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Schwann cells differentiated from skin-derived precursors provide neuroprotection via autophagy inhibition in a cellular model of Parkinson’s disease

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Neural Regeneration Research 2022年第6期17卷 1357-1363页

作者： Jia-Nan Yan Hai-Ying Zhang Jun-Rui Li Ying Chen Yong-Cheng Jiang Jia-Bing Shen Kai-Fu Ke Xiao-Su Gu Department of Neurology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Clinical Medicine The First Clinical Medical College of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurology and suzhou Clinical Research Center of Neurological Disease The Second Afflicted Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina

Autophagy has been shown to play an important role in Parkinson’s disease.We hypothesized that skin-derived precursor cells exhibit neuroprotective effects in Parkinson’s disease through affecting autophagy.In this study,6-hydroxydopamine-damaged SH-SY5Y cells were pretreated with a culture medium containing skin-derived precursors differentiated into Schwann cells(SKP-SCs).The results showed that the SKP-SC culture medium remarkably enhanced the activity of SH-SY5Y cells damaged by 6-hydroxydopamine,reduced excessive autophagy,increased tyrosine hydroxylase expression,reducedα-synuclein expression,reduced the autophagosome number,and activated the PI3K/AKT/mTOR pathway.Autophagy activator rapamycin inhibited the effects of SKP-SCs,and autophagy inhibitor 3-methyladenine had the opposite effect.These findings confirm that SKP-SCs modulate the PI3K/AKT/mTOR pathway to inhibit autophagy,thereby exhibiting a neuroprotective effect in a cellular model of Parkinson’s disease.This study was approved by the Animal Ethics Committee of Laboratory Animal Center of Nantong University(approval No.S20181009-205)on October 9,2018.

关键词： alpha-synuclein autophagosomes autophagy neural regeneration neuroprotection Parkinson’s disease PI3K/AKT/mTOR pathway skin-derived precursor Schwann cells

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Neuroprotective effects of insulin-like growth factor-2 in 6-hydroxydopamine-induced cellular and mouse models of Parkinson’s disease

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Neural Regeneration Research 2023年第5期18卷 1099-1106页

作者： Hai-Ying Zhang Yong-Cheng Jiang Jun-Rui Li Jia-Nan Yan Xin-Jue Wang Jia-Bing Shen Kai-Fu Ke Xiao-Su Gu Department of Neurology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Clinical Medicine The First Clinical Medical College of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina

Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson’s disease using 6-hydroxydopamine. When SH-SY5 Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson’s disease and in a mouse model of Parkinson’s disease. Next, we pretreated cell models of Parkinson’s disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson’s disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor downregulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3 K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulinlike growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3 K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson’s disease treatment.

关键词： 6-hydroxydopamine alpha-synuclein insulin-like growth factor-2 receptor insulin-like growth factor-2 neurodegeneration neuroprotection Parkinson’s disease skin-derived precursor Schwann cells

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Alcohol dehydrogenase 5 of Helicoverpa armigera interacts with the CYP6B6 promoter in response to 2-tridecanone

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Insect Science 2020年第5期27卷 1053-1066页

作者： Jie Zhao Qian Wei Xin-Rong gu su-Wei Ren xiao-Ning Liu Xinjiang Key Laboratory of Biological Resources and Genetic Engineering College of Life Sciences and TechnologyXinjiang UniversityUrumqiXinjiangChina Key Laboratory of Oasis Agricultural Pest Management and Plant Protection Resources Utilization College of AgricultureShihezi UniversityShiheziXinjiangChina

Alcohol dehydrogenase 5(ADH5)is a member of medium-chain dehydro-genase/reductase family and takes part in cellular formaldehyde and S-nitrosoglutathione metabolic network.2-tridecanone(2-TD)is a toxic compound in many Solanaceae crops to defend against a variety of herbivory insects.In the broader context of insect development and pest control strategies,this study investigates how a new ADHS from Helicoverpa armigera(HaADH5)regulates the expression of CYP6B6,a gene involved in molting and metamorphosis,in response to 2-TD treatment.Cloning of the HaADH5 complementary DNA sequence revealed that its 1002 bp open reading frame encodes 334 amino acids with a predicted molecular weight of 36.5 kD.HaADH5 protein was purified in the Es-cherichia coli Transetta(pET32a-HaADH5)strain using a prokaryotic expression system.The ability of HaADH5 protein to interact with the 2-TD responsive region within the promoter of CYP6B6 was confirmed by an in vitro electrophoretic mobility shift assay and transcription activity validation in yeast.Finally,the expression levels of both HaADH5 and CYP6B6 were found to be significantly decreased in the midgut of 6th instar larvae after 48 h of treatment with 10 mg/g 2-TD artificial diet.These results indicate that upon 2-TD treatment of cotton bollworm,HaADHS regulates the expression of CYP6B6 by interacting with its promoter.As HaADH5 regulation of CYP6B6 expression may con-tribute to the larval xenobiotic detoxification,molting and metamorphosis,HaADH5 is a.candidate target for controlling the growth and development of cotton bollworm.

关键词： alcohol dehydrogenase DNA-protein interaction Helicoverpa armigera regulatory factor 2-tridecanone

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Achyranthes bidentata polypeptide protects dopaminergic neurons from apoptosis induced by rotenone and 6-hydroxydopamine

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Neural Regeneration Research 2018年第11期13卷 1981-1987页

作者： su Peng Li Xu Jin-Yu Ma xiao-Song gu Cheng sun Key Laboratory for Neuroregeneration of Jiangsu Province and Ministry of Education Co-Innovatioin Center of NeuroregenerationNantong University

It has been well documented that Achyranthes bidentata polypeptides（ABPPs） are potent neuroprotective agents in several types of neurons. However, whether ABPPs protect dopaminergic neurons from apoptosis induced by neurotoxins is still unknown. This study was designed to observe the effect of ABPPk, a purified fraction of ABPPs, on apoptosis of dopaminergic neurons. SH-5YHY cells and primary dopaminergic neurons were pre-treated with ABPPk（25, 50, or 100 ng/mL） for 12 hours. Cells were then exposed to 6-hydroxydopamine（50 or 150 μM） or rotenone（50 or 200 μM） for 36 hours to induce cell apoptosis. Our results demonstrate that ABPPk markedly increased viability in SH-SY5Y cells and primary dopaminergic neurons, decreased lactate dehydrogenase activity and number of apoptotic dopaminergic neurons, elevated mitochondrial membrane potential, and increased Bcl-2/Bax ratio. These findings suggest that ABPPk protects dopaminergic neurons from apoptosis, and that ABPPk treatment might be an effective intervention for treating dopaminergic neuronal loss associated with disorders such as Parkinson＇s disease.

关键词： nerve regeneration Achyranthes bidentata polypeptides neuroprotection cell apoptosis neurotoxin mitochondrial dysfunction cell viability Bcl-2/Bax neural regeneration

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Improving the UV-light stability of silicon heterojunction solar cells through plasmon-enhanced luminescence downshifting of YVO_(4):Eu^(3+),Bi^(3+)nanophosphors decorated with Ag nanoparticles

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Journal of Energy Chemistry 2023年第6期81卷 212-220,I0007页

作者： Cheng-Kun Wu Shuai Zou Chen-Wei Peng Si-Wei gu Meng-Fei Ni Yu-Lian Zeng Hua sun xiao-Hong Zhang xiao-Dong su School of Physical Science and Technology and Jiangsu Key Laboratory of Thin FilmsSoochow UniversitySuzhou 215006JiangsuChina Institute of Functional Nano&Soft Materials(FUNSOM) Soochow UniversitySuzhou 215123JiangsuChina

The ultraviolet(UV)light stability of silicon heterojunction(SHJ)solar cells should be addressed before large-scale production and applications.Introducing downshifting(DS)nanophosphors on top of solar cells that can convert UV light to visible light may reduce UV-induced degradation(UVID)without sacrificing the power conversion efficiency(PCE).Herein,a novel composite DS nanomaterial composed of YVO_(4):Eu^(3+),Bi^(3+)nanoparticles(NPs)and AgNPs was synthesized and introduced onto the incident light side of industrial SHJ solar cells to achieve UV shielding.The YVO_(4):Eu^(3+),Bi^(3+)NPs and Ag NPs were synthesized via a sol-gel method and a wet chemical reduction method,respectively.Then,a composite structure of the YVO_(4):Eu^(3+),Bi^(3+)NPs decorated with Ag NPs was synthesized by an ultrasonic method.The emission intensities of the YVO_(4):Eu^(3+),Bi^(3+)nanophosphors were significantly enhanced upon decoration with an appropriate amount of~20 nm Ag NPs due to the localized surface plasmon resonance(LSPR)effect.Upon the introduction of LSPR-enhanced downshifting,the SHJ solar cells exhibited an~0.54%relative decrease in PCE degradation under UV irradiation with a cumulative dose of 45 k W h compared to their counterparts,suggesting excellent potential for application in UV-light stability enhancement of solar cells or modules.

关键词： Downshifting Silver nanoparticles Localized surface plasmon resonance UV-light stability Silicon heterojunction solar cells

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Oceanic plate subduction history in the western Pacific Ocean:Constraint from late Mesozoic evolution of the Tan-Lu Fault Zone

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Science China Earth Sciences 2018年第4期61卷 386-405页

作者： guang ZHU Cheng LIU Chengchuan gu Shuai ZHANG Yunjian LI Nan su Shiye xiao School of Resource and Environmental Engineering Hefei University of Technology

The NE-to NNE-striking Tan-Lu Fault Zone(TLFZ) is the largest fault zone in East China, and a typical representative for the circum-Pacific tectonics. Its late Mesozoic evolution resulted from subduction of the Paleo-Pacific Plate,and can be used for indication to the subduction history. The TLFZ reactivated at the end of Middle Jurassic since its origination in Middle Triassic. This phase of sinistral motion can only be recognized along the eastern edge of the Dabie-sulu orogenis,and indicates initiation of the Paleo-Pacific(Izanagi) Plate subduction beneath the East China continent. After the Late Jurassic standstill, the fault zone experienced intense sinistral faulting again at the beginning of Early Cretaceous under N-S compression that resulted from the NNW-ward, low-angle, high-speed subduction of the Izanagi Plate. It turned into normal faulting in the rest of Early Cretaceous, which was simultaneous with the peak destruction of the North China Craton caused by backarc extension that resulted from rollback of the subducting Izanagi Plate. The TLFZ was subjected to sinistral, transpressive displacement again at the end of Early Cretaceous. This shortening event led to termination of the North China Craton destruction. The fault zone suffered local normal faulting in Late Cretaceous due to the far-field, weak backarc extension. The late Mesozoic evolution of the TLFZ show repeated alternation between the transpressive strike-slip motion and normal faulting. Each of the sinistral faulting event took place in a relatively short period whereas every normal faulting event lasted in a longer period, which are related to the subduction way and history of the Paleo-Pacific Plates.

关键词：中生代历史进化太平洋板早白垩纪海洋西方

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Lymphocytes≥2.9(10^(9)/L)in Newly Diagnosed Diabetes Are A Predictor of Future CVD Events

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Current Medical Science 2022年第2期42卷 327-332页

作者： Hong-mei ZHANG xiao-yong LI Ning LIN Yi-xin NIU Hong-xia gu Shuai LU Zhen YANG Li QIN Qing su Department of Endocrinology Xinhua HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai200092China Department of Endocrinology Xinhua HospitalSchool of MedicineShanghai Jiaotong University(Chongming Branch)Shanghai202150China

Objective Atherosclerosis is considered a chronic inflammatory condition.The immune system is a key mediator in the initiation and progression of atherosclerosis.In a previous study,we found that the immune system was activated in diabetes and that total white blood cell(WBC)counts were elevated significantly in diabetic patients.To investigate whether WBC subtype counts in newly diagnosed diabetes are risk factors for future cardiovascular disease(CVD)events,we conducted a prospective population-based cohort study.Methods A total of 1498 newly diagnosed diabetic patients aged 40 to 70 years old were followed up for three years.Participants with previous CVD history and abnormal WBC counts were excluded.CVD events were recorded during follow-up.Results We found that the baseline lymphocyte counts were independently associated with cardiovascular events during follow-up,with the Exp(β)(95%CI)at 1.749(1.084-2.821).Lymphocyte count≥2.9(10^(9)/L)was significantly associated with the development of CVD(HR,2.29;95%CI,1.12-4.67).The corresponding incidence of CVD per 1000 person-year for the lymphocyte count≤2.8(10^(9)/L)and lymphocyte count≥2.9(10^(9)/L)groups were 11.26 and 26.38,respectively.Conclusion We concluded that even in a normal range,higher lymphocyte levels may result in a significantly higher CVD risk among diabetic patients.Lymphocyte count≥2.9(10^(9)/L)is an independent predictor of developing future CVD events.

关键词： lymphocytes risk cardiovascular events diabetes

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Rab27b is Involved in Lysosomal Exocytosis and Proteolipid Protein Trafficking in Oligodendrocytes

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Neuroscience Bulletin 2016年第4期32卷 331-340页

作者： Yun-Tian Shen Yun gu Wen-Feng su Jing-fei Zhong Zi-Han Jin xiao-Song gu Gang Chen Jiangsu Key Laboratory of Neuroregeneration Co-innovation Center of NeuroregenerationNantong University Xinglin College Nantong University

Myelination by oligodendrocytes in the central nervous system requires coordinated exocytosis and endocytosis of the major myelin protein, proteolipid protein （PLP）. Here, we demonstrated that a small GTPase, Rab27b, is involved in PLP trafficking in oligodendrocytes. We showed that PLP co-localized with Rab27b in late endosomes/lysosomes in oligodendrocytes. Short hairpin- mediated knockdown of Rab27b not only reduced lysosomal exocytosis but also greatly diminished the surface expression of PLP in oligodendrocytes. In addition, knockdown of Rab27b reduced the myelin-like membranes induced by co-culture of oligodendrocytes and neurons. Our data suggest that Rab27b is involved in myelin biogenesis by regulating PLP transport from late endosomes/ lysosomes to the cell membrane in oligodendrocytes.

关键词： Myelination Neuron-glial interaction Oligodendrocyte Lysosome Rab27b

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Inhibition of nuclear factor-κB activity enhanced chemosensitivity to cisplatin in human lung adeno-carcinoma A549 cells under chemical hypoxia conditions

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Chinese Medical Journal 2013年第17期126卷 3276-3282页

作者： LI Fang HUANG Li su xiao-li gu Qi-hua HU Cheng-ping Department of Respiratory Diseases Xiangya Hospital Central South University Changsha Hunan 410007 China

Background Tumor hypoxia, one of the features of solid tumors, is associated with chemo-resistance. Recently, nuclear factor-KB （NF-κB） was found to be activated during hypoxia. However, the impact of NF-κB activation on chemo-resistance during hypoxia remains unknown. Methods Human lung adenocarcinoma A549 cells were transfected with NF-κB p65siRNA and treated with cobalt chloride （COCI2） to mimic hypoxia in the presence or absence of cisplatin. NF-KB expression was measured by Western blotting, immune-fluorescence and real-time PCR. Hypoxia-inducible factor-1α （HIF-1α） and Bcl-2 expression were determined by Western blotting. Cell apoptosis and survival with half-maximum inhibitory concentration （IC50） of cisplatin were determined by Annexin V-FITC/PI and 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT）, respectively. Results Exposure ofA549 cells to COCl2 increased nuclear HIF-1α protein expression, and enhanced NF-KB p65 protein nuclear accumulation （the mark of NF-κB activation） in a time and dose dependant manner. COCI2 did not promote apoptosis in A549 cells; on the contrary, it reduced cisplatin-induced apoptosis and increased the IC50 of cisplatin. However, when we inhibited CoCI2-induced activation of NF-κB through NF-κB p65siRNA, cisplatin-induced apoptosis was increased and IC50 of cisplatin was reduced to levels similar to those in control cells. Meanwhile, CoCI2-induced Bcl-2 over- expression was down-regulated in the presence of cisplatin when NF-κB activity was inhibited. Conclusion Up-regulating Bcl-2 might be involved in NF-κB activation induced resistance to cisplatin in A549 cells under CoCl2-induced chemical hypoxia.

关键词： lung adenocarcinoma nuclear factor-κB chemical hypoxia chemotherapy Bcl-2

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Rab27a/Slp2-a complex is involved in Schwann cell myelination

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Neural Regeneration Research 2016年第11期11卷 1830-1838页

作者： Wen-feng su Yun gu Zhong-ya Wei Yun-tian Shen Zi-han Jin Ying Yuan xiao-song gu Gang Chen Jiangsu Key Laboratory of Neuroregeneration Co-innovation Center of NeuroregenerationNantong University Affiliated Hospital of Nantong University

Myelination of Schwann cells in the peripheral nervous system is an intricate process involving myelin protein trafficking. Recently, the role and mechanism of the endosomal/lysosomal system in myelin formation were emphasized. Our previous results demonstrated that a small GTPase Rab27a regulates lysosomal exocytosis and myelin protein trafficking in Schwann cells. In this present study, we established a dorsal root ganglion （DRG） neuron and Schwann cell co-culture model to identify the signals associated with Rab27a during myelination. First, Slp2-a, as the Rab27a effector, was endogenously expressed in Schwann cells. Second, Rab27a expression significantly increased during Schwann cell myelination. Finally, Rab27a and Slp2-a silencing in Schwann cells not only reduced myelin protein expression, but also impaired formation of myelin-like membranes in DRG neuron and Schwann cell co-cultures. Our findings suggest that the Rab27a/ Slp2-a complex affects Schwann cell myelination in vitro.

关键词： nerve regeneration Schwann cells dorsal root ganglion neurons co-culture myelin proteins myelination Rab27 effectors Rab27a Slp2-a neural regeneration

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