Current Research in Toxicology最新文献

{"title":"Cytotoxicity and inhibitory potential of CUDC-101 in non-small cell lung cancer cells with rare EGFR L861Q mutation","authors":"Chunhong Chu ,&nbsp;Huixia Xu ,&nbsp;Chenxue Liu ,&nbsp;Xiangkai Wei ,&nbsp;Lanxin Li ,&nbsp;Rui Wang ,&nbsp;Wenrui Cui ,&nbsp;Guoliang Zhang ,&nbsp;Chenyang Liu ,&nbsp;Ke Wang ,&nbsp;Lei An ,&nbsp;Fei He","doi":"10.1016/j.crtox.2024.100194","DOIUrl":"10.1016/j.crtox.2024.100194","url":null,"abstract":"<div><div>The epidermal growth factor receptor (EGFR) represents an effective target for the treatment of non-small cell lung cancer. In the treatment of classical EGFR mutations, EGFR tyrosine kinase inhibitors have achieved desirable clinical efficacy. However, the effectiveness of tyrosine kinase inhibitors (TKIs) against the L861Q mutation has not been fully established. In this study, the four cell lines containing the L861Q mutation were constructed by CRISPR and the anti-tumour effects of CUDC-101 on them were investigated in vitro by various chemosensitivity methods, with afatinib serving as a positive control. The results demonstrated that CUDC-101 inhibited the proliferation and clonogenic capacity on the four cells through the ERK or AKT pathways, decreased the mitochondrial membrane potential of the cells, blocked the cell cycle and promoted apoptosis. Our findings suggest that CUDC-101 may be a promising treatment option for NSCLC patients with the EGFR exon 18 substitution mutation L861Q.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100194"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol – Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescue","authors":"Aline Yammine ,&nbsp;Imen Ghzaiel ,&nbsp;Vivien Pires ,&nbsp;Amira Zarrouk ,&nbsp;Omar Kharoubi ,&nbsp;Hélène Greige-Gerges ,&nbsp;Lizette Auezova ,&nbsp;Gérard Lizard ,&nbsp;Anne Vejux","doi":"10.1016/j.crtox.2024.100153","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100153","url":null,"abstract":"<div><p>On murine N2a cells, 7-ketocholesterol induced an oxiapotophagic mode of cell death characterized by oxidative stress (reactive oxygen species overproduction on whole cells and at the mitochondrial level; lipid peroxidation), apoptosis induction (caspase-9, −3 and −7 cleavage, PARP degradation) and autophagy (increased ratio LC3-II / LC3-I). Oxidative stress was strongly attenuated by diphenyleneiodonium chloride which inhibits NAD(P)H oxidase. Mitochondrial and peroxisomal morphological and functional changes were also observed. Down regulation of PDK1 / Akt signaling pathways as well as of GSK3 / Mcl-1 and Nrf2 pathways were simultaneously observed in 7-ketocholesterol-induced oxiapoptophagy. These events were prevented by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol. The inhibition of the cytoprotection by LY-294002, a PI3-K inhibitor, demonstrated an essential role of PI3-K in cell rescue. The rupture of oxidative stress in 7-ketocholesterol-induced oxiapoptophagy was also associated with important modifications of glutathione peroxidase, superoxide dismutase and catalase activities as well as of glutathione peroxidase-1, superoxide dismutase-1 and catalase level and expression. These events were also counteracted by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol. The inhibition of the cytoprotection by mercaptosuccinic acid, a glutathione peroxidase inhibitor, showed an essential role of this enzyme in cell rescue. Altogether, our data support that the reactivation of PI3-K and glutathione peroxidase activities by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol are essential to prevent 7KC-induced oxiapoptophagy.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100153"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000069/pdfft?md5=cc94eed3c51e0bb23ed2a0f7ac637582&pid=1-s2.0-S2666027X24000069-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139737550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen sulfide donor NaHS inhibits formaldehyde-induced epithelial-mesenchymal transition in human lung epithelial cells via activating TGF-β1/Smad2/3 and MAPKs signaling pathways","authors":"Haopei Wang ,&nbsp;Miaomiao Jia ,&nbsp;Yuxin Chang,&nbsp;Xingwei Ling,&nbsp;Wenyan Qi,&nbsp;Hongtao Chen,&nbsp;Feipeng Chen,&nbsp;Haiyang Bai,&nbsp;Yuhan Jiang,&nbsp;Chengfan Zhou","doi":"10.1016/j.crtox.2024.100199","DOIUrl":"10.1016/j.crtox.2024.100199","url":null,"abstract":"<div><div>Formaldehyde (FA) long term exposure leads to abnormal pulmonary function and small airway obstruction of the patients. Hydrogen sulfide (H₂S) is one of the recognized gaseous transmitters involved in a wide range of cellular functions. It is unknown the involvement of H₂S in FA-induced lung injury. The purpose of this study is to investigate the therapeutic potential and mechanism of H₂S on FA-induced epithelial-mesenchymal transition (EMT) of human lung epithelial cells. The cell viability of Beas2B and A549 cells after FA treatment were assessed using MTT assay. The endogenous H₂S was visualized by fluorescence microscopy using of the 7-azido-4-methylcoumarin (AzMC). Cell morphology was observed under phase contrast microscope. The mRNAs and proteins level were evaluated by reverse transcription-polymerase chain reaction and western blotting assays. FA treatment downregulated the endogenous H₂S levels and the mRNAs and proteins level of H₂S synthesizing enzymes, such as cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) in Beas2B and A549 cells. FA treatment changed the cell morphology of Beas2B cells from cuboid to a spindle-shape, while declined the protein level of E-cadherin and increased the protein level of Vimentin. Moreover, FA treatment increased the proteins level of transforming growth factor-β1 (TGF-β1), phosphorylated-Smad2 (p-Smad2), phosphorylated-Smad3 (p-Smad3), phosphorylated-extracellular signal-regulated kinase (p-ERK), phosphorylated-c-Jun N-terminal kinase (p-JNK), and phosphorylated-P38 (p-P38). Furthermore, the inhibitors of TGF-β receptor type 1 (TGFβRI) and mitogen-activated protein kinases (MAPKs) signaling pathways reversed FA-induced decrease in E-cadherin expression and increase in Vimentin expression in Beas2B cells. Sodium hydrogen sulfide (NaHS) increased the level of H₂S, while reversed FA-induced the low expression of E-cadherin and the high expression of Vimentin, TGF-β1, p-Smad2, p-Smad3, p-ERK, p-JNK, and p-P38. These findings indicates FA treatment downregulating the endogenous H₂S in human lung epithelial cells. NaHS may inhibit FA-induced EMT in human lung epithelial cells via modulating TGF-β1/Smad2/3 and MAPKs signaling pathways. Therefore, we demonstrated that supplementation of exogenous H₂S may inhibit FA-induced lung injury.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100199"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen replacement therapy reverses spatial memory loss and pyramidal cell neurodegeneration in the prefrontal cortex of lead-exposed ovariectomized Wistar rats","authors":"Abiodun Shukrat Lasisi-Sholola ,&nbsp;Sodiq Opeyemi Hammed ,&nbsp;Richard Adedamola Ajike ,&nbsp;Roland Eghoghosoa Akhigbe ,&nbsp;Oladele Ayobami Afolabi","doi":"10.1016/j.crtox.2024.100200","DOIUrl":"10.1016/j.crtox.2024.100200","url":null,"abstract":"<div><h3>Background</h3><div>Although menopause is a component of chronological aging, it may be induced by exposure to heavy metals like lead. Interestingly, lead exposure, just like the postmenopausal state, has been associated with spatial memory loss and neurodegeneration; however, the impact of hormone replacement therapy (HRT) on menopause and lead-induced spatial memory loss and neurodegeneration is yet to be reported.</div></div><div><h3>Aim</h3><div>The present study investigated the effect and associated mechanism of HRT on ovariectomized-driven menopausal state and lead exposure-induced spatial memory loss and neurodegeneration.</div></div><div><h3>Materials and methods</h3><div>Thirty adult female Wistar rats were randomized into 6 groups (n = 5 rats/group); the sham-operated vehicle-treated, ovariectomized (OVX), OVX + HRT, lead-exposed, OVX + lead, and OVX + Lead + HRT groups. Treatment was daily via gavage and lasted for 28 days.</div></div><div><h3>Results</h3><div>Ovariectomy and lead exposure impaired spatial memory deficit evidenced by a significant reduction in novel arm entry, time spent in the novel arm, alternation, time exploring novel and familiar objects, and discrimination index. These findings were accompanied by a marked distortion in the histology of the prefrontal cortex, and a decline in serum dopamine level and pyramidal neurons. In addition, ovariectomy and lead exposure induced metabolic disruption (as depicted by a marked rise in lactate level and lactate dehydrogenase and creatinine kinase activities), oxidative stress (evidenced by a significant increase in MDA level, and decrease in GSH level, and SOD and catalase activities), inflammation (as shown by significant upregulation of myeloperoxidase activity, and TNF-α and IL-1β), and apoptosis (evidenced by a rise in caspase 3 activity) of the prefrontal cortex. The observed biochemical and histological perturbations were attenuated by HRT.</div></div><div><h3>Conclusions</h3><div>This study revealed that HRT attenuated ovariectomy and lead-exposure-induced spatial memory deficit and pyramidal neurodegeneration by suppressing oxidative stress, inflammation, and apoptosis of the prefrontal cortex.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100200"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental transfer of tofacitinib in the ex vivo dual-side human placenta perfusion model","authors":"Gaby A.M. Eliesen ,&nbsp;Milou Fransen ,&nbsp;Hedwig van Hove ,&nbsp;Petra H.H. van den Broek ,&nbsp;Rick Greupink","doi":"10.1016/j.crtox.2024.100149","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100149","url":null,"abstract":"<div><p>Tofacitinib is a small molecule Janus kinase (JAK) inhibitor, introduced to the European market in 2017, for the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. In the treatment of women with autoimmune diseases, pregnancy is a relevant issue, as such diseases typically affect women in their reproductive years. Currently, there is limited data on the use of tofacitinib during pregnancy. To estimate the extent of placental transfer in the absence of clinical data, we conducted <em>ex vivo</em> dual-side perfused human placental cotyledon perfusions. Term placentas were perfused for 180 min with tofacitinib (100 nM, added to the maternal circuit) in a closed-closed configuration. At the end of the perfusions, drug concentrations in the maternal and fetal reservoirs were near equilibrium, at 35.6 ± 5.5 and 24.8 ± 4.7 nM, respectively. Transfer of tofacitinib was similar to that observed for the passive diffusion marker antipyrine (100 µg/mL, added to the maternal reservoir). Final antipyrine maternal and fetal concentrations amounted to 36.9 ± 3.0 and 36.7 ± 1.3 µg/mL, respectively. In conclusion, in the <em>ex vivo</em> perfused placenta tofacitinib traverses the placental barrier rapidly and extensively. This suggests that substantial fetal tofacitinib exposure will take place after maternal drug dosing.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100149"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000021/pdfft?md5=750bbc6c92fbedeaeb8bafe931bcf4db&pid=1-s2.0-S2666027X24000021-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139419305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D human stem-cell-derived neuronal spheroids for in vitro neurotoxicity testing of methylglyoxal, highly reactive glycolysis byproduct and potent glycating agent","authors":"Teresa Coccini ,&nbsp;Francesca Caloni ,&nbsp;Luciana Alessandra Russo ,&nbsp;Laura Villani ,&nbsp;Davide Lonati ,&nbsp;Uliana De Simone","doi":"10.1016/j.crtox.2024.100176","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100176","url":null,"abstract":"<div><p>Human-derived three-dimensional (3D) <em>in vitro</em> models are advanced <em>human cell-based</em> model for their complexity, relevance and application in toxicity testing. Intracellular accumulation of methylglyoxal (MGO), the most potent glycating agent in humans, mainly generated as a by-product of glycolysis, is associated with age-related diseases including neurodegenerative disorders.</p><p>In our study, 3D human stem-cell-derived neuronal spheroids were set up and applied to evaluate cytotoxic effects after short-term (5 to 48 h) treatments with different MGO concentrations, including low levels, taking into consideration several biochemical endpoints.</p><p>In MGO-treated neurospheroids, reduced cell growth proliferation and decreased cell viability occurred early from 5-10 μM, and their compactness diminished starting from 100 μM, apparently without affecting spheroid size. MGO markedly caused loss of the neuronal markers MAP-2 and NSE from 10-50 μM, decreased the detoxifying Glo1 enzyme from 50 μM, and activated NF-kB by nuclear translocation.</p><p>The cytochemical evaluation of the 3D sections showed the presence of necrotic cells with loss of nuclei. Apoptotic cells were observed from 50 μM MGO after 48 h, and from 100 μM after 24 h. MGO (50–10 µM) also induced modifications of the cell–cell and cell-ECM interactions. These effects worsened at the higher concentrations (300–500 µM).</p><p>In 3D neuronal spheroids, MGO tested concentrations comparable to human samples levels measured in MGO-associated diseases, altered neuronal key signalling endpoints relevant for the pathogenesis of neurodegenerative diseases and aging. The findings also demonstrated that the use of 3D neuronal spheroids of human origin can be useful in a strategy <em>in vitro</em> for testing MGO and other dicarbonyls evaluation.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100176"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X2400029X/pdfft?md5=215eca89a24ba4180c3d12b699dc970d&pid=1-s2.0-S2666027X2400029X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141308252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using targeted fetal rat testis genomic and endocrine alterations to predict the effects of a phthalate mixture on the male reproductive tract","authors":"L. Earl Gray Jr ,&nbsp;Christy S. Lambright ,&nbsp;Nicola Evans ,&nbsp;Jermaine Ford ,&nbsp;Justin M. Conley","doi":"10.1016/j.crtox.2024.100180","DOIUrl":"10.1016/j.crtox.2024.100180","url":null,"abstract":"<div><p>Administration of phthalates <em>in utero</em> disrupts gene expression and hormone levels in the fetal rat testis, which are key events in an Adverse Outcome Pathway (AOP) for the Phthalate Syndrome. These measures can be used to predict the postnatal adverse effects of phthalate esters (PEs) on male rat sexual differentiation. Here, pregnant rats were exposed to dibutyl (DBP)- and diisononyl (DINP) phthalate on gestational days 14 to 18 individually and as a mixture (DBP,250 mg/kg/d; DINP, 750 mg/kg/d; and DBP 250 mg/kg/d plus DINP 750 mg/kg/d). We found that each PE reduced testosterone production (T Prod) and related gene transcripts by about 50 % and that they acted in a dose additive manner, reducing T Prod and gene expression by 75 % as a mixture. Based upon effects on T Prod, DINP was 0.33 times as potent as DBP and thus the DBP + DINP mixture was predicted to be equivalent to 500 mg DBP/kg/d.</p><p>Logistic regression models of T Prod predicted that the adverse effects of the DBP + DINP mixture group versus the DBP and DINP individual treatments would reduce anogenital distance (AGD) by 27 % versus 10 %, increase hypospadias in 18 % versus &lt; 1 %, induce epididymal agenesis in 46 % versus 10 %, and increase areolae/nipples in 4.8 % versus &lt; 0.1 % of the, respectively. These predictions were highly consistent with effects from previously published dose response studies on the male reproductive effects of DBP. In summary, these results support the use of this New Approach Method to predict the detrimental effects of PEs and PE mixtures, replacing or reducing the need to run long-term, resource and animal use intensive extended one-generation reproduction studies for this class of chemicals.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100180"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000331/pdfft?md5=0c74927333f72ddbcf93a0ec39b540c1&pid=1-s2.0-S2666027X24000331-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141415617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis as an emerging target in sickle cell disease","authors":"Vitor Fortuna ,&nbsp;Jaqueline Lima ,&nbsp;Gabriel F. Oliveira ,&nbsp;Yasmin S. Oliveira ,&nbsp;Bruk Getachew ,&nbsp;Sergei Nekhai ,&nbsp;Michael Aschner ,&nbsp;Yousef Tizabi","doi":"10.1016/j.crtox.2024.100181","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100181","url":null,"abstract":"<div><p>Sickle cell disease (SCD) is an inherited hemoglobin disorder marked by red blood cell sickling, resulting in severe anemia, painful episodes, extensive organ damage, and shortened life expectancy. In SCD, increased iron levels can trigger ferroptosis, a specific type of cell death characterized by reactive oxygen species (ROS) and lipid peroxide accumulation, leading to damage and organ impairments. The intricate interplay between iron, ferroptosis, inflammation, and oxidative stress in SCD underscores the necessity of thoroughly understanding these processes for the development of innovative therapeutic strategies. This review highlights the importance of balancing the complex interactions among various factors and exploitation of the knowledge in developing novel therapeutics for this devastating disease.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100181"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000343/pdfft?md5=1490b17318a14897e021de212f1f903c&pid=1-s2.0-S2666027X24000343-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141429304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"iPSC-derived and Patient-Derived Organoids: Applications and challenges in scalability and reproducibility as pre-clinical models","authors":"Elisa Heinzelmann ,&nbsp;Francesco Piraino ,&nbsp;Mariana Costa ,&nbsp;Aline Roch ,&nbsp;Maxim Norkin ,&nbsp;Virginie Garnier ,&nbsp;Krisztian Homicsko ,&nbsp;Nathalie Brandenberg","doi":"10.1016/j.crtox.2024.100197","DOIUrl":"10.1016/j.crtox.2024.100197","url":null,"abstract":"<div><div>Recent advancements in stem cell technology have led to the development of organoids – three-dimensional (3D) cell cultures that closely mimic the structural and functional characteristics of human organs. These organoids represent a significant improvement over traditional two-dimensional (2D) cell cultures by preserving native tissue architecture and cellular interactions critical for physiological relevance.</div><div>This review provides a comprehensive comparison between two main types of organoids: induced Pluripotent Stem Cell (iPSC)-derived and Adult Stem Cell (ASC)-derived (also known as Patient-Derived Organoids, PDOs). iPSC-derived organoids, derived from reprogrammed cells, exhibit remarkable plasticity, and can model a wide range of tissues and developmental stages. They are particularly valuable for studying early human development, genetic disorders, and complex diseases. However, challenges such as prolonged differentiation protocols and variability in maturation levels remain significant hurdles. In contrast, ASC-derived organoids, generated directly from patient tissues, faithfully recapitulate tissue-specific characteristics and disease phenotypes. This fidelity makes them indispensable for personalized medicine applications, including drug screening, disease modeling, and understanding individualized treatment responses.</div><div>The review highlights the unique advantages and limitations of each organoid type, emphasizing their roles in advancing biomedical research and drug discovery. It addresses key challenges in organoid technology, such as scalability, reproducibility, and the need for standardized culture protocols. Furthermore, it explores recent innovations in scaffold-guided organoid engineering and the integration of organoids with advanced technologies like artificial intelligence and high-throughput screening.</div><div>The integration of organoids with cutting-edge technologies holds promise for enhancing their utility in modeling complex human diseases and accelerating drug discovery and development. By providing more physiologically relevant models of human organs, organoid technology is poised to revolutionize biomedical research, offering new insights into disease mechanisms and personalized therapeutic strategies.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100197"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early prediction of cognitive impairment in adults aged 20 years and older using machine learning and biomarkers of heavy metal exposure","authors":"Ali Nabavi ,&nbsp;Farimah Safari ,&nbsp;Mohammad Kashkooli ,&nbsp;Sara Sadat Nabavizadeh ,&nbsp;Hossein Molavi Vardanjani","doi":"10.1016/j.crtox.2024.100198","DOIUrl":"10.1016/j.crtox.2024.100198","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive impairment poses a growing health challenge as populations age. Heavy metals are implicated as environmental risk factors, but their role is not fully understood. Machine learning can integrate multi-factorial data to predict cognitive outcomes.</div></div><div><h3>Objective</h3><div>To develop and validate machine learning models for early prediction of cognitive impairment risk using demographics, clinical factors, and biomarkers of heavy metal exposure.</div></div><div><h3>Method</h3><div>A retrospective analysis was conducted using 2011–2014 NHANES data. Participants aged ≥ 20 underwent cognitive testing. Variables included demographics, medical history, lifestyle factors, and blood and urine levels of lead, cadmium, manganese, and other metals. Machine learning algorithms were trained on 90 % of data and evaluated on 10 %. Performance was assessed using metrics like accuracy, AUC, and sensitivity.</div></div><div><h3>Result</h3><div>A final sample of 2,933 participants was analyzed. The stacking ensemble model achieved the best performance with an AUC of 0.778 for test data, sensitivity of 0.879. Important predictors included age, gender, hypertension, education, urinary cadmium and blood manganese levels.</div></div><div><h3>Conclusion</h3><div>Machine learning can effectively predict cognitive impairment risk using comprehensive clinical and exposure data. Incorporating heavy metal biomarkers enhanced prediction and provided insights into environmental contributions to cognitive decline. Prospective studies are needed to validate models over time.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100198"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}