المؤلفون: Shaopeng Wang, Guang Yang, Jing Li, Xiaofang Liu, Cong Zhang, Liping Jiang, Ningning Wang, Xiance Sun, Xueyan Wu, Xiaofeng Yao

المصدر: Journal of Agricultural and Food Chemistry. 69:5206-5215

مصطلحات موضوعية: 0106 biological sciences, Inflammation, Kidney, complex mixtures, 01 natural sciences, Proinflammatory cytokine, Mice, chemistry.chemical_compound, Mitophagy, medicine, Animals, Humans, Respiratory system, Mice, Inbred BALB C, 2-Undecanone, 010401 analytical chemistry, HEK 293 cells, General Chemistry, Ketones, 0104 chemical sciences, Cell biology, HEK293 Cells, medicine.anatomical_structure, chemistry, Particulate Matter, Kidney inflammation, medicine.symptom, General Agricultural and Biological Sciences, 010606 plant biology & botany

الوصف: Exposure to particulate matter has been associated with diseases of the respiratory and cardiovascular systems. Owing to the dense vasculature of the kidney, it has also been identified as a PM2.5 target organ. A potential contributor to PM2.5-mediated damage may be the promotion of inflammation. The essential oil 2-undecanone (2-methyl nonyl ketone) is an H. cordata isolate, and it has been shown to possess diverse pharmacologic effects, including anti-inflammatory properties. In this study we explored the ability of 2-undecanone to protect against PM2.5-induced kidney inflammation and the exact mechanisms in this process. We found that PM2.5 elevated the levels of certain inflammatory cytokines in BALB/c mice and in HEK 293 cells. Supplementation with 2-undecanone attenuated this PM2.5-induced inflammatory injury. Interestingly, in HEK 293 cells, the PM2.5-associated inflammation was aggravated by the mitophagy inhibitor Medivi-1, while it was attenuated by rapamycin, indicating that the mechanism of 2-undecanone-mediated inhibition of inflammation may relate to mitophagy. Meanwhile, 2-undecanone induces mitophagy in HEK 293 cells by suppressing Akt1-mTOR signaling. These results indicate that PM2.5 can induce kidney inflammation, and mitophagy induced by 2-undecanone may play a protective role against this renal inflammation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b495a1034bdec4bd31a488721857c799Test
https://doi.org/10.1021/acs.jafc.1c01305Test

المؤلفون: Kai Yue, Yansheng Wu, Beibei Ye, Peng Chen, Qingchuan Lai, Xudong Wang, Chao Jing, Yue Wu, Mengqian Zhou, Yuansheng Duan, Xingchen Li, Xiaofeng Yao, Dandan Liu, Hong Li, Linqi Li, Shengchi Zhang

المصدر: Theranostics

مصطلحات موضوعية: Male, 0301 basic medicine, Esophageal Neoplasms, Carcinogenesis, Medicine (miscellaneous), Snail, medicine.disease_cause, Metastasis, Mice, 0302 clinical medicine, Cell Movement, PSMD14, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Mice, Inbred BALB C, biology, SNAIL, EMT, Esophageal cancer, Pyrrolidinones, Up-Regulation, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Chemosensitivity, Research Paper, medicine.drug, Proteasome Endopeptidase Complex, Epithelial-Mesenchymal Transition, Mice, Nude, Antineoplastic Agents, 03 medical and health sciences, Downregulation and upregulation, Esophageal squamous cell carcinoma, In vivo, Cell Line, Tumor, biology.animal, Biomarkers, Tumor, medicine, Animals, Humans, Neoplasm Invasiveness, Cell Proliferation, Cisplatin, business.industry, Ubiquitination, medicine.disease, Thiolutin, 030104 developmental biology, Trans-Activators, Cancer research, Snail Family Transcription Factors, business

الوصف: Metastasis and chemoresistance are major causes of poor prognosis in patients with esophageal squamous cell carcinoma (ESCC), manipulated by multiple factors including deubiquitinating enzyme (DUB). DUB PSMD14 is reported to be a promising therapeutic target in various cancers. Here, we explored the antitumor activity of Thiolutin (THL), the PSMD14 inhibitor, as a new therapy strategy in ESCC. Methods: Through 4-NQO-induced murine ESCC model, we investigated the expression of PSMD14 in esophageal tumorigenesis. Ubiquitin-AMC assay was performed to evaluate DUB activity of PSMD14 with THL treatment. The effect of THL on epithelial-to-mesenchymal transition (EMT), invasion, stemness and chemosensitivity was detected by using in vitro and in vivo experiments. Immunoprecipitation and in vivo ubiquitination assay were conducted to examine whether THL could impair the deubiquitination and stability of SNAIL regulated by PSMD14. Results: Compared with normal esophageal epithelium, PSMD14 was upregulated in 4-NQO-induced murine esophageal epithelium dysplasia and ESCC tissues. THL could significantly weaken DUB activity of PSMD14. Furthermore, the results of in vitro and in vivo assays showed that THL efficiently suppressed motility and stemness and increased sensitivity to cisplatin in ESCC. Mechanically, THL impaired the interaction between PSMD14 and SNAIL, then promoted the ubiquitination and degradation of SNAIL to inhibit EMT which plays a crucial role in ESCC metastasis, stemness and chemosensitivity. TCGA database analysis revealed that high concomitant PSMD14/SNAIL expression predicted shorter overall survival in esophageal cancer. Conclusion: Our findings demonstrate for the first time that suppression of PSMD14/SNAIL axis by THL could be a novel and promising therapeutic approach for ESCC clinical therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c47c33d3831d41492d14a4c177dc6b7Test
https://doi.org/10.7150/thno.46109Test

المؤلفون: Xudong Wang, Mengqian Zhou, Wenchao Zhang, Hui Wei, Xiaofeng Yao, Beibei Ye, Chao Jing, Yuansheng Duan, Xingchen Li, Shanshan Zhuo, Kai Yue, Yansheng Wu, Dandan Liu, Linqi Li, Qingchuan Lai

المصدر: Theranostics

مصطلحات موضوعية: 0301 basic medicine, Carcinogenesis, Medicine (miscellaneous), medicine.disease_cause, Deubiquitinating enzyme, Mice, 0302 clinical medicine, PSMD14, E2F1, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Mice, Inbred BALB C, Deubiquitinating Enzymes, Prognosis, Pyrrolidinones, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Chemoresistance, medicine.drug, Research Paper, Proteasome Endopeptidase Complex, Mice, Nude, Biology, 03 medical and health sciences, stomatognathic system, Cell Line, Tumor, medicine, otorhinolaryngologic diseases, Animals, Humans, Protein kinase B, neoplasms, PI3K/AKT/mTOR pathway, Cell Proliferation, Squamous Cell Carcinoma of Head and Neck, SOXB1 Transcription Factors, Ubiquitination, Head and neck squamous cell carcinoma, medicine.disease, Thiolutin, Head and neck squamous-cell carcinoma, stomatognathic diseases, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, biology.protein, Trans-Activators, Chromatin immunoprecipitation, Proto-Oncogene Proteins c-akt, E2F1 Transcription Factor

الوصف: Increasing evidence reveals a close relationship between deubiquitinating enzymes (DUBs) and cancer progression. In this study, we attempted to identify the roles and mechanisms of critical DUBs in head and neck squamous cell carcinoma (HNSCC). Methods: Bioinformatics analysis was performed to screen differentially expressed novel DUBs in HNSCC. Immunohistochemistry assay was used to measure the expression of DUB PSMD14 in HNSCC specimens and adjacent normal tissues. The level of PSMD14 in HNSCC tumorigenesis was investigated using a 4-NQO-induced murine HNSCC model. The function of PSMD14 was determined through loss-of-function assays. Chromatin immunoprecipitation, immunoprecipitation and in vivo ubiquitination assay were conducted to explore the potential mechanism of PSMD14. The anti-tumor activity of PSMD14 inhibitor Thiolutin was assessed by in vitro and in vivo experiments. Results: We identified PSMD14 as one of significantly upregulated DUBs in HNSCC tissues. Aberrant expression of PSMD14 was associated with tumorigenesis and malignant progression of HNSCC and further indicated poor prognosis. The results of in vitro and in vivo experiments demonstrated PSMD14 depletion significantly undermined HNSCC growth, chemoresistance and stemness. Mechanically, PSMD14 inhibited the ubiquitination and degradation of E2F1 to improve the activation of Akt pathway and the transcription of SOX2. Furthermore, PSMD14 inhibitor Thiolutin exhibited a potent anti-tumor effect on HNSCC in vivo and in vitro by impairing DUB activity of PSMD14. Conclusion: Our findings demonstrate the role and mechanism of PSMD14 in HNSCC, and provide a novel and promising target for diagnosis and clinical therapy of HNSCC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41457b31fc40f3f3f83e381a98fab731Test
http://europepmc.org/articles/PMC7806466Test

المؤلفون: Xiaofeng Yao, Zhanchen Dong

المصدر: Mitochondrion. 62

مصطلحات موضوعية: Calcium metabolism, Chemistry, Endoplasmic reticulum, Biological Transport, Cell Biology, Mitochondrion, medicine.disease, Cell biology, Mitochondria, medicine.anatomical_structure, Insulin resistance, Liver, Lysosome, medicine, Molecular Medicine, Glucose homeostasis, Homeostasis, Humans, Calcium, Insulin Resistance, Molecular Biology, Ion channel

الوصف: Due to the rapid rise in the prevalence of chronic metabolic disease, more and more clinicians and basic medical researchers focus their eyesight on insulin resistance (IR), an early and central event of metabolic diseases. The occurrence and development of IR are primarily caused by excessive energy intake and reduced energy consumption. Liver is the central organ that controls glucose homeostasis, playing a considerable role in systemic IR. Decreased capacity of oxidative metabolism and mitochondrial dysfunction are being blamed as the direct reason for the development of IR. Mitochondrial Ca2+ plays a fundamental role in maintaining proper mitochondrial function and redox stability. The maintaining of mitochondrial Ca2+ homeostasis requires the cooperation of ion channels in the inner and outer membrane of mitochondria, such as mitochondrial calcium uniporter complex (MCUC) and voltage-dependent anion channels (VDACs). In addition, the crosstalk between the endoplasmic reticulum (ER), lysosome and plasma membrane with mitochondria is also significant for mitochondrial calcium homeostasis, which is responsible for an efficient network of cellular Ca2+ signaling. Here, we review the recent progression in the research about the regulation factors for mitochondrial Ca2+ and how the dysregulation of mitochondrial Ca2+ homeostasis is involved in the pathogenesis of hepatic IR, providing a new perspective for further exploring the role of ion in the onset and development of IR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cfc720ddd7f470f439832cb7753808dcTest
https://pubmed.ncbi.nlm.nih.gov/34856389Test

المؤلفون: Rui Jin, Xuan Zhou, Xiaofeng Yao, Qiang Zhang, Ping Li, Chao Jing, Yu Wang, Wenchao Zhang, Yuansheng Duan, Xudong Wang, Yingjie Tao

المصدر: Cancer Letters. 432:38-46

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, Lung Neoplasms, Adenoid cystic carcinoma, Perineural invasion, Mice, Nude, Motility, Apoptosis, medicine.disease_cause, Metastasis, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Movement, Tumor Cells, Cultured, medicine, Animals, Humans, Cell Proliferation, Mice, Inbred BALB C, Mutation, business.industry, Liver Neoplasms, NF-kappa B, Zinc Finger E-box-Binding Homeobox 1, NF-κB, Prognosis, Salivary Gland Neoplasms, medicine.disease, Carcinoma, Adenoid Cystic, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Survival Rate, Insulin-Like Growth Factor Binding Protein 2, 030104 developmental biology, Oncology, chemistry, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Cancer research, Signal transduction, business, Nuclear localization sequence, Signal Transduction

الوصف: Metastasis is a major cause of poor prognosis in patients suffered with salivary adenoid cystic carcinoma (SACC), in which many factors are implicated. In this study, we identified that IGFBP2, overexpressed in SACC, correlated positively with perineural invasion or metastasis and indicated worse outcome. Moreover, IGFBP2 overexpression could dramatically improve motility and invasion capacity of SACC cells in vitro. Mechanically, IGFBP2 enhanced expression of ZEB1 in a NF-κB (p65)-dependent manner and then promoted epithelial-mesenchymal transition (EMT) in SACC. In addition, IGFBP2 mutation in the nuclear localization signal could impede nuclear translocation of p65, lower ZEB1 expression, and abrogate the EMT process. In xenograft models, IGFBP2 overexpression promoted lung and liver metastases of SACC cells; while if nuclear IGFBP2 was reduced, the formation of metastases in lung and liver was weakened. Together, these results for the first time demonstrate that IGFBP2 plays an important role in invasion and metastasis of SACC through the NF-κB/ZEB1 signaling pathway and IGFBP2 may be a novel biomarker and target for SACC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d4ac1ce9543ace508a445463d56d618Test
https://doi.org/10.1016/j.canlet.2018.06.008Test

المؤلفون: Tianming Qiu, Xiance Sun, Rushan Yan, Zhidong Wang, Sen Wei, Guang Yang, Ni Gao, Liping Jiang, Xiaofang Liu, Jie Bai, Pei Pei, Shuangyue Qi, Xiaofeng Yao, Lei Yang

المصدر: Cell Death and Disease, Vol 9, Iss 10, Pp 1-16 (2018)

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Programmed cell death, Cell Survival, Taurine, Immunology, Inflammation, Real-Time Polymerase Chain Reaction, Arsenic, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Microscopy, Electron, Transmission, Non-alcoholic Fatty Liver Disease, Nonalcoholic fatty liver disease, Autophagy, Pyroptosis, medicine, Animals, Humans, Arsenic trioxide, lcsh:QH573-671, Arsenic toxicity, integumentary system, lcsh:Cytology, Inflammasome, Hep G2 Cells, Cell Biology, medicine.disease, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, medicine.symptom, Signal Transduction, medicine.drug

الوصف: Arsenic exposure causes nonalcoholic steatohepatitis (NASH). Inflammation is a key contributor to the pathology of nonalcoholic fatty liver disease (NAFLD), including NASH. However, it is unclear how arsenic induces inflammation. In mouse livers, we show that arsenic trioxide (As2O3) induced NASH, increased autophagy and NLRP3 inflammasome activation, increased lipid accumulation, and resulted in dysregulation of lipid-related genes. Supplemented with taurine (Tau) attenuated the inflammation and autophagy caused by As2O3. In HepG2 cells, we found that As2O3-induced pyroptotic cell death was dependent upon the activation of NLRP3 inflammasome, which was CTSB-dependent. In addition, inhibiting autophagy alleviated the As2O3-induced increase of cytosolic CTSB expression and subsequent release of LDH, activation of the NLRP3 inflammasome, and pyroptosis. Moreover, we found that Tau alleviated As2O3-induced elevation of autophagy, CTSB expression, and activation of the NLRP3 inflammasome, and reduced the release of LDH, pyroptotic cell death, and inflammation. Interestingly, As2O3-induced lipid accumulation could not be alleviated by either inhibition of autophagy nor by inhibition of CTSB. Additionally, neither inhibition of the NLRP3 inflammasome or Tau treatment could alleviate lipid accumulation. These results demonstrated that As2O3-induced pyroptosis involves autophagy, CTSB, and the NLRP3 inflammasome cascade, and that Tau alleviates As2O3-induced liver inflammation by inhibiting the autophagic-CTSB-NLRP3 inflammasomal pathway rather than decreasing lipid accumulation. These findings give insight into the association of autophagy, inflammation, pyroptosis, and NASH induced by As2O3.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::35d25f4c13dce5ef8942ce371d4fcc7dTest
http://link.springer.com/article/10.1038/s41419-018-1004-0Test

المؤلفون: Shaopeng Wang, Xiaofeng Yao, Guang Yang, Jing Li, Xiance Sun, Xiaofang Liu, Yuhang Jiao, Liping Jiang, Cong Zhang, Ningning Wang, Yunfeng Hou, Ling Yang, Qian Chu

المصدر: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 147

مصطلحات موضوعية: Male, Programmed cell death, animal structures, Inflammasomes, Inflammation, Toxicology, Cathepsin B, Patulin, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0404 agricultural biotechnology, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Autophagy, Pyroptosis, Animals, Humans, 030304 developmental biology, Cathepsin, 0303 health sciences, Mice, Inbred BALB C, Caspase 1, Inflammasome, 04 agricultural and veterinary sciences, General Medicine, Hep G2 Cells, 040401 food science, Cell biology, chemistry, Gene Expression Regulation, Liver, medicine.symptom, Chemical and Drug Induced Liver Injury, Food Science, medicine.drug

الوصف: Patulin (PAT), a kind of mycotoxin, is produced by many common fungi in fruit and vegetable-based products. It has been shown to cause hepatotoxicity. However, the possible mechanisms are not completely elucidated. The present study aimed to characterize the role of autophagic-inflammasomal pathway on pyroptosis induced by PAT. In mouse livers, PAT induced pyroptosis, and increased inflammation through the activation of NLRP3 inflammasome. In liver cells, we noticed that PAT induced pyroptotic cell death, which was confirmed by the activation of GSDMD, caspase-1, the release of LDH, and the result of PI/Hoechst assay. In addition, PAT-induced pyroptosis was dependent upon the activation of NLRP3 inflammasome and the release of cathepsin B. Cells had less expression of caspase-1 and IL-1β protein levels after treated by NLRP3 inhibitor MCC950 or cathepsin B inhibitor CA-074Me. The expression of GSDMD and IL-1β protein levels were also decrease after treated by caspase-1 inhibitor Ac-YVAD-cmk. Moreover, autophagy inhibitor 3-methyladenine (3-MA) attenuated PAT-induced increase in cytoplasmic cathepsin B expression, and subsequent LDH release, the activation of NLRP3 inflamosomes, pyroptotic cell death, and inflammation. These findings suggested that PAT-induced pyroptosis maybe through autophagy-cathepsin B-inflammasomal pathway in the liver. These results provide new mechanistic insights into PAT-induced hepatotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::62c43a67ebc00d59660169919387ca26Test
https://pubmed.ncbi.nlm.nih.gov/33217525Test

المؤلفون: Chengyan Geng, Junjie Mei, Xiaofeng Yao, Zhiguo Li, Qiujuan Li, Jun Cao, Liping Jiang

المصدر: International journal of medicinal mushrooms. 21(6)

مصطلحات موضوعية: 0106 biological sciences, Antioxidant, Asia, genetic structures, medicine.medical_treatment, Apoptosis, Pharmacology, Mitochondrion, Polysaccharide, 01 natural sciences, Applied Microbiology and Biotechnology, 010608 biotechnology, Drug Discovery, medicine, Humans, chemistry.chemical_classification, Membrane Potential, Mitochondrial, Reactive oxygen species, biology, Chemistry, Cytochrome c, Basidiomycota, Fungal Polysaccharides, Hep G2 Cells, biology.organism_classification, Mitochondria, Tacrine, biology.protein, Inonotus obliquus, Medicine, Traditional, Reactive Oxygen Species, medicine.drug

الوصف: Tacrine is the first drug licensed for the treatment of Alzheimer disease. Unfortunately, reversible hepatotoxicity limits its clinical use. In our previous study, we found that tacrine induced apoptosis in HepG2 cells by reactive oxygen species (ROS) formation and mitochondria dysfunction. Inonotus obliquus is a mushroom traditionally used as a folk medicine in Asia. In this study, the possible protective effect of polysaccharides from I. obliquus was investigated. The results showed that I. obliquus polysaccharides (IOP) reduced tacrine-induced apoptosis in HepG2 cells. Inhibition of tacrine-induced ROS generation, 8-OHdG formation in mitochondrial DNA, and loss of the mitochondrial transmembrane potential by IOP were also observed. Furthermore, IOP decreased the cytochrome c release and activation of caspase-3 induced by tacrine. These data suggest that IOP could inhibit tacrine-induced apoptosis in HepG2 cells. The protection is mediated by an antioxidant protective mechanism. Consumption of IOP may be a plausible way to prevent tacrine-induced hepatotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7aa2be95e17d3fea9a9d0d85c55c3d9fTest
https://pubmed.ncbi.nlm.nih.gov/31679230Test

المؤلفون: Yu Qiao, Jingxuan Yang, Shanshan Sun, Chuanqiang Wu, Yu Wang, Minghui Zhao, Xudong Wang, Xuan Zhou, Mingyang Liu, Min Li, Feng Yu, Lun Zhang, Zhaoqing Li, Chao Zhang, Yu Ren, Lingping Kong, Yuqing Zhang, Chao Jing, Xiaofeng Yao, Yansheng Wu, Wenyu Guo

المصدر: Clinical Cancer Research. 24:2665-2677

مصطلحات موضوعية: STAT3 Transcription Factor, 0301 basic medicine, Cancer Research, Antineoplastic Agents, Mice, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Cell Line, Tumor, otorhinolaryngologic diseases, medicine, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, RNA, Small Interfering, STAT3, neoplasms, Protein kinase B, PI3K/AKT/mTOR pathway, Cell Proliferation, Cisplatin, Cetuximab, biology, Squamous Cell Carcinoma of Head and Neck, Chemistry, Cell Cycle, EZH2, HOTAIR, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Disease Models, Animal, stomatognathic diseases, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research, biology.protein, RNA Interference, RNA, Long Noncoding, HOX Transcript Antisense RNA, Signal Transduction, medicine.drug

الوصف: Purpose: PI3K and STAT3 are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate head and neck squamous cell cancer (HNSCC) growth. The lncRNA HOX transcript antisense RNA (HOTAIR) was found to modulate the progression of HNSCC. In this study, we attempted to establish the correlation of PI3K/STAT3/HOTAIR signaling with the progression of HNSCC and its sensitivity toward platinum-based and targeted anti-EGFR combination therapy. Experimental Design: We first analyzed the STAT3/HOTAIR and PI3K/AKT level in human HNSCC samples. We then activated or suppressed STAT3/HOTAIR and determined the effects on HNSCC cell proliferation in vitro and the growth of UM1 xenograft tumor, an orthotopic model of HNSCC. The sensitivity of HNSCC cells toward cisplatin and cetuximab was determined by in vitro assays. Results: HNSCC samples showed significantly robust expression/activation of STAT3, HOTAIR, PI3K, and AKT, compared with normal squamous epithelium. STAT3 inhibition with WP1066 decreased HOTAIR level and sensitized HNSCC to cisplatin or cetuximab. STAT3 promoted HOTAIR transcription and its interaction with pEZH2-S21, resulting in enhanced growth of HNSCC cells. In addition, overexpression of HOTAIR promoted the growth of UM1 xenograft tumors in vivo. Conclusions: Our results suggest that STAT3 signaling promotes HNSCC progression via regulating HOTAIR and pEZH2-S21 in HNSCC with PI3K overexpression/activation. These findings provide a rationale to target the STAT3/HOTAIR/pEZH2-S21 regulatory axis for treating patients with HNSCC. Clin Cancer Res; 24(11); 2665–77. ©2018 AACR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::89eb7b49550e79381c323aa3511cf71fTest
https://doi.org/10.1158/1078-0432.ccr-16-2248Test

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