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: Yu Shuang, Xiaofeng Yao, Jing Liu, Juntao Niu, Wenyu Guo, Chao Li

المصدر: Human cell. 35(4)

مصطلحات موضوعية: Cancer Research, Carcinogenesis, Squamous Cell Carcinoma of Head and Neck, Cell Biology, Gene Expression Regulation, Neoplastic, Extracellular Vesicles, MicroRNAs, Head and Neck Neoplasms, Cell Line, Tumor, Carcinoma, Squamous Cell, Humans, Laryngeal Neoplasms, Cell Proliferation, Smad4 Protein

الوصف: Serum-derived extracellular vesicles (EVs) containing non-coding RNAs have been indicated to serve as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma (LSCC), while their functional role remains to be explored. Here, we summarize the possible mechanism explaining the laryngeal carcinogenesis and the associated changes with the involvement of extracellular microRNA (miR)-27a from serum of LSCC patients. Serum-derived EVs from LSCC patients were found to increase the proliferative activity and decreased the apoptotic activity of LSCC cells. miRNA microarrays revealed that miR-27a expression was elevated after EV treatment. miR-27a expression was elevated in LSCC tissues and predicted a poor prognosis for patients. Downregulation of miR-27a inhibited the effect of EVs to reduce the activity of LSCC cells in vitro and to suppress tumor development in vivo. miR-27a targeted SMAD family member 4 (Smad4) to mediate the Wnt/β-catenin pathway, which was induced under the influence of EVs. Smad4 was downregulated in LSCC tissues, and simultaneous overexpression of miR-27a and Smad4 resulted in reduced cell activity and tumorigenicity. In conclusion, serum-derived EVs support the laryngeal carcinogenesis at least partially via transferring miR-27a. miR-27a targets Smad4 and is a biomarker to predict LSCC prognosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f34c381784aa042a36d7987b03754855Test
https://pubmed.ncbi.nlm.nih.gov/35545731Test

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: 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: Yufang Ma, Xiance Sun, Guang Yang, Liping Jiang, Xiaofeng Yao, Xiaoxia Shi, Jingyuan Zhang, Xiuyan Han, Zhanchen Dong, Jian Kang, Shanshan Sha, Tianming Qiu

المصدر: Food and Chemical Toxicology. 157:112540

مصطلحات موضوعية: Lysosomal membrane, Blotting, Western, Toxicology, Mass Spectrometry, Permeability, chemistry.chemical_compound, Tubulin, Autophagy, Humans, Adaptor Proteins, Signal Transducing, Fluorocarbons, Membranes, biology, Permease, Chemistry, Membrane Proteins, Hep G2 Cells, General Medicine, Isotype, Cell biology, Perfluorooctane, Sulfonate, biology.protein, Tyrosine, Lysosomes, After treatment, Food Science

الوصف: Perfluorooctane sulfonate (PFOS) is one kind of persistent organic pollutants. In previous study, we found that PFOS induced autophagy-dependent lysosomal membrane permeabilization (LMP) in hepatocytes, and siRNA against lysosomal permease spinster 1 (SPNS1) relieved PFOS-induced LMP. However, whether and how SPNS1 functioned as the link between autophagy and LMP was still not defined. In this study, we constructed a stable cell line expressing high levels of SPNS1. We found that SPNS1 interacted specifically with α-tubulin of tyrosinated isotype by pull-down assay. After treatment with PFOS, the level of tyrosinated α-tubulin was autophagy-dependently decreased. SPNS1-tyrosinated α-tubulin interaction was disrupted subsequently, which led to LMP eventually. We also found that stable high-expression of SPNS1 in hepatocytes accelerated lysosomal acidification, and deteriorated PFOS-induced LMP. This study pointed out that SPNS1-tyrosinated α-tubulin interaction mediated the cross-talk between autophagy and LMP induced by PFOS, shedding new light on the mechanism of PFOS hepatotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f79f1d604a3f0dd3a9f9b362cda63600Test
https://doi.org/10.1016/j.fct.2021.112540Test

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: Ye Tao, Jinling Wang, Xiance Sun, Xiaofeng Yao, Dan Liu, Zhanchen Dong

المصدر: Mitochondrion. 54

مصطلحات موضوعية: 0301 basic medicine, Bioenergetics, Chemistry, Cell Survival, Cell Biology, Mitochondrion, Extracellular vesicles, DNA, Mitochondrial, Microvesicles, Cell biology, Mitochondria, 03 medical and health sciences, Extracellular Vesicles, 030104 developmental biology, 0302 clinical medicine, Molecular Medicine, Animals, Humans, Viability assay, Energy Metabolism, Molecular Biology, 030217 neurology & neurosurgery, Intracellular, Function (biology)

الوصف: Intercellular transfer of mitochondria and mitochondrial components through extracellular vesicles (EVs), including microvesicles and exosomes, is an area of intense interest. The cargos that are carried by EVs define their biological activities. Mitochondria are in charge of bioenergetics and maintenance of cell viability. Increasing evidences indicate the presence of intact mitochondria or mitochondrial components in EVs, which raises many questions, how they are engulfed into EVs and what do they do? Here, we present what is currently known about the presence and function of various mitochondrial constituent in EVs. We also review current understanding about how and why mitochondrial components are encapsulated into EVs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d05da9f267b48f679c844190e193a038Test
https://pubmed.ncbi.nlm.nih.gov/32861876Test

المؤلفون: Chengyan Geng, Qiujuan Li, Xiaofeng Yao, Liping Jiang, Zeyun Gao, Yong Liu, Xiaoxia Shi, Xuan Wang, Jun Cao, Zhiguo Li

المصدر: Toxicology in vitro : an international journal published in association with BIBRA. 66

مصطلحات موضوعية: 0301 basic medicine, Cell Survival, ATG5, Autophagy-Related Proteins, Toxicology, Autophagy-Related Protein 5, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Adenosine Triphosphate, Autophagy, Humans, Glycolysis, Lactic Acid, Cell Proliferation, A549 cell, Chemistry, Cell growth, Cell Cycle, General Medicine, Transfection, Cell cycle, Cell biology, Cysteine Endopeptidases, 030104 developmental biology, Glucose, Anaerobic glycolysis, 030220 oncology & carcinogenesis, Cadmium

الوصف: Cadmium (Cd) is a pervasive harmful metal in the environment. It is a well-known inducer of tumorigenesis, but its mechanism is still unclear. We have previously reported that Cd-induced autophagy was apoptosis-dependent and prevents apoptotic cell death to ensure the growth of A549 cells. In this study, the mechanism was further investigated. Cd treatment increased glucose uptake and lactate release significantly. Meanwhile, the protein level of GLUT1，HKII，PKM2 and LDHA increased in a time-dependent manner, indicating that Cd induced aerobic glycolysis in A549 and HELF cells. The inhibitors of autophagy, 3MA, and CQ, repressed Cd-induced glycolysis-related proteins, indicating that autophagy was involved in Cd-induced glycolysis in A549 and HELF cells. Knockdown of ATG4B or ATG5 by siATG4B and siATG5 decreased Cd-induced glycolysis, while overexpression of ATG4B enhanced glycolysis. These results demonstrated that Cd-induced glycolysis was autophagy-dependent. Then, glycolysis inhibitor, 2DG and siPKM2 could inhibit Cd-induced cell viability and cell cycle progression compared to only Cd treatment, indicating that glycolysis played an important role in Cd-induced cell growth. Finally, co-treatment of transfection of ATG4B-DNA plasmids with 2DG or siPKM2 further demonstrated that the autophagy-glycolysis axis played an important role in Cd-induced cell cycle progression. Taken together, our results suggested that Cd-induced glycolysis is autophagy-dependent and the autophagy-glycolysis axis underlies the mechanism of Cd-induced cell growth in A549 and HELF cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fbbf1aea4bde2a61bb0478037340cedbTest
https://pubmed.ncbi.nlm.nih.gov/32200033Test

المؤلفون: Ming Sun, Cong Zhang, Xiance Sun, Liping Jiang, Xiaofeng Yao, Shaopeng Wang, Xueyan Wu, Guang Yang, Yueran Bai, Xiaofang Liu, Qian Chu

المصدر: Chemico-Biological Interactions. 288:24-31

مصطلحات موضوعية: 0301 basic medicine, Programmed cell death, animal structures, Down-Regulation, Antineoplastic Agents, Apoptosis, Toxicology, Patulin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Autophagy, Humans, Viability assay, Cytotoxicity, Membrane Potential, Mitochondrial, Membrane potential, chemistry.chemical_classification, Reactive oxygen species, Chemistry, TOR Serine-Threonine Kinases, Liver Neoplasms, RNA-Binding Proteins, Hep G2 Cells, General Medicine, Acetylcysteine, Up-Regulation, Cell biology, 030104 developmental biology, 030220 oncology & carcinogenesis, Toxicity, Reactive Oxygen Species, Microtubule-Associated Proteins, Proto-Oncogene Proteins c-akt

الوصف: Patulin (PAT) is a secondary metabolite produced by certain species of Penicillium, Byssochlamys and Aspergillus. It has been shown to induce liver toxicity, but the possible molecular mechanisms are not completely elucidated. In our study, we treated Human Hepatoma G2 (HepG2) cells by 3-methyladenine (3-MA), an autophagosome formation inhibitor, and rapamycin, an autophagosome formation stimulator. The results showed that 3-MA protected the HepG2 cells against PAT cytotoxicity, while rapamycin decreased the cell viability. Thus, autophagy may play an important role in PAT-induced toxicity. To uncover the mechanism by which cells decrease proliferation and activation of autophagy, we found that collapses of mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) level were increased under treatment with PAT. Further, we elucidated that the expression of p-Akt1 and p-MTOR was inhibited during this process. N-acetyl-l-cysteine (NAC), a ROS inhibitor, protected against PAT-induced cytotoxicity, decreased the protein expression of LC3-II, and up-regulated the level of p-Akt1 and p-MTOR. These findings suggested that PAT-induced autophagic cell death was ROS-dependent in HepG2 cells. In conclusion, it is possible that PAT elicited autophagy through ROS-Akt1-MTOR pathway in the HepG2 cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::10e37e3f74769ac0811f1466158d10b9Test
https://doi.org/10.1016/j.cbi.2018.03.018Test

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