"Molecular & Cellular Toxicology"

Kim, Sang Yean; Eun, Jung Woo; Kim, Hyung Seok; Yang, Hee Doo; Na, Min Jeong; Ahn, Young Min; Jung, Hae Ok; Nam, Suk Woo

doi: 10.1007/s13273-020-00076-8pmid: N/A

BackgroundPericardial effusion (PE) can develop in patients with virtually any condition that affects the pericardium, including acute pericarditis and a variety of systemic disorders. Thus, definite differentiation of malignant pericardial effusion and rapid diagnosis are known to have therapeutic and prognostic importance.ObjectiveThe aim of this study was to identify novel molecular markers for the detection of cancer in patients with pericardial disorder.ResultsWe performed one-way ANOVA analysis of whole transcriptome scans of 18 PEs from the patients with pericardial disorder including cancer. It resulted in 4385 outlier genes. Hierarchical clustering analysis showed two distinct clusters [cancer patient’s PEs (G1 + G2) vs. non-cancer PEs (G3)] within the dendrogram. To identify cancer-specific molecular signature, Welch’s t test of G1 and G3 was performed and 1639 gene elements were suggested as stringent classifiers between cancer PE and non-cancer PE. Gene set enrichment analysis of PE signature suggested that CD24, SDC1, and ST14 were strong molecular markers for identifying cancer patients among patients with pericardial disorder.ConclusionOur results suggest that etiology-specific molecular signatures can discriminate cancer patients within pericardial disorder patients. CD24, SDC1, and ST14 are strong molecular markers for such discrimination.

Lee, Hong-Jai; Shin, Bo-Young; Moon, Jae-Seung; Fadriquela, Ailyn; Nuwormegbe, Selikem Abla; Ho, Chun-Chang; Shin, Jin-Su; Yoon, Jee-Sang; Lee, Sang-Kyou; Kim, Soo-Ki

doi: 10.1007/s13273-020-00081-xpmid: N/A

Eom, Hye-Jin; Nam, Sang-Eun; Rhee, Jae-Sung

doi: 10.1007/s13273-020-00088-4pmid: N/A

BackgroundsThe environmental impacts of microplastics (MPs) are increasingly of concern, particularly for their sources, global distribution, and persistency in aquatic ecosystems. Although the ubiquitous and persistent nature of MPs in waterbodies is evident, their effects and health implications for aquatic animals are still open to debate.ObjectiveThe brine shrimp, Artemia franciscana was exposed to different concentrations (1–1000 particles mL−1) of four sizes (1, 3, 6, and 10 μm) of non-functionalized polystyrene microbeads. To measure MPs effects, several physiological and biochemical parameters such as ingestion and egestion, stress biomarkers [e.g., heat shock protein 70 (hsp70) family, enzymatic activities of catalase (CAT) and superoxide dismutase (SOD)], acetylcholinesterase (AChE) activity, and survival rate for 30 days were analyzed.ResultsExposure to waterborne MPs showed clear ingestion and egestion in A. franciscana. Exposure to relatively larger sizes of 1000 particles mL−1 MPs dose–dependently increased mRNA expression of hsp70 families and enzymatic activities of CAT and SOD within 96 h. Significant inhibitory effects on AChE activity were observed in response to 1000 particles mL−1 with increases in mortality for 30 days. Thirty-day survival of juveniles was dose-dependently affected, with greater effects seen at 1000 particles mL−1 of MPs.ConclusionOur results suggest that MPs exposure to the early stages of brine shrimp could be detrimental for population maintenance through inhibition of cholinergic system and the induction of acute cell stress, including oxidative stress.

Lim, Je-Oh; Ko, Je-Won; Jung, Tae-Yang; Kim, Woong-Il; Pak, So-Won; Shin, In-Sik; Yun, Won-Kee; Kim, Hyoung-Chin; Heo, Jeong-Doo; Kim, Jong-Choon

doi: 10.1007/s13273-020-00080-ypmid: N/A

BackgroundSilica dioxide nanoparticles (SiONPs) have been used for various medical applications, including therapeutics and imaging, and the use of SiONPs has increased gradually over the years. However, despite an increase in the use of SiONPs, not much is known about mechanism of action of SiONPs and their pulmonary toxicity.ObjectiveThe present study investigated the pulmonary toxicity of SiONPs and explored the underlying mechanism of action, primarily focusing on thioredoxin-interacting protein (TXNIP)/NOD-like receptor pyrin domain-containing 3 (NLRP3) in SiONPs-treated mice. We investigated the toxic effects of SiONPs in the lung of BALB/c mice administered 5, 10, and 20 mg/kg SiONPs for 3 days.ResultsExposure to SiONPs markedly increased inflammatory cell counts, including those of neutrophils and macrophages, and levels of inflammatory mediators, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in a dose-dependent manner in the bronchoalveolar lavage fluid. Moreover, the inflammation was verified upon histopathological analysis. In addition, exposure to SiONPs increased the expression of TXNIP in a dose-dependent manner and, in turn, upregulated NLRP3 inflammasome proteins, which subsequently induced IL-1β production.ConclusionCollectively, exposure to SiONPs induced inflammation in the lungs of mice, which resulted in the activation of IL-1β production via the TXNIP-NLRP3 axis. Our results provide useful information on the pulmonary toxicity induced by SiONPs and provide insights into the underlying mechanism of action.

Shin, Woo-Ri; Lee, Mun-Jong; Sekhon, Simranjeet Singh; Kim, Ji Hun; Kim, Sun Chang; Cho, Byung-Kwan; Ahn, Ji-Young; Kim, Yang-Hoon

doi: 10.1007/s13273-020-00087-5pmid: N/A

BackgroundDevelopment of genetically modified crops has rapidly increased in last few years. The most widely grown GM crops express genes that confer herbicide tolerance and insect resistance. Detection system of GM crops is important for safety evaluation before its consumption.ObjectiveThe purpose of this research is to detect GM crops, especially PAT, in food-samples.ResultsThe bar gene (PAT protein, herbicide resistant) was cloned in pGEX-4T-1 and expressed by E. coli. The high-affinity PAT-specific single-stranded DNA (ssDNA) aptamers were obtained from a random DNA library. MOE docking study was performed to identify the potential binding region of the selected aptamers on PAT. Aptamer-linked immobilized sorbent assay (ALISA) method was used to detect PAT.ConclusionWe screened aptamer against PAT for developing an efficient detection method. The selected PAT specific aptamers, HRPA-05 and HRPA-07, showed the distinct target binding behaviors, and detected PAT protein by aptamer-linked immobilized sorbent assay method with high efficiency and selectivity.

Lee, SeonHyung; Kim, Ji Hun; Han, Beom-Ku; Kim, Won-Il; Cho, Byung-Kwan; Woo, Sung Min; Kim, Yang-Hoon; Ahn, Ji-Young

doi: 10.1007/s13273-020-00085-7pmid: N/A

BackgroundActinobacillus pleuropneumoniae (A. pleuropneumoniae) produces hemolytic cytotoxins, ApxI, ApxII, ApxIII, and ApxIV, causing a huge loss to the swine industry.Objective We developed the PadLysis protocol for extracting genomic DNA (gDNA) for the LAMP—LeucoCrystal Violet (LCV) colorimetric detection. A paper-based well pad for gDNA extraction was fabricated using a wax printing method. Furthermore, the LAMP amplicons were detected in situ with colorimetric dye, LCV.Results Wax-printed well pads (WPWPs) have hydrophobic wax barriers by printing a well pattern that allows the establishment of simple and equipment-free PadLysis protocol consisting of the three steps: (1) 2 min lysis, (2) 2 min washing, and (3) 1 min drying. This proposed platform allowed direct LAMP amplification for A. pleuropneumoniae field isolates. We optimized LCV chemical components to enable the accurate LAMP signal readouts. The overall assay takes up to 45 min including 5 min PadLysis, 40 min LAMP amplification, and LCV signal observation with the naked eye.ConclusionOur WPWPs–LAMP–LCV approach can be used as a rapid screening tool for A. pleuropneumoniae pleuropneumonia (APP) caused by ApxIA toxin in future outbreak areas.

Magdy, Ahmed; Sadaka, Emad; Hanafy, Nemany; El-Magd, Mohammed A.; Allahloubi, Nasr; El Kemary, Maged

doi: 10.1007/s13273-020-00078-6pmid: N/A

BackgroundSilver nanoparticles (AgNPs) have anti-cancer effects with fewer side effects than standard chemotherapeutic agents, however, they exert oxidative stress-based adverse effects on normal cells and so their applications have raised concern about possible health and environmental risks.ObjectiveWe evaluated whether green tea extract (GTE), which contains potent antioxidants, could ameliorate AgNPs geno-, cyto-, and histotoxicities without decreasing their therapeutic potential against Ehrlich ascetic carcinoma (EAC).ResultsGTE enhanced the anti-cancer effect of AgNPs against EAC cells and ameliorated the genotoxic effect of AgNPs as indicated by lowering chromosomal aberrations and micronucleus frequencies. Additionally, GTE relieved most of degenerative histological changes induced by AgNPs. GTE restored the increased MDA and the decreased SOD, GPx and CAT serum levels induced by AgNPs to levels comparable to normal. The pre-treatment with GTE and AgNPs showed better improvement than the post-treatment strategy.ConclusionsGTE can not only ameliorate AgNPs-induced adverse effects but also improve their anti-cancer effect against EAC. So, it could be useful in the treatment of liver dysfunction associated with AgNPs.

Knickle, Allison; Rasmussen, Andrea; Hoskin, David W.

doi: 10.1007/s13273-020-00089-3pmid: N/A

BackgroundMyricetin is a polyphenolic compound that is cytostatic and/or cytotoxic for several cancer cell types; however, little is known about its effect on mammary carcinoma cells.ObjectiveThe objective of this study is to determine whether myricetin affects the growth of mammarycarcinoma cells.ResultsMyricetin inhibited the growth of 4T1 and E0771 mouse mammary carcinoma cells to a greater extent than either resveratrol or epigallocatechin-3-gallate, which are also present in red wine and green tea, respectively, and also have anti-cancer activities. Reduced growth of myricetin-treated 4T1 and E0771 cells was the result of apoptosis that was associated with disruption of the outer membrane of mitochondria. Myricetin-induced apoptosis of 4T1 and E0771 cells was prevented by the antioxidant N-acetyl cysteine, indicating that cytotoxicity was the result of oxidative stress caused by the accumulation of reactive oxygen species.ConclusionWe conclude that the pro-oxidant action of myricetin and ensuing apoptosis of mammary carcinoma cells indicate that myricetin may be useful in breast cancer treatment.

Sheikh, Nilofer; Patowary, Himangshu; Laskar, Rafiul Amin

doi: 10.1007/s13273-020-00077-7pmid: N/A

BackgroundMalathion (organophosphate) and cypermethrin (pyrethroid) are widely in use to facilitate protection of major food crops in agriculture, due to which it is important to understand their toxic potential. Allium cepa L. has been considered as a reliable genetic model to detect the toxicity of all sorts of pollutants.ObjectiveThe objective of the present work is to determine the cytotoxic and genotoxic effects of two widely used pesticides (malathion and cypermethrin) using A. cepa assay. Allium root growth inhibition test showed 0.5% concentration as the EC50 value in both the pesticides. In the toxicity experiment, 1/10 × EC50; 1/5 × EC50; EC50; 2 × EC50 and 3 × EC50 concentrations of both the pesticides along with a control were employed in Allium assay.ResultsCytotoxic study showed mitotic index decreased with increasing the pesticides concentrations and exposure time. A series of mitotoxicity was observed under the influence of malathon and cypermethrin. Most types of chromosome aberrations observed in high percentage were stickiness, disturbance, c-metaphase, chromosome bridges in anaphase, lagging chromosome, and binucleate lesions. It was observed that malathion and cypermethrin are highly genotoxic to the onion, causing aberration at different phases of mitosis which can arrest cellular growth and may lead to senescence.ConclusionIn conclusion, the present results showed that malathion and cypermethrin can get absorbed in the exposed plant parts or other non-target organisms in the vicinity, and may adversely affect their genomes, thus cause significant harm to crop plants and the environment as well.

Fu, Xufeng; Yang, Xiuyu; Du, Xing; Cui, Qinghua

doi: 10.1007/s13273-020-00082-wpmid: N/A

BackgroundsMethylmercury (MeHg) is regarded as a developmental neurotoxicant but the detailed mechanism remains not completely clear.MethodsThe Xenopus laevis embryos were exposed to methylmercury chloride and the expression of neurodevelopment and oxidative stress genes was detected by qRT-PCR or Western blotting. PC12 cells were exposed to various levels of H2O2, and then cell cycle, neurite length, neurodevelopment-related genes, protein expression of apoptosis and autophagy were detected.ResultsThe genes of neurodevelopment and oxidative stress were disrupted by methylmercury chloride and H2O2 were increased interestingly in X. laevis embryos. Then, PC12 cells were exposed to H2O2 and the results showed the cell cycle, neurite length, and neurodevelopment-related genes, the proteins apoptosis and autophagy were changed.ConclusionThese results supported the idea that neurodevelopment-related gene expression was regulated by oxidative stress and that apoptosis and autophagy pathways were activated by H2O2 and involved in methylmercury neurotoxicity.