简介:Objective:Cancercellradioresistanceisastumblingblockinradiationtherapy.TheactivityinthenuclearfactorkappaB(NFκB)pathwaycorrelateswithanti-apoptoticmechanismsandincreasedradioresistance.TheIKKcomplexplaysamajorroleinNFκBactivationuponnumeroussignals.Inthisstudy,weexaminedtheinteractionbetweenionizingradiation(IR)anddifferentmembersoftheIKK-NFκBpathway,aswellasupstreamactivators,RAF1,ERK,andAKT1.Methods:Theeffectof4GyofIRontheexpressionoftheRAF1-ERK-IKK-NFκBpathwaywasexaminedinA549andH1299lungcancercelllinesusingWesternblotanalysisandconfocalmicroscopy.WeexaminedchangesinradiationsensitivityusinggenesilencingorpharmacologicalinhibitorsofERKandIKKβ.Results:IKKα,IKKγ,andIκBαincreaseduponexposuretoIR,therebyaffectingnuclearlevelsofNFκB(phospho-p65).ERKinhibitionorsiRNA-mediateddown-regulationofRAF1suppressedthepost-irradiationsurvivaloftheexaminedlungcancercelllines.AsimilareffectwasdetectedonsurvivaluponsilencingIKKα/IKKγorinhibitingIKKβ.Conclusions:ExposureoflungcancercellstoIRresultsinNFκBactivationviaIKK.ThegeneticorpharmacologicalblockageoftheRAF1-ERK-IKK-NFκBpathwaysensitizescellstotherapeuticdosesofradiation.Therefore,theIKKpathwayisapromisingtargetfortherapeuticinterventionincombinationwithradiotherapy.
简介:摘要目的:通过术前对高度近视并发白内障患者行Kappa角测定,从而评估Kappa角对高度近视并发白内障患者行区域折射多焦点人工晶状体(MIOL)植入术后视觉质量的影响。方法:回顾性系列病例研究。收集2018年10月至2019年10月因高度近视并发白内障于潍坊市眼科医院行白内障超声乳化抽吸联合区域折射MIOL植入术的患者53例(53眼),年龄42~66(52.2±6.3)岁。根据患者术前测量的Kappa角,即视轴与瞳孔中心的距离(r),将患者分为A组(0<r≤0.182 mm)27例(27眼)和B组(0.182 mm<r≤0.5 mm)26例(26眼)。术后随访3个月并记录2组患者视力,通过客观视觉质量分析仪(OQASII)评估患者客观视觉质量,同时以问卷调查方式记录患者术后脱镜率以及光晕、眩光等视觉不良症状。组间数据比较采用独立样本t检验或t'检验、χ2检验或Fisher确切概率法。结果:术后3个月,2组间患者的裸眼远视力(UCDVA)、裸眼中视力(UCIVA)、裸眼近视力(UCNVA)及最佳矫正远视力(BCDVA)、最佳矫正中视力(BCIVA)、最佳矫正近视力(BCNVA)差异均无统计学意义。A组客观散射指数值为2.11±1.05,B组为2.89±1.24,组间差异有统计学意义(t=-2.48,P=0.016)。A、B组患者的调制传递函数截止频率分别为(32.2±13.3)c/deg和(26.4±11.2)c/deg,2组差异无统计学意义。2组患者在100%、20%、9%对比度下的模拟对比度视力(OV)差异均无统计学意义。此外,2组患者术后的脱镜率和眩光发生率差异亦无统计学意义,但B组光晕发生率高于A组(x2=4.44,P=0.047)。结论:Kappa角对高度近视并发白内障患者行区域折射MIOL植入术后的远、中、近视力无影响,但Kappa角较大的患者术后的客观视觉质量较低,同时Kappa角增大可能引起光晕等视觉不良症状。
简介:摘要目的研究NF-κB在非小细胞肺癌中的表达与临床病理特征的关系。方法免疫组化方法检测62例非小细胞肺癌及20例癌旁肺肿瘤肺组织中NF-κB的表达。结果NF-κB在NSCLC中阳性表达率(77%(48/62))显著高于癌旁非肿瘤肺组织(45%(9/20)),差异有统计学意义(P<0.05)。NF-B阳性表达率在患者的性别、年龄、病理类型、解剖学位置、肿瘤最大径方面,差异无统计学意义(P>0.05);在细胞分化程度、淋巴结转移和TNM分期方面,差异有统计学意义(P<0.05)。结论非小细胞肺癌中存在NF-B的高表达,且与非小细胞肺癌的增殖、侵袭、转移有关。NF-κB可作为非小细胞肺癌治疗的新靶点。
简介:AbstractBackground:Vascular endothelial dysfunction is considered a key pathophysiologic process for the development of acute lung injury. In this study, we aimed at investigating the effects of unfractionated heparin (UFH) on the lipopolysaccharide (LPS)-induced changes of vascular endothelial-cadherin (VE-cadherin) and the potential underlying mechanisms.Methods:Male C57BL/6 J mice were randomized into three groups: vehicle, LPS, and LPS + UFH groups. Intraperitoneal injection of 30 mg/kg LPS was used to induce sepsis. Mice in the LPS + UFH group received subcutaneous injection of 8 U UFH 0.5 h before LPS injection. The lung tissue of the mice was collected for assessing lung injury by measuring the lung wet/dry (W/D) weight ratio and observing histological changes. Human pulmonary microvascular endothelial cells (HPMECs) were cultured and used to analyze the effects of UFH on LPS- or tumor necrosis factor-alpha (TNF-α)-induced vascular hyperpermeability, membrane expression of VE-cadherin, p120-catenin, and phosphorylated myosin light chain (p-MLC), and F-actin remodeling, and on the LPS-induced activation of the phosphatidylinositol-3 kinase (PI3K)/serine/threonine kinase (Akt)/nuclear factor kappa-B (NF-κB) signaling pathway.Results:In vivo, UFH pretreatment significantly attenuated LPS-induced pulmonary histopathological changes (neutrophil infiltration and erythrocyte effusion, alveolus pulmonis collapse, and thicker septum), decreased the lung W/D, and increased protein concentration (LPS vs. LPS + UFH: 0.57 ± 0.04 vs. 0.32 ± 0.04 mg/mL, P = 0.0092), total cell count (LPS vs. LPS + UFH: 9.57 ± 1.23 vs. 3.65 ± 0.78 × 105/mL, P= 0.0155), polymorphonuclear neutrophil percentage (LPS vs. LPS+ UFH: 88.05% ± 2.88% vs. 22.20% ± 3.92%, P = 0.0002), and TNF-α (460.33 ± 23.48 vs. 189.33 ± 14.19 pg/mL, P = 0.0006) in the bronchoalveolar lavage fluid. In vitro, UFH pre-treatment prevented the LPS-induced decrease in the membrane expression of VE-cadherin (LPS vs. LPS + UFH: 0.368 ± 0.044 vs. 0.716 ± 0.064, P = 0.0114) and p120-catenin (LPS vs. LPS + UFH: 0.208 ± 0.018 vs. 0.924 ± 0.092, P = 0.0016), and the LPS-induced increase in the expression of p-MLC (LPS vs. LPS + UFH: 0.972 ± 0.092 vs. 0.293 ± 0.025, P = 0.0021). Furthermore, UFH attenuated LPS- and TNF-α-induced hyperpermeability of HPMECs (LPS vs. LPS + UFH: 8.90 ± 0.66 vs. 15.84 ± 1.09 Ω·cm2, P = 0.0056; TNF-α vs. TNF-α + UFH: 11.28 ± 0.64 vs. 18.15 ± 0.98 Ω·cm2, P = 0.0042) and F-actin remodeling (LPS vs. LPS + UFH: 56.25 ± 1.51 vs. 39.70 ± 1.98, P = 0.0027; TNF-α vs. TNF-α + UFH: 55.42 ± 1.42 vs. 36.51 ± 1.20, P = 0.0005) in vitro. Additionally, UFH decreased the phosphorylation of Akt (LPS vs. LPS + UFH: 0.977 ± 0.081 vs. 0.466 ± 0.035, P = 0.0045) and I kappa B Kinase (IKK) (LPS vs. LPS + UFH: 1.023 ± 0.070 vs. 0.578 ± 0.044, P = 0.0060), and the nuclear translocation of NF-κB (LPS vs. LPS + UFH: 1.003 ± 0.077 vs. 0.503 ± 0.065, P = 0.0078) in HPMECs, which was similar to the effect of the PI3K inhibitor, wortmannin.Conclusions:The protective effect of UFH against LPS-induced pulmonary endothelial barrier dysfunction involves VE-cadherin stabilization and PI3K/Akt/NF-κB signaling.
简介:【摘要】目的:将本体感觉神经肌肉促进疗法( PNF)加入脑卒中偏瘫患者的手功能康复治疗过程中,并研究其对治疗效果的促进作用。 方法:选取2019年 10 月至 2020年 6月间入我院接受治疗的脑卒中偏瘫患者 80例,按照进入医院的先后顺序随机进行分组,观察组 40例,对照组 80例。其中,对照组采用常规手功能康复疗法,观察组在常规手功能康复疗法的基础上加入 PNF技术。 结果:两组患者均治疗
简介:目的探讨IL-6、NF-κβ和骨形成标志物(BALP和BGP)在大鼠骨质疏松模型中的表达水平和在骨质疏松发病中的特征。方法将60只5月龄雌性SD大鼠随机分为对照组、假手术组和卵巢切除组。在术后第2、、4、5、6月,每组随机取4只大鼠检测BMD、IL-6、BALP和BGP。用实时定量RT-PCR检测其骨组织中的IL-6和NF-κβ基因表达水平。结果术后第4、5、6月卵巢切除组大鼠的骨密度(P〈0.01)与假手术组和对照组相比显著降低,血清IL-6水平在术后第2至6月明显升高(P〈001),血清BALP和BGP于术后4、5、6月显著增高(P〈0.05)。实时定量RT-PCR分析表明卵巢切除组大鼠IL-6和NF-κβ的mRNA表达水平随时间而增加,且与骨密度呈负相关,Ib-6和NF-κβ为正相关。结论本研究表明骨质疏松大鼠的IL-6、NF-κβ和骨形成标志物水平明显增高。这些分子在骨质疏松发病中具有重要作用。
简介:通过观察结肠的mucosal为ulcerative大肠炎(UC)探索划分植物的艾灸的机制组织病理学说的变化和原子因素kappaB(NF-B)和peroxisome的表示UC老鼠的激活proliferators的受体(PPAR)mRNA。
简介:摘要目的探讨Salubrinal调控射线诱导口腔癌细胞凋亡的作用机制。方法构建放射抗拒口腔癌细胞KBR (4 Gy/次,7~10d 1次共4次);克隆形成实验检测Salubrinal预处理后口腔癌细胞放射敏感性;蛋白印迹法检测射线及Salubrinal调控口腔癌细胞NF-κB-HIF-1α信号通路及凋亡标志蛋白cleaved PARP的表达;Annexin V、PI染色、流式细胞仪检测凋亡分数。结果克隆形成实验示Salubrinal增加口腔癌细胞放射敏感性,KB及KBR细胞放射增敏比分别为1.19和1.24。蛋白印迹法结果示射线诱导口腔癌细胞NF-κB-HIF-1α细胞活化具有时间依赖性,而Salubrinal抑制射线诱导其异常活化。Salubrinal增加射线诱导口腔癌细胞凋亡标志蛋白cleaved PARP表达及凋亡指数,而NF-κB激活剂TNF-α逆转了这一作用,提示Salubrinal通过抑制NF-κB活化增加射线调控口腔癌细胞凋亡。进一步应用NF-κB抑制剂Bay11-7082同样增加射线诱导口腔癌细胞凋亡,KB及KBR细胞系Bay11-7082+IR组cleaved PARP的表达为2.67±0.26、1.91±0.17,IR组为2.1±0.16、1.44±0.15(P<0.05)。结论Salubrinal抑制射线诱导NF-κB活化增加射线诱导口腔癌细胞凋亡进而调控口腔癌细胞放射敏感性。
简介:摘要目的探讨KiSS-1和NF-κB在食管鳞状细胞癌组织中的表达及临床病理意义。方法应用免疫组织化学方法检测40例食管鳞状细胞癌和5例正常食管粘膜组织中KiSS-1和NF-κB的表达情况。结果Kiss-1在食管鳞状细胞癌组织中表达降低,与淋巴结转移关系密切(P<0.05);NF-κB的表达与病理组织分级、淋巴结转移有关(P<0.05);食管鳞状细胞癌中KiSS-1和NF-κB的表达呈负相关(r=-0.676,P<0.05)。结论Kiss-l基因的表达减低或者缺失与食管鳞状细胞癌的发生发展及浸润转移有关,Kiss-l基因可能通过抑制NF-κB从而发挥抑制食管癌转移的作用。