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Nano Research 2023年第1期16卷 735-745页

作者： Wenyan Yu Cuiping Xuan Bingbing Liu Lei Zhou Na Yin Enpeng Gong Zhenzhong Zhang Yinchao Li Kaixiang Zhang Jinjin Shi School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases Zhengzhou 450001China Collaborative Innovation Center of New Drug Research and Safety Evaluation Zhengzhou 450001China

antisense oligonucleotide(ASO)for anti-apoptosis is emerging as a highly promising therapeutic agents for ischemic stroke with complex pathological ***,its therapeutic efficacy is seriously limited by a number of challenges including inefficient internalization,low blood-brain barrier(BBB)penetration,poor stability,and potential toxicity of the ***,a carrier-free programmed spherical nucleic acid nanostructure is developed for effective ischemic stroke therapy via integrating multifunctional modules into one DNA *** co-encoding caspase-3-ASO and transferrin receptor(TfR)aptamer into circle template,the spherical nucleic acid nanostructure(TD)was obtained via *** experimental results demonstrated that the developed TD displayed efficient BBB penetration capability(6.4 times)and satisfactory caspase-3 silence effect(2.3 times)due to the dense DNA packaging in *** together,our study demonstrated that the carrier-free programmed spherical nucleic acid nanostructure could significantly improve the therapeutic efficacy of ischemic stroke and was a promising therapeutic tool for various brain damage-related diseases.

关键词： antisense oligonucleotide caspase-3 blood-brain barrier(BBB)penetration anti-apoptosis ischemic stroke

Neuroprotective Effects of Molecular Hydrogen:A Critical Review

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Neuroscience Bulletin 2021年第3期37卷 389-404页

作者： Wei Chen Han-Ting Zhang Shu-Cun Qin Taishan Institute for Hydrogen Biomedicine Shandong First Medical University and Shandong Academy of Medical SciencesTai'an 271000China Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis Shandong First Medical University and Shandong Academy of Medical SciencesTai’an 271000China Departments of Neuroscience and Behavioral Medicine and Psychiatry Rockefeller Neurosciences InstituteWest Virginia University Health Sciences CenterMorgantownWV 26506USA

Molecular hydrogen(H_(2))is a physiologically inert ***,during the last 10 years,increasing evidence has revealed its biological functions under pathological *** specifically,H_(2) has protective effects against a variety of diseases,particularly nervous system disorders,which include ischemia/reperfusion injury,traumatic injury,subarachnoid hemorrhage,neuropathic pain,neurodegenerative diseases,cognitive dysfunction induced by surgery and anesthesia,anxiety,and *** addition,H_(2) plays protective roles mainly through anti-oxidation,anti-inflammation,antiapoptosis,the regulation of autophagy,and preservation of mitochondrial function and the blood-brain ***,H_(2) is easy to use and has neuroprotective effects with no major side-effects,indicating that H_(2) administration is a potential therapeutic strategy in clinical *** we summarize the H_(2) donors and their ***,we review the effectiveness and safety of H_(2) in the treatment of various nervous system diseasesbased on preclinical and clinical studies,leading to the conclusion that H_(2) can be a simple and effective clinical therapy for CNS diseases such as ischemia-reperfusion brain injury,Parkinson's disease,and diseases characterized by cognitive *** potential mechanisms involved in the neuroprotective effect of H_(2) are also analyzed.

关键词： Molecular hydrogen(H_(2)) Neurological disease Neuroprotection anti-oxidation anti-inflammation anti-apoptosis

Dandelion polyphenols protect against acetaminophen-induced hepatotoxicity in mice via activation of the Nrf-2/HO-1 pathway and inhibition of the JNK signaling pathway

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Chinese Journal of Natural Medicines 2020年第2期18卷 103-113页

作者： REN Yong-Shen ZHENG Yao DUAN Huan LEI Lei DENG Xin LIU Xin-Qiao MEI Zhi-Nan DENG Xu-Kun School of Pharmaceutical Sciences South-Central University for NationalitiesWuhan 430074China

We investigated the liver protective activity of dandelion polyphenols(DP)against acetaminophen(APAP;Paracetamol)-induced *** were acclimated for 1 week and randomly divided into the following groups(n=9 per group):Control,APAP,APAP+DP(100 mg·kg^–1),APAP+DP(200 mg·kg^–1),and APAP+DP(400 mg·kg^–1)*** were pretreated with DP(100,200,and 400 mg·kg^–1)by oral gavage for 7 d before being treated with 350 mg·kg^–1 APAP for 24 h to induced *** liver injury was observed,and hepatotoxicity was analyzed after 24 h by evaluation of biochemical markers,protein expressions levels,and liver *** with DP was able to restore serum liver characteristics(aspartate transaminase,AST;alanine aminotransferase,ALT;alkaline phosphatase,AKP),improve redox imbalance(superoxide dismutase,SOD;glutathione,GSH;malondialdehyde,MDA),and decrease inflammatory factors(tumor necrosis factor-α,TNF-α;interleukin-1β,IL-1β).Pretreatment with DP also significantly inhibited the expression levels of nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2).Furthermore,DP pretreatment could inhibit the apoptosis of liver cells caused by APAP through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 *** also down-regulated p-JNK protein expression levels to inhibit APAP-induced mitochondrial oxidative stress and up-regulated the expression of Nrf-2 and its target gene *** histopathological staining demonstrated that DP pretreatment could inhibit APAP-induced hepatocyte infiltration,congestion,and *** results demonstrate that DP pretreatment could protect against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway.

关键词： Dandelion polyphenols APAP-induced liver injury Oxidative stress anti-inflammation anti-apoptosis JNK pathways Nrf-2/HO-1 pathways

Characteristics of neural growth and cryopreservation of the dorsal root ganglion using three-dimensional collagen hydrogel culture versus conventional culture

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Neural Regeneration Research 2021年第9期16卷 1856-1864页

作者： Ze-Kai Cui Shen-Yang Li Kai Liao Zhi-Jie Wang Yong-Long Guo Luo-Sheng Tang Shi-Bo Tang Jacey Hongjie Ma Jian-Su Chen Department of Ophthalmology the Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Aier Eye Institute ChangshaHunan ProvinceChina Aier School of Ophthalmology Central South UniversityChangshaHunan ProvinceChina Institute of Ophthalmology Medical CollegeJinan UniversityGuangzhouGuangdong ProvinceChina Department of Ophthalmology First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Key Laboratory for Regenerative Medicine of Ministry of Education Jinan UniversityGuangzhouGuangdong ProvinceChina CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghaiChina Imaging and Functional Center Guangzhou Aier Eye HospitalGuangzhouGuangdong ProvinceChina

In vertebrates, most somatosensory pathways begin with the activation of dorsal root ganglion(DRG) neurons. The development of an appropriate DRG culture method is a prerequisite for establishing in vitro peripheral nerve disease models and for screening therapeutic drugs. In this study, we compared the changes in morphology, molecular biology, and transcriptomics of chicken embryo DRG cultured on tissue culture plates(T-DRG) versus three-dimensional collagen hydrogels(C-DRG). Our results showed that after 7 days of culture, the transcriptomics of T-DRG and C-DRG were quite different. The upregulated genes in C-DRG were mainly related to neurogenesis, axon guidance, and synaptic plasticity, whereas the downregulated genes in C-DRG were mainly related to cell proliferation and cell division. In addition, the genes related to cycles/pathways such as the synaptic vesicle cycle, cyclic adenosine monophosphate signaling pathway, and calcium signaling pathway were activated, while those related to cell-cycle pathways were downregulated. Furthermore, neurogenesis-and myelination-related genes were highly expressed in C-DRG, while epithelial–mesenchymal transition-, apoptosis-, and cell division-related genes were suppressed. Morphological results indicated that the numbers of branches, junctions, and end-point voxels per C-DRG were significantly greater than those per T-DRG. Furthermore, cells were scattered in T-DRG and more concentrated in C-DRG, with a higher ratio of 5-ethynyl-2′-deoxyuridine(EdU)-positive cells in T-DRG compared with C-DRG. C-DRG also had higher S100 calcium-binding protein B(S100 B) and lower α-smooth muscle actin(α-SMA) expression than T-DRG, and contained fewer terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)-positive cells after 48 hours of serum starvation. After cryopreservation, C-DRG maintained more intact morphological characteristics, and had higher viability and less TUNEL-positive cells than T-DRG. Furthermore, newly for

关键词： anti-apoptosis collagen hydrogel cryopreservation dorsal root ganglion neurogenesis RNA-seq Schwann cell tissue engineering

Relationships Between Icariin and anti-Apoptotic miRNA-21 in Mouse Blastocyst Development In vitro

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Journal of Integrative Agriculture 2013年第4期12卷 663-669页

作者： SHI Ya-ran WANG Zhan-he CAO Yong-chun LU Yan TIAN Jin-ling ZhANG Chao JIA Zi-ye CHEN Wu GAO Jian-ming Animal Science and Technology College Beijing University of Agriculture

In this study, the effect of icariin, a flavonoid from the Chinese traditional medicine epimedium, on miRNA-21 of mouse developmental blastocysts in vitro and the development of preimplantation embryos were studied. The possible effective targets of icariin promoting preimplantation embryo development in vitro and anti-apoptosis were determined. The embryos were cultured in modified CZB medium （mCZB） as control group. The experimental group （Ica group） was supplemented with 0.6 μg mL-1 icariin. Mouse pronuclear embryos were cultured in vitro until blastocysts. The development rates of preimplantation embryos were observed. The total cell number, apoptotic cell number and the rate of apoptotic cells in blastocysts were analysed by the staining of Hoechst33342 and labeling of TUNEL and detected under a laser confocal scanning microscope. The miRNA-21 expression, the mRNA levels of pro-apoptotic Caspase3, and the target genes of miRNA-21： pro-apoptotic PTEN, anti-apoptotic Bcl-2 were detected by real-time RT-PCR. The results showed that percentages of morulaes and blastocysts in Ica group were both extremely higher than control group （（85.14±6.57）% vs. （72.04±11.58）%; （82.50±7.11）% vs. （66.80±11.70）%, respectively, P〈0.01）. The total cell number ofblastocysts had extreme difference between Ica group and control group （（61.40±9.64） vs. （46.23±4.50）, P〈0.01）. The apoptotic cell number and rate of apoptotic cells of blastocysts were both reduced in Ica group （（1.47±0.51） vs. （2.94±0.66）; （2.40±0.27）% vs. （6.25±0.62）%, respectively, P〈0.01）. Compared to control group, addition of icariin into mCZB extremely increased the expression of anti-apoptotic miRNA-21 （P〈0.01）, down-regulated pro-apoptotic Caspase3 （P〈0.05） and PTEN （P〈0.01）, up-regulated anti-apoptotic Bcl-2 （P〈0.01）. In conclusion, icariin could reduce the apoptosis, promote the embryo development in vitro by enhancing miRNA-21 expression to up-regulated anti-apoptotic genes and down-regulated pro- apoptotic genes

关键词： blastocysts icariin miRNA-21 anti-apoptosis mice

antioxidant and antiapoptotic Polyphenols from Green Tea Extract Ameliorate CCl4-Induced Acute Liver Injury in Mice

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Chinese Journal of Integrative Medicine 2020年第10期26卷 736-744页

作者： DIAO Jian-xin OU Jin-ying DAI Huan LI Hai-ye HUANG Wei HUA He-yu XIE Ting WANG Ming YANG Yun-gao School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou(510515)China Department of Internal Medicine Yongxing County People’s HospitalChengzhou(423000)Hunan ProvinceChina Department of Traditional Chinese Medicine Zhujiang Hospital of Southern Medical UniversityGuangzhou(510515)China

Objective To investigate the phenolic composition,antioxidant properties,and hepatoprotective mechanisms of polyphenols from green tea extract(GTP)in carbon tetrachloride(CCl4)-induced acute liver injury mouse *** High-performance liquid chromatography was used to analyze the chemical composition of the *** activity of GTP was assessed by O2∙-,OH∙,DPPH∙,and ferric-reducing antioxidant power(FRAP)assay in *** Kunming mice were divided into 6 groups including control,model,low-,medium-,and high-doses GTP(200,400,800 mg/kg)and vitamin E(250 mg/kg)groups,10 in each *** and vitamin E were administered at a level of abovementioned doses twice per day for 7 days prior to exposure to a single injection of *** effects of GTP were evaluated in a CCl4-induced mouse model of acute liver injury,using commercial enzyme linked immunosorbent assay kits,histopathological observation,terminal deoxynucleotidyl transferase-mediated dUTPNick-end labeling(TUNEL)assay and Western *** GTP contained 98.56µg gallic acid equivalents per milligram extract total polyphenols,including epicatechingallate,epigallocatechin gallate,epicatechin,and *** with the model group,low-,medium-,or high doses GTP significantly decreased serum levels of alanine aminotransferase and aspartate transaminase(Papoptosis in the CCl4-exposed liver(P<0.01).Phosphorylated nuclear factor kappa-B(NF-κB),p53,Bcl-2 associated x protein/B-cell lymphoma/leukemia-2 gene,cytochrome C,and cleaved caspase-3 levels were downregulated compared with the model gro

关键词： polyphenol carbon tetrachloride acute liver injury anti-oxidant anti-apoptosis green tea

Hyperoside protects the blood-brain barrier from neurotoxicity of amyloid beta 1–42

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Neural Regeneration Research 2018年第11期13卷 1974-1980页

作者： Chen-Yang Liu Kuan Bai Xiao-Hui Liu Li-Mi Zhang Gu-Ran Yu Department of Neurology Jiangsu Traditional Chinese Medicine Hospital the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine Nanjing Jiangsu Province China Graduate School of Nanjing University of Traditional Chinese Medicine Nanjing Jiangsu Province China

Mounting evidence indicates that amyloid β protein（Aβ） exerts neurotoxicity by disrupting the blood-brain barrier（BBB） in Alzheimer＇s disease. Hyperoside has neuroprotective effects both in vitro and in vivo against Aβ. Our previous study found that hyperoside suppressed Aβ1-42-induced leakage of the BBB, however, the mechanism remains unclear. In this study, bEnd.3 cells were pretreated with 50, 200, or 500 μM hyperoside for 2 hours, and then exposed to Aβ1-42 for 24 hours. Cell viability was determined using 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide assay. Flow cytometry and terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay were used to analyze cell apoptosis. Western blot assay was carried out to analyze expression levels of Bax, Bcl-2, cytochrome c, caspase-3, caspse-8, caspase-9, caspase-12, occludin, claudin-5, zonula occludens-1, matrix metalloproteinase-2（MMP-2）, and MMP-9. Exposure to Aβ1-42 alone remarkably induced bEnd.3 cell apoptosis; increased ratios of cleaved caspase-9/caspase-9, Bax/Bcl-2, cleav ed caspase-8/caspase-8, and cleaved caspase-12/caspase-12; increased expression of cytochrome c and activity of caspase-3; diminished levels of zonula occludens-1, claudin-5, and occludin; and increased levels of MMP-2 and MMP-9. However, hyperoside pretreatment reversed these changes in a dose-dependent manner. Our findings confirm that hyperoside alleviates fibrillar Aβ1-42-induced BBB disruption, thus offering a feasible therapeutic application in Alzheimer＇s disease.

关键词： nerve regeneration Alzheimer's disease amyloid beta 1-42 blood-brain barrier bEnd.3 cells tight junction proteins hyperoside anti-apoptosis neural regeneration

Protective Effect of Fresh/Dry Dandelion Extracts on APAP-Overdose-Induced Acute Liver Injury

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Chinese Journal of Integrative Medicine 2022年第8期28卷 683-692页

作者： ZHENG Yao LEI Lei LIANG Shuai AI Jiao DENG Xin LI Yan-qiu ZHANG Tian-pei PU Shi-biao REN Yong-shen School of Pharmaceutical Science South-Central University for NationalitiesWuhan430074China College of Chinese Materia Medica Yunnan University of Chinese MedicineKunming650500China

Objecitvie:To compare the liver protective activity of fresh/dried dandelion extracts against acetaminophen(APAP)-induced ***:Totally 90 Kunming mice were randomly divided into10 groups according to body weight(9 mice for each group).The mice in the normal control and model(vehicle control)groups were administered sodium carboxymethyl cellulose(CMC-Na,0.5%)*** groups were pretreated with high and low-dose dry dandelion extract(1,000 or 500 g fresh herb dried and then decocted into 120 mL solution,DDE-H and DDE-L);low-,medium-and high-dose dandelion juice(250,500,1,000 g/120 mL,DJ-L,DJ-M,and DJ-H);fresh dandelions evaporation juice water(120 mL,DEJW);dry dandelion extract dissolved by pure water(1 kg/120 mL,DDED-PW);dry dandelion extract dissolved by DEJW(120 g/120 mL,DDED-DEJW)by oral gavage for 7 days at the dosage of 0.5 mL solution/10 g body weight;after that,except normal control group,all other groups were intraperitonealy injected with 350 mg/kg APAP to induce liver *** hours after APAP administration,serum and liver tissue were collected and serum alanine aminotransferase(AST),aspartate transaminase(ALT),alkaline phosphatase(AKP),malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD)activities were quantified by biochemical kits;tumor necrosis factor(TNF-α),interleukin(IL)-2,and IL-1β contents in liver tissue were determined by enzyme linked immunosorbent assay *** changes in liver tissues were observed by hematoxylin and eosin staining;TUNEL Assay and Hoechst 33258 staining were applied for cell apoptosis *** expressions of heme oxygenase-1(HO-1),nuclear factor erythroid-2-related factor 2(Nrf-2),caspase-9,B-cell leukemia/lymphoma 2(Bcl-2),Bax and p-JNK were determined by Western blot ***:Pretreatment with fresh dandelion juice(FDJ,including DJ-L,DJ-M,DJ-H,DEJW and DDED-DEJW)significantly decreased the levels of serum ALT,AST,AKP,TNF-α and IL-1β compared with veh

关键词： fresh dandelion juice acetaminophen-induced liver injury oxidative stress anti-inflammation anti-apoptosis

Neuroprotective mechanisms of rutin for spinal cord injury through anti-oxidation and anti-inflammation and inhibition of p38 mitogen activated protein kinase pathway

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Neural Regeneration Research 2018年第1期13卷 128-134页

作者： Hong-liang Song Xiang Zhang Wen-zhao Wang Rong-han Liu Kai Zhao Ming-yuan Liu Wei-ming Gong Bin Ning Department of Spinal Surgery Jinan Central Hospital Affiliated to Shandong University Hospital Pharmacy Jinan Central Hospital Affiliated to Shandong University Department of Gynecology and Obstetrics Jinan Maternity and Child Care Hospital

Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.

关键词： nerve regeneration spinal cord injury rutin oxidative stress antioxidant anti-inflammation p38 mitogen activated protein kinase pathway anti-apoptosis caspase-3 caspase-9 neural regeneration

Neuroprotective effects of erythropoietin on neurodegenerative and ischemic brain diseases: the role of erythropoietin receptor

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Neural Regeneration Research 2017年第9期12卷 1381-1389页

作者： Carolina Castillo Hernández Carlos Felipe Burgos Angela Hidalgo Gajardo Tiare Silva-Grecchi Javiera Gavilan Jorge Roberto Toledo Jorge Fuentealba Laboratory of Screening of Neuroactive Compounds Department of Physiology School of Biological Sciences University of Concepción Laboratory of Biotechnology and Biopharmaceutical Department of Pathophysiology School of Biological Sciences University of Concepción

Erythropoietin （Epo） is a fundamental hormone in the regulation of hematopoiesis, and other secondary roles mediated by the binding of the hormone to its specific receptor （EpoR）, which leads to an activation of key signaling pathways that induce an increase in cell differentiation, apoptosis control and neuroprotection. It has been suggested that their ftmction depends on final conformation of glycosylations, related with affinity to the receptor and its half-life. The presence of EpoR has been reported in different tissues including central nervous system, where it has been demonstrated to exert a neuroprotective function against oxidative stress conditions, such as ischemic injury and neurodegenerative diseases. There is also evidence of an increase in EpoR expression in brain cell lysates of Alzheimer＇s patients with respect to healthy patients. These results are related with extensive in vitro experimental data of neuroprotection obtained from cell lines, primary cell cultures and hippocampal slices. Additionally, this data is correlated with in vivo experiments （water maze test） in mouse models of Alzheimer＇s disease where Epo treatment improved cognitive function. These stud- ies support the idea that receptor activation induces a neuroprotective effect in neurodegenerative disorders including dementias, and especially Alzheimer＇s disease. Taken together, available evidence suggests that Epo appears to be a central element for EpoR activation and neuroprotective properties in the central nervous system. In this review, we will describe the mechanisms associated with neuroprotection and its relation with the activation of EpoR in order with identify new targets to develop pharmacological strategies.

关键词： erythropoietin erythropoietin receptor neuroprotection anti-apoptosis Alzheimer's disease