Publications by authors named "Yi-Jun Wu"

105 Publications

Factors Associated with Malignancy in Patients with Maximal Thyroid Nodules ≥2 Cm.

Cancer Manag Res 2021 4;13:4473-4482. Epub 2021 Jun 4.

Department of Thyroid Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.

Purpose: The relationship between large thyroid nodules and the risk of malignancy is controversial. This study aimed to examine the relationship between thyroid nodule size and the risk of malignancy of maximal thyroid nodules ≥2 cm and the risk of accompanied by occult thyroid carcinoma.

Methods: This was a retrospective study of patients who underwent near-total or total thyroidectomy for thyroid nodules from January 2016 to January 2019 at the First Affiliated Hospital,Zhejiang University School of Medicine. Clinical, biochemical, and pathological characteristics were examined for association with malignancy using univariable, multivariable, and receiver operating characteristic curve analyses.

Results: Finally, 367 patients (277 females (75.5%) and 90 males (24.5%)) with a mean age of 49.0±13.5 years were included. Multivariable logistic regression analysis showed that age (OR=0.959, 95% CI: 0.939-0.979, <0.001), Hashimoto's thyroiditis (OR=2.437, 95% CI: 1.162-5.112, =0.018), the diameter of maximal nodule (small) (OR=0.706, 95% CI: 0.541-0.919, =0.010), and punctate echogenic foci (OR=2.837, 95% CI: 1.598-5.286, <0.001) were independently associated with malignancy. Of 223 patients who had non-suspicious malignant nodules (TI-RADS <4), 12.7% (n=29) patients showed malignancy at postoperative pathology. Only age was associated with occult PTC in the univariable analyses (OR=0.962, 95% CI: 0.934-0.991, =0.011). When TPOAb was used as a continuous variable for statistical analysis, it showed a significant difference in the ROC curve, and the results showed TPOAb >31.4 mIU/L was more associated with occult PTC (=0.006). A predictive model including four independent risk factors of malignancy showed an optimal discriminatory accuracy (area under the curve, AUC) of 0.783 (95% CI=0.732-0.833).

Conclusion: Relatively young age (<54.5 years), Hashimoto's thyroiditis, the diameter of the maximal nodule, and punctate echogenic foci were independently associated with thyroid malignancy in patients with maximal thyroid nodules ≥2 cm. Young age (<54.5 years) and TPOAb >31.4 mIU/L were associated with occult PTC.
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http://dx.doi.org/10.2147/CMAR.S303715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186937PMC
June 2021

Individual and combined hepatocytotoxicity of DDT and cadmium .

Toxicol Ind Health 2021 May 15;37(5):270-279. Epub 2021 Apr 15.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China.

The organochlorine insecticide dichlorodiphenyltrichloroethane (DDT) and heavy metal cadmium (Cd) are widespread environmental pollutants. They are persistent in the environment and can accumulate in organisms. Although the individual toxicity of DDT and Cd has been well documented, their combined toxicity is still not clear. Since liver is their common target, in this study, the individual and combined toxicity of DDT and Cd in human liver carcinoma HepG2 and human normal liver THLE-3 cell lines were investigated. The results showed that DDT and Cd inhibited the viability of HepG2 and THLE-3 cells dose-dependently and altered lysosomal morphology and function. Intracellular reactive oxygen species and lipid peroxidation levels were induced by DDT and Cd treatment. The combined cytotoxicity of DDT and Cd was greater than their individual cytotoxicity, and the interaction between Cd and DDT was additive on the inhibition of cell viability and lysosomal function of HepG2 cells. The interaction was antagonistic on the inhibition of cell viability of THLE-3 cells. These results may facilitate the evaluation of the cumulative risk of pesticides and heavy metal residues in the environment.
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http://dx.doi.org/10.1177/07482337211007361DOI Listing
May 2021

Paeoniflorin Derivative in Paeoniae Radix Aqueous Extract Suppresses Alpha-Toxin of .

Front Microbiol 2021 20;12:649390. Epub 2021 Mar 20.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

The emergence and dissemination of bacterial infections is paralyzing our public health systems worldwide. Worse still, there are no effective antibiotics against bacterial toxins, which facilitate the infection. Natural herbs that target bacterial toxins may be a better choice for therapy of infectious diseases. However, most natural drugs present unknown compositions and unclear mechanisms. Here we demonstrated that the Chinese herb Paeoniae Radix aqueous extract (PRAE) could suppress alpha-toxin (α-toxin) of . We observed that the paeoniflorin derivative (PRAE-a) derivative in PRAE significantly abolished the hemolytic activity of α-toxin. The analyses of high-performance liquid chromatography (HPLC), mass spectrometer (MS), Fourier transform infrared spectrometer (FTIR), and nuclear magnetic resonance (NMR) showed that PRAE-a was a glycoside compound with a paeoniflorin nucleus. We further found that PRAE-a disrupted the pore-forming ability of α-toxin by prevention of the dimer to heptamer. Therefore, PRAE-a proved to be an effective therapy for lung infections in mice by inhibiting α-toxin. Collectively, these results highlighted that PRAE-a can be used as an antibacterial agent to attenuate virulence by targeting α-toxin.
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http://dx.doi.org/10.3389/fmicb.2021.649390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019018PMC
March 2021

Lapatinib alleviates TOCP-induced axonal damage in the spinal cord of mouse.

Neuropharmacology 2021 05 23;189:108535. Epub 2021 Mar 23.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, PR China.

Neuregulin-1 (NRG1), a family of EGF-like factors that activates ErbB receptors, can regulate the proliferation, migration, and myelinating of Schwann cells. We previously reported that NRG1/ErbB signal is responsible for organophosphate (OP)-induced delayed neuropathy (OPIDN) in hens, a susceptive animal model to neuropathic organophosphorous compounds. Our previous study discovered that a neuropathic OP, tri-o-cresyl phosphate (TOCP) activated NRG1/ErbB signaling pathway in both spinal cord and sciatic nerves of hens during the formation of OPIDN and lapatinib, a non-selective antagonist of ErbB1 and ErbB2 receptors, alleviated the toxicity. In this study, we intended to further look into the potential role of NRG1 in the pathogenesis of TOCP-induced axon damage in spinal cord and sciatic nerves and whether lapatinib could also rescue this damage in mice, an OPIDN-resistant animal model. The results revealed that no obvious toxic signs were observed after single TOCP exposure. However, slight histopathological wreck in lumbar spinal cord and sciatic nerves was found following TOCP intoxication, and the damage in sciatic nerves was characterized by axon degeneration of myelin sheath but not the loss of neural skeleton. Only histopathological damage induced by TOCP in spinal cord could be prevented by lapatinib. The translational expression of NRG1/ErbB signaling molecules was analyzed by both in vivo and in vitro studies. In general, NRG1/ErbB pathway was activated by TOCP while combined treatment with lapatinib attenuated TOCP-induced NRG1/ErbB signaling cascade. The results implied that NRG1/ErbB system may predominately play functional role in spinal cord (central nervous system) but not in sciatic nerves (peripheral nervous system) of mouse subjected to neurotoxic OP, which was confirmed by the study in vitro that lapatinib was not able to attenuate TOCP-induced neurotoxicity in rodent Schwann cell line RSC 96 cells.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108535DOI Listing
May 2021

Decrease of an intracellular organic osmolyte contributes to the cytotoxicity of organophosphate in neuroblastoma cells in vitro.

Toxicology 2021 04 19;453:152725. Epub 2021 Feb 19.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxilu Road, Beijing, 100101, China.

Organophosphorus compounds (OP) causes prominent delayed neuropathy in vivo and cytotoxicity to neuronal cells in vitro. The primary target protein of OP's neurotoxicity is neuropathy target esterase (NTE), which can convert phosphatidylcholine (PC) to glycerophosphocholine (GPC). Recent studies reveal that autophagic cell death is important for the initiation and progression of OP-induced neurotoxicity both in vivo and in vitro. However, the mechanism of how OP induces autophagic cell death is unknown. Here it is found that GPC is an important organic osmolyte in the neuroblastoma cells, and treatment with tri-o-cresyl phosphate (TOCP), a representative OP, leads to the decrease of GPC and imbalance of extracellular and intracellular osmolality. Knockdown of GPC metabolizing enzyme glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) reverses TOCP-induced autophagic cell death, which further supports the notion that the reduced GPC level leads to the autophagic cell death. Furthermore, it is found that autophagic cell death is due to the induction of reactive oxygen species (ROS) and mitochondrial damage by imbalance of osmolality with TOCP treatment. In summary, this study reveals that TOCP treatment decreases GPC level and intracellular osmolality, which induces ROS and mitochondrial damage and leads to the cell death and neurite degradation by autophagy. This study lays the foundation for further investigations on the potential therapeutic approaches for OP neurotoxicity or NTE mutation-related neurological diseases.
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http://dx.doi.org/10.1016/j.tox.2021.152725DOI Listing
April 2021

Computational Prediction of Protein Arginine Methylation Based on Composition-Transition-Distribution Features.

ACS Omega 2020 Oct 19;5(42):27470-27479. Epub 2020 Oct 19.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

Arginine methylation is one of the most essential protein post-translational modifications. Identifying the site of arginine methylation is a critical problem in biology research. Unfortunately, biological experiments such as mass spectrometry are expensive and time-consuming. Hence, predicting arginine methylation by machine learning is an alternative fast and efficient way. In this paper, we focus on the systematic characterization of arginine methylation with composition-transition-distribution (CTD) features. The presented framework consists of three stages. In the first stage, we extract CTD features from 1750 samples and exploit decision tree to generate accurate prediction. The accuracy of prediction can reach 96%. In the second stage, the support vector machine can predict the number of arginine methylation sites with 0.36 -squared. In the third stage, experiments carried out with the updated arginine methylation site data set show that utilizing CTD features and adopting random forest as the classifier outperform previous methods. The accuracy of identification can reach 82.1 and 82.5% in single methylarginine and double methylarginine data sets, respectively. The discovery presented in this paper can be helpful for future research on arginine methylation.
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http://dx.doi.org/10.1021/acsomega.0c03972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594152PMC
October 2020

Predicting ATP-Binding Cassette Transporters Using the Random Forest Method.

Front Genet 2020 25;11:156. Epub 2020 Mar 25.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

ATP-binding cassette (ABC) proteins play important roles in a wide variety of species. These proteins are involved in absorbing nutrients, exporting toxic substances, and regulating potassium channels, and they contribute to drug resistance in cancer cells. Therefore, the identification of ABC transporters is an urgent task. The present study used 188D as the feature extraction method, which is based on sequence information and physicochemical properties. We also visualized the feature extracted by t-Distributed Stochastic Neighbor Embedding (t-SNE). The sample based on the features extracted by 188D may be separated. Further, random forest (RF) is an efficient classifier to identify proteins. Under the 10-fold cross-validation of the model proposed here for a training set, the average accuracy rate of 10 training sets was 89.54%. We obtained values of 0.87 for specificity, 0.92 for sensitivity, and 0.79 for MCC. In the testing set, the accuracy achieved was 89%. These results suggest that the model combining 188D with RF is an optimal tool to identify ABC transporters.
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http://dx.doi.org/10.3389/fgene.2020.00156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109328PMC
March 2020

Identification of metabolite biomarkers in serum of rats exposed to chlorpyrifos and cadmium.

Sci Rep 2020 03 19;10(1):4999. Epub 2020 Mar 19.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, P.R. China.

Chlorpyrifos (CPF) and cadmium (Cd) are widespread environmental pollutants, which are often present in drinking water and foods. However, the combined effects of CPF and Cd were not entirely clear at present. There was also no biomarker available to diagnose the poisoning of the two chemicals at low dose for long-term exposures. In this study, we investigated the change of serum metabolites of rats with subchronic exposure to CPF, Cd, and CPF plus Cd using gas chromatography-mass spectrometer-based metabolomics approach. We performed a stepwise optimization algorithm based on receiver operating characteristic to identify serum metabolite biomarkers for toxic diagnosis of the chemicals at different doses after 90-day exposure. We found that aminomalonic acid was the biomarker for the toxicity of Cd alone administration, and serine and propanoic acid were unique biomarkers for the toxicities of CPF plus Cd administrations. Our results suggest that subchronic exposure to CPF and Cd alone, or in combination at their low doses, could cause disturbance of energy and amino acid metabolism. Overall, we have shown that analysis of serum metabolomics can make exceptional contributions to the understanding of the toxic effects following long-term low-dose exposure of the organophosphorus pesticide and heavy metal.
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http://dx.doi.org/10.1038/s41598-020-61982-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081290PMC
March 2020

Metabolomic biomarkers in urine of rats following long-term low-dose exposure of cadmium and/or chlorpyrifos.

Ecotoxicol Environ Saf 2020 Jun 14;195:110467. Epub 2020 Mar 14.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, PR China. Electronic address:

Heavy metals and pesticides can be easily enriched in food chains and accumulated in organisms, thus pose significant threat to human health. However, their combined effects for long-term exposure at low dose has not been thoroughly investigated; especially there was no biofluid biomarker available to noninvasively diagnose the toxicosis of the combined exposure of the two chemicals at their low levels. In this study, we investigated the change of urine metabolites of rats with 90-day exposure to heavy metal cadmium (Cd) and/or organophosphorus pesticide chlorpyrifos (CPF) using gas chromatography-mass spectrometry (GC-MS)-based metabolomics approach. Our results showed that the interaction of Cd and CPF mainly displayed an antagonistic effect. We identified the panels of metabolite biomarkers in urine: benzoic acid and mannose were unique biomarkers for Cd exposure; creatinine and N-phenylacetyl glycine were unique biomarkers for CPF exposure; anthranilic acid, ribitol, and glucose were unique biomarkers for Cd plus CPF exposure. Our results suggest that 90-day exposure to Cd and/or CPF could cause a disturbance in energy and amino acid metabolism. And urine metabolomics analysis can help understand the toxicity of low dose exposure to mixed environmental chemicals.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110467DOI Listing
June 2020

A safety type of genetically engineered bacterium that degrades chemical pesticides.

AMB Express 2020 Feb 18;10(1):33. Epub 2020 Feb 18.

Laboratory of Molecular Toxicology, State Key Laboratory for Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxilu Road, Beijing, 100101, People's Republic of China.

Chemical pesticides are used widely and their residues are found in the environment. Pesticide pollution has become a global problem. To find an economical, effective and safety way to degrade residues of pesticides in environment, we constructed a genetically engineered bacterium (GEB) having the ability to degrade pesticides, emit green fluorescence and has a containment system by using a dual plasmid expression system. One plasmid contains the genes of enhanced green fluorescent protein (EGFP) and carboxylesterase B1 (CarE B1), which were cloned downstream of lambda P promoter and expressed constitutively. The gene of CarE B1 encodes an insect-detoxifying enzyme possessing the degradability to organochloride pesticides, organophosphorus pesticides, carbamates, and pyrethoid insecticides. The other is the conditional suicide plasmid for containment system, in which the lethal gene used was the nuclease gene of Serratia marcescens without the leader-coding sequence and was placed downstream of T7 promoter. The GEB has wide prospects of application on cleanup of pesticide residues with its degradability to several pesticides and containment system.
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http://dx.doi.org/10.1186/s13568-020-00967-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028883PMC
February 2020

The progressive alteration of urine metabolomic profiles of rats following long-term and low-dose exposure to permethrin.

Biomarkers 2020 Feb 1;25(1):94-99. Epub 2019 Dec 1.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China.

Permethrin is a type of widely used pyrethroid pesticide. Although acute toxicity of permethrin has been well-characterised, the non-acute toxicity of permethrin upon long-term exposure at low dose has been seldom studied yet. The current study investigates the time-course change of the metabolomic profiles of urine following the low level long-term exposure of permethrin and identified biomarkers of the chronic toxicity of permethrin. Male Wistar rats were administrated orally with permethrin (75 mg/kg body weight/day, 1/20 LD) daily for consecutive 90 days. The urine samples from day 30, day 60, and day 90 after the first dosing were collected and analysed by H NMR spectrometry. Serum biochemical analysis was also carried out. Permethrin caused significant changes in the urine metabolites such as taurine, creatinine, acetate, lactate, dimethylamine, dimethylglycine, and trimethylamine--oxide. These biological markers indicated prominent kidney and liver toxicity induced by permethrin. However, there was no change in serum biochemical parameters for the toxicity, indicating that metabolomic approach was much more sensitive in detecting the chronic toxicity. The time-course alteration of metabolomic profiles of the urine based on H NMR reflects the progressive development of the chronic toxicity with the long-term low-level exposure of permethrin.
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http://dx.doi.org/10.1080/1354750X.2019.1697755DOI Listing
February 2020

Time-Course Changes in Urine Metabolic Profiles of Rats Following 90-Day Exposure to Propoxur.

Sci Rep 2019 11 18;9(1):16989. Epub 2019 Nov 18.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxilu Road, Beijing, 100101, P.R. China.

As a major kind of carbamate insecticide, propoxur plays an important role in agriculture, veterinary medicine, and public health. The acute toxicity of propoxur is mainly neurotoxicity due to the inhibition of cholinesterase. However, little is known regarding the toxicity of propoxur upon long-term exposure at low dose. In this study, Wistar rats were orally administrated with low dose (4.25 mg/kg body weight/day) for consecutive 90 days. And the urine samples in rats treated with propoxur for 30, 60, and 90 days were collected and analyzed by employing H NMR-based metabolomics approach. We found that propoxur caused significant changes in the urine metabolites, including taurine, creatinine, citrate, succinate, dimethylamine, and trimethylamine-N-oxide. And the alteration of the metabolites was getting more difference compared with that of the control as the exposure time extending. The present study not only indicated that the changed metabolites could be used as biomarkers of propoxur-induced toxicity but also suggested that the time-course alteration of the urine metabolomic profiles could reflect the progressive development of the toxicity following propoxur exposure.
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http://dx.doi.org/10.1038/s41598-019-52787-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861282PMC
November 2019

Indicators of multifocality in papillary thyroid carcinoma concurrent with Hashimoto's thyroiditis.

Am J Cancer Res 2019 1;9(8):1786-1795. Epub 2019 Aug 1.

Thyroid Disease Diagnosis and Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University Hang Zhou 310003, China.

Currently, no definitive diagnostic tool is available to distinguish unifocal and multifocal papillary thyroid carcinoma (PTC). This study aims to identify potential diagnostic markers of multifocal PTC. In 471 Hashimoto's thyroiditis (HT) patients, the significant difference was revealed in anti-thyroid peroxidase antibody (TPOAb) concentration, the cytokeratin-19 (CK-19) expression, the occurrence of the B-Raf proto-oncogene serine/threonine kinase (BRAF) mutations and the rearrangement in transformation (RET)/PTC. The patients' samples were assayed for the expression of CK-19, cyclooxygenase-2 (COX-2), galectin-3, and the protein human bone marrow endothelial cell marker-1 (HBME-1) using immunohistochemistry. The BRAF gene mutation was detected using a sequencer. Differences were examined using the Kruskal-Wallis test and the Chi-squared and Fisher's exact tests. The results showed that the elevated CK-19 expression, and the presence of BRAF mutations and RET/PTC rearrangements were indicators of multifocal PTC in HT, suggesting the need for total bilateral thyroidectomy. Among HT patients with TPOAb > 1300 IU/Ml, the occurrence of central lymph node metastasis is significantly higher in multi-focal PTC than single-focal PTC. Therefore, these markers may prove useful for discerning between uni- and multifocal PTC, thereby preventing unnecessary surgery in the treatment of unifocal PTC and promoting sufficient treatment of multifocal PTC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726987PMC
August 2019

Ivermectin reverses the drug resistance in cancer cells through EGFR/ERK/Akt/NF-κB pathway.

J Exp Clin Cancer Res 2019 Jun 18;38(1):265. Epub 2019 Jun 18.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxilu Rd., Chaoyang, Beijing, 100101, China.

Background: Discovery and development of novel drugs that are capable of overcoming drug resistance in tumor cells are urgently needed clinically. In this study, we sought to explore whether ivermectin (IVM), a macrolide antiparasitic agent, could overcome the resistance of cancer cells to the therapeutic drugs.

Methods: We used two solid tumor cell lines (HCT-8 colorectal cancer cells and MCF-7 breast cancer cells) and one hematologic tumor cell line (K562 chronic myeloid leukemia cells), which are resistant to the chemotherapeutic drugs vincristine and adriamycin respectively, and two xenograft mice models, including the solid tumor model in nude mice with the resistant HCT-8 cells and the leukemia model in NOD/SCID mice with the resistant K562 cells to investigate the reversal effect of IVM on the resistance in vitro and in vivo. MTT assay was used to investigate the effect of IVM on cancer cells growth in vitro. Flow cytometry, immunohistochemistry, and immunofluorescence were performed to investigate the reversal effect of IVM in vivo. Western blotting, qPCR, luciferase reporter assay and ChIP assay were used to detect the molecular mechanism of the reversal effect. Octet RED96 system and Co-IP were used to determine the interactions between IVM and EGFR.

Results: Our results indicated that ivermectin at its very low dose, which did not induce obvious cytotoxicity, drastically reversed the resistance of the tumor cells to the chemotherapeutic drugs both in vitro and in vivo. Mechanistically, ivermectin reversed the resistance mainly by reducing the expression of P-glycoprotein (P-gp) via inhibiting the epidermal growth factor receptor (EGFR), not by directly inhibiting P-gp activity. Ivermectin bound with the extracellular domain of EGFR, which inhibited the activation of EGFR and its downstream signaling cascade ERK/Akt/NF-κB. The inhibition of the transcriptional factor NF-κB led to the reduced P-gp transcription.

Conclusions: These findings demonstrated that ivermectin significantly enhanced the anti-cancer efficacy of chemotherapeutic drugs to tumor cells, especially in the drug-resistant cells. Thus, ivermectin, a FDA-approved antiparasitic drug, could potentially be used in combination with chemotherapeutic agents to treat cancers and in particular, the drug-resistant cancers.
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http://dx.doi.org/10.1186/s13046-019-1251-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580523PMC
June 2019

A fungicide miconazole ameliorates tri-o-cresyl phosphate-induced demyelination through inhibition of ErbB/Akt pathway.

Neuropharmacology 2019 04 14;148:31-39. Epub 2018 Dec 14.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxilu Road, Beijing, 100101, China. Electronic address:

Organophosphorus compound (OP)-induced delayed neuropathy (OPIDN) is characterized by distal axonal degeneration and demyelination of the central and peripheral axons, which leads to progressive muscle weakness, ataxia and paralysis in several days after OP intoxication. This study aimed to investigate the possible use of an imidazole fungicide miconazole as a novel therapy for OPIDN. Adult hens, the most commonly used animal models in OPIDN studies, were orally given tri-o-cresyl phosphate (TOCP). We showed that miconazole, which was administered daily to hens beginning on the 7th day after TOCP exposure, drastically ameliorated the neurotoxic symptoms and histopathological damages in spinal cord and sciatic nerves. Mechanistically, miconazole inhibited the TOCP-induced activation of ErbB/Akt signaling, and enhanced the myelin basic protein (MBP) expression. In a glial cell model sNF96.2 cells, miconazole restored the TOCP-inhibited MBP expression, and promoted cell differentiation as well as cell migration by inhibiting the activation of ErbB/Akt signaling pathway. In sum, miconazole, a synthetic imidazole fungicide, could ameliorate the symptoms and histopathological changes of OPIDN, probably by promoting glial cell differentiation and migration to enhance myelination via inhibiting the activation of ErbB/Akt. Thus, miconazole is a promising candidate therapy for the clinical treatment of OPIDN.
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http://dx.doi.org/10.1016/j.neuropharm.2018.12.015DOI Listing
April 2019

Disruption of Kidney Metabolism in Rats after Subchronic Combined Exposure to Low-Dose Cadmium and Chlorpyrifos.

Chem Res Toxicol 2019 01 13;32(1):122-129. Epub 2018 Dec 13.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents , Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , P. R. China.

Cadmium (Cd) and chlorpyrifos (CPF) often coexist in the environment and induce combined toxicity to organisms. Here we studied the combined nephrotoxicity of environmentally relevant low doses of Cd and CPF. We treated the mice for 90 days with different doses of Cd and CPF and their mixtures via oral gavage. Then histopathological evaluation and biochemical analysis for kidney tissues were carried out. The change of metabolites in kidney was detected by using a metabolomics approach using GC-MS. We found that Cd, CPF, and their mixtures caused oxidative damage as well as disturbance of renal amino acid metabolism. We identified potential metabolite biomarkers in kidney, which included acetic acid for CPF treatment, glycerol and carboxylic acid for Cd treatment, and l-ornithine for the mixture of CPF and Cd treatment, respectively. In addition, we found that Cd promoted the metabolism of CPF in kidney. This may contribute to the result that the toxicity of the mixtures was lower than the sum of the toxicities of Cd and CPF alone. In conclusion, our results indicated that CPF and Cd could disrupt the kidney metabolism in rats even when they were exposed to a very low dose of CPF and Cd.
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http://dx.doi.org/10.1021/acs.chemrestox.8b00219DOI Listing
January 2019

Regeneration of a Bioengineered Thyroid Using Decellularized Thyroid Matrix.

Thyroid 2019 01 18;29(1):142-152. Epub 2018 Dec 18.

1 Thyroid Disease Diagnosis and Treatment Center; School of Medicine, Zhejiang University, Hangzhou, P.R. China.

Background: Hypothyroidism is a common hormone deficiency condition. Regenerative medicine approaches, such as a bioengineered thyroid, have been proposed as potential therapeutic alternatives for patients with hypothyroidism. This study demonstrates a novel approach to generate thyroid grafts using decellularized rat thyroid matrix.

Methods: Isolated rat thyroid glands were perfused with 1% sodium dodecyl sulfate to generate a decellularized thyroid scaffold. The rat thyroid scaffold was then recellularized with rat thyroid cell line to reconstruct the thyroid by perfusion seeding technique. As a pilot study, the decellularized rat thyroid scaffold was perfused with human-derived thyrocytes and parathyroid cells.

Results: The decellularization process retained the intricate three-dimensional microarchitecture with a perfusable vascular network and native extracellular matrix components, allowing efficient reseeding of the thyroid matrix with the FRTL-5 rat thyroid cell line generating three-dimensional follicular structures in vitro. In addition, the recellularized thyroid showed successful cellular engraftment and thyroid-specific function, including synthesis of thyroglobulin and thyroid peroxidase. Moreover, the decellularized rat thyroid scaffold could further be recellularized with human-derived thyroid cells and parathyroid cells to reconstruct a humanized bioartificial endocrine organ, which maintained expression of critical genes such as thyroglobulin, thyroid peroxidase, and parathyroid hormone.

Conclusion: These findings demonstrate the utility of a decellularized thyroid extracellular matrix scaffold system for the development of functional, bioengineered thyroid tissue, which could potentially be used to treat hypothyroidism.
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http://dx.doi.org/10.1089/thy.2018.0068DOI Listing
January 2019

Activation of Neuregulin 1/ErbB Signaling Is Involved in the Development of TOCP-Induced Delayed Neuropathy.

Front Mol Neurosci 2018 23;11:129. Epub 2018 Apr 23.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Organophosphate-induced delayed neuropathy (OPIDN) is characterized by progressive axonal degeneration and demyelination of the spinal cord and sciatic nerves. The neuregulin 1/epidermal growth factor receptor (ErbB) signaling pathway is crucial for axonal myelination. In this study, we investigated whether the neuregulin 1/ErbB signaling pathway mediated the progression of OPIDN. Adult hens were given tri--cresyl phosphate (TOCP), a typical neuropathic organophosphorus compound, to induce OPIDN. The ErbB inhibitor lapatinib was administered to hens 4 h prior to and 4 days after TOCP exposure. The neuregulin 1/ErbB signaling pathway was examined for their role in maintaining spinal cord and sciatic nerve fiber integrity. Schwann cell line sNF96.2 was used as the cell model. The results showed that TOCP (750 mg/kg body weight, .) induced prominent ataxia and significant axon degeneration in the spinal cord and sciatic nerves. Lapatinib (25 mg/kg body weight, .) treatment attenuated OPIDN clinically and histopathlogically and partially prevented the TOCP-induced activation of neuregulin 1/ErbB signaling pathway. Lapatinib also prevented the TOCP-induced inhibition of neuropathy target esterase (NTE), a key enzyme during the development of OPIDN, and the disturbed metabolism of phosphatidylcholine in sciatic nerves. In addition, lapatinib was shown, , to protect sNF96.2 cells from TOCP-induced dedifferentiation through neuregulin 1/ErbB signaling. Our results suggest that neuregulin 1/ErbB, through regulation of NTE activity in the peripheral nervous system, mediates the progression of OPIDN. Thus, this signal may serve as a potential target for the treatment of OPIDN.
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http://dx.doi.org/10.3389/fnmol.2018.00129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5925568PMC
April 2018

A novel p53 paralogue mediates antioxidant defense of mosquito cells to survive dengue virus replication.

Virology 2018 06 1;519:156-169. Epub 2018 May 1.

Departments of Public Health and Parasitology, Chang Gung University, Kwei-San, Tao-Yuan 33332, Taiwan; Graduate Institute of Biomedical Sciences, Chang Gung University, Kwei-San, Tao-Yuan 33332, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Kwei-San, Tao-Yuan, Taiwan. Electronic address:

Mosquito cells allow dengue viruses (DENVs) to undergo replication without causing serious deleterious effects on the cells, leading to advantages for dissemination to other cells. Despite this, increased accumulation of reactive oxygen species (ROS) is usually detected in C6/36 cells with DENV2 infection as shown in mammalian cells. Uniquely, oxidative stress caused by the ROS is alleviated by eliciting antioxidant defense which leads to protection of mosquito cells from the infection. In the present study, a novel p53 paralogue (p53-2) was identified and proved to be regulated in C6/36 cells with DENV2 infection. With a gene-knockdown technique, p53-2 was demonstrated to transcribe catalase which plays a critical role in reducing ROS accumulation and the death rate of infected cells. Ecologically, a higher survival rate of mosquito cells is a prerequisite for prosperous production of viral progeny, allowing infected mosquitoes to remain healthy and active for virus transmission.
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http://dx.doi.org/10.1016/j.virol.2018.04.011DOI Listing
June 2018

[Effect of hyperforin on learning and memory abilities and Aβ₁₋₄₂, βAPP and BACE1 protein expressions in hippocampus of Alzheimer's disease model mice].

Zhongguo Zhong Yao Za Zhi 2016 Aug;41(15):2877-2882

The First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China.

To investigate the effect of the hyperforin (HF) on learning and memory function and Aβ₁₋₄₂, βAPP and BACE1 protein expressions in hippocampus of five-month-old APP/PS1 double transgenic mice, and discuss the underlying mechanism of HF. The five-month-old APP/PS1 double transgenic mice were randomly divided into the model group, rosiglitazone group (12 mg•kg⁻¹•d⁻¹) and HF high dose, middle dose and low dose groups (600, 300 and 150 mg•kg⁻¹•d⁻¹) in each group; in addition, 15C57BL/6J mice with the same months and background were selected as normal group. Drugs were diluted in the same volume before using, and then administrated by ig for 7 months, 1 time a day; the mice in normal group and model group received the same volume of distilled water. The learning and memory ability was tested by Morris water maze; Aβ₁₋₄₂, βAPP and BACE1proteinexpressionlevelswere tested by immunohistochemistry and Western blot. The Morris water maze results showed that as compared with the normal group, the learning and memory ability was significantly impaired in mice of model group (P<0.01); as compared with the model group, the learning and memory ability was improved in mice of rosiglitazone group and HF high, middle and low dose groups(P<0.01 or P<0.05). Immunohistochemistry and western blot results showed thatas compared with the normal group, the Aβ₁₋₄₂, βAPP and BACE1 protein expression levels in hippocampus were significantly increased in mice of model group (P<0.01);as compared with the model group, Aβ₁₋₄₂, βAPP and BACE1 protein expression levels in hippocampus were decreased in mice of rosiglitazone group and HF high, middle and low dose groups (P<0.01 or P<0.05). HF may improve the learning and memory ability of AD model mice via inhibition of βAPP and BACE1 protein expressions, thus reduced the generation of Aβ₁₋₄₂ proteins and amyloid plaque deposits in the brain.
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http://dx.doi.org/10.4268/cjcmm20161522DOI Listing
August 2016

The p53 gene with emphasis on its paralogues in mosquitoes.

J Microbiol Immunol Infect 2017 Dec 29;50(6):747-754. Epub 2017 Jun 29.

Departments of Public Health and Parasitology, Chang Gung University, Kwei-San, Tao-Yuan 33332, Taiwan; Graduate Institute of Biomedical Sciences, Chang Gung University, Kwei-San, Tao-Yuan 33332, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Kwei-San, Tao-Yuan, Taiwan. Electronic address:

The p53 gene is highly important in human cancers, as it serves as a tumor-suppressor gene. Subsequently, two p53 homologues, i.e., p73 and p63, with high identity of amino acids were identified, leading to construction of the p53 family. The p53 gene is highly important in human cancer because it usually transcribes genes that function by causing apoptosis in mammalian cells. In contrast, p63 and p73 tend to be more important in modulating development than inducing cell death, even though they share similar protein structures. Relatively recently, p53 was also identified in mosquitoes and many other insect species. Uniquely, its structure lacks the sterile alpha motif domain which is a putative protein-protein interaction domain and exclusively exists at the C-terminal region in p73 and p63 in mammals. A phylogenetic analysis revealed that the p53 gene derived from mosquitoes is composed of two paralogues, p53-1 and p53-2. Of these, only p53-2 is responsively upregulated by dengue 2 virus (DENV2) in C6/36 cells which usually survive the infection. This indicates that the p53 gene is closely related to DENV infection in mosquito cells. The specific significance of p53-2's involvement in cell survival from virus-induced stress is described and briefly discussed in this report.
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http://dx.doi.org/10.1016/j.jmii.2017.06.006DOI Listing
December 2017

Subchronic toxicity of low dose propoxur, permethrin, and their combination on the redox status of rat liver.

Chem Biol Interact 2017 Jun 26;272:21-27. Epub 2017 Apr 26.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China. Electronic address:

Carbamates and pyrethroids are widely used pesticides. However, their joint toxicity at low doses with long-term exposure remains unknown. Therefore, we investigated the subchronic joint hepatotoxicity of the two representative pesticides within these two classes, i.e., propoxur (PR) and permethrin (PE) in rats. The male Wistar rats were orally treated with three different doses of PR, PE and their mixtures for 90 consecutive days. Liver weight, serum clinical chemistry parameters and histopathological changes were measured to access the hepatotoxicity. In addition, oxidative stress markers in liver were measured using biochemical assays. The results showed that PR reduced liver weight and lead to prominent liver histological changes. Moreover, PR dose-dependently induced lipid peroxidation and reduced superoxide dismutase activity. In contrast, PE induced a relatively mild hepatotoxicity. Intriguingly, the mixture of PR and PE did not reduce liver weight or increase serum aspartate transaminase activity. In addition, the mixture did not reduce the antioxidant enzyme activity as PR did. Thus, these results showed that PR induced prominent hepatotoxicity with subchronic exposure, and there is a potential antagonistic interaction between PR and PE on the oxidative damage in liver of rats.
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http://dx.doi.org/10.1016/j.cbi.2017.04.023DOI Listing
June 2017

Metabolomic analysis for combined hepatotoxicity of chlorpyrifos and cadmium in rats.

Toxicology 2017 06 19;384:50-58. Epub 2017 Apr 19.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China. Electronic address:

Pesticides and heavy metals are widespread environmental pollutants. Although the acute toxicity of organophosphorus pesticide chlorpyrifos (CPF) and toxic heavy metal cadmium (Cd) is well characterized, the combined toxicity of CPF and Cd, especially the hepatotoxicity of the two chemicals with long-term exposure at a low dose, remained unclear. In this study, we investigated the toxicity in the liver of rats upon subchronic exposure to CPF and Cd at environmentally relevant doses. Rats were given three different doses (1/135 LD, 1/45 LD and 1/15 LD) of CPF and Cd as well as their mixtures by oral gavage for 90days. After treatment, the liver tissues were subjected to histopathological examination and biochemical analysis. Gas chromatography-mass spectrometry (GC-MS) was used to analyze the metabolomic changes in the rat liver upon CPF, Cd and their mixtures treatment. The results showed that CPF and Cd-induced oxidative damage and disrupted energy, amino acid, and fatty acid metabolism in the liver. Eleven biomarkers in liver were identified for CPF-, Cd-, and their mixture-treated rats. Three metabolites, i.e., butanedioic acid, myo-inositol, and urea, were identified as unique biomarkers for the mixture-treated rats. Moreover, we found that Cd could accelerate the metabolism of CPF in the liver when given together to the rats, which may lead to the potential antagonistic interaction between CPF and Cd. In conclusion, our results indicated that even at environmentally relevant doses, CPF and Cd could disrupt the liver metabolism. In addition, the accelerated metabolism of CPF by Cd may lead to their potential antagonistic interaction.
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http://dx.doi.org/10.1016/j.tox.2017.04.008DOI Listing
June 2017

Cadmium and chlorpyrifos inhibit cellular immune response in spleen of rats.

Environ Toxicol 2017 Jul 15;32(7):1927-1936. Epub 2017 Mar 15.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, China.

Cadmium (Cd) and chlorpyrifos (CPF) are common pollutants coexisting in the environment, and both of them have been reported to have immunotoxicity to organisms. However, the joint effects of these two chemicals on the immune system are still unknown. In this study, we used CdCl and CPF to study their combined effects on immune functions in the spleen of rats. In in vivo experiments, SD rats were exposed to different doses of CdCl (0.7 and 6 mg kg body weight/day) and CPF (1.7 and 15 mg kg body weight/day) or their combinations for consecutive 28 days. The proliferation and cytokine production ability of the splenocytes isolated from the treated animals were assessed. In in vitro experiments, we used different concentrations of CdCl and CPF to treat concanavalin A (Con A)-induced splenocytes isolated from untreated rats. We found that the combination of CPF and high dose of CdCl had a synergistic inhibitory effect on production of IFN-γ by spleen cells induced by Con A. The in vitro results showed that two chemicals had different effects on the cell proliferation and cytokine production depending on the exposure doses and time. This result suggests that exposure to both CdCl and CPF at the environmentally-relevant low dose may be potentially more hazardous than exposure to each individual toxicant.
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http://dx.doi.org/10.1002/tox.22415DOI Listing
July 2017

Joint toxicity of chlorpyrifos and cadmium on the oxidative stress and mitochondrial damage in neuronal cells.

Food Chem Toxicol 2017 May 9;103:246-252. Epub 2017 Mar 9.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China. Electronic address:

Pesticides and heavy metals can be easily biomagnified in food chains and bioaccumulated in individuals, thus pose significant threat to human health. However, their joint toxicity for long-term exposure at low dose has not been thoroughly investigated. In the present study, we investigated the oxidative damages in brain of rats exposed subchronically to organophosphorus pesticide chlorpyrifos (CPF) and heavy metal cadmium (Cd), and their mixtures at the environmentally relevant doses. Rats were given different doses of CPF and Cd by oral gavage for three months. After treatment, brain tissues were subjected for biochemical analysis. Mitochondrial damage and reactive oxidative species were also measured in neuroblastoma SH-SY5Y cells treated with CPF, Cd and their mixtures. The results showed that CPF and Cd generated protein and lipid peroxidation, disturbed the total antioxidant capability, and altered mitochondria ultrastructure in the brain. Lipids and proteins were sensitive to the oxidative damage induced by CPF and Cd. CPF and Cd decreased mitochondrial potential and induced reactive oxygen species in SH-SY5Y cells. However, the mixture did not display higher toxicity than the sum of that of the individual treatments. Thus, CPF and Cd could have a potential antagonistic interaction on the induction of oxidative stress.
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http://dx.doi.org/10.1016/j.fct.2017.03.013DOI Listing
May 2017

Autophagy in Tri-o-cresyl Phosphate-Induced Delayed Neurotoxicity.

J Neuropathol Exp Neurol 2017 01;76(1):52-60

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China.

The widely used organophosphorus compound tri-o-cresyl phosphate (TOCP) elicits delayed neurotoxicity characterized by progressive axonal degeneration in the spinal cord and peripheral nerves. However, the precise mechanisms of TOCP-induced delayed neurotoxicity are not clear. Because autophagy has been linked to the pathogenesis of neurodegenerative diseases, we aimed to characterize autophagy in the progression of TOCP-induced delayed neurotoxicity. In vivo experiments using the adult hen animal model showed that autophagy in spinal cord axons and in sciatic nerves was markedly induced at the early preclinical stage of TOCP-induced delayed neurotoxicity; it was decreased as the delayed neurotoxicity progressed to the overt neuropathy stage. In cultured human neuroblastoma SH-SY5Y cells, TOCP reduced cell growth, and induced prominent autophagy. The autophagy inhibitor 3-methyladenine could attenuate TOCP-induced cytotoxicity, indicating that the autophagy is accountable for TOCP-induced neurotoxicity. In addition, we found that TOCP-induced Parkin translocation to mitochondria in SH-SY5Y cells, suggesting that autophagy may function to degrade mitochondria after TOCP exposure. These results suggest that autophagy may play an important role in the initiation and progression of axonal damage during TOCP-induced neurotoxicity.
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http://dx.doi.org/10.1093/jnen/nlw108DOI Listing
January 2017

Disturbed phospholipid homeostasis in endoplasmic reticulum initiates tri-o-cresyl phosphate-induced delayed neurotoxicity.

Sci Rep 2016 11 24;6:37574. Epub 2016 Nov 24.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

Tri-o-cresyl phosphate (TOCP) is a widely used organophosphorus compound, which can cause a neurodegenerative disorder, i.e., organophosphate-induced delayed neurotoxicity (OPIDN). The biochemical events in the initiation of OPIDN were not fully understood except for the essential inhibition of neuropathy target esterase (NTE). NTE, located in endoplasmic reticulum (ER), catalyzes the deacylation of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) to glycerophosphocholine (GPC). The present study aims to study the changes of ER phospholipids profile as well as levels of important intermediates of phospholipid synthesis such as diacylglycerol (DAG) and phosphatidic acid (PA) at the initiation stage of OPIDN. Hens are the most commonly used animal models of OPIDN. The spinal cord phospholipidomic profiles of hens treated by TOCP were studied by using HPLC-MS-MS. The results revealed that TOCP induced an increase of PC, LPC, and sphingomyelin (SM) levels and a decrease of GPC, phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), lysophosphatidylserine (LPS), phosphatidylglycerol (PG), and phosphatidylinositol (PI) levels., Levels of DAG and PA were also decreased. Pretreatment with phenylmethylsulfonyl fluoride (PMSF) 24 h before TOCP administration prevented OPIDN and restored the TOCP-induced changes of phospholipids except GPC. Thus, the disruption of ER phospholipid homeostasis may contribute to the initiation of organophosphate-induced delayed neurotoxicity.
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http://dx.doi.org/10.1038/srep37574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121615PMC
November 2016

Comparison of vitrification and conventional slow freezing for cryopreservation of ovarian tissue with respect to the number of intact primordial follicles: A meta-analysis.

Medicine (Baltimore) 2016 Sep;95(39):e4095

aDepartment of Gynecology bDepartment of General Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.

Background: Vitrification is the standard method for cryopreserving human oocytes and embryos, but its effects on ovarian tissue are uncertain. The purpose of this meta-analysis was to compare the proportion of intact primordial follicles in ovarian tissue cryopreserved with vitrification versus slow freezing.

Methods: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until November 11, 2014 using combinations of the search terms: ovarian tissue, cryopreservation, vitrification, follicle, follicles. Inclusion criteria were randomized controlled trails, two-arm prospective studies, and retrospective studies in which ovarian tissues were preserved by vitrification or conventional slow freezing. The primary outcome was the proportion of intact primordial follicles.

Results: Six studies were included in the meta-analysis. The number of patients ranged from 3 to 20, and age ranged from 20 to 43 years. Total number of morphologically intact follicles ranged from 14 to 2058, among which 6 to 724 were primordial. The pooled odds ratio (OR) showed no significant difference in the proportion of intact primordial follicles after slow freezing or vitrification (OR = 1.228, 95% confidence interval [CI]: 0.769-1.961, P = 0.390). Sensitivity analysis using the leave-one-out approach indicated no considerable changes in the direction and magnitude of the pooled estimates when individual studies were excluded one at a time, indicating good reliability of the current analysis.

Conclusions: Vitrification and slow freezing produce equivalent results with respect to intact primordial follicles for the cryopreservation of human ovarian tissue. However, the included studies varied in the cryopreservation protocols used.
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http://dx.doi.org/10.1097/MD.0000000000004095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5265884PMC
September 2016

Antioxidant activities of protein hydrolysates obtained from the housefly larvae.

Acta Biol Hung 2016 Sep;67(3):236-46

State Key Laboratory of Integrated Management of Pest Insects & Rodents, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China.

The housefly is an important resource insect and the housefly larvae are ideal source of food additives. The housefly larvae protein hydrolysates were obtained by enzymatic hydrolysis by alcalase and neutral proteinase. Their antioxidant activities were investigated, including the superoxide and hydroxyl radicalscavenging activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity, reducing power and metal chelating activity. The antioxidant activities of both hydrolysates increased with their increasing concentrations. The alcalase hydrolysate (AH) showed higher scavenging activities against hydroxyl radical and superoxide anion radical at low concentrations and higher metal-chelating activity than the neutral proteinase hydrolysate (NPH). The NPH exhibited higher scavenging activity against DPPH free radical and higher reducing power than the AH. Both hydrolysates showed more than 50% superoxide anion radical-scavenging activity at 10 μg/mL. These results indicate that both housefly larvae protein hydrolysates display high antioxidant activities and they could serve as potential natural antioxidant food additives.
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http://dx.doi.org/10.1556/018.67.2016.3.2DOI Listing
September 2016

Direct interaction of avermectin with epidermal growth factor receptor mediates the penetration resistance in Drosophila larvae.

Open Biol 2016 Apr 13;6(4):150231. Epub 2016 Apr 13.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China

With the widespread use of avermectins (AVMs) for managing parasitic and agricultural pests, the resistance of worms and insects to AVMs has emerged as a serious threat to human health and agriculture worldwide. The reduced penetration of AVMs is one of the main reasons for the development of the resistance to the chemicals. However, the detailed molecular mechanisms remain elusive. Here, we use the larvae of Drosophila melanogaster as the model organism to explore the molecular mechanisms underlying the development of penetration resistance to AVMs. We clearly show that the chitin layer is thickened and the efflux transporter P-glycoprotein (P-gp) is overexpressed in the AVM-resistant larvae epidermis. We reveal that the activation of the transcription factor Relish by the over-activated epidermal growth factor receptor (EGFR)/AKT/ERK pathway induces the overexpression of the chitin synthases DmeCHS1/2 and P-gp in the resistant larvae. Interestingly, we discover for the first time, to the best of our knowledge, that AVM directly interacts with EGFR and leads to the activation of the EGFR/AKT/ERK pathway, which activates the transcription factor Relish and induces the overexpression of DmeCHS1/2 and P-gp. These findings provide new insights into the molecular mechanisms underlying the development of penetration resistance to drugs.
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http://dx.doi.org/10.1098/rsob.150231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852453PMC
April 2016
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