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TMEM16F may be a new therapeutic target for Alzheimer's disease

Neural Regeneration Research 2023年第3期18卷 643-651页

作者： Zhi-Qiang Cui xiao-Ying Hu Tuo Yang Jing-Wei Guan Ying Gu Hui-Yuan Li Hui-Yu Zhang qing-huan xiao xiao-Hong Sun Department of Neurology The Fourth Affiliated Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Department of Ion Channel Pharmacology School of PharmacyChina Medical UniversityShenyangLiaoning ProvinceChina

TMEM16F is involved in many physiological processes such as blood coagulation,cell membrane fusion and bone *** of TMEM16F has been studied in various central nervous system *** TMEM16F level has been also found to participate in microglial phagocytosis and ***-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer’s ***,few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer’s *** this study,we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in *** performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 *** results showed that TMEM16F was elevated in 9-month-old APP/PS1 *** TMEM16F knockdown in mice,spatial memory ability was improved,microglia polarization to the M2 phenotype was promoted,NLRP3 inflammasome activation was inhibited,cell apoptosis and Aβplaque deposition in brain tissue were reduced,and brain injury was *** used amyloid-beta(Aβ_(25-35))to stimulate human microglia to construct microglia models of Alzheimer’s *** levels of TMEM16F,inducible nitric oxide synthase(iNOS),proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aβ_(25-35) treated group compared with that in the control ***16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3,reduced the release of proinflammatory factors interleukin-1,interleukin-6 and tumor necrosis factor-α,and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1βand *** inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist *** findings suggest that TMEM16F participates i

关键词： Alzheimer’s disease Aβplaque inflammatory cytokines M1 phenotype M2 phenotype microglia polarization neuroinflammation NLRP3 inflammasome siRNA TMEM16F

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Decreased fragile histidine triad expression in colorectal cancer and its association with apoptosis inhibition

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World Journal of Gastroenterology 2007年第7期13卷 1018-1026页

作者： Jie Cao xiao-Ping Chen Wang-Lin Li JieXia Hong Du Wei-Biao Tang Hui Wang Xi-Wen then huan-qing xiao Yu-Yuan Li Department of Gastrointestinal Surgery Affiliated Guangzhou First People's Hospital Guangzhou Medical College Guangzhou 510180 Guangdong Province China Center of Hepatic Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 Hubei Province China Department of Pathology Affiliated Guangzhou First People's Hospital Guangzhou Medical College Guangzhou 510180 Guangdong Province China Department of Gastroenterology Affiliated Guangzhou First People's Hospital Guangzhou Medical College Guangzhou 510180 Guangdong Province China Supported by the Natural Science Foundation of Guangdong Province No. 06020005

AIM： To detect the expression of fragile histidine triad （FHIT） in normal colorectal tissue, colorectal adenoma and colorectal cancer （CRC） tissue, and to analyze its relationship with the clinicopathological features of CRC, and apoptosis-associatecl proteins （Bcl-2, Bax, survivin） and apoptosis in colorectal cancer. METHODS： FHIT mRNA analysis was performed by nested reverse transcription-polymerase chain reaction （RT-PCR） assay. Tissue microarray （TMA） was established to detect the expression of FHIT, Bcl-2, Bax and survivin genes in 80 CRC tissue specimens, 16 colorectal adenoma tissue specimens and 16 hemorrhoid （PPH） tissue specimens during the same period of time as the control. Citrate-microwave-SP was used as immunohistochemical method. The relationship between clinicopathological factors, such as differentiation grades and 5-year survival rate was observed. TUNEL assay was used to detect the apoptosis index in 80 CRC tissue specimens. RESULTS： Ten out of 26 （38.5%） CRC tissue specimens expressed aberrant FHIT transcripts, none of the aberrant FHIT transcripts was observed in the matchednormal tissue and colorectal adenoma tissue by nested RT-PCR assay. The positive rate of FHIT gene expression in normal colorectal tissue, colorectal adenoma and carcinoma tissue was 93.75%, 68.75% and 46.25%, respectively. Clinicopathological analysis of patients showed that the decreased FHIT gene expression was not associated with age, sex, serum CEA levels, tumor site and size, histological classification. However, the expression of FHIT was correlated with differentiation grades, pathological stages, lymph node metastases and 5-year survival rate after operation. The positive rate of apoptosis-associated proteins （Bax, Bcl-2 and survivin） in CRC tissue was 72.50%, 51.25% and 77.50%, respectively. The expression of these apoptosisassociated proteins in CRC tissue was correlated with the expression of FHIT. The mean apoptosis index in FHIT negative tumors was signific

关键词： Colorectal cancer Fragile histidine triad Expression Apoptosis

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伊拉克战争后的国际格局:美国因素

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山东大学学报（哲学社会科学版） 2004年第2期 155-160页

作者：郇庆治杨晓燕山东大学政治学与公共管理学院山东济南250100

伊拉克战争确证了国际格局中美国因素自冷战结束以来发生的重大变化。从表面上说 ,美国因为“9·11事件”和反恐怖主义需要而战略内向收缩 ,但就更深层次而言 ,恰恰是二者促成了美国后冷战时代一种外向扩张型国际秩序观。

关键词：国际格局美国伊拉克战争

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鸡生长激素在毕赤酵母中的表达、纯化和活性鉴定

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中国畜牧兽医 2016年第11期43卷 2970-2975页

作者：郁建锋何赛金泽楷周欢庆董小敏龚道清顾志良常熟理工学院常熟215500 扬州大学扬州225009

生长激素(growth hormone,GH)与受体结合调节靶细胞的功能在机体的生长发育及代谢过程中起着极其重要的作用。为获得高纯度具有生物学活性的鸡生长激素(chicken growth hormone,cGH),试验将C端融合了6个组氨酸的cGH成熟片段基因序列克... 详细信息

生长激素(growth hormone,GH)与受体结合调节靶细胞的功能在机体的生长发育及代谢过程中起着极其重要的作用。为获得高纯度具有生物学活性的鸡生长激素(chicken growth hormone,cGH),试验将C端融合了6个组氨酸的cGH成熟片段基因序列克隆入毕赤酵母表达载体pPIC9K中,使用电转法将重组质粒导入毕赤酵母GS115,以1%的甲醇诱导重组菌(GS115-pPIC9K-cGH)96h,表达大小约为25ku的目的蛋白cGH,经Ni离子亲和层析和聚丙烯酰胺葡聚糖凝胶层析获得95%以上的cGH重组蛋白。实时荧光定量检测结果表明,纯化的cGH重组蛋白可刺激鸡肝癌细胞LMH内的胰岛素样生长因子Ⅰ(insulin-like growth factorⅠ,IGF-Ⅰ)基因的mRNA表达上调,表明所发酵纯化的重组蛋白cGH具有生物学活性,这为其结构和功能的研究及生产应用奠定了基础。

关键词：鸡生长激素毕赤酵母表达纯化生物学活性

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汽车传动轴压装工艺分析

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机械制造与自动化 2011年第6期40卷 47-50页

作者：王力华晓青隋立军上海大学精密机械系上海200072

在对比汽车传动轴传统单端压装和两端压装的基础上,使用有限元软件Abaqus对汽车传动轴过盈压装进行有限元模拟仿真,通过分析不同工艺参数如过盈量、轴管长度、不同过盈组合形式等对传动轴支反力RF,轴管径向塑变U1和轴向应力S33的影响,... 详细信息

在对比汽车传动轴传统单端压装和两端压装的基础上,使用有限元软件Abaqus对汽车传动轴过盈压装进行有限元模拟仿真,通过分析不同工艺参数如过盈量、轴管长度、不同过盈组合形式等对传动轴支反力RF,轴管径向塑变U1和轴向应力S33的影响,对传动轴压装工艺进行论证。

关键词：传动轴加工压装仿真接触分析 Abaqus

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Integrating lipidomics and gut microbiota to study the anti-hyperlipidemia effect of Sargentodoxae Caulis extract

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Traditional Medicine Research 2025年第1期10卷 1-11页

作者： xiao-xiao Zhang Li Jia Xiu-Jun Zhan Charity Ngina qing-Rui Zhang xiao-Ge Li Qi-Bao Jiang Shi Bai Miao-Miao Jiang National Key Laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjin 301617China Haihe Laboratory of Modern Chinese Medicine Tianjin 301617China School of Medicine Taizhou UniversityTaizhou 318000China.

Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&*** in ***,and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book“Illustrated Classics of Materia Medica”.It has been used effectively to treat blood stasis too in modern clinical ***,the anti-hyperlipidemia effect of SC is not fully *** paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body,and its new role in treating ***:The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut ***,we explored the potential mechanism of SC in treating hyperlipidemia by pathway ***:The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice,as well as repair the morphological and structural damage to *** to the Model group,the SC extract significantly reduced the liver index,epididymal fat index,and Lee’s *** also significantly decreased serum levels of total cholesterol,triglycerides,low-density lipoprotein cholesterol,peroxisome proliferator-activated receptor gamma(PPAR-γ),D-lactate,and free fatty acids,while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha(PPAR-α).These changes were statistically ***-targeted lipidomics,based on LC-MS,were utilized to investigate the lipid metabolism characteristics in serum,liver,and epididymal fat of the *** was observed that,compared to the blank group,the Model group exhibited significant changes primarily in glycerol lipids and *** treatment group also displayed alterations in these lipids.A total of 38,81,and 27 differential lipids were identified in serum,liver,and epididymal fat samples,*** these,14 common differenti

关键词： hyperlipidemia Sargentodoxae Caulis lipidomics intestinal flora

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中药癌痛克对人胃癌细胞SGC-7901增殖、凋亡作用及机制研究

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中华普通外科学文献（电子版） 2008年第4期2卷 17-19页

作者：肖焕擎杨洁孙政李书华广州市第一人民医院普外科广州510180 广州市中医医院消化内科广州医学院病理教研室

目的通过观察不同浓度癌痛克对胃癌细胞株SGC-7901增殖及凋亡的作用,以及在相应状态下细胞内视网膜母细胞瘤(Rb)基因相对表达量的改变,探讨中药癌痛克的抗胃癌作用机制。方法以不同浓度癌痛克作用SGC-7901细胞,CCK-8检测细胞增殖抑制率... 详细信息

目的通过观察不同浓度癌痛克对胃癌细胞株SGC-7901增殖及凋亡的作用,以及在相应状态下细胞内视网膜母细胞瘤(Rb)基因相对表达量的改变,探讨中药癌痛克的抗胃癌作用机制。方法以不同浓度癌痛克作用SGC-7901细胞,CCK-8检测细胞增殖抑制率,流式细胞术检测细胞凋亡率细胞周期,RT-PCR方法检测细胞内Bcl-2基因表达变化。结果2～50μg/ml癌痛克可抑制SGC-7901细胞增殖并诱导其凋亡,其抑制及诱导凋亡效应呈浓度依赖性;细胞周期分析处于G1期细胞百分比明显增多,处于G2/M期的细胞减少,Rb基因mRNA表达上调。结论中药癌痛克可通过抑制SGC-7901细胞增殖或诱导其凋亡,且其机制可能通过上调Rb基因表达途径使细胞阻滞在G1期,进而诱导细胞凋亡。

关键词：癌痛克胃癌凋亡

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Nitric Oxide Enhances the Sensitivity of Alpaca Melanocytes to Respond to a-melanocyte stimulating hormone by Up-regulating Melanocortin-1 Receptor

Nitric Oxide Enhances the Sensitivity of Alpaca Melanocytes ...

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中国畜牧兽医学会动物解剖学及组织胚胎学分会第五次会员代表大会暨第十六次学术研讨会

作者： DONG Yan-jun,CAO Jing,WANG Hai-dong,ZHANG Jie,ZHU Zhi-wei,BAI Rui,HAO huan-qing,HE xiao-yan,Fan Rui wen,DONG Chang-sheng~(**) College of Animal Science and Technology,Shanxi Agricultural University,030801,Taigu,Shanxi,China.

Nitric oxide(NO) and a-melanocyte stimulating hormone(a-MSH) have been correlated with the synthesis of *** NO-dependent signaling of cellular response to activate the hypothalamopituitary proopiomelanocortin system,thereby enhances the hypophysial secretion of a-MSH to stimulatea-MSH-receptor responsive *** this study we investigated whether an NO-induced pathway can enhance the ability of the melanocyte to respond to a-MSH on melanogenesis in alpaca skin melanocytes in *** is important for us to know how to enhance the coat color of *** set up three groups for experiments using the third passage number of alpaca melanocytes:the control cultures were allowed a total of 5 days growth;the UV group cultures like the control group but the melanocytes were then irradiated everyday(once) with 312 mJ/cm of UVB;the UV+L-NAME group is the same as group UV but has the addition of 300μM L-NAME(every 6 hours).To determine the inhibited effect of NO produce,NO produces were *** determine the effect of the NO to the key protein and gene of a-MSH pathway on melanogenesis,the key gene and protein of the a-MSH pathway were measured by quantitative real-time PCR and western *** results provide exciting new evidence that NO can enhance a-MSH pathway in alpaca skin melanocytes by elevated *** we suggest that the NO pathway may more rapidly cause the synthesis of melanin in alpaca skin under UV,which at that time elevates the expression of MC1R and stimulates the keratinocytes to secrete a-MSH to enhance the a-MSH pathway on melanogenesis. This process will be of considerable interest in future studies.

关键词： Nitric oxide(NO) a-melanocyte stimulating hormone(a-MSH) Melanocortin-1 receptor(MC1R) Alpaca Melanocyte

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miR-483-3p增强胰腺癌对吉西他滨敏感性及分子机制研究

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大连理工大学学报 2025年第1期65卷 30-37页

作者：刘青肖桂山大连理工大学化工学院辽宁大连116024

吉西他滨耐药限制了其对胰腺癌的治疗效果,而传统化学药物无法有效克服吉西他滨对胰腺癌的耐药.研究表明,microRNA(miRNA)的异常表达与肿瘤发生、发展和化疗耐药性有关.对miR-483-3p在胰腺癌吉西他滨耐药中的作用和潜在机制进行了研究.q... 详细信息

吉西他滨耐药限制了其对胰腺癌的治疗效果,而传统化学药物无法有效克服吉西他滨对胰腺癌的耐药.研究表明,microRNA(miRNA)的异常表达与肿瘤发生、发展和化疗耐药性有关.对miR-483-3p在胰腺癌吉西他滨耐药中的作用和潜在机制进行了研究.qPCR结果显示miR-483-3p在胰腺癌耐药细胞中显著下调.miR-483-3p minics瞬时转染显著提高了耐药细胞内miR-483-3p的表达水平,显著减弱了耐药细胞的增殖、迁移、转移和侵袭能力,恢复了吉西他滨的反应性.Western blot结果显示miR-483-3p抑制PI3K和p-AKT蛋白的表达水平,抑制Bcl2蛋白表达,促进Bax、Bad和cleaved-Caspase-3蛋白表达,促进细胞凋亡进程.总之,研究结果表明miR-483-3p通过抑制PI3K/AKT信号通路促进细胞凋亡,增加胰腺癌对吉西他滨的敏感性,miR-483-3p可能是吉西他滨耐药胰腺癌患者的潜在治疗策略.

关键词： miR-483-3p 胰腺癌吉西他滨耐药性 miRNA

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An Extended Method for Constructing Travelling Wave Solutions to Nonlinear Partial Differential Equations

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Communications in Theoretical Physics 2005年第3X期44卷 407-414页

作者： JIAO xiao-Yu WANG Jin-huan ZHANG Hong-qing Department of Applied Mathematics Dalian University of Technology Dalian 116024 China

In this paper, an extended method is proposed for constructing new forms of exact travelling wave solutions to nonlinear partial differential equations by making a more general transformation. For illustration, we apply the method to the asymmetric Nizhnik-Novikov-Vesselov equation and the coupled Drinfel＇d-Sokolov-Wilson equation and successfully cover the previously known travelling wave solutions found by Chen＇s method .

关键词： soliton solution asymmetric Nizhnik-Novikov-Vesselov equation coupled Drinfel'd-Sokolov-Wilson equation

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