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: 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: 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: Wenqi, Xu, Shaopeng, Wang, Liping, Jiang, Xiance, Sun, Ningning, Wang, Xiaofang, Liu, Xiaofeng, Yao, Tianming, Qiu, Cong, Zhang, Jing, Li, Haoyuan, Deng, Guang, Yang

المصدر: Humanexperimental toxicology. 41

مصطلحات موضوعية: Inflammation, Air Pollutants, Canada, China, India, Environmental Exposure, United States, Oxidative Stress, Risk Factors, Autophagy, Animals, Humans, Particulate Matter, Renal Insufficiency, Chronic, DNA Damage

الوصف: The harm of air pollution to public health has become a research hotspot, especially atmospheric fine-particulate matter (PM

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::659f1df3231fe3c885423d1bbc69bb78Test
https://pubmed.ncbi.nlm.nih.gov/35174736Test

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: 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: 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: Zhanchen, Dong, Jianyu, Wang, Tianming, Qiu, Jialu, Wu, Yu, An, Xiaoxia, Shi, Xiance, Sun, Liping, Jiang, Xiaofang, Liu, Guang, Yang, Jun, Cao, Xiaofeng, Yao

المصدر: Science of The Total Environment. 825:153933

مصطلحات موضوعية: Fluorocarbons, Environmental Engineering, Voltage-Dependent Anion Channel 1, Calcium-Binding Proteins, Mitochondrial Membrane Transport Proteins, Pollution, Mitochondria, Mice, Inbred C57BL, Mice, Alkanesulfonic Acids, Liver, Tubulin, Autophagy, Animals, Humans, Environmental Chemistry, Calcium, Insulin Resistance, Cation Transport Proteins, Waste Management and Disposal

الوصف: Perfluorooctane sulfonate (PFOS), one kind of persistent organic pollutants, is associated with insulin resistance (IR) in general population. However, the exact mechanism is still obscure. In this study, we found that 50 μM PFOS caused IR in L-02 hepatocytes after 1 h, and induced autophagy and mitochondrial calcium (Ca

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::59d78593d0d1936fd0b1b5d2435b6751Test
https://doi.org/10.1016/j.scitotenv.2022.153933Test