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Cytotoxic exposure

Nikhil Maheshwari, Fahim Halim Khan, Riaz Mahmood
Pentachlorophenol (PCP) is a class 2B human carcinogen that is used as an insecticide, herbicide, and wood preservative. PCP is rapidly absorbed and enters the blood where it can interact with erythrocytes. We have examined the effect of PCP on human erythrocytes. Treatment of erythrocytes with PCP increased the intracellular generation of reactive oxygen and nitrogen species. It also increased lipid and protein oxidation accompanied by decrease in glutathione levels and total sulfhydryl content. The activities of all major antioxidant enzymes were altered...
March 20, 2019: Environmental Science and Pollution Research International
Sai Priya Anand, Jonathan R Grover, William D Tolbert, Jérémie Prévost, Jonathan Richard, Shilei Ding, Sophie Baril, Halima Medjahed, David T Evans, Marzena Pazgier, Walther Mothes, Andrés Finzi
To minimize immune responses against infected cells, HIV-1 limits the surface expression of its envelope glycoprotein (Env). Here we demonstrate that this mechanism is specific for the Env conformation and affects the efficiency of ADCC. Using flow cytometry and confocal microscopy we show that broadly neutralizing antibodies (bNAbs) targeting the "closed" conformation of Env induce its internalization from the surface. In contrast, non-neutralizing antibodies (nNAbs) are displayed on the cell surface for prolonged period of times...
March 20, 2019: Journal of Virology
Geoffrey T Gibney, Omid Hamid, Jose Lutzky, Anthony J Olszanski, Tara C Mitchell, Thomas F Gajewski, Bartosz Chmielowski, Brent A Hanks, Yufan Zhao, Robert C Newton, Janet Maleski, Lance Leopold, Jeffrey S Weber
BACKGROUND: Epacadostat is a potent inhibitor of the immunosuppressive indoleamine 2,3-dioxygenase 1 (IDO1) enzyme. We present phase 1 results from a phase 1/2 clinical study of epacadostat in combination with ipilimumab, an anti-cytotoxic T-lymphocyte-associated protein 4 antibody, in advanced melanoma (NCT01604889). METHODS: Only the phase 1, open-label portion of the study was conducted, per the sponsor's decision to terminate the study early based on the changing melanoma treatment landscape favoring exploration of programmed cell death protein 1 (PD-1)/PD-ligand 1 inhibitor-based combination strategies...
March 20, 2019: Journal for Immunotherapy of Cancer
Ahmed F Halbus, Tommy S Horozov, Vesselin N Paunov
Copper oxide nanoparticles (CuONPs) have been widely recognized as good antimicrobial agents but are heavily regulated due to environmental concerns of their postuse. In this work, we have developed and tested a novel type of formulation for copper oxide (CuONPs) which have been functionalized with (3-glycidyloxypropyl)trimethoxysilane (GLYMO) to allow further covalent coupling of 4-hydroxyphenylboronic acid (4-HPBA). As the boronic acid (BA) groups on the surface of CuONPs/GLYMO/4-HPBA can form reversible covalent bonds with the diol groups of glycoproteins on the bacterial cell surface, they can strongly bind to the cells walls resulting in a very strong enhancement of their antibacterial action which is not based on electrostatic adhesion...
March 20, 2019: ACS Applied Materials & Interfaces
Ping Zhang, Cameron I Curley, Kari Mudie, Midori Nakagaki, Geoffrey R Hill, Jason A Roberts, Siok-Keen Tey
The effect of anti-thymocyte globulin (ATG) on the outcome of hematopoietic stem cell transplantation (SCT) is dependent on formulation, dose and exposure. However, ATG levels are not routinely measured and therapeutic levels are not well defined. In ex vivo T cell-deplete SCT, the potential effect of residual ATG has important implications on the timing of adoptive T cell transfer. Here we measured active rabbit ATG concentration using a flow cytometry-based method that can be implemented in any laboratory...
March 19, 2019: Bone Marrow Transplantation
Julie Chauvin, Laure Gibot, Elena Griseti, Muriel Golzio, Marie-Pierre Rols, Nofel Merbahi, Patricia Vicendo
Numerous studies have reported cold atmospheric plasma cytotoxic activities in various cancer cell lines, either by direct exposure to non-thermal plasma or indirectly by activating a medium (plasma-activated medium, PAM) prior to cell treatment. We suggested the use of in vitro 3D tumor model spheroids to determine the potential of PAM for cancer therapy at the tissue scale, especially in human tumor tissue. This work aimed to better understand the effect of PAM on human colorectal tumor spheroids by describing the in vitro-induced-cell death kinetics and associated mechanisms to further improve its therapeutic potential...
March 19, 2019: Scientific Reports
Amelie Tsoutsoulopoulos, Katrin Gohlsch, Niklas Möhle, Andreas Breit, Sebastian Hoffmann, Olaf Krischenowski, Harald Mückter, Thomas Gudermann, Horst Thiermann, Michaela Aufderheide, Dirk Steinritz
The CULTEX® Radial Flow System (RFS) is a modular in vitro system for the homogenous exposure of cells to airborne particles at the air-liquid interface (ALI). A former pre-validation study successfully demonstrated the general applicability of the CULTEX® RFS and its transferability, stability and reproducibility. Based on these results, the methodology was optimized, validated and prediction models for acute inhalation hazards were established. Cell viability of A549 cells after ALI exposure to 20 pre-selected test substances was assessed in three independent laboratories...
March 16, 2019: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Ana C S Souza, Laís K Silva, Thais B Queiroz, Eduardo S Marques, Clélia A Hiruma-Lima, Isabel O M Gaivão, Edson L Maistro
Citral, 3,7-dimethyl-2,6-octadien-1-al, one of the main components of the essential oils obtained from several plants, is used as a food additive and as a fragrance for detergents, cosmetics and other toiletries. The literature shows disparity regarding citral genotoxicity. Thus, the main objective of our work was to evaluate the genotoxic effects of citral in human cell cultures, HepG2 and leukocytes. Cytotoxicity assays (trypan blue and MTT) showed citral toxic effects in HepG2 cells (with metabolizing liver enzymes), which contrasted with the absence of toxicity in leukocytes...
March 20, 2019: Drug and Chemical Toxicology
Shu-Li Lin, Yi-Tsai Su, Sheng-Wei Feng, Wei-Jen Chang, Kan-Hsin Fan, Haw-Ming Huang
Natural killer (NK) cells are innately immune to the body's immune system and can actively recognize and kill cancer cells. This study explores the potential for enhancing the killing ability of NK cells by co-culturing the NK cells with the target cells under a static magnetic field (SMF). In this study, NK92-MI cell lines were cultured in the presence of a 0.4-T SMF. The effect of the SMF on NK cell viability was evaluated by means of an MTT assay. Culturing tests were performed with inhibitors of the DAG/IP3, STAT3, ERK, JNK and p38 pathways in order to examine the possible signaling cascade responsible for the SMF effect on the NK92-MI cell viability...
March 19, 2019: Electromagnetic Biology and Medicine
O Antonoglou, K Lafazanis, S Mourdikoudis, G Vourlias, T Lialiaris, A Pantazaki, C Dendrinou-Samara
Heterometal oxide nanoparticles of bioessential metals are shedding new light to nanoparticle-inspired bioapplications. Pairing bioreactive elements like copper and iron can affect the redox dynamic and biological profile of the nanomaterial. Given the complexity of physicochemical properties, biological activity and toxicity concerns, extensive exploration is demanded, especially when active and less active oxidation states participate as in case of cuprous-ferric delafossite CuFeO2 (copper(I)-iron(III)), a less widespread nanomaterial...
June 2019: Materials Science & Engineering. C, Materials for Biological Applications
Kaustav Dutta Chowdhury, Avik Sarkar, Sujan Chatterjee, Debajyoti Patra, Dipanwita Sengupta, Soumi Banerjee, Pratip Chakraborty, Gobinda Chandra Sadhukhan
Andrographolide regimen in single or in combination with anticancer drugs is a promising new strategy to reverse chemoresistance in heaptocellular carcinoma. Apoptosis inducing factor (AIF) may regulate a complementary, cooperative or redundant pathway, along with caspase cascades. Despite these findings, mechanisms underlying caspase-dependent and-independent signaling pathways in andrographolide -induced apoptosis in cisplatin-resistant human hepatocellular carcinoma cell line (HepG2CR) remain unclear. Andrographolide treatment effectively reduced NF-κβ nuclear localization by modulating protein kinase A- protein phosphatase 2 A- Iκβ kinase (PKA/PP2 A/IKK) axis that in turn maintains initiator caspase8 activity...
March 5, 2019: Environmental Toxicology and Pharmacology
R Delahunty, M Lee, H Wong, J Johns, J McKendrick, B Lee, S Kosmider, P Cooray, S Ananda, J Desai, B Tran, J Tie, P Gibbs, R Wong
BACKGROUND/AIM: In the treatment of metastatic colorectal cancer (mCRC), exposure to all three active cytotoxic agents; 5-fluorouracil/capecitabine, irinotecan and oxaliplatin improves overall survival. The addition of biologic agents (bevacizumab and cetuximab/panitumumab) further improves survival. The uptake of available systemic agents for mCRC in routine practice in Australia is poorly described. METHODS: The ACCORD database was interrogated to determine demographics, treatments and outcomes for patients diagnosed with mCRC between 1/01/2011 and 1/01/2016 at 6 Melbourne centres...
March 18, 2019: Internal Medicine Journal
Malene V Christensen, Kenneth T Kongstad, Teis Esben Sondergaard, Dan Staerk, Hanne M Nielsen, Henrik Franzyk, Reinhard Wimmer
Current methods for assessment of cellular uptake of cell-penetrating peptides (CPPs) often rely on detection of fluorophore-labeled CPPs. However, introduction of the fluorescent probe often confers changed physicochemical properties, so that the fluorophore-CPP conjugate may exhibit cytotoxic effects and membrane damage not exerted by the native CPP. In the present study, introduction of fluorine probes was investigated as an alternative to fluorophore labeling of a CPP, since this only confers minor changes to its overall physicochemical properties...
March 18, 2019: Journal of Biomolecular NMR
Joanna Cymerys, Andrzej Kowalczyk, Katarzyna Mikołajewicz, Anna Słońska, Małgorzata Krzyżowska
Herpes simplex virus type 1 (HSV-1) has the ability to replicate in neurons and glial cells and to produce encephalitis leading to neurodegeneration. Accumulated evidence suggests that nitric oxide (NO) is a key molecule in the pathogenesis of neurotropic virus infections. NO can exert both cytoprotective as well as cytotoxic effects in the central nervous system (CNS) depending on its concentration, time course exposure, and site of action. In this study, we used an in vitro model of HSV-1-infected primary neuronal and mixed glial cultures as well as an intranasal model of HSV-1 in BALB/c mice to elucidate the role of NO and nonapoptotic Fas signalling in neuroinflammation and neurodegeneration...
2019: Oxidative Medicine and Cellular Longevity
Chih-Hao Chiu, Poyu Chen, Alvin Chao-Yu Chen, Yi-Sheng Chan, Kuo-Yao Hsu, Higashikawa Rei, Kin Fong Lei
Tendinopathy is a common painful musculoskeletal disorder treated by injection of analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs), which are believed to have cytotoxicity toward tenocytes. Ascorbic acid is an antioxidant that promotes collagen biosynthesis and prevents free radical formation. It is believed to protect tenocytes from oxidative stress. The optimal concentration of ascorbic acid, especially when used in conjunction with anesthetics and NSAIDs injection, to treat different stages of tendinopathies is unknown...
January 2019: Dose-response: a Publication of International Hormesis Society
Om Makwana, Hannah Flockton, Gina Smith, Gary Watters, Rizwan Nisar, Wanda Fields, Betsy Bombick
Chronic exposure to cigarette smoke can lead to endothelial dysfunction and potentially endothelial cell death. Here, we exposed Human Aortic Endothelial Cells (HAECs) to whole smoke conditioned media (WSCM) over a range of nicotine equivalence (n.e.) concentrations (0-8000 ng/mL n.e.). After 24 h, Neutral Red Uptake (NRU) and reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) to formazan was determined for each exposure concentration and compared to control. IC50 values in the NRU assay were: 4582 ng/mL n...
March 15, 2019: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Mansour Rezazadeh Azari, Yousef Mohammadian, Jalal Pourahmad, Fariba Khodagholi, Habibollah Peirovi, Yadollah Mehrabi, Meisam Omidi, Athena Rafieepour
Co-exposure to carboxylic acid functionalized multi-walled carbon nanotubes (F-MWCNTs) and polycyclic aromatic hydrocarbons (PAHs) such as benzo a pyrene (BaP) in ambient air have been reported. Adsorption of BaP to F-MWCNTs can influence combined toxicity. Studying individual toxicity of F-MWCNTs and BaP might give unrealistic data. Limited information is available on the combined toxicity of F-MWCNTs and BaP in human cells. The objective of the present work is to evaluate the toxicity of F-MWCNTs and BaP individually and combined in human lung adenocarcinoma (A549 cells)...
March 16, 2019: Environmental Science and Pollution Research International
Marilucia Santorum, Rose Meire Costa Brancalhão, Ana Tereza Bittencourt Guimarães, Carlos Roberto Padovani, Gianluca Tettamanti, Daniela Carvalho Dos Santos
Due to increased use of agrochemicals and growing concerns about ecotoxicology, the development of new insecticides, moving away from those with neurotoxic and broad spectrum effects towards insecticides that are safer for the environment and nontarget beneficial species, has been a research priority. Novaluron stands out among these newer insecticides, is an insect growth regulator that is used for the control of insect pests in crops grown close to mulberry plantations. Mulberry serves as food for the silkworm Bombyx mori, which is a nontarget insect of great economic importance to silk production...
March 1, 2019: Environmental Pollution
Yung-Ho Hsu, Hsiao-Chi Chuang, Yu-Hsuan Lee, Yuh-Feng Lin, Yi-Jie Chen, Ta-Chih Hsiao, Mei-Yi Wu, Hui-Wen Chiu
Traffic emission is responsible for most small-sized particulate matter (PM) air pollution in urban areas. Several recent studies have indicated that traffic-related PM may aggravate kidney disease. Furthermore, exposure to particulate air pollution may be related to the risk of chronic kidney disease (CKD). However, the underlying molecular mechanisms have not been adequately addressed. In the present study, we studied the mechanisms of renal damage that might be associated with exposure to PM. In a real world of whole-body exposure to traffic-related PM model for 3-6 months, PM in urban ambient air can affect kidney function and induce autophagy, endoplasmic reticulum (ER) stress and apoptosis in kidney tissues...
March 13, 2019: Free Radical Biology & Medicine
Rosângela Mayer Gonçalves, Jonathan Paulo Agnes, Marina Delgobo, Priscila Oliveira de Souza, Marcos P Thomé, Luana Heimfarth, Guido Lenz, José Cláudio Fonseca Moreira, Alfeu Zanotto-Filho
Glioblastoma multiforme is the most aggressive type of primary brain tumor associated with few therapeutic opportunities and poor prognosis. In this study, we evaluated the efficacy of combining temozolomide (TMZ) with suberoylanilide hydroxamic acid (SAHA) - a specific histone deacetylases inhibitor - in glioma models in vitro and in vivo. In glioma cell lines, combined TMZ/SAHA promoted more cytotoxicity, G2/M arrest and apoptosis than either drugs alone. G2/M arrest was detected as soon as 24 h post drug exposure and preceded apoptosis, which occurred from 72 h treatment...
March 13, 2019: Biochemical Pharmacology
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