and my colleagues: Nelly Buron, Mathieu Porceddu, and Cécile Martel, PhD. Please feel free to contact me should you have any questions. Enjoy the reading ?? ? #toxicology #liver #dili #hepatotoxicity #mitochondria

[New paper] Predicting drug-induced hepatotoxicity – such as steatosis – and identifying its mechanisms can benefit from Mitologics’ technology and expertise. That is the topic of our latest research article published in April 2024 in Toxicological Sciences. In this work, 32 steatogenic and 13 nonsteatogenic drugs were tested for their ability to inhibit mitochondrial fatty acid oxidation (mtFAO) in mitochondria isolated from mouse liver. The set of predictive toxicology tests showed a sensitivity and a positive predictive value above 88% to anticipate the occurrence of drug-induced steatosis in patients. Further assays explored the ability of tests to shed light on the mechanisms triggering this specific form of drug-induced liver injury (DILI). Pharmaco-induced mtFAO impairment was approached via the assessment of mitochondrial respiration with different fatty acids (palmitoyl-coenzyme A + L-carnitine, palmitoyl-L-carnitine and octanoyl-L-carnitine) and was completed with the study of glutamate- and succinate-driven mitochondrial respiration. The combination of these predictive toxicology tests with our established MiToxView? approach can thus help to identify potential hepatotoxic drugs early at the drug discovery stage and bring a better understanding of the mechanisms of drug-induced hepatotoxicity. A heartfelt thanks to Bernard Fromenty, PhD?co-leader of the EXPRES team (NuMeCan, Inserm, Université de Rennes) and his team, with whom Mitologics has been working since 2009. This collaboration, part of the project MITOXDRUGS, has been supported by the ANR (Agence nationale de la recherche) (Project ANR-16-CE18-0010, Programme PRCE 2016-2019). Read more ?? and please leave any questions or feedback. We’ll be happy to answer. https://lnkd.in/e-c_66vU ? #toxicology #liver #dili #hepatotoxicity #mitochondria

??EXCLUSIVE EVENT?? ?????????????????? ???????????????????????????? ???????????????????? ???????? ???????????????????????????? Join us on ?????????????? ???????? for a one-off webinar! Ambroise GARRY, the Group Head for Global Investigative Toxicology within preclinical safety at Sanofi will present some of the work his team has carried out studying cardiotoxicity in human iPSC-derived cardiomyocytes. He will discuss data acquired using holotomography to study the cell responses to established drugs known primarily for inducing phospholipidosis, which may also trigger cell death. Cardiotoxicity is a significant cause of clinical trials failure in new drug candidates, contributing to the overall failure rate of around 90% for all drug candidates.?Phenotypic screening provided by technologies such as high-content live cell imaging could provide an opportunity to catch failures at an earlier, in vitro stage, and increase the translatability of drugs to clinic. Topics covered: ·???????Cardiovascular derisking with label-free live cell imaging ·???????Drug-induced phospholipidosis ·???????Label-free quantification of lipid droplets, lamellar bodies, and cytotoxicity evaluation in cells ·???????IC50 calculation from live cell imaging ·???????Doxorubicin-induced cardiotoxicity This event will ???????? ???? ?????????????????? ???????????? ???? ?????? ?????????????????? ??????????:?? - 22nd October at 4 pm CEST/ 10 am EDT / 7 am PDT - 22nd October at 10 pm CEST/ 4 pm EDT / 1 pm PDT - 23rd October at 1 am CEST/ 22nd October 7 pm EDT / 22nd October 4 pm PDT Register here! https://bit.ly/47Z4j6s

Methotrexate accumulation in target intestinal mucosa and white blood cells differs from non-target red blood cells of patients with Crohn's disease New study in Basic & Clinical Pharmacology & Toxicology aimed to measure intracellular methotrexate polyglutamate concentrations in red blood cells, white blood cells (PBMCs) and intestinal mucosa of patients with Crohn's disease using low-dose methotrexate. It found that methotrexate polyglutamate concentrations in PBMCs were up to 18 times higher than in red blood cells. Concentrations in PBMCs of patients who discontinued their methotrexate treatment decreased rapidly. The distribution of the methotrexate polyglutamate species (1 up to 6 glutamate chains) differed between mucosa, PBMCs en red blood cells, with remarkbly long-chain concentrations in the intestinal mucosa. These findings help to understand the complex pharmacokinetics?of methotrexate and could have implications when methotrexate polyglutamate concentrations?will be measured for therapeutic drug monitoring in the future. Study conducted by Maartje van de Meeberg,?Janani Sundaresan, Marry Lin,?Gerrit Jansen, Eduard Struys, Herma Fidder, Bas Oldenburg,?Wout G. N. Mares,?Nofel Mahmmod, Dirk van Asseldonk, Svend Rietdijk,?Loes H. C. Nissen,?Nanne K. H. de Boer, Gerd Bouma, Maja Bulatovi?-?alasan and Robert de Jonge,?on behalf on the Dutch Initiative on Crohn and Colitis (ICC). Read the full paper here: https://lnkd.in/dXUVk8HR

In vivo CART with CD8-LNP: exiting preclinical and toxicology results from small/large animal models. Very promising platform for autoimmune therapy.

?? Visit Our Poster Presentation at the ACT Meeting! We’re excited to announce that Dr. Janet Olugbodi, Study Director of Pharmacology and Toxicology, will be presenting her latest work on CAR T-cell therapy for Acute Lymphoblastic Leukemia (ALL): ??"Comprehensive Evaluation of CAR T-Cell Efficacy and Safety in a Mouse Model of ALL Using Integrated Biodistribution and Kinetics Analysis." ?? Dr. Olugbodi’s research dives deep into CAR T-cell #biodistribution and safety profiles, with findings that could help advance life-saving treatments for ALL patients. Don't miss this chance to engage and explore groundbreaking work in immunotherapy. Join us November 18th in the Exhibition Hall! Schedule a meeting with Janet at #ACTOX24 here: https://lnkd.in/gMEcf-ps Janet O O. #ACTOX2024 #ACT2024 #toxicology #pharmacology #immunotherapy #leukemia #research #cartcells #efficacy

Drug-induced liver injury (DILI) remains a major cause of drug attrition, due to the limitations of?in vitro?#hepatotoxicity assays?and?in vivo?models. Most medications are metabolised in the liver, making it one of the primary tissues affected by adverse drug reactions. Earlier identification means that promising drugs can undergo modifications to address toxicity and lower attrition rates. This requires preclinical assays with greater human relevance and sensitivity. The #PhysioMimix?Liver-on-a-chip DILI Assay allows prediction of human liver responses to acute and chronic drug exposure, in the presence/absence of underlying disease. This?in vitro?hepatotoxicity assay consists of human primary liver parenchymal and non-parenchymal cells (NPCs) cultured in 3D under perfusion to form tissues from which it is possible to detect functional liver-specific endpoints (including clinical biomarkers such as albumin and ALT/AST). The assay allows sensitive assessment of compound toxicity with full dose–response curves and, by incorporating Kupffer cells, allows for the evaluation of immune-mediated toxicity. CN Bio #DILI #LiverOnChip #drugmetabolism #toxicology