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L-type Calcium Channels are Involved in Iron-induced Neurotoxicity in Primary Cultured Ventral Mesencephalon Neurons of Rats

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Neuroscience Bulletin 2020年第2期36卷 165-173页

作者： Yu-Yu Xu Wen-Ping wan sha Zhao Ze-Gang Ma Department of Physiology School of Basic MedicineQingdao UniversityQingdao 266071China Institute of Brain Science and Disorders Qingdao UniversityQingdao 266071China

In the present study,we investigated the mechanisms underlying the mediation of iron transport by Ltype Ca^2+ channels(LTCCs)in primary cultured ventral mesencephalon(VM)neurons from *** found that cotreatment with 100 lmol/L FeSO4 and MPP^+(1-methyl-4-phenylpyridinium)significantly increased the production of intracellular reactive oxygen species,decreased the mitochondrial transmembrane potential and increased the caspase-3 activation compared to MPP^+ treatment ***-treatment with 500 lmol/L CaCl2 further aggravated the FeSO4-induced neurotoxicity in MPP^+-treated VM ***-treatment with 10 lmol/L isradipine,an LTCC blocker,alleviated the neurotoxicity induced by co-application of FeSO4 and FeSO4/*** studies indicated that MPP^+treatment accelerated the iron influx into VM *** addition,FeSO4 treatment significantly increased the intracellular Ca^2+ *** effects were blocked by *** results suggest that elevated extracellular Ca^2+ aggravates ironinduced *** mediate iron transport in dopaminergic neurons and this,in turn,results in elevated intracellular Ca^2+ and further aggravates iron-induced neurotoxicity.

关键词： L-type Ca^2+channels Iron overload Parkinson’s disease Isradipine Dopamine neuron

The biology,function,and applications of exosomes in cancer

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2783-2797页

作者： Jinyi Liu Liwen Ren sha Li wan Li Xiangjin Zheng Yihui yang Weiqi Fu Jie Yi Jinhua wang Guanhua Du The State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing 100050China Key Laboratory of Drug Target Research and Drug Screen Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100050China Department of Clinical Laboratory Peking Union Medical College HospitalBeijing 100730China

Exosomes are cell-derived nano vesicles with diameters from 30 to 150 nm,released upon fusion of multi vesicular bodies with the cell *** can transport nucleic acids,proteins,and lipids for intercellular communication and activate signaling pathways in target *** cancers,exosomes may participate in growth and metastasis of tumors by regulating the immune response,blocking the epithelial-mesenchymal transition,and promoting *** are also involved in the development of resistance to chemotherapeutic *** in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of *** of their amphipathic structure,exosomes are natural drug delivery vehicles for cancer therapy.

关键词： Exosomes Tumor immunity Tumor metastasis Drug resistance Biomarkers Drug delivery

Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway

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Acta Pharmaceutica Sinica B 2021年第11期11卷 3465-3480页

作者： Xiangjin Zheng wan Li Huanli Xu Jinyi Liu Liwen Ren Yihui yang sha Li Jinhua wang Tengfei Ji Guanhua Du The State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100050China Key Laboratory of Drug Target Research and Drug Screen Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100050China Department of Pharmacology Capital Medical UniversityBeijing 100069China

Glioblastoma multiforme(GBM)in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for *** of sinomenine,an alkaloid from the Chinese medicinal plant,Sinomenium acutum,showed that it had inhibitory effects on several kinds of ***,we synthesized a sinomenine derivative,sino-wcj-33(SW33),tested it for antitumor activity on GBM and explored the underlying ***33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 *** also arrested the cell cycle at G2/M phase and induced mitochondria-dependent *** gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3 K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the ***33 also induced autophagy through the PI3 K/AKT/mTOR and AMPK/mTOR ***,SW33 appears to be a promising drug for treating GBM effectively and safely.

关键词： SW33 GBM G2/M phase Apoptosis Autophagy mTOR Anti-inflammation Safety

Single-seed sowing increased pod yield at a reduced seeding rate by improving root physiological state of Arachis hypogaea

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Journal of Integrative Agriculture 2020年第4期19卷 1019-1032页

作者： LIANG Xiao-yan GUO Feng FENG Ye ZHANG Jia-lei yang sha MENG Jing-jing LI Xin-guo wan Shu-bo shandong Institute of Sericulture Yantai 264002P.R.China Biotechnology Research Center Shandong Academy of Agricultural SciencesJinan 250100P.R.China shandong Provincial Key Laboratory of Crop Genetic Improvement Ecology and PhysiologyJinan 250100P.R.China Agriculture Bureau of Yiyuan Zibo 256100P.R.China shandong Academy of Agricultural Sciences Jinan 250100P.R.China

Double-seed sowing(two seeds per hole)is the dominant pattern of peanut sowing in China,but within-hole plant competition usually limits their growth and yield ***,the traditional double-seed sowing method does not facilitate mechanization during *** objective of this study was to determine if single-seed sowing at a proper seeding rate yielded better than traditional double-seed sowing pattern and the differences of physiological metabolism of roots.A field experiment was conducted in two consecutive years to compare pod yields of single-seed sowing at 180000(S180),225000(S225),and 270000 seeds ha^-1(S270)with that of double-seed sowing at 270000 seeds ha^-1(D270)using a completely randomized block design with four *** the root bleeding sap rate,nutrient content,and the main hormone contents in root bleeding sap were also comparatively *** the pod yields of single-seed sowing at the three densities were higher than that of traditional double-seed sowing(D270),S225 yielded better than the other two single-seed sowing treatments(S180 and S270).The increased pod yield in single-seed sowing at 225000 seeds ha^-1 was mainly due to the higher pod dry weight per plant and harvest *** improved pod dry weight and shoot growth had closely relationship with the enhanced root physiological traits such as the increased root bleeding sap rate,content of free amino acids,soluble sugars,K^+,Mg^2+,Zn^2+,and Ca^2+of the individual plant *** improved activity of root reductive,nitrate reductase(NR)and ATPase and higher zeatin and zeatin riboside(Z+ZR)content of root bleeding sap were alsocrucial to the pod and shoot growth of ***-seed sowing at a moderate seeding rate(S225)is a potential practice to increase pod yield and to save seed cost.

关键词： peanut sowing pattern seeding rate root traits yield

Calcium/calmodulin modulates salt responses by binding a novel interacting protein SAMS1 in peanut(Arachis hypogaea L.)

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The Crop Journal 2023年第1期11卷 21-32页

作者： sha yang Jianguo wang Zhaohui Tang Yan Li Jialei Zhang Feng Guo Jingjing Meng Feng Cui Xinguo Li Shubo wan Institute of Crop Germplasm Resources Shandong Academy of Agricultural SciencesJinan 250100ShandongChina Institute of Agricultural Resources and Environment Shandong Academy of Agricultural SciencesJinan 250100ShandongChina shandong Academy of Agricultural Sciences/shandong Provincial Key Laboratory of Crop Genetic Improvement Ecology and PhysiologyJinan 250100ShandongChina

The Ca^(2+)/CaM signal transduction pathway helps plants adapt to environmental stress. However, our knowledge on the functional proteins of C^(2+)/CaM pathway in peanut(Arachis hypogeae L.) remains limited. In the present study, a novel calmodulin 4(CaM4)-binding protein S-adenosyl-methionine synthetase 1(SAMS1) in peanut was identified using a yeast two-hybrid assay. Expression of AhSAMS1was induced by Ca^(2+), ABA, and salt stress. To elucidate the function of AhSAMS1, physiological and phenotypic analyses were performed with wild-type and transgenic materials. Overexpression of AhSAMS1increased spermidine and spermidine synthesis while decreased the contents of ethylene, thereby eliminating excessive reactive oxygen species(ROS) in transgenic lines under salt stress. AhSAMS1 reduced uptake of Na+and leakage of K+from mesophyll cells, and was less sensitive to salt stress during early seedling growth, in agreement with the induction of SOS and NHX genes Transcriptomics combined with epigenetic regulation uncovered relationships between differentially expressed genes and differentially methylated regions, which raised the salt tolerance and plants growth. Our findings support a model in which the role of AhSAMS1 in the ROS-dependent regulation of ion homeostasis was enhanced by Ca^(2+)/CaM while AhSAMS1-induced methylation was regulated by CaM, thus providing a new strategy for increasing the tolerance of plants to salt stress.

关键词： AhCaM4 AhSAMS1 Protein interaction Polyamines Salt tolerance

Sphingosine kinase 1 promotes growth of glioblastoma by increasing inflammation mediated by the NF-κB/IL-6/STAT3 and JNK/PTX3 pathways

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Acta Pharmaceutica Sinica B 2022年第12期12卷 4390-4406页

作者： wan Li Hongqing Cai Liwen Ren Yihui yang Hong yang Jinyi Liu sha Li Yizhi Zhang Xiangjin Zheng Wei Tan Guanhua Du Jinhua wang The State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing 100050China Key Laboratory of Drug Target Research and Drug Screen Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100050China Department of Neurosurgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology Center for Cancer Precision MedicineNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China School of Pharmacy Xinjiang Medical UniversityUrumqi 830011China Xinjiang Institute of Materia Medica Urumqi 830004China

Glioblastoma(GBM)is the most challenging malignant tumor of the central nervous system because of its high morbidity,mortality,and recurrence ***,mechanisms of GBM are still unclear and there is no effective drug for GBM in the ***,it is urgent to identify new drug targets and corresponding drugs for *** this study,in silico analyses and experimental data show that sphingosine kinase 1(SPHK1)is up-regulated in GBM patients,and is strongly correlated with poor prognosis and reduced overall *** of SPHK1 promoted the proliferation,invasion,metastasis,and clonogenicity of GBM cells,while silencing SPHK1 had the opposite ***1 promoted inflammation through the NF-κB/IL-6/STAT3 signaling pathway and led to the phosphorylation of JNK,activating the JNK-JUN and JNK-ATF3 pathways and promoting inflammation and proliferation of GBM cells by transcriptional activation of ***1 interacted with PTX3 and formed a positive feedback loop to reciprocally increase expression,promote inflammation and GBM *** of SPHK1 by the inhibitor,PF543,also decreased tumorigenesis in the U87-MG and U251-MG SPHK1 orthotopic mouse *** summary,we have characterized the role and molecular mechanisms by which SPHK1 promotes GBM,which may provide opportunities for SPHK1-targeted therapy.

关键词： Glioblastoma Drug target SPHK1 Inflammation NF-κB/IL-6/STAT3 signal pathway ATF3 PXT3

Arbuscular mycorrhizal fungi combined with exogenous calcium improves the growth of peanut(Arachis hypogaea L.)seedlings under continuous cropping

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Journal of Integrative Agriculture 2019年第2期18卷 407-416页

作者： CUI Li GUO Feng ZHANG Jia-lei yang sha MENG Jing-jing GENG Yun wanG Quan LI Xin-guo wan Shu-bo Biotechnology Research Center Shandong Academy of Agricultural Sciences/Key Laboratory of Crop Genetic Improvement and Ecological Physiology of Shandong ProvinceJinan 250100P.R.China Scientific Observing and Experimental Station of Crop Cultivatio n in East China Ministry of AgricultureJinan 250100P.R.China College of Life Sciences Shandong Normal UniversityJinan 250014P.R.China shandong Academy of Agricultural Sciences Jinan 250100P.R.China

The growth and yield of peanut are negatively affected by continuous *** mycorrhizal fungi(AMF)and calcium ions(Ca^(2+))have been used to improve stress resistance in other plants,but little is known about their roles in peanut seedling growth under continuous *** study investigated the possible roles of the AMF Glomus mosseae combined with exogenous Ca^(2+)in improving the physiological responses of peanut seedlings under continuous *** combined with exogenous Ca^(2+)can enhance plant biomass,Ca^(2+)level,and total chlorophyll *** exogenous Ca^(2+)application,the F_v/F_m in arbuscular mycorrhizal(AM)plant leaves was higher than that in the control plants when they were exposed to high irradiance *** peroxidase,superoxide dismutase,and catalase activities in AM plant leaves also reached their maximums,and accordingly,the malondialdehyde content was the lowest compared to other ***,root activity,and content of total phenolics and flavonoids were significantly increased in AM plant roots treated by Ca^(2+)compared to either *** inoculation or Ca^(2+)treatment *** levels of AhCaM,AhCDPK,AhRAM1,and AhRAM2 were significantly improved in AM plant roots under exogenous Ca^(2+)*** implied that exogenous Ca^(2+)might be involved in the regulation of *** colonization of peanut plants,and in turn,AM symbiosis might activate the Ca^(2+)signal transduction *** combination of AMF and Ca^(2+)benefitted plant growth and development under continuous cropping,suggesting that it is a promising method to cope with the stress caused by continuous cropping.

关键词： Arachis hypogaea L. arbuscular mycorrhizal fungi continuous cropping exogenous calcium

Comparable effects of Jiedu Granule, a compound Chinese herbal medicine, and sorafenib for advanced hepatocellular carcinoma: A prospective multicenter cohort study

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Journal of Integrative Medicine 2020年第4期18卷 319-325页

作者： He-tong Zhao Yong-bin Meng Xiao-feng Zhai Bin-bin Cheng sha-sha Yu Man Yao Hui-xia Yin Xu-ying wan Yun-ke yang Hui Liu Feng Shen Chang-quan Ling School of Traditional Chinese Medicine Naval Medical UniversityShanghai 200433China Department of Integrated Traditional Chinese and Western Medicine Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200433China Department of Integrative Medicine Zhongshan HospitalFudan UniversityShanghai 200032China The Third Department of Hepatic Surgery Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200433China

Objective:Sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma(HCC),and Chinese herbal medicine has also been used to manage advanced *** present work evaluates the effectiveness and safety of Jiedu(JD)Granule,a compound of traditional Chinese herbal medicine,side-by-side with sorafenib for the treatment of advance ***:Patients with advanced HCC receiving treatment with JD Granule or sorafenib were enrolled from December 2014 to March *** primary endpoint was overall survival(OS).The secondary endpoints were progression-free survival(PFS)and *** score matching(PSM)analysis was used to control for possible selection bias from the study group allocation ***:Of the 325 patients included,161 received JD Granule and 164 received *** significant differences were found in OS or PFS among patients receiving JD Granule compared to sorafenib(P>0.05).Median OS of the two study groups was 6.83 months(95%confidence interval[CI]:5.83–9.47)in the group receiving JD Granule and 8 months(95%CI:6.67–9.80)in the group receiving sorafenib,with half-,1-and 2-year survival rates of 53.6%,31.2%and 13.2%vs 60.1%,35.5%and 14.2%,*** after PSM,the median survival time did not differ between the JD Granule group(9.03 months;95%CI:6.37–14.2)and the sorafenib group(7.93 months;95%CI:6.5–9.97),with comparable half-,1-and 2-year survival *** most common adverse events(AEs)were diarrhea(13.7%)and fatigue(5.6%)in the JD Granule group,and hand-foot skin reaction(46.3%)and diarrhea(36.6%)in the sorafenib *** JD Granule was more cost-effective than sorafenib treatment for advanced ***:Compared to sorafenib,JD Granule was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC.

关键词： Carcinoma,hepatocellular Jiedu Granule Sorafenib Chinese herbal medicine

MELK is an oncogenic kinase essential for metastasis,mitotic progression,and programmed death in lung carcinoma

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Signal Transduction and Targeted Therapy 2021年第1期6卷 83-94页

作者： Qin Tang wan Li Xiangjin Zheng Liwen Ren Jinyi Liu sha Li Jinhua wang Guanhua Du The State Key Laboratory of Bioactive Substance and Function of Natural Medicines BeijingChina Key Laboratory of Drug Target Research and Drug Screen Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical College100050 BeijingChina

Lung cancer is the fastest growth rate of morbidity and mortality in nearly a decade,and remains difficult to ***,the molecular mechanisms underlying its development are still *** this study,bioinformatics analysis showed that MELK was highly expressed in lung cancer and negatively correlated to the survival of lung adenocarcinoma(LUAD).Immunohistochemistry analysis of LUAD patient tissues revealed there were a high level of MELK expression in *** of MELK expression inhibits the migration and invasion of LUAD cells,which may be mediated by Twist1,Slug,MMP7,and *** of MELK promoted the growth of LUAD cells in medium,3D Matrigel,and nude *** of MELK by OTSSP167 arrested cycle of LUAD cells at G2/M phase via PLK1-CDC25C-CDK1 pathway,and triggered apoptosis-mediated ***,these data indicate that MELK is critical for metastasis,mitotic progression,and programmed death of LUAD and may be a promising therapeutic target for LUAD.

关键词： metastasis PLK1 lung