In Frankenstein's footsteps. Maintenance of human cells outside the body. Issue 1
Toxicol In Vitro. 2022 May 17:105387. doi: 10.1016/j.tiv.2022.105387. Online ahead of print.ABSTRACTAlthough science can endeavour to do a great many things, unachievable thus far, these activities should be, but seldom are, tempered with the question, should we really do it? This is not necessarily implying a moral code to scientific activity, but at least suggests that we probably should consider the long-term consequences of certain scientific activities to human society and the environment. Indeed, scientists have struggled with the consequences of their discoveries, not least Nobel himself, who set up the Nobel prize ...
Source: Toxicology in Vitro - May 20, 2022 Category: Toxicology Authors: Walter Pfaller Paul Jennings Source Type: research

Silibinin inhibits ethanol- or acetaldehyde-induced ferroptosis in liver cell lines
This study elucidates the modulation of ferroptosis in silibinin's protective effects on ethanol- or acetaldehyde-induced liver cell damage by using human carcinomatous liver HepG2 cells and immortalized liver HL7702 cells. Our results show that ferroptosis is induced in the cells treated with ethanol or acetaldehyde, as evidenced by the increased ROS stress and iron level. Silibinin resolves the oxidative stress and reduces iron level. Ferroptosis induced by ethanol- or acetaldehyde involving nuclear receptor co-activator 4 (NCOA4)-dependent autophagic degradation of ferritin, a protein for storing iron is rescued by sili...
Source: Toxicology in Vitro - May 20, 2022 Category: Toxicology Authors: Xiao-Yu Song Peng-Cheng Liu Wei-Wei Liu Jia Zhou Toshihiko Hayashi Kazunori Mizuno Shunji Hattori Hitomi Fujisaki Takashi Ikejima Source Type: research

In-house performance assessment of 3D QobuR-Reconstructed Human Cornea-Like Epithelium (RhCE) for the evaluation of eye hazard
The objective of this study was to stablish the experimental procedures and evaluate the performance assessment of QobuR-RhCE, an in-house RhCE model to be used for the evaluation of eye hazard. We define the essential structural, functional and procedural elements of the test method components to help assuring that the proposed test method is based on the same concepts as the validated reference methods. Performance assessment was evaluated in accordance with the revised performance standards for the assessment of proposed similar or modified in vitro reconstructed human cornea-like epithelium and the minimum list of refe...
Source: Toxicology in Vitro - May 20, 2022 Category: Toxicology Authors: Manuel Chac ón Natalia V ázquez Mairobi Persinal-Medina Sergio Alonso-Alonso Ignacio Alcalde Jes ús Merayo-Lloves Álvaro Meana Source Type: research

Donor-to-donor variability of a human three-dimensional bronchial epithelial model: A case study of cigarette smoke exposure
In this report, 3D differentiated bronchial epithelial cells from three donors were used to investigate donor-to-donor variability, with an aqueous extract of cigarette smoke (CS) used as the test substance. Ciliary function, cytokine secretion, and histopathology, which are affected by CS, were examined, and transcriptomic analysis was also performed. The results revealed that interleukin-8 secretion and oxidative stress-related gene expression were consistently altered for all donors; however, their amplitudes varied. Moreover, one of the donors showed unique responses to CS, suggesting that this donor was an outlier. Th...
Source: Toxicology in Vitro - May 20, 2022 Category: Toxicology Authors: Sakura Mori Kanae Ishimori Kazushi Matsumura Shinkichi Ishikawa Shigeaki Ito Source Type: research

Paclitaxel is evidence to reduce growing ovarian follicle growth in mice model study
Toxicol In Vitro. 2022 May 15:105386. doi: 10.1016/j.tiv.2022.105386. Online ahead of print.ABSTRACTWe aimed to investigate the effects of paclitaxel on ovarian follicle development and oocyte meiotic competence. Early secondary follicles were cultured individually with or without paclitaxel 2.5 × 10-10, 2.5 × 10-9, and 2.5 × 10-8 M for 12 days. Thereafter, the follicles were treated with human chorionic gonadotropin (hCG) and epidermal growth factor (EGF). Follicle morphology, oocytes meiotic maturation, immunofluorescence for α-tubulin of the oocytes, mRNA expression of growth differentiation factor 9 (GDF9), B-cell ...
Source: Toxicology in Vitro - May 18, 2022 Category: Toxicology Authors: Mila Maidarti Wataru Tarumi Seido Takae Budi Wiweko Nao Suzuki Source Type: research

Paclitaxel is evidence to reduce growing ovarian follicle growth in mice model study
Toxicol In Vitro. 2022 May 15:105386. doi: 10.1016/j.tiv.2022.105386. Online ahead of print.ABSTRACTWe aimed to investigate the effects of paclitaxel on ovarian follicle development and oocyte meiotic competence. Early secondary follicles were cultured individually with or without paclitaxel 2.5 × 10-10, 2.5 × 10-9, and 2.5 × 10-8 M for 12 days. Thereafter, the follicles were treated with human chorionic gonadotropin (hCG) and epidermal growth factor (EGF). Follicle morphology, oocytes meiotic maturation, immunofluorescence for α-tubulin of the oocytes, mRNA expression of growth differentiation factor 9 (GDF9), B-cell ...
Source: Toxicology in Vitro - May 18, 2022 Category: Toxicology Authors: Mila Maidarti Wataru Tarumi Seido Takae Budi Wiweko Nao Suzuki Source Type: research

Paclitaxel is evidence to reduce growing ovarian follicle growth in mice model study
Toxicol In Vitro. 2022 May 15:105386. doi: 10.1016/j.tiv.2022.105386. Online ahead of print.ABSTRACTWe aimed to investigate the effects of paclitaxel on ovarian follicle development and oocyte meiotic competence. Early secondary follicles were cultured individually with or without paclitaxel 2.5 × 10-10, 2.5 × 10-9, and 2.5 × 10-8 M for 12 days. Thereafter, the follicles were treated with human chorionic gonadotropin (hCG) and epidermal growth factor (EGF). Follicle morphology, oocytes meiotic maturation, immunofluorescence for α-tubulin of the oocytes, mRNA expression of growth differentiation factor 9 (GDF9), B-cell ...
Source: Toxicology in Vitro - May 18, 2022 Category: Toxicology Authors: Mila Maidarti Wataru Tarumi Seido Takae Budi Wiweko Nao Suzuki Source Type: research

Inhibition of epithelial SHH signaling exerts a dual protective effect against inflammation and epithelial-mesenchymal transition in inflammatory bowel disease
This study demonstrated that the inhibition of SHH signaling by small molecule might have therapeutic benefit in IBD, and provided compelling experimental evidence that SHH signaling inhibitors can impose anti-inflammatory effects in intestinal epithelial cells while preserving their epithelial characteristics by restricting the induction of EMT.PMID:35569705 | DOI:10.1016/j.tiv.2022.105382 (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - May 15, 2022 Category: Toxicology Authors: Mahsa Ghorbaninejad Anna Meyfour Samaneh Maleknia Shabnam Shahrokh Meghdad Abdollahpour-Alitappeh Hamid Asadzadeh-Aghdaei Source Type: research

Inhibition of epithelial SHH signaling exerts a dual protective effect against inflammation and epithelial-mesenchymal transition in inflammatory bowel disease
This study demonstrated that the inhibition of SHH signaling by small molecule might have therapeutic benefit in IBD, and provided compelling experimental evidence that SHH signaling inhibitors can impose anti-inflammatory effects in intestinal epithelial cells while preserving their epithelial characteristics by restricting the induction of EMT.PMID:35569705 | DOI:10.1016/j.tiv.2022.105382 (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - May 15, 2022 Category: Toxicology Authors: Mahsa Ghorbaninejad Anna Meyfour Samaneh Maleknia Shabnam Shahrokh Meghdad Abdollahpour-Alitappeh Hamid Asadzadeh-Aghdaei Source Type: research

Inhibition of epithelial SHH signaling exerts a dual protective effect against inflammation and epithelial-mesenchymal transition in inflammatory bowel disease
This study demonstrated that the inhibition of SHH signaling by small molecule might have therapeutic benefit in IBD, and provided compelling experimental evidence that SHH signaling inhibitors can impose anti-inflammatory effects in intestinal epithelial cells while preserving their epithelial characteristics by restricting the induction of EMT.PMID:35569705 | DOI:10.1016/j.tiv.2022.105382 (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - May 15, 2022 Category: Toxicology Authors: Mahsa Ghorbaninejad Anna Meyfour Samaneh Maleknia Shabnam Shahrokh Meghdad Abdollahpour-Alitappeh Hamid Asadzadeh-Aghdaei Source Type: research

Weak complex formation of adverse drug reaction-associated HLAB57, B58, and B15 molecules
In this study, we compared the molecular structures and intracellular localization of HLA-B*57:01, HLA-B*58:01, and HLA-B*15:02, which pose risks for developing drug hypersensitivity, as well as HLA-B*57:03 and HLA-B*15:01 that do not present such risks. We found that HLA molecules posing risks have a low affinity for the subunit β2-microglobulin; notably, the weak hydrogen bond formed via Gln96 of the HLA molecule contributes to this behavior. We also clarified that these HLA molecules are easily accumulated in the endoplasmic reticulum, exhibiting a low expression on the cell surface. Considering that these hypersensiti...
Source: Toxicology in Vitro - May 14, 2022 Category: Toxicology Authors: Tomohiro Shirayanagi Akira Kazaoka Kenji Watanabe Liang Qu Naoki Sakamoto Tyuji Hoshino Kousei Ito Shigeki Aoki Source Type: research

Inhibition of serine/arginine-rich protein kinase-1 (SRPK1) prevents cholangiocarcinoma cells induced angiogenesis
This study aimed to examine the expression of SRPK1 and the effects of SRPK1 inhibition on the viability and angiogenesis activity of CCA cells using a selective SRPK1 inhibitor, SPHINX31. Here, we demonstrate that SPHINX31 (0.3-10 μM) had no inhibitory effects on CCA cells' viability and proliferation. However, SPHINX31 decreased the mRNA expression of pro-angiogenic VEGF-A165a isoform. In addition, SPHINX31 attenuated SRSF1 phosphorylation and nuclear localization, and increased the ratio of VEGF-A165b/total VEGF-A proteins. Moreover, when HUVECs were grown in conditioned medium from SPHINX31-treated CCA cells, migratio...
Source: Toxicology in Vitro - May 14, 2022 Category: Toxicology Authors: Kittiya Supradit Boonyakorn Boonsri Jinchutha Duangdara Thanvarin Thitiphatphuvanon Chinnawut Suriyonplengsaeng Thaned Kangsamaksin Tavan Janvilisri Rutaiwan Tohtong Kiren Yacqub-Usman Anna M Grabowska David O Bates Kanokpan Wongprasert Source Type: research

Differential cytotoxic activity of pharmacological inhibitors of IGF1R-related pathways in JAK2 < sup > V617F < /sup > driven cells
Toxicol In Vitro. 2022 May 11:105384. doi: 10.1016/j.tiv.2022.105384. Online ahead of print.ABSTRACTMyeloproliferative neoplasms (MPN) belong to a group of clonal diseases of hematopoietic stem cells characterized by aberrant proliferation of mature myeloid lineages. The constitutive activation of the JAK2/STAT signaling pathway is now well established to play a central role in MPN pathogenesis; however, accumulating evidence now indicates that the IGF1R-mediated signaling pathway contributes to the maintenance of the malignant phenotype. Studies using inhibitors of IGF1-mediated signaling have reported cytotoxic effects i...
Source: Toxicology in Vitro - May 14, 2022 Category: Toxicology Authors: Jaqueline Cristina Fernandes Bruna Alves Fenerich Ant ônio Bruno Alves-Silva Natasha Peixoto Fonseca Juan Luiz Coelho-Silva Priscila Santos Scheucher Eduardo Magalh ães Rego Lorena L ôbo Figueiredo-Pontes Jo ão Agostinho Machado-Neto Fabiola Traina Source Type: research

Pentachlorophenol mediated regulation of DAMPs and inflammation: In vitro study
Toxicol In Vitro. 2022 May 9:105378. doi: 10.1016/j.tiv.2022.105378. Online ahead of print.ABSTRACTPentachlorophenol (PCP) was once widely employed organochlorine pesticide and wood preservative in United States. Due to its toxicity, the U.S. Environmental Protection Agency classified it as a restricted-use pesticide and established as a liver carcinogen. Earlier reports have indicated increased production of inflammatory mediators like IL-1β and TNF-α by immune cells, including NK cells, lymphocytes, or monocytes, on PCP exposure. Yet, there is little to no knowledge regarding the molecular mechanisms affected by acute ...
Source: Toxicology in Vitro - May 13, 2022 Category: Toxicology Authors: Shilpa Thota Rizwana Begum Gagandeep Kaur Prathyusha Bagam Waneene Dorsey Sanjay Batra Source Type: research

The cytotoxicity effect of a bis-MPA-based dendron, a bis-MPA-PEG dendrimer and a magnetite nanoparticle on stimulated and non-stimulated human blood lymphocytes
Toxicol In Vitro. 2022 May 9:105377. doi: 10.1016/j.tiv.2022.105377. Online ahead of print.ABSTRACTDendrimers and dendrons offer a high surface area and nanoscale size and magnetic nanoparticles can be easily detected and manipulated due to their magnetic properties. The aim of the present study is to investigate the in vitro toxicity of Polyester-8-hydroxyl-1-carboxyl bis-MPA dendron, generation 3 (bis-MPA), Hyperbranched G4-PEG6k-OH (PEG) dendrimer and magnetite nanoparticle (Fe3O4), in human lymphocytes. Cell viability assays were performed on non-stimulated and lipopolysaccharide (LPS) stimulated lymphocytes, after exp...
Source: Toxicology in Vitro - May 13, 2022 Category: Toxicology Authors: Maria-Anthi Kakavoulia Maria Karakota Martha Kaloyianni Eleftherios Halevas Marina Sagnou Panagiota Angeliki Galliou Georgios Koliakos Source Type: research