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Hesperidin ameliorates H_(2)O_(2)-induced bovine mammary epithelial cell oxidative stress via the Nrf2 signaling pathway

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1737-1750页

作者： Qi Huang Jiashuo Liu Can Peng Xuefeng Han Zhiliang Tan CAS Key Laboratory for Agro‑Ecological Processes in Subtropical Region National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionHunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125HunanChina State Key Laboratory of Animal Nutrition and Feeding Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijing 100193China

Background Hesperidin is a citrus flavonoid with anti-inflammatory and antioxidant potential. However, its protective effects on bovine mammary epithelial cells(b MECs) exposed to oxidative stress have not been *** In this study, we investigated the effects of hesperidin on H_(2)O_(2)-induced oxidative stress in b MECs and the underlying molecular mechanism. We found that hesperidin attenuated H_(2)O_(2)-induced cell damage by reducing reactive oxygen species(ROS) and malondialdehyde(MDA) levels, increasing catalase(CAT) activity, and improving cell proliferation and mitochondrial membrane potential. Moreover, hesperidin activated the Keap1/Nrf2/ARE signaling pathway by inducing the nuclear translocation of Nrf2 and the expression of its downstream genes NQO1 and HO-1, which are antioxidant enzymes involved in ROS scavenging and cellular redox balance. The protective effects of hesperidin were blocked by the Nrf2 inhibitor ML385, indicating that they were Nrf2 *** Our results suggest that hesperidin could protect b MECs from oxidative stress injury by activating the Nrf2 signaling pathway, suggesting that hesperidin as a natural antioxidant has positive potential as a feed additive or plant drug to promote the health benefits of bovine mammary.

关键词： Bovine mammary epithelial cell Hesperidin Nrf2 signaling pathway Oxidative stress

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2,4-D Hyper Accumulation Induced cellular Responses of Azolla pinnata R. Br. to Sustain Herbicidal Stress

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Phyton-International Journal of Experimental Botany 2020年第4期89卷 999-1017页

作者： Arnab Kumar De Arijit Ghosh Debabrata Dolui Indraneel Saha Malay Kumar Adak Plant physiology and Plant molecular Biology Research Unit Department of BotanyUniversity of KalyaniWest BengalIndia

In the present experiment with ongoing concentration(0µM,100µM,250µM,500µM and 1000µM)of 2,4-D,the responses of Azolla pinnata *** evaluated based on cellular ***,plants were significantly tolerated up to 1000µM of 2,4-D with its *** was accompanied by a steady decline of indole acetic acid(IAA)concentration in tissues with 78.8%over the *** bound H^(+)-ATPase activity was over expressed within a range of 1.14 to 1.25 folds with activator(KCl)and decreased within a range of 57.3 to 74.6%in response to inhibitor(Vanadate)*** regards to IAA metabolism,plants recorded a linear increase with wall bound oxidase activity up to maximum concentration of 2,*** variations were more moderated when wall bound IAA-oxidase recorded a linear increase proportionate to the 2,4-D *** was more extended with the presence of different isoforms of IAA-oxidase which was much more pronounced with distinct polymorphisms of expressed proteins,however,not independent to the 2,4-D *** like spermine,spermidine and putrescine(spm,spd and put)were not consistent in concentration with the dosages of 2,*** these,plants were induced to apoplastic NAD(P)H oxidase activity maximally by 1.6 folds under 500µM 2,4-D over ***,putrescine responded more or less consistently and recorded maximally 11.9 folds at 500µM 2,4-D as compared to the ***(P)H oxidase activity recorded maximally 1.6 folds against control and remain consistent throughout the concentrations of 2,*** along with APX were more linear in responses through the concentration of 2,4-D except CAT as compared to *** enzymatic antioxidative activity,peroxidases(GPX and APX)were overexpresed in a similar manner except for catalase with a non-significant *** stabilization of cellular redox,glutathione reductase attended maximum value by 2.45 folds at 1000µM evidenced with significant variations in protein polymo

关键词： Azolla 2,4-D antioxidative enzymes comet assay HPLC

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Journal of Geriatric cardiology 2010年第3期7卷 171-175页

作者： Yun-Feng Lan Yi Wen Zhou Fang Jin-Lao Gao Yan Liu Men Lin Hong-Juan Wang Yi-Cheng Fu Prori S.G Carlo. Napolitano C Yang Li Institute of Geriatric cardiology of Chinese PLA General Hospital Beijing 100853 China molecular cardiology IRCCS Fondazione S. Maugen Pavia Italy the Department of cardiology University of Pavia Pavia Italy

Objective To characterize early afterdepolarizations （EADs） caused triggered activity （TA） among calsequestrin-2 （CASQ2） knock-in （CASQ2 KI） mice and its relationship with aging. Methods Electrophysiological properties of ventricular myocytes from 3- month （mo, young）, 9-mo （adult-l） and 12-too （adult-2） in wild-type （WT） and CASQ2 KI mice were investigated with patch-clamp technique. Results The incidences of EADs and TA in CASQ2 KI cardiomyocytes increased with increasing age. In contrast, WT mice cardiomyocytes showed no significant change in matched-age groups. Compared with that in 3-mo CASQ2 KI mice, the 50% repolarization of action potential （APD50） showed prolongation in both 9-mo and 12-mo ones （9.2±0.9 ms of 9-mo and 10.3 ± 1.2 ms of 12- mo vs. 5.6± 0.3 ms of 3-mo）, while the 90 % repolarization of action potential （APD90） was similar among 3 age groups. Compared with 3-mo mice, the 9-mo and 12-mo CASQ2 KI mice showed markedly reduced transient outward potassium current （Ito） densities but increased L-type calcium current （ICa-L） densities. Conlcusion This study suggested that events of EADs and TA in CASQ2 KI mice increased with increasing age, It might be associated partly with the augment of cellular calcium concentration and the prolongation of APD50 induced by decrease of Ito and increase of ICa-L in adult CASQ2 KI mice

关键词： Calsequestrin early afterdepolarization triggered activity gene mutation transgenic mice

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Eliminate mitochondrial diseases by gene editing in germ-line cells and embryos

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Protein & Cell 2015年第7期6卷 472-475页

作者： Si Wang Fei Yi Jing Qu National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Department of molecular and cellular physiology Stanford University School of Medicine Stanford CA 94305 USA State Key Laboratory of Reproductive Biology Institute of Zoology Chinese Academy of SciencesBeijing 100101 China

Nuclease-based gene editing technologies have opened up opportunities for correcting human genetic diseases. For the first time, scientists achieved targeted gene editing of mitochondrial DNA in mouse oocytes fused with patient cells. This fascinating progression may encourage the development of novel therapy for human maternally inherent mitochondrial diseases.

关键词： Mitochondrial Disease Mouse Oocyte Cluster Regularly Interspaced Short Palindromic Repeat Gene Editing Human Genetic Disease

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GENERATION OF TRANSGENIC MICE FOR IN VIVO DETECTION OF INSULIN-CONTAINING GRANULE EXOCYTOSIS AND QUANTIFICATION OF INSULIN SECRETION

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Journal of Innovative Optical Health Sciences 2009年第4期2卷 397-405页

作者： JINLING LU NATALIA GUSTAVSSON QIMING LI GEORGE KRADDA THOMAS C.SUUDHOF WEIPING HAN Laboratory of Metabolic Medicine Singapore Bioimaging Consortium A*STAR Singapore 138667 Department of molecular and cellular physiology and Howard Hughes Medical Institute Stanford University School of Medicine Palo Alto CA 94304USA Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Singapore 117597

Insulin secretion is a complex and highly regulated *** much progress has been made in understanding the cellular mechanisms of insulin secretion and regulation,it remains unclear how conclusions from these studies apply to living *** few studies have been done to address these issues is largely due to the lack of suitable tools in detecting secretory events at high spatial and temporal resolution in *** combined with genetically encoded biosensor,optical imaging is a powerful tool for visualization of molecular events in *** this study,we generated a DNA construct encoding a secretory granule resident protein that is linked with two spectrally separate fluorescent proteins,a highly pH-sensitive green pHluorin on the intra-granular side and a red mCherry in the *** exocytosis of secretory granules,the dim pHluorin inside the acidic secretory granules became highly fluorescent outside the cells at neutral pH,while mCherry fluorescence remained constant in the process,thus allowing ratiometric quantification of insulin secretory ***,mCherry fluorescence enabled tracking the movement of secretory granules in living *** validated this approach in insulin-secreting cells,and generated a transgenic mouse line expressing the optical sensor specifically in pancreaticβ-*** transgenic mice will be a useful tool for future investigations of molecular mechanism of insulin secretion in vitro and in vivo.

关键词： Insulin secretion diabetes optical imaging secretory granule exocytosis.

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Modulation of cell physiology under hypoxia in pancreatic cancer

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World Journal of Gastroenterology 2021年第28期27卷 4582-4602页

作者： Matias Estaras Antonio Gonzalez Department of physiology Institute of Molecular Pathology BiomarkersUniversity of ExtremaduraCaceres 10003Spain Department of physiology Cell Biology and Communication Research GroupUniversity of ExtremaduraCaceres 10003Spain

In solid tumors,the development of vasculature is,to some extent,slower than the proliferation of the different types of cells that form the tissue,both cancer and stroma *** a consequence,the oxygen availability is compromised and the tissue evolves toward a condition of *** presence of hypoxia is variable depending on where the cells are localized,being less extreme at the periphery of the tumor and more severe in areas located deep within the tumor ***,the cells do not *** pathways that are critical for cell fate such as endoplasmic reticulum stress,apoptosis,autophagy,and others are all involved in cellular responses to the low oxygen availability and are orchestrated by hypoxia-inducible *** stress and inflammation are critical conditions that develop under *** with changes in cellular bioenergetics,all contribute to cell ***,cell-to-cell interaction is established within the tumor such that cancer cells and the microenvironment maintain a bidirectional ***,the release of extracellular vesicles,or exosomes,represents short and long loops that can convey important information regarding invasion and *** a result,the tumor grows and its malignancy ***,one of the most lethal tumors is pancreatic *** paper reviews the most recent advances in the knowledge of how cells grow in a pancreatic tumor by adapting to *** the physiological processes that help the tumor increase its size and their regulation will be of major relevance for the treatment of this deadly tumor.

关键词： Hypoxia Cancer Tumor Pancreas Proliferation Cell survival

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Functional recovery and muscle atrophy in pre-clinical models of peripheral nerve transection and gap-grafting in mice:effects of 4-aminopyridine

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Neural Regeneration Research 2023年第2期18卷 439-444页

作者： Jung Il Lee M A Hassan Talukder Zara Karuman Anagha A.Gurjar Prem Kumar Govindappa Jagadeeshaprasad M.Guddadarangaiah Kristen M.Manto Grant D.Wandling John P.Hegarty David L.Waning John C.Elfar Department of Orthopaedics and Rehabilitation Center for Orthopaedic Research and Translational ScienceThe Pennsylvania State University College of MedicineHersheyPAUSA Department of Orthopaedic Surgery Korea University Guro HospitalSeoulSouth Korea Department of cellular and molecular physiology The Pennsylvania State University College of MedicineHersheyPAUSA

We recently demonstrated a repurposing beneficial effect of 4-aminopyridine(4-AP),a potassium channel blocker,on functional recove ry and muscle atrophy after sciatic nerve crush injury in ***,this effect of 4-AP is unknown in nerve transection,gap,and grafting *** evaluate and compare the functional recovery,nerve morphology,and muscle atrophy,we used a novel stepwise nerve transection with gluing(STG),as well as 7-mm irreparable nerve gap(G-7/0)and 7-mm isografting in 5-mm gap(G-5/7)models in the absence and presence of 4-AP *** surgery,sciatic functional index was determined wee kly to evaluate the direct in vivo global motor functional *** 12 weeks,nerves were processed for whole-mount immunofluorescence imaging,and tibialis anterior muscles were harvested for wet weight and quantitative histomorphological analyses for muscle fiber crosssectional area and minimal Feret's *** post-injury sciatic functional index values in STG and G-5/7 models were significantly greater than those in the G-7/0 model.4-AP did not affect the sciatic functional index recovery in any *** to STG,nerve imaging revealed more misdirected axons and distorted nerve architecture with *** muscle weight,cross-sectional area,and minimal Feret's diameter were significantly smaller in G-7/0 model compared with STG and G-5/7,4-AP treatment significantly increased right TA muscle mass,cross-sectional area,and minimal Feret's diameter in G-7/0 *** findings demonstrate that functional recovery and muscle atrophy after peripheral nerve injury are directly related to the intervening nerve gap,and 4-AP exerts diffe rential effects on functional recove ry and muscle atrophy.

关键词： 4-aminopyridine functional recovery muscle atrophy nerve gap nerve grafting nerve imaging nerve transection

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Hydrogen sulfide is endogenously generated in rat skeletal muscle and exerts a protective effect against oxidative stress

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Chinese Medical Journal 2013年第5期126卷 930-936页

作者： DU Jian-tong LI Wei YANG Jin-yan TANG Chao-shu LI Qi JIN Hong-fang Department of Clinical Medicine Capital Medical UniversityBeijing 100069 China Department of Pediatrics Peking University First Hospital Beijing100034 China Department of physiology and Pathophysiology Peking UniversityHealth Science Center Beijing 100191 China Key Laboratory of molecular cardiology Ministry of EducationBeijing 100191 China

Background Skeletal muscle has recently been recognized as an endocrine organ that can express, synthesize and secrete a variety of bioactive molecules which exert significant regulatory effects. Hydrogen sulfide （H2S） iS endogenously produced in mammalian tissues and participates in a number of physiological and pathophysiological processes. We aimed to verify whether H2S could be endogenously generated and released by rat skeletal muscle, and determine the biological effects of H2S in rat skeletal muscle. Methods The study was divided into two parts： detection of endogenous H2S generation and release in rat skeletal muscle and determination of antioxidative activity of skeletal muscle-derived H2S. H2S content and production in tissues were ,detected by sensitive sulfur electrode method. The expressions of H2S producing enzymes cystathionine i^-synthase, cystathionine y-lyase and mercaptopyruvate sulfurtransferase were detected by real-time PCR and western blotting and their tissue distributions were observed by immunohistochemical and immunofluorescent analysis. Rat skeletal muscular ischemia-reperfusion （I-R） injury model was created and evaluated by histological analysis under microscope. The malondialdehyde （MDA） contents, hydrogen peroxide levels, superoxide anion and superoxide dismutase （SOD） activities were detected using spectrophotometer. Results H2S could be endogenously generated and released by skeletal muscle of Sprague-Dawley rats （H2S content：（2.06＋0.43） nmol/mg; H2S production：（0.17＋0.06） ***）. Gene and protein expressions of the three H2S producing enzymes ~vere detected in skeletal muscle, as well as the liver and kidney. Endogenous H2S content and production were decreased in skeletal muscles of rats with I-R skeletal muscle injury （P 〈0.05）. Furthermore, H2S significantly protected rat skeletal muscle against I-R injury and resulted in decreased MDA content, reduced hydrogen peroxide and superoxide anion levels, but increased SOD ac

关键词： skeletal muscle hydrogen sulfide oxidative stress ischemic-reperfusion injury

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Decreased serum albumin level indicates poor prognosis of COVID-19 patients: hepatic injury analysis from 2,623 hospitalized cases

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Science China(Life Sciences) 2020年第11期63卷 1678-1687页

作者： Wei Huang Chenze Li Zhiquan Wang Hong Wang Ning Zhou Jiangang Jiang Li Ni Xin A.Zhang Dao-Wen Wang Division of cardiology Department of Internal Medicineand Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological DisordersTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430010China Department of cardiology Chinese PLA Central War Command General HospitalWuhan 430010China Stephenson Cancer Center and Department of physiology University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA

Coronavirus disease 2019(COVID-19) is a global pandemic which has caused numerous deaths worldwide. The present study investigated the roles of hypoproteinemia in the clinical outcome and liver dysfunction of COVID-19 patients. In this retrospective study, we extracted data from 2,623 clinically confirmed adult COVID-19 patients(≥18 years old) between January 29,2020 and March 6, 2020 in Tongji Hospital, Wuhan, China. The patients were divided into three groups—non-critically ill,critically ill, and death groups—in accordance with the Chinese Clinical Guideline for COVID-19. Serum albumin, low-density lipoproteins cholesterol(LDL-C), and high-density lipoproteins cholesterol(HDL-C) concentrations and inflammatory cytokines levels were measured and compared among these three groups. The median age of these 2,623 patients was 64 years old(interquartile range(IQR), 52–71). Among the patients enrolled in the study, 2,008(76.6%) were diagnosed as non-critically ill and 615(23.4%) were critically ill patients, including 383(14.6%) critically ill survivors and 232(8.8%) critically ill deaths in the hospital. Marked hypoalbuminemia occurred in 38.2%, 71.2%, and 82.4% patients in non-critically ill, critically ill, and death groups, respectively, on admission and 45.9%, 77.7%, and 95.6% of these three groups, respectively, during hospitalization. We also discovered that serum low-density lipoprotein(LDL) and HDL levels were significantly lower in critically ill and death groups compared to non-critically ill group. Meanwhile, the patients displayed dramatically elevated levels of serum inflammatory factors, while a markedly prolonged activated partial thromboplastin time(APTT) in critically ill patients reflected coagulopathy. This study suggests that COVID-19-induced cytokine storm causes hepatotoxicity and subsequently critical hypoalbuminemia, which are associated with exacerbation of disease-associated inflammatory responses and progression of the disease and ultimately

关键词： albumin hepatic injury COVID-19

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Potential preservative mechanisms of cardiac rehabilitation pathways on endothelial function in coronary heart disease

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Science China Life Sciences 2024年

作者： Wen-Tao Sun Jian-Yong Du Jia Wang Yi-Long Wang Er-Dan Dong Research Center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital)School of Health and Life SciencesUniversity of Health and Rehabilitation Sciences Department of cardiology and Institute of Vascular Medicine Peking University Third HospitalThe Institute of Cardiovascular SciencesPeking UniversityState Key Laboratory of Vascular Homeostasis and RemodelingPeking University

Cardiac rehabilitation, a comprehensive exercise-based lifestyle and medical management, is effective in decreasing morbidity and improving life quality in patients with coronary heart disease. Endothelial function, an irreplaceable indicator in coronary heart disease progression, is measured by various methods in traditional cardiac rehabilitation pathways, including medicinal treatment, aerobic training, and smoking cessation. Nevertheless, studies on the effect of some emerging cardiac rehabilitation programs on endothelial function are limited. This article briefly reviewed the endothelium-beneficial effects of different cardiac rehabilitation pathways, including exercise training, lifestyle modification and psychological intervention in patients with coronary heart disease, and related experimental models, and summarized both uncovered and potential cellular and molecular mechanisms of the beneficial roles of various cardiac rehabilitation pathways on endothelial function. In exercise training and some lifestyle interventions, the enhanced bioavailability of nitric oxide, increased circulating endothelial progenitor cells(EPCs), and decreased oxidative stress are major contributors to preventing endothelial dysfunction in coronary heart disease. Moreover, the preservation of endothelial-dependent hyperpolarizing factors and inflammatory suppression play roles. On the one hand, to develop more endothelium-protective rehabilitation methods in coronary heart disease, adequately designed and sized randomized multicenter clinical trials should be advanced using standardized cardiac rehabilitation programs and existing assessment methods. On the other hand, additional studies using suitable experimental models are warranted to elucidate the relationship between some new interventions and endothelial protection in both macro-and microvasculature.

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