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Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage

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Neural Regeneration Research 2019年第6期14卷 1013-1024页

作者： Yang Wang De-Jun Bao Bin Xu Chuan-Dong Cheng Yong-Fei Dong Xiang-pin Wei Chao-Shi Niu Department of Neurosurgery First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of China Anhui medical university Auhui Province medical Genetic Center Anhui Province Key Laboratory of Brain Function and Brain Disease

The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not been thoroughly investigated. Consequently, in this study, we examined the potential role of the Wnt/Frizzled signaling pathway in early brain injury in rat models of subarachnoid ***, possible neuroprotective mechanisms were also investigated. Experimental subarachnoid hemorrhage rat models were induced by injecting autologous blood into the prechiasmatic cistern. Experiment 1 was designed to examine expression of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. In total, 42 adult rats were divided into sham(injection of equivalent volume of saline), 6-, 12-, 24-, 48-, 72-hour, and 1-week subarachnoid hemorrhage groups. Experiment 2 was designed to examine neuroprotective mechanisms of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. Rats were treated with recombinant human Wnt1(rhwnt1), small interfering Wnt1(siwnt1) RNA, and monoclonal antibody of Frizzled1(anti-Frizzled1) at 48 hours after subarachnoid hemorrhage. Expression levels of Wnt1, Frizzled1, β-catenin, peroxisome proliferator-activated receptor-γ, CD36, and active nuclear factor-κB were examined by western blot assay and immunofluorescence staining. Microglia type conversion and inflammatory cytokine levels in brain tissue were examined by immunofluorescence staining and enzyme-linked immunosorbent assay. Our results show that compared with the sham group, expression levels of Wnt1, Frizzled1, and β-catenin were low and reduced to a minimum at 48 hours, gradually returning to baseline at 1 week after subarachnoid hemorrhage. rhwnt1 treatment markedly increased Wnt1 expression and alleviated subarachnoid hemorrhage-induced early brain injury(within 72 hours), including cortical cell

关键词： nerve regeneration subarachnoid hemorrhage Wnt/Frizzled signaling pathway early brain injury nuclear factor-κB M2 type microglia peroxisome proliferator-activated receptor-γ inflammatory cytokines neural regeneration

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Correlation between synaptic protein expression and synaptic reorganization in the hippocampal CA3 region in a rat model of post-traumatic epilepsy

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Neural Regeneration Research 2010年第15期5卷 1156-1160页

作者： Gaolian Zhang Jianmin Huang Bang Zhao Haineng Huang Yuanyang Deng HuadongHuang Qirong He Jianping Liang Department of Neurosurgery First Affiliated Hospital Guangxi Traditional Chinese Medicine University Nanning 530023 Guangxi Zhuang Autonomous Region China Department of Neurology Hospital Affiliated to Youjiang Medical University for Nationafities Baise 533000 Guangxi Zhuang Autonomous Region China Department of Neurosurgery Hospital Affiliated to Youjiang Medical University for Nationalities Baise 533000 Guangxi Zhuang Autonomous Region China

Postsynaptic density protein-95 and synaptophysin participate in synaptic reorganization in the forebrain of epilepsy models. However, the time-effect relationship between dynamic synapsin expression in hippocampus and synaptic reorganization in the post-traumatic epilepsy model remains unclear. FeCI2 was injected into the hippocampal CA3 region of the right forebrain in rats to induce post-traumatic epilepsy. Postsynaptic density protein-95 and synaptophysin expression was detected using immunohistochemistry. Epileptiform discharge induced by FeCI2 injection was determined in rat forebrain neurons, revealing decreased postsynaptic density protein-95 expression at 24 hours and lowest levels at 7 days. Synaptophysin expression was markedly reduced at 24 hours, but increased at 7 days. Postsynaptic density protein-95 and synaptophysin expression was consistent with abnormal mossy fiber sprouting and synaptic reorganization following neuronal injury in the hippocampal CA3 region of FeCI2-induced epilepsy models.

关键词： post-traumatic epilepsy hippocampus FeCI2 forebrain postsynaptic density protein-95 synaptophysin brain injury neural regeneration

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Altered expression of stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs)in cancer:will they become a new battlefield for oncotherapy?

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Chinese Journal of Cancer 2016年第5期35卷 214-222页

作者： Jing Wen Ying-Cheng Huang Huan-Huan Xiu Zhi-Ming Shan Kang-Qing Xu Department of Anesthesiology The First Affiliated HospitalSun Yat-sen University zhongshan School of Medicine Sun Yat-sen University

The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from gene transcription to cell apoptosis by driving calcium-dependent signaling *** evidence has implicated the dysregulation of STIM-ORAI and IP_3Rs in tumorigenesis and tumor *** controlling the activities,structure,and/or expression levels of these Ca^(2+)-transporting proteins,malignant cancer cells can hijack them to drive essential biological functions for tumor ***,the molecular mechanisms underlying the participation of STIM-ORAI and IP_3Rs in the biological behavior of cancer remain *** this review,we summarize recent advances regarding STIM-ORAI and IP_3Rs and discuss how they promote cell proliferation,apoptosis evasion,and cell migration through temporal and spatial rearrangements in certain types of malignant *** understanding of the essential roles of STIM-ORAI and IP_3Rs may provide new pharmacologic targets that achieve a better therapeutic effect by inhibiting their actions in key intracellular signaling pathways.

关键词： Stromal interaction molecule (STIM), Calcium release-activated calcium channel protein (ORAI),Inositol 1,4,5-trisphosphate receptors (IP3Rs), Ca2+, Tumorigenesis

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Elevated neutrophil extracellular traps by HBV-mediated S100A9-TLR4/RAGE-ROS cascade facilitate the growth and metastasis of hepatocellular carcinoma

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Cancer Communications 2023年第2期43卷 225-245页

作者： Xi Zhan RuiWu Xue-Hua Kong Yan You Kun He Xiao-Yu Sun Yong Huang Wei-Xian Chen Liang Duan Department of Laboratory Medicine The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400000P.R.China Department of Laboratory Medicine The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016P.R.China Key Laboratory of Laboratory medical Diagnostics Ministry of EducationDepartment of Laboratory MedicineChongqing Medical UniversityChongqing 400010P.R.China Department of Pathology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400000P.R.China Department of Hepatobiliary Surgery The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400000P.R.China

Background:Neutrophil extracellular traps(NETs)are considered significant contributors to cancer progression,especially ***,it is still unclear whether NETs are involved in hepatitis B virus(HBV)-related hepatocarcinogenesis and have potential clinical significance during evaluation and management for hepatocellular carcinoma(HCC).In this study,we aimed to investigate the functional mechanism of NETs in HBV-related hepatocarcinogenesis and their clinical ***:A total of 175 HCC patients with and without HBV infection and 58 healthy controls were enrolled in this *** weremeasured in tissue specimens,freshly isolated neutrophils and blood serum from these patients,and the correlation of circulating serum NETs levels with malignancy was *** mechanism by which HBV modulates NETs formation was explored using cell-based *** addition,in vitro and in vivo experiments were further performed to clarify the functional mechanism of NETs on the growth and metastasis of ***:We observed an elevated level of NETs in blood serum and tissue specimens from HCC patients,especially those infected with *** facilitated the growth and metastasis of HCC both in vitro and in vivo,which were mainly dominated by increased angiogenesis,epithelial-mesenchymal transition(EMT)-related cell migration,matrix metalloproteinases(MMPs)-induced extracellular matrix(ECM)degradation and NETs-mediated cell *** of NETs generation by DNase 1 effectively abrogated the NETs-aroused HCC growth and *** addition,HBV-induced S100A9 accelerated the generation of NETs,which was mediated by activation of toll-like receptor(TLR4)/receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)***,circulatory NETs were found to correlate with viral load,TNM stage and metastasis status in HBV-related HCC,and the identified NETs could predict extrahepatic metastasis,with an area under the ROC curve(A

关键词： hepatocellular carcinoma hepatitis B virus metastasis neutrophil extracellular trap RAGE ROS S100A9 TLR4

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Evaluation of the safety and quality of day-case cataract surgery based on 4151 cases

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International Journal of Ophthalmology(English edition) 2019年第2期12卷 291-295页

作者： Min Zhuang Wen Fan Ping Xie Song-Tao Yuan Qing-Huai Liu Chen Zhao Department of Ophthalmology the First Affiliated Hospital with Nanjing Medical University Department of Ophthalmology the Fourth Affiliated Hospital of Nantong University (Yancheng No.1 People’s Hospital) Eye Institute Eye & ENT Hospital Shanghai Medical College Fudan University Shanghai Key Laboratory of Visual Impairment and Restoration Key Laboratory of Myopia of State Health Ministry (Fudan university)

AIM: To evaluate the safety, quality and prospects of day-case cataract surgery performed in a Jiangsu public tertiary hospital METHODS: The general and clinical data for patients who underwent day-case cataract surgery between August 1, 2014 and December 31, 2016 at this hospital were collected. The incidences of intraoperative and postoperative complications, preoperative and postoperative bestcorrected visual acuities(BCVAs), delayed discharge rate, rate of unplanned re-admission to hospital, and patient satisfaction were analyzed. RESULTS: A total of 4151 patients received cataract phacoemulsification surgery to correct age-related, congenital, traumatic, or complicated cataracts. Of these, age-related cataracts were the most frequently occurring. Patient age ranged from 18 to 101 y and the vast majority of patients were between 60 and 80 years old. Of the 4151 patients, 64.73%(2687/4151) had a systemic disease. The number of patients increased over the years, with the average number of patients per month being 90.4, 124.83, and 183.42 in 2014, 2015 and 2016, respectively. The average preoperative BCVA was 0.102±0.057 and average postoperative BCVAs at 1 d, 1 wk, and 1 mo post surgery were 0.453±0.264, 0.657±0.285, and 0.734±0.244, respectively. For intraoperative complications, 4.12%(171/4151) had posterior capsule rupture, 0.79%(33/4151) had iris or ciliary body injury, and 0.048%(2/4151) had suprachoroidal hemorrhage. For postoperative complications, 4.38%(182/4151) had cornea edema, 7.78%(323/4151) had intraocular hypertension, 0.096%(4/4151) had IOL toxicity syndrome, 0.28%(12/4151) had retained lens cortex, and 0.048%(2/4151) had hyphema. The delayed discharge rate was 0.82%(44/4151) and the unplanned re-admission to the hospital was 0(0/4151). The patient satisfaction rate was 91.42%(3795/4151). CONCLUSION: Day-case cataract surgery is safe and effective with good prospects for development.

关键词： day-case cataract surgery medical safety medical quality complications re-admission rate satisfaction

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Expression of dectin-1 during fungus infection in human corneal epithelial cells

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International Journal of Ophthalmology(English edition) 2014年第1期7卷 34-37页

作者： Cui Li Gui-Qiu Zhao Cheng-Ye Che Na Li Jing Lin Qiang Xu Qian Wang Ying Liu Sheng Qiu Department of Ophthalmology the Affiliated Hospital of Medical CollegeQingdao University

AIM: To evaluate the expression of dendritic cell-associated C-type lectin-1(dectin-1) in human corneal epithelial(HCE) cells infected by fungus. · METHODS: A total of 20 cases of healthy donor corneas were group A,and 20 patients(20 eyes) suffered from fungal keratitis(FK) composed group B. Real-time qPCR and immunohistochemistry were applied to detect dectin-1 expression in corneal epithelium of both groups. HCE cells were cultured with aspergillus fumigatus(AF) antigens in vitro. The expression of dectin-1 mRNA was measured by real-time qPCR at the stimulation of 0,4,8 and 24h separately. Dectin-1 protein was detected by immunocytochemistry at 0 and 24h separately. ·RESULTS: Dectin-1 expressed in corneal epithelium of normal persons and FK patients. Vitro cellular experiment showed that the expression of dectin-1 mRNA in HCE cells began to increase after stimulation of AF antigens at 4h,and dectin-1 protein expression increased after stimulation at 24h. · CONCLUSION: Dectin-1 expressed in corneal epithelium of normal persons. AF antigens stimulation can elevate the expression of dectin-1 in HCE cells in vitro.

关键词： dectin-1 corneal epithelial cells fungal keratitis human

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Granulocyte-macrophage colony-stimulating factor and interleukin 4 induce the malignant transformation of the bone marrow- derived human adult mesenchymal stem cells

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Chinese medical Journal 2011年第5期124卷 729-733页

作者： ZHOU Xiao-gang YANG Yi YANG Jin-song ZHOU Jian FANG Tao-lin DAI Wen-da CHEN Zheng-rong Department of Orthopaedic Surgery Zhongshan Hospital Fudan University Shanghai 200032 China Department of Orthopedics The First Affiliated Hospital of Gaungxi Medical University Nanning Guangxi 530021 China

Background The purpose of the study was to examine the effects of granulocyte-macrophage colony-stimulating factor （GM-CSF） and interleukin 4 （IL-4） on the bone-marrow-derived human adult mesenchymal stem cells （hMSCs）. Methods The hMSCs were isolated and cultured with GM-CSF and IL-4 for a period of one month. A single colony of transformed cells was then isoloated and their phenotype was characterized by morphology, surface marker expression, and in vivo *** After one month culture, the transformed mesenchymal cells exhibited the morphology and phenotype similar to those of tumor cells, and also caused multiple fast growing lung deposits when it was injected into immunodeficient *** Cytokines-driven malignant transformation of hMSCs may be a useful model for studying signaling pathways initiating malignant transformation of hMSC.

关键词： bone marrow-derived mesenchymal stem cells malignant transformation interleukin 4 granulocyte-macrophage colony-stimulating factor

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Lipopolysaccharides protect mesenchymal stem cell against cardiac ischemia-reperfusion injury by HMGB1/STAT3 signaling

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Journal of Geriatric Cardiology 2023年第11期20卷 801-812页

作者： Jing-Yi WEN Hui-Xi PENG Dan WANG Zhi-Min WEN Yu-Tong LIU Jian QU Hong-Xuan CUI Yu-Ying WANG Yan-Lin DU Ting WANG Cong GENG Bing XU Department of Clinical Pharmacy the Second Affiliated Hospital of Dalian Medical UniversityDalianLiaoningChina Department of Pharmacy the Second Affiliated Hospital of Inner Mongolia Medical UniversityHohhotInner MongoliaChina Department of Pharmacy Ordos Central HospitalOrdosInner MongoliaChina Department of Clinical Laboratory the Second Affiliated Hospital of Dalian Medical UniversityDalianLiaoningChina

BACKGROUND Myocardial ischemia-reperfusion(I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells(MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box1(HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3(STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains *** In vitro, hypoxia/reoxygenation injury model was established by Anaero Pack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1and STAT3 by Western *** The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor(VEGF), hepatocyte growth factor(HGF), insulin growth factor(IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in *** These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3signaling.

关键词： STAT3 HMGB1 ischemia

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Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats

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World Journal of Gastroenterology 2017年第21期23卷 3805-3814页

作者： Yi Tan Jane Kim Jing Cheng Madeleine Ong Wei-Guo Lao Xing-Liang Jin Yi-Guang Lin Linda Xiao Xue-Qiong Zhu Xian-Qin Qu School of medical and Molecular Biosciences University of Technology Sydney The Second affiliated hospital of Wenzhou medical university

AIM To investigate protective effects and molecular mechanisms of green tea polyphenols(GTP) on nonalcoholic fatty liver disease(NAFLD) in Zucker fatty(ZF) *** Male ZF rats were fed a high-fat diet(HFD) for 2 wk then treated with GTP(200 mg/kg) or saline(5 m L/kg) for 8 wk, with Zucker lean rat as their control. At the end of experiment, serum and liver tissue were collected for measurement of metabolic parameters, alanine aminotransferase(ALT) and aspartate aminotransferase(AST), inflammatory cytokines and hepatic triglyceride and liver histology. Immunoblotting was used to detect phosphorylation of AMP-activated protein kinase(AMPK) acetyl-Co A carboxylase(ACC), and sterol regulatory element-binding protein 1c(SREBP1c). RESULTS Genetically obese ZF rats on a HFD presented with metabolic features of hepatic pathological changes comparable to human with NAFLD. GTP intervention decreased weight gain(10.1%, P = 0.052) and significantly lowered visceral fat(31.0%, P < 0.01). Compared with ZF-controls, GTP treatment significantly reduced fasting serum insulin, glucose and lipids levels. Reduction in serum ALT and AST levels(both P < 0.01) were observed in GTP-treated ZF rats. GTP treatment also attenuated the elevated TNFα and IL-6 in the circulation. The increased hepatic TG accumulation and cytoplasmic lipid droplet were attenuated by GTP treatment, associated with significantly increased expression of AMPK-Thr172(P < 0.05) and phosphorylated ACC and SREBP1c(both P < 0.05), indicating diminished hepatic lipogenesis and triglycerides out flux from liver in GTP treated rats. CONCLUSION The protective effects of GTP against HFD-induced NAFLD in genetically obese ZF rats are positively correlated to reduction in hepatic lipogenesis through upregulating the AMPK pathway.

关键词： Non-alcoholic fatty liver disease Green tea polyphenols Hepatic lipogenesis Inflammatory cytokines AMP-activated protein kinase

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Clinical application of a shape-preserving rapid corneal donor dehydrater

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International Journal of Ophthalmology(English edition) 2022年第5期15卷 736-740页

作者： Yu Sun Xiao-Lin Qi Xiao Lin Xiao-Yu Zhang Li Gao Hua Gao Shandong first medical university&Shandong Academy of medical Sciences JinanShandong ProvinceChina Eye hospital of Shandong first medical university Shandong Eye hospital JinanShandong ProvinceChina State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of OphthalmologyShandong Eye InstituteShandong First Medical University&Shandong Academy of Medical SciencesSchool of OphthalmologyShandong First Medical UniversityJinanShandong ProvinceChina Eye hospital affiliated to Shandong university of Chinese Medicine JinanShandong ProvinceChina

AIM:To describe the design and clinical application of a corneal donor dehydrator which can quickly dehydrate corneas and keep its original ***:The corneal donor material is placed on stainless steel beads with different diameters in the dehydrating box to make the cornea the same shape as the steel ***,the cornea is placed inside the dehydrater for rapid dehydrating using the internal cleaning and ventilation *** 83 eyes underwent deep anterior lamellar keratoplasty(DALK)using corneal donor tissue preserved with corneal dehydrater,and 60 patients(60 eyes)received DALK by the same surgeon using corneal donor tissue preserved with glycerol were included in the control *** best corrected visual acuity(BCVA),the thickness and transparency of the corneal buttons were ***:After the completion of dehydrating,all the donor corneas maintained a normal shape without any shrinkage or distortion,and the average intraoperative rehydration time was 43.3±12.1 s during *** mean BCVA of the dehydrater group was 0.30±0.18 at 1 wk and 0.32±0.16 at 1 mo,which were statistically better than that of the control group(P<0.001).The score of corneal buttons transparency were lower than that of the control group with statistical difference(P<0.001).The thickness of corneal buttons at 1 wk and at 1 mo in the dehydrater group was significantly better than that of the control group respectively(P<0.001).One week after operation,no corneal button turbidity or edema was observed in both ***:The dehydrater can quickly dehydrate the corneal material in a clean and airtight environment and maintain the original shape of the corneal donor during the dehydrating *** dehydrater is recommended for long-term high-quality preservation in areas where corneal materials cannot be used within a reasonable time period.

关键词： keratoplasty corneal donor dehydration organ culture storage eye bank

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