المؤلفون: Xiance Sun, Chengyan Geng, Qiujuan Li, Xiaofang Liu, Xiaofeng Yao, Min Chen, Dandan Li, Guang Yang, Liping Jiang, Chang Feng

المصدر: Chemico-Biological Interactions. 273:212-218

مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Population, Peroxisome proliferator-activated receptor, 030204 cardiovascular system & hematology, Biology, Toxicology, Mice, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Tumor Cells, Cultured, medicine, Animals, Humans, Oil Red O, PPAR alpha, education, Triglycerides, chemistry.chemical_classification, Mice, Inbred ICR, education.field_of_study, Fenofibrate, Dose-Response Relationship, Drug, Triglyceride, Lipid metabolism, Aurovertins, Hep G2 Cells, General Medicine, Peroxisome, Lipid Metabolism, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Liver, chemistry, Hepatocyte, Hepatocytes, lipids (amino acids, peptides, and proteins), Injections, Intraperitoneal, medicine.drug

الوصف: Citreoviridin (CIT) is a mycotoxin produced by Penicillum citreonigrum, Aspergillus terreus and Eupenicillium ochrosalmoneum. CIT occurs naturally in moldy rice and corn. CIT is associated with the development of atherosclerosis in the general population. Alteration in hepatic lipid metabolism is a pathogenic factor in atherosclerosis. However the effect and the underlying mechanism of CIT on hepatic lipid metabolism are largely unknown. In this study, we reported that CIT induced triglyceride accumulation in mice liver and human liver HepG2 cells as shown in oil red O staining. CIT (0.1 mg/kg-0.3 mg/kg) for 6 weeks elevated liver triglyceride contents in mice. CIT inhibited the transactivation activity of peroxisome proliferator-activated receptor-α (PPAR-α) in hepatocyte in vivo and in vitro, as shown by the reduced mRNA levels of PPAR-α target genes which play key roles in lipid metabolism in various aspects. PPAR-α agonist fenofibrate attenuated CIT-induced triglyceride accumulation in HepG2 cells. Furthermore, CIT increased serum total cholesterol/high-density lipoprotein cholesterol ratio, a strong risk factor for cardiovascular disease. In summary, we reported that CIT induced PPAR-α-dependent hepatic triglyceride accumulation and dyslipidemia. Our data will provide new mechanistic insights into CIT-induced lipid alterations.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e173680234d4fddfa3244d0babbf605Test
https://doi.org/10.1016/j.cbi.2017.06.021Test

المؤلفون: Xiance Sun, Dandan Li, Liping Jiang, Wei Wu, Xiaofeng Yao, Jun Cao, Tianming Qiu, Chang Feng, Min Chen

المصدر: Biochemical and Biophysical Research Communications. 477:781-785

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Glucose uptake, Population, Biophysics, 010501 environmental sciences, Biology, 01 natural sciences, Biochemistry, mTORC2, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, Humans, Insulin, education, Molecular Biology, Protein kinase B, Cells, Cultured, 0105 earth and related environmental sciences, Fluorocarbons, education.field_of_study, Dose-Response Relationship, Drug, Hep G2 Cells, Cell Biology, medicine.disease, Enzyme Activation, Glucose, 030104 developmental biology, Endocrinology, Alkanesulfonic Acids, Hepatocytes, Phosphorylation, Insulin Resistance, Signal transduction, Proto-Oncogene Proteins c-akt, Signal Transduction

الوصف: Perfluorooctane sulfonate (PFOS), a persistent organic pollutant, is blamed to be associated with the incidence of insulin resistance in the general human population. In this study, we found that PFOS inhibited the phosphorylation and activation of protein kinase B (AKT), a key mediator of cellular insulin sensitivity, in human hepatoma HepG2 cells. The mRNA level of the gluconeogenic gene PEPCK, a downstream target gene of AKT, was increased in PFOS-treated cells. Due to stimulated gluconeogenesis, insulin-stimulated glucose uptake was decreased in HepG2 cells. In our previous study, we found that PFOS disturbed autophagy in HepG2 cells. We proposed that PFOS could inhibit the activation of AKT through inhibiting mTORC2, a key regulator of autophagy. In this study, we found that the levels of triglyceride were increased in HepG2 cells. PFOS-induced accumulation of hepatic lipids also contributed to the inhibition of AKT. Eventually, the inhibition of AKT led to insulin resistance in PFOS-treated cells. Our data would provide new mechanistic insights into PFOS-induced hepatic insulin resistance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cc177a711b1463e4ee4e6aad679109b6Test
https://doi.org/10.1016/j.bbrc.2016.06.135Test

المؤلفون: Lei Yang, Liping Jiang, Tianming Qiu, Zhidong Wang, Xiance Sun, Ni Gao, Xiaofeng Yao, Pei Pei, Xiaofang Liu, Guang Yang

المصدر: Journal of cellular physiology. 234(4)

مصطلحات موضوعية: 0301 basic medicine, Blood Glucose, Male, Taurine, medicine.medical_specialty, Physiology, Clinical Biochemistry, Population, Autophagy-Related Proteins, Mechanistic Target of Rapamycin Complex 2, Carbohydrate metabolism, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Arsenic Trioxide, Internal medicine, medicine, Autophagy, Animals, Humans, Phosphorylation, education, Mechanistic target of rapamycin, education.field_of_study, biology, Glycogen, Gluconeogenesis, Cell Biology, Hep G2 Cells, medicine.disease, Mice, Inbred C57BL, PPAR gamma, 030104 developmental biology, Endocrinology, chemistry, Liver, 030220 oncology & carcinogenesis, biology.protein, Hepatocytes, Insulin Resistance, Rosiglitazone, Glycolysis, Proto-Oncogene Proteins c-akt, medicine.drug, Signal Transduction

الوصف: Inorganic arsenic (iAs) is reportedly associated with the increased incidence of type 2 diabetes in the population. Here, we found that iAs exposure significantly decreased the expression of glycolytic genes and glycogen content and increased gluconeogenesis gene levels in C57/BL6J mice. The expression of peroxisome proliferator-activated receptor γ (PPARγ), and mechanistic target of rapamycin complex 2 (mTORC2) were decreased in the livers of iAs-treated mice. Furthermore, in iAs-treated HepG2 cells, we found that PPARγ agonist rosiglitazone (RGS) increased the expression of mTORC2, inhibited autophagy, and improved glucose metabolism. mTORC2 agonist palmitic acid inhibited autophagy and improved glucose metabolism as well as the autophagosome formation inhibitor 3-methyladenine. Taurine, a natural compound, reversed impaired glucose metabolism and decreased expression of PPARγ and mTORC2 induced by iAs in mice liver and HepG2 cells. These data indicated that taurine administration could ameliorate iAs-induced insulin resistance through activating PPARγ-mTORC2 signalling and subsequently inhibiting hepatic autophagy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::727c901d0de7fca5b6893009439e5d07Test
https://pubmed.ncbi.nlm.nih.gov/30362509Test

المؤلفون: Chengyan Geng, Huiyuan Luo, Qiujuan Li, Zhiguo Li, Dan Mei, Jun Cao, Hong Ge, Liping Jiang, Lian Zhao, Xiaofeng Yao

المصدر: Chemico-biological interactions. 277

مصطلحات موضوعية: 0301 basic medicine, Male, Pathology, medicine.medical_specialty, Lung Neoplasms, Biology, Toxicology, Focal adhesion, 03 medical and health sciences, Subcutaneous injection, Mice, 0302 clinical medicine, HMGA2, Downregulation and upregulation, Cell Movement, medicine, Animals, Humans, Neoplasm Invasiveness, Lung, A549 cell, Gene knockdown, HMGA2 Protein, General Medicine, Transfection, Up-Regulation, 030104 developmental biology, medicine.anatomical_structure, Matrix Metalloproteinase 9, A549 Cells, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Matrix Metalloproteinase 2, Environmental Pollutants, Cadmium

الوصف: Cadmium (Cd) is a toxic metal widely found in a number of environmental matrices, and it induces serious adverse effects in various organs and tissues. In this study, the role of high mobility group A2 (HMGA2) in promoting migration and invasion in Cd-treated A549 cells and lung tissues of mice was investigated. Our findings showed that exposure to Cd (2 μM) for 48 h or subcutaneous injection of Cd daily for 6 weeks significantly enhanced the expression of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), phosphorylated focal adhesion kinase (p-FAK), and HMGA2 in A549 cells or lung tissues of mice. In A549 cells, HMGA2 knockdown significantly decreased expression of MMP-9, MMP-2 and p-FAK and inhibited the migration and invasion compared to that of only Cd-treated cultures. Overexpression of HMGA2 in HEK-293T cells increased expression of MMP-9, MMP-2 and p-FAK and enhanced the migration and invasion compared with the empty vector transfection group. In conclusion, upregulation of HMGA2 plays an important role in Cd-enhanced migration and invasion. Suppressing HMGA2 expression might have potential values in prevention of Cd-resulted toxicities.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8e540273501e1fb6783e1712f15596b0Test
https://pubmed.ncbi.nlm.nih.gov/28830677Test

المؤلفون: Zhaoqing Li, Sinan Wang, Na Ye, Jiabin Dong, Xuan Zhou, Minghui Zhao, Yansheng Wu, Yu Wang, Xudong Wang, Yu Ren, Xin Qu, Qiang Shen, Linhgping Kong, Kailiang Zhang, Yu Qiao, Chao Zhang, Shanshan Sun, Xiaofeng Yao, Wenyu Guo, Rui Jin, Lun Zhang, Haiying Chen, Chao Jing, Jia Zhou

مصطلحات موضوعية: 0301 basic medicine, STAT3 Transcription Factor, Cancer Research, medicine.medical_specialty, Beta-catenin, Cell Survival, Cell, Antineoplastic Agents, Salicylanilides, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Internal medicine, Cell Line, Tumor, medicine, Animals, Humans, STAT3, beta Catenin, Cell Proliferation, biology, Cell growth, Squamous Cell Carcinoma of Head and Neck, Cell cycle, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Oncology, Apoptosis, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Catenin, Cancer research, biology.protein, Carcinoma, Squamous Cell, Niclosamide, Signal transduction, Signal Transduction

الوصف: Signal transducer and activator of transcription 3 (STAT3) is involved in the tumor growth and metastasis of human head and neck squamous cell carcinoma (HNSCC) and is therefore a target with therapeutic potential. In this study, we show that HJC0152, a recently developed anticancer agent and a STAT3 signaling inhibitor, exhibits promising antitumor effects against HNSCC both in vitro and in vivo via inactivating STAT3 and downstream miR-21/β-catenin axis. HJC0152 treatment efficiently suppressed HNSCC cell proliferation, arrested the cell cycle at the G0–G1 phase, induced apoptosis, and reduced cell invasion in both SCC25 and CAL27 cell lines. Moreover, HJC0152 inhibited nuclear translocation of phosphorylated STAT3 at Tyr705 and decreased VHL/β-catenin signaling activity via regulation of miR-21. Loss of function of VHL remarkably compromised the antitumor effect of HJC0152 in both cell lines. In our SCC25-derived orthotopic mouse models, HJC0152 treatment significantly abrogated STAT3/β-catenin expression in vivo, leading to a global decrease of tumor growth and invasion. With its favorable aqueous solubility and oral bioavailability, HJC0152 holds the potential to be translated into the clinic as a promising therapeutic strategy for patients with HNSCC. Mol Cancer Ther; 16(4); 578–90. ©2017 AACR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce55a0ac3093153620dc592d3f16ec7fTest
https://europepmc.org/articles/PMC5380531Test/

المؤلفون: Fangfang Song, Lun Zhang, Kexin Chen, Fengju Song, Hong Zheng, Xiaofeng Yao, Xiaoling Zhu, Qiang Zhang

مصطلحات موضوعية: Oncology, Adult, Male, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, China, endocrine system diseases, Adolescent, Alcohol Drinking, Endocrinology, Diabetes and Metabolism, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Papillary thyroid cancer, Young Adult, Endocrinology, Asian People, Gene Frequency, Risk Factors, Internal medicine, Genotype, medicine, Humans, Genetic Predisposition to Disease, Thyroid Neoplasms, Allele, Age of Onset, Genotyping, Allele frequency, Thyroid cancer, Genetic Association Studies, Aged, Genetics, Carcinoma, Smoking, Case-control study, Thyroid Cancer and Nodules, Middle Aged, medicine.disease, Carcinoma, Papillary, Thyroid Cancer, Papillary, Case-Control Studies, Lymphatic Metastasis, Female

الوصف: Papillary thyroid cancer (PTC) is a common malignancy that frequently harbors a high prevalence of somatic mutations in the oncogenic BRAF gene. As a novel prognostic molecular marker, this gene has drawn much attention in recent years for its potential utility in the risk prognosis and management of PTC. However, the contribution of the germline variants in this gene to PTC remains unclear. The study herein was aimed to investigate the potential association between the inherited BRAF variants and PTC based on a case-control study.We selected four single-nucleotide polymorphisms (SNPs) and took a systematic step to interrogate whether these SNPs of BRAF are associated with PTC risk by genotyping these SNPs from 368 patients with PTC and 564 healthy controls.In comparison of cases and controls for the four SNPs, no differences were observed in the genotypic and allelic frequencies, nor was there evidence of an association between BRAF SNPs and overall risk of PTC. After stratification, however, we found a significantly increased risk of PTC attributed to the SNP variants rs17161747, rs1042179, and rs3748093 for those with a family history of cancer, for smokers, and for both those of age45 years and nondrinkers, respectively. Further, in the PTC cases, those carrying the rs3748093 variant seemed to be less susceptible to developing lymph node metastases, but more likely to suffer from PTC at an earlier age (45 years).These preliminary results may provide evidence for the involvement of the common genetic variants scattered throughout the BRAF oncogene in the prediction of PTC onset and progression. In the future, enlarging the number of samples and performing functional studies in this gene may help to validate whether the association truly exists.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::088f46872df8395b767417ccf1c815c9Test
https://europepmc.org/articles/PMC3539251Test/

المؤلفون: Qiang Zhang, Yansheng Wu, Xiaofeng Yao, Liuyang Zhang, Xuan Zhou, Lun Zhang

المصدر: Journal of cancer research and clinical oncology. 138(2)

مصطلحات موضوعية: Adult, Male, Cancer Research, medicine.medical_specialty, China, Multivariate analysis, Kaplan-Meier Estimate, Logistic regression, Gastroenterology, Group A, Group B, Young Adult, Tongue, Internal medicine, Medicine, Humans, Survival rate, Aged, Neoplasm Staging, Hematology, business.industry, Cancer, General Medicine, Middle Aged, medicine.disease, Prognosis, Tongue Neoplasms, Survival Rate, medicine.anatomical_structure, Logistic Models, Oncology, Lymphatic Metastasis, Multivariate Analysis, Female, Neoplasm Recurrence, Local, business

الوصف: The purpose of this study was to compare the prognosis of oral tongue cancer patients and base of tongue cancer patients. One hundred oral tongue cancer patients (group A) were matched with 50 base of tongue cancer patients (group B) for gender, age, T-stage, and tumor differentiation in this study. Survival rate was performed using the Kaplan–Meier analysis, and multivariate analysis was conducted using the Logistic regression model. There was difference in the survival rate between the two groups. Three- and 5-year OS (overall survival) of the two groups were 65.0, 51.0% for group A and 40.0, 28.0% for group B, respectively. For the two groups, 3- and 5-year DSS (disease-specific survival) were 61.0, 46.0% for group A and 38.0, 26.0% for group B, respectively. Multivariate analysis showed that recurrence (P = 0.019) and regional lymph node metastasis (P = 0.043) were significant between the group A and group B patients. The oral tongue cancer patients had a better prognosis than base of tongue cancer patients. The difference in prognosis between the oral tongue cancer and the base of tongue cancer patients in this study was closely associated with the recurrence and regional lymph node metastasis. We conclude that the individual treatment should be used for base of tongue cancer patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f830ca3366a70bd1ab4ccdf9e4b396acTest
https://pubmed.ncbi.nlm.nih.gov/22139349Test