المؤلفون: Yaxun Sun, Xiaofeng Yao, Xiang Zhou, Chenyang Jiang, Jiefang Zhang, Xia Sheng, Min Wang, Ying Yang, Yiwen Pan, Lan Su, Xueying Chen, Guosheng Fu

المصدر: Pacing and Clinical Electrophysiology. 45:993-1003

مصطلحات موضوعية: Male, Bundle of His, Cardiac Pacing, Artificial, Ventricular Septum, General Medicine, Middle Aged, Electrocardiography, Treatment Outcome, Feasibility Studies, Humans, Female, Cardiology and Cardiovascular Medicine, Aged, Retrospective Studies

الوصف: Left bundle branch area pacing (LBBAP) aims to capture the cardiac conduction system in area of the left bundle branch. Currently, LBBAP is mainly performed using lumen-less pacing leads (LLLs) with preshaped sheath. However, the data on LBBAP with stylet-driven leads (SDLs) without sheath is limited.This study presents the feasibility, safety, and pacing characteristics of LBBAP using SDLs without the support of sheath.A total of 25 patients with bradycardia indications who received LBBAP implantation with an attempt of SDL (FINELINE II 4471 lead, Boston Scientific, MA, US) between August 2020 and April 2021 at Sir Run Run Shaw Hospital were included in this retrospective cohort study. Twenty of them finally were paced with SDL in priority (SDL-LBBAP group). Twenty propensity score matching patients who underwent LBBAP with LLL (Select Secure 3830 lead, Medtronic, MN, US) and 20 right ventricular septal pacing (RVSP) with regular active fixation lead respectively in the same period (the LLL-LBBAP group and RVSP group) were compared using ECG characteristics, pacing parameters and complications during 6-month follow-up.LBBAP was successful with SDL in 23 of 25 patients (92%) and 20 of them were paced with SDL first. In the SDL-LBBAP group, the average age was 70.4 ± 8.2 years, and 55% of patients were male. Paced QRS duration and the stimulus to peak left ventricular activation time (Sti-LVAT) in SDL-LBBAP group were similar with those in LLL-LBBAP group and significantly shorter than those in RVSP group (126.1±14.1 ms vs. 124.8±10.9 ms, p = 1.00; 77.7 ± 11.2 ms vs. 73.5 ± 9.3 ms, P = .75; 126.1 ± 14.1 ms vs. 147.7 ± 22.5 ms, P.001; 77.7 ± 11.2 ms vs. 97.0 ± 13.2 ms, P.001). The pacing threshold and R-wave amplitude of SDL-LBBAP group were 0.53 ± 0.18V and 11.53 ± 3.63 mV at baseline respectively, which were comparable with the other two groups. During the 6-month follow-up, the pacing parameters remained stable and no lead-related complications were recorded.It is feasible and safe to use stylet-directed pacing lead for permanent LBBAP without a delivery sheath. Similar to LLL, LBBAP using SDL showed stable parameters and narrower paced QRS duration compared with RVSP, which could be an alternative to LLL in LBBAP.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ba20eae06829454cbc4f6ca11083e5adTest
https://doi.org/10.1111/pace.14504Test

المؤلفون: Weizhuo Yuan, Tianming Qiu, Xiaofeng Yao, Chenbing Wu, Yan Shi, Ningning Wang, Jingyuan Zhang, Liping Jiang, Xiaofang Liu, Guang Yang, Jie Bai, Xiance Sun

المصدر: Toxicology letters. 370

مصطلحات موضوعية: Liver Cirrhosis, Inflammasomes, NLR Family, Pyrin Domain-Containing 3 Protein, Hepatic Stellate Cells, Humans, General Medicine, Toxicology, HSP47 Heat-Shock Proteins, Arsenic

الوصف: The activation of hepatic stellate cells (HSCs) is a key event during the progression of liver fibrosis (LF). We have previously indicated that NLRP3 inflammasome plays a crucial role in arsenic-induced HSCs activation. However, the mechanism of cascade responses between NLRP3 inflammasome and HSCs activation is unclear. Here, we showed that the transcription and protein level of Hsp47 was upregulated after 4 μM arsenic treatment, both in vivo and in vitro. Additionally, arsenic-induced HSCs activation was remarkably alleviated by the interference of Hsp47. Furthermore, blockage of NLRP3 significantly mitigated the activation of the NLRP3 inflammasome and decreased the expression of Hsp47, thereby attenuating the arsenic-induced HSCs activation. However, the ablation of Hsp47 did not affect the activation of the NLRP3 inflammasome. Notably, the protein-protein interaction between NLRP3 and Hsp47 was observed both in vivo and in vitro, and the target amino acid sequences were further identified. In summary, the present study indicated that NaAsO

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b18fa0f260bb14af96d7731c9d0521bfTest
https://pubmed.ncbi.nlm.nih.gov/35963424Test

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

المصدر: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 164

مصطلحات موضوعية: Male, Diethylhexyl Phthalate, Testis, Ferroptosis, Humans, Testosterone, General Medicine, Tumor Suppressor Protein p53, Toxicology, Reactive Oxygen Species, Lipids, Food Science

الوصف: Exposure to Di (2-ethylhexyl) phthalate (DEHP) has been associated with toxic effects of the reproductive system. However, the exact mechanism remains to be elucidated. In this study we explored the testicular toxicity induced by DEHP, and the probable molecular mechanism in the process. In vivo, the results demonstrated that DEHP affected testosterone levels and blood-testosterone barrier (BTB) integrity and caused ferroptosis. We further demonstrated that DEHP up-regulated the expression of p38α, p-p38α, p53, p-p53, SAT1, ALOX15. This view has also been confirmed in TM4 cells. After pre-treatment with fer-1 or si-MAPK14, the expression of either p53, p-p53, SAT1 and ALOX15 up-regulated by MEHP was inhibited in vitro. Interestingly, p38α can prevent the accumulation of lipid ROS, and the production of lipid ROS in turn promoted the expression of p38α, thus forming a feedback loop during the ferroptosis. In this process, a vicious cycle consisting of p38α, p53, SAT1, ALOX15, lipid ROS was involved. This study provides new mechanistic insights into DEHP-induced toxicity of the reproductive system.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ac744e3453214d24768b9c532653c2fdTest
https://pubmed.ncbi.nlm.nih.gov/35447293Test

المؤلفون: Yuhan, Zhu, Jingyuan, Zhang, Xiaofeng, Yao, Tianming, Qiu, Liping, Jiang, Ningning, Wang, Yan, Shi, Chenbing, Wu, Weizhuo, Yuan, Guang, Yang, Xiaofang, Liu, Jie, Bai, Lili, Men, Xiance, Sun

المصدر: Food and Chemical Toxicology. 160:112771

مصطلحات موضوعية: Male, Pore Forming Cytotoxic Proteins, Arsenites, Ubiquitination, General Medicine, Phosphate-Binding Proteins, Toxicology, Sodium Compounds, Cell Line, Rats, Rats, Sprague-Dawley, Liver, NLR Family, Pyrin Domain-Containing 3 Protein, Hepatocytes, Pyroptosis, Animals, Humans, Insulin Resistance, Food Science

الوصف: As an environmental toxicant, arsenic exposure may cause insulin resistance (IR). Previous studies have shown that pyroptosis plays an important role in the occurrence and development of IR. Although gasdermin D (GSDMD) functions as an executor of pyroptosis, the relationship between GSDMD-mediated pyroptosis and hepatic IR remains unclear. Here, we observed that sodium arsenite (NaAsO

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::735fb184bdef1ad96575515e3936262aTest
https://doi.org/10.1016/j.fct.2021.112771Test

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: 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, 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: Xiaoming Liu, Guang Yang, Xiaofeng Yao, Qinghua Sun, Liping Jiang, Min Chen, X Gao, Shaopeng Wang, Xiance Sun

المصدر: Human & Experimental Toxicology. 36:1177-1185

مصطلحات موضوعية: 0301 basic medicine, DNA damage, Health, Toxicology and Mutagenesis, Catechols, Gene Expression, Toxicology, medicine.disease_cause, Umbilical vein, Superoxide dismutase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Diethylhexyl Phthalate, Malondialdehyde, Human Umbilical Vein Endothelial Cells, medicine, Humans, chemistry.chemical_classification, Reactive oxygen species, Molecular Structure, biology, Superoxide Dismutase, General Medicine, Glutathione, Molecular biology, Comet assay, Checkpoint Kinase 2, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, biology.protein, Comet Assay, Fatty Alcohols, Tumor Suppressor Protein p53, Reactive Oxygen Species, Oxidative stress, DNA Damage

الوصف: Mono (2-ethylhexyl) phthalate (MEHP) is the principal metabolite of di (2-etylhexyl) phthalate, which is widely used as a plasticizer, especially in medical devices. MEHP has toxic effects on cardiovascular system. The aim of this study was to investigate the possibility that 6-gingerol may inhibit the oxidative DNA damage of MEHP in human umbilical vein endothelial cells (HUVECs) and the potential mechanism. The comet assay was used to monitor DNA strand breaks. We have shown that 6-gingerol significantly reduced the DNA strand breaks caused by MEHP. MEHP increased the levels of reactive oxygen species and malondialdehyde, decreased the level of glutathione and activity of superoxide dismutase, and altered the mitochondrial membrane potential. In addition, DNA damage-associated proteins (p53 and p-Chk2 (T68)) were significantly increased by the treatment of MEHP. Those effects can all be protected by 6-gingerol. The results firmly indicate that 6-gingerol may have a strong protective ability against the DNA damage caused by MEHP in HUVECs, and the mechanism may relate to the antioxidant activity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6047f202225368d680080ad5e1076c1eTest
https://doi.org/10.1177/0960327116681650Test