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: 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: 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: Yahui Wang, Dongya Zhang, Xiaofeng Yao

المصدر: Journal of molecular neuroscience : MN. 65(1)

مصطلحات موضوعية: 0301 basic medicine, Male, MAP Kinase Signaling System, p38 mitogen-activated protein kinases, MAP Kinase Kinase 3, Ischemia, Nitric Oxide Synthase Type II, Pharmacology, Blood–brain barrier, Neuroprotection, p38 Mitogen-Activated Protein Kinases, Rats, Sprague-Dawley, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Downregulation and upregulation, Edema, medicine, Animals, Humans, Protein Kinase Inhibitors, business.industry, Infarction, Middle Cerebral Artery, General Medicine, medicine.disease, Rats, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, HEK293 Cells, Matrix Metalloproteinase 9, Blood-Brain Barrier, Ectopic expression, medicine.symptom, business, Reperfusion injury, 030217 neurology & neurosurgery

الوصف: The mechanism contributing to blood-brain barrier (BBB) disruption, involved in poststroke edema and hemorrhagic transformation, is important but elusive. We investigated microRNA-21 (miR-21)-mediated mechanism in the disruption of BBB following cerebral ischemia-reperfusion (I/R) injury. Rats with cerebral I/R injury were prepared after middle cerebral artery occlusion and subsequent reperfusion. The underlying regulatory mechanisms of miR-382 were investigated with treatment of miR-382 mimics, miR-382 inhibitors, or SB203580 (an inhibitor of the MAPK signaling pathway) prior to I/R modeling. Compared with sham-operated rats, rats following I/R showed increased Longa's scores, ischemic hemisphere volume, cerebral infarct volume, EB content in brain tissues, enhanced levels of p38, iNOS, and MMP-9. The ectopic expression of miR-21 by mimics and MAPK signaling inhibition by SB203580 reduced Longa's scores, ischemic hemisphere volume, cerebral infarct volume, EB content in brain tissues, decreased levels of p38, MAP2K3, iNOS, and MMP-9. The luciferase activity determination showed miR-21 bound to MAP2K3 in its 3'UTR. miR-21 downregulation mediated by inhibitors appeared to yield an opposed trend. We also found that MAPK signaling inhibition by SB203580 could rescue rats with treatment of miR-382 inhibitors. The study highlights the neuroprotective role of MiR-21 during cerebral I/R injury and its preventive effect against BBB disruption by blocking the MAPK signaling pathway via targeted inhibition of MAP2K3, potentially opening a novel therapeutic avenue for the treatment of cerebral ischemia.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5d7f79f5f9812b5a2cfa50fdb195877cTest
https://pubmed.ncbi.nlm.nih.gov/29696468Test

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: Jun Cao, Chengyan Geng, Yue Ding, Xiaofeng Yao, Laifu Zhong, Liping Jiang, Chunpeng Gao

المصدر: Toxicology in Vitro. 28:667-674

مصطلحات موضوعية: Cell Survival, Apoptosis, Mitochondrion, Toxicology, medicine.disease_cause, Cathepsin B, Lysosome, medicine, Humans, Cathepsin, biology, Cytochrome c, Hydrazones, Cytochromes c, Dipeptides, Hep G2 Cells, General Medicine, Mitochondria, Cell biology, medicine.anatomical_structure, Nitroimidazoles, Tacrine, biology.protein, Cholinesterase Inhibitors, Lysosomes, Reactive Oxygen Species, Oxidative stress, medicine.drug

الوصف: Tacrine (THA) is a competitive inhibitor of cholinesterase. Administration of THA for the treatment of Alzheimer’s disease results in a reversible hepatotoxicity in 30–50% of patients, as indicated by elevated alanine aminotransferase levels. However, the intracellular mechanisms have not yet been elucidated. In our previous study, we found that THA induced cytotoxicity and mitochondria dysfunction by ROS generation and 8-OHdG formation in mitochondrial DNA in HepG2 cells. In this study, the mechanism underlying was further investigated. Our results demonstrated that THA induced dose-dependent apoptosis with cytochrome c release and activation of caspase-3. THA-induced apoptosis was inhibited by treating cells with a ROS inhibitor, YCG063. In addition, we observed that THA led to an early lysosomal membrane permeabilization and release of cathepsin B. Pretreatment with CA-074Me, a specific cathepsin B inhibitor resulted in a significant but not complete decrease in tacrine-induced apoptosis. These data suggest that tacrine-induced cell apoptosis involves both mitochondrial damage and lysosomal membrane destabilization, and ROS is the critical factor that integrates tacrine-induced mitochondrial and lysosomal death pathways.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3ab2e7bd26ce279f3d17549ea6b0c595Test
https://doi.org/10.1016/j.tiv.2014.02.001Test

المؤلفون: Chengyan Geng, Jun Cao, Xiance Sun, Guang Yang, Jian Kang, Liping Jiang, Chuan-Zhou Gao, Liming Xu, Xiaofeng Yao, Laifu Zhong, Yufang Ma

المصدر: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 67

مصطلحات موضوعية: Autophagosome, Programmed cell death, Biology, Toxicology, Permeability, chemistry.chemical_compound, Western blot, Lysosome, medicine, Autophagy, Humans, Viability assay, PI3K/AKT/mTOR pathway, Fluorocarbons, medicine.diagnostic_test, Acridine orange, General Medicine, Hep G2 Cells, Intracellular Membranes, Cell biology, medicine.anatomical_structure, Biochemistry, chemistry, Alkanesulfonic Acids, Lysosomes, Food Science

الوصف: Perfluorooctane sulfonate (PFOS) is an emerging persistent organic pollutant widely distributed in the environment, wildlife and human. In this study, as observed under the transmission electron microscope, PFOS increased autophagosome numbers in HepG2 cells, and it was confirmed by elevated LC3-II levels in Western blot analysis. PFOS increased P62 level and chloroquine failed to further increase the expression of LC3-II after PFOS treatment, indicating that the accumulation of autophagosome was due to impaired degradation rather than increased formation. With acridine orange staining, we found PFOS caused lysosomal membrane permeabilization (LMP). In this study, autophasome formation inhibitor 3-methyladenine protected cells against PFOS toxicity, autophagy stimulator rapamycin further decreased cell viability and increased LDH release, cathepsin inhibitor did not influence cell viability of PFOS-treated HepG2 cells significantly. These further supported the notion that autophagic cell death contributed to PFOS-induced hepatotoxicity. In summary, the data of the present study revealed that PFOS induced LMP and consequent blockage of autophagy flux, leading to an excessive accumulation of the autophagosomes and turning autophagy into a destructive process eventually. This finding will provide clues for effective prevention and treatment of PFOS-induced hepatic disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1670925a5dbbbc5104dcbb0ced875b12Test
https://pubmed.ncbi.nlm.nih.gov/24561269Test

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