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Galectin 2 regulates JAK/STAT3 signaling activity to modulate oral squamous cell carcinoma proliferation and migration in vitro
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作者 XINRU FENG LI XIAO 《BIOCELL》 SCIE 2024年第5期793-801,共9页
Background:Galectin 2(LGALS2)is a protein previously reported to serve as a mediator of disease progression in a range of cancers.The function of LGALS2 in oral squamous cell carcinoma(OSCC),however,has yet to be expl... Background:Galectin 2(LGALS2)is a protein previously reported to serve as a mediator of disease progression in a range of cancers.The function of LGALS2 in oral squamous cell carcinoma(OSCC),however,has yet to be explored,prompting the present study to address this literature gap.Methods:Overall,144 paired malignant tumor tissues and paracancerous OSCC patient samples were harvested and the LGALS2 expression levels were examined through qPCR and western immunoblotting.The LGALS2 coding sequence was introduced into the pcDNA3.0 vector,to enable the overexpression of this gene,while an LGALS2-specific shRNA and corresponding controls were also obtained.The functionality of LGALS2 as a regulator of the ability of OSCC cells to grow and undergo apoptotic death in vitro was assessed through EdU uptake and CCK-8 assays,and flow cytometer,whereas a Transwell system was used to assess migratory activity and invasivity.An agonist of the Janus Kinase 2(JAK2)/Signal Transducer and Activator of Transcription 3(STAT3)pathway was also used to assess the role of this pathway in the context of LGALS2 signaling.Results:Here,we found that lower LGALS2 protein and mRNA expression were evident in OSCC tumor tissue samples,and these expression levels were associated with clinicopathological characteristics and patient survival outcomes.Silencing LGALS2 enhanced proliferation in OSCC cells while rendering these cells better able to resist apoptosis.The opposite was instead observed after LGALS2 was overexpressed.Mechanistically,the ability of LGALS2 to suppress the progression of OSCC was related to its ability to activate the JAK/STAT3 signaling axis.Conclusion:Those results suggest a role for LGALS2 as a suppressor of OSCC progression through its ability to modulate JAK/STAT3 signaling,supporting the potential utility of LGALS2 as a target for efforts aimed at treating OSCC patients. 展开更多
关键词 LGALS2 Oral squamous cell carcinoma(OSCC) Janus Kinase 2/signal Transducer and activator of transcription 3(JAK2-STAT3) PROGRESSION
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Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions 被引量:8
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作者 Yang-Hui Bi Wen-Qi Han +4 位作者 Ruo-Fei Li Yun-Jiao Wang Zun-Shu Du Xue-Jiang Wang Ying Jiang 《World Journal of Gastroenterology》 SCIE CAS 2019年第16期1936-1949,共14页
BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate de... BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2(PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.AIM To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.METHODS A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with Nmethyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen(PCNA), STAT3,and PKM2 were examined by Western blot and immunofluorescence.RESULTS We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liverprecancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression,PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells.Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.CONCLUSION The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells. 展开更多
关键词 WARBURG effect Hepatic PROGENITOR cell signal transducer and activator of transcription 3 PYRUVATE kinase M2 LIVER PRECANCEROUS lesion
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Mechanism of Yanghe Pingchaun granules on airway remodeling in asthmatic rats based on IL-6/JAK2/STAT3 signaling axis
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作者 LV Chuan ZHU Hui-zhi +4 位作者 LIU Xiang-guo CAO Xiao-mei XIA Yong-qi ZHANG Qiu-ping YU Zi-qi 《Journal of Hainan Medical University》 CAS 2024年第1期15-21,共7页
Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(... Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis. 展开更多
关键词 Yanghe Pingchuan Granules Interleukin-6/Janus kinase 2/signal transducing activator of transcription 3(IL-6/JAK2/STAT3)signal axis Asthma Airway remodeling Mechanism study
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Role of Toll-like receptor 4 and Janus kinase and signal transducer and activator of transcription signal transduction pathway in sepsis-induced brain damage 被引量:1
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作者 Haiyan Yin Jianrui Wei +2 位作者 Rui Zhang Xiaoling Ye Youfeng Zhu 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第32期2511-2515,共5页
The Janus kinase and signal transducer and activator of transcription (JAK/STAT) signal transduction pathway is involved in sepsis-induced functional damage to the heart, liver, kidney, and other organs. However, th... The Janus kinase and signal transducer and activator of transcription (JAK/STAT) signal transduction pathway is involved in sepsis-induced functional damage to the heart, liver, kidney, and other organs. However, the cellular and molecular mechanisms underlying sepsis-induced brain damage remain elusive. In the present study, we found severe loss of neurons in the hippocampal CA1 region in rats with sepsis-induced brain damage following intraperitoneal injection of endotoxin, The expression of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 was significantly increased in brain tissues following lipopolysaccharide exposure. AG490 (JAK2 antagonist) and rapamycin (STAT3 antagonist) significantly reduced neuronal loss and suppressed the increased expression of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 in the hippocampal CA1 region in sepsis-induced brain damaged rats. Overall, these data suggest that blockade of the JAK/STAT signal transduction pathway is neuroprotective in sepsis-induced brain damage via the inhibition of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 exoression. 展开更多
关键词 brain damage Janus kinase and signal transducer and activator of transcription SEPSIS signal transduction pathway Toll-like receptor 4
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Mechanism of ELL-associated factor 2 and vasohibin 1 regulating invasion,migration,and angiogenesis in colorectal cancer 被引量:2
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作者 Ming-Liang Feng Ming-Jun Sun +3 位作者 Bo-Yang Xu Meng-Yuan Liu Hui-Jing Zhang Can Wu 《World Journal of Gastroenterology》 SCIE CAS 2023年第24期3770-3792,共23页
BACKGROUND As a novel endogenous anti-angiogenic molecule, vasohibin 1(VASH1) is not only expressed in tumor stroma, but also in tumor tissue. Moreover, studies have shown that VASH1 may be a prognostic marker in colo... BACKGROUND As a novel endogenous anti-angiogenic molecule, vasohibin 1(VASH1) is not only expressed in tumor stroma, but also in tumor tissue. Moreover, studies have shown that VASH1 may be a prognostic marker in colorectal cancer(CRC). Knockdown of VASH1 enhanced transforming growth factor-β1(TGF-β1)/Smad3 pathway activity and type Ⅰ/Ⅲ collagen production. Our previous findings suggest that ELL-associated factor 2(EAF2) may play a tumor suppressor and protective role in the development and progression of CRC by regulating signal transducer and activator of transcription 3(STAT3)/TGF-β1 signaling pathway. However, the functional role and mechanism of VASH1-mediated TGF-β1 related pathway in CRC has not been elucidated.AIM To investigate the expression of VASH1 in CRC and its correlation with the expression of EAF2. Furthermore, we studied the functional role and mechanism of VASH1 involved in the regulation and protection of EAF2 in CRC cells in vitro.METHODS We collected colorectal adenocarcinoma and corresponding adjacent tissues to investigate the clinical expression of EAF2 protein and VASH1 protein in patients with advanced CRC. Following, we investigated the effect and mechanism of EAF2 and VASH1 on the invasion, migration and angiogenesis of CRC cells in vitro using plasmid transfection.RESULTS Our findings indicated that EAF2 was down-regulated and VASH1 was upregulated in advanced CRC tissue compared to normal colorectal tissue. KaplanMeier survival analysis showed that the higher EAF2 Level group and the lower VASH1 Level group had a higher survival rate. Overexpression of EAF2 might inhibit the activity of STAT3/TGF-β1 pathway by up-regulating the expression of VASH1, and then weaken the invasion, migration and angiogenesis of CRC cells.CONCLUSION This study suggests that EAF2 and VASH1 may serve as new diagnostic and prognostic markers for CRC, and provide a clinical basis for exploring new biomarkers for CRC. This study complements the mechanism of EAF2 in CRC cells, enriches the role and mechanism of CRC cellderived VASH1, and provides a new possible subtype of CRC as a therapeutic target of STAT3/TGF-β1 pathway. 展开更多
关键词 ELL-associated factor 2 Vasohibin 1 Transforming growth factor-β1 signal transducer and activator of transcription 3 Colorectal cancer ANGIOGENESIS
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Ca^(2+) involvement in activation of extracellular-signal- regulated-kinase 1/2 and m-calpain after axotomy of the sciatic nerve 被引量:4
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作者 Lisa B. Martensson Charlotta Lindwall Blom Lars B. Dahlin 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第4期623-628,共6页
Detailed mechanisms behind regeneration after nerve injury, in particular signal transduction and the fate of Schwann cells (SCs), are poorly understood. Here, we investigated axotomy-induced activation of extracell... Detailed mechanisms behind regeneration after nerve injury, in particular signal transduction and the fate of Schwann cells (SCs), are poorly understood. Here, we investigated axotomy-induced activation of extracellular- signal-regulated kinase-1/2 (ERK1/2; important for proliferation) and m-calpain in vitro, and the relation to Ca2+ deletion and Schwann cell proliferation and death after rat sciatic nerve axotomy. Nerve segments were cultured for up to 72 hours with and without ethylene glycol-bis(β-aminoethyl ether)- N,N,N',N'-tetraacetic acid (EGTA). In some experiments, 5-bromo-2′-deoxyuridine (BrdU) was added during the last 24 hours to detect proliferating cells and propidium iodide (PI) was added at the last hour to detect dead and/or dying cells. Immunohistochemistry of sections of the cultured nerve segments was performed to label m-calpain and the phosphorylated and activated form of ERK1/2. The experiments revealed that immunoreactivity for p-ERK1/2 increased with time in organotypically cultured SCs. p-ERK1/2 and m-calpain were also observed in axons. A significant increase in the number of dead or dying SCs was observed in nerve segments cultured for 24 hours. When deprived of Ca2+, activation of axonal m-calpain was reduced, whereas p-ERK1/2 was increased in SCs. Ca2+ deprivation also significantly reduced the number of proliferating SCs, and instead increased the number of dead or dying SCs. Ca2+ seems to play an important role in activation of ERK1/2 in SCs and in SC survival and proliferation. In addition, extracellular Ca2+ levels are also required for m-calpain activation and up-regulation in axons. Thus, regulation of Ca2+ levels is likely to be a useful method to promote SC proliferation. 展开更多
关键词 nerve regeneration P-ERK1/2 M-CALPAIN nerve injury signal transduction cell proliferation cell death ACTIVATION AXOTOMY sciatic nerve neural regeneration
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Leptin transiently antagonizes ghrelin and long-lastingly orexin in regulation of Ca^(2+) signaling in neuropeptide Y neurons of the arcuate nucleus 被引量:4
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作者 Daisuke Kohno Shigetomo Suyama Toshihiko Yada 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第41期6347-6354,共8页
AIM: To explore the mechanism for interactions of leptin with ghrelin and orexin in the arcuate nucleus (ARC) activating neuropeptide Y (NPY) neurons during physiological regulation of feeding, METHODS: Single n... AIM: To explore the mechanism for interactions of leptin with ghrelin and orexin in the arcuate nucleus (ARC) activating neuropeptide Y (NPY) neurons during physiological regulation of feeding, METHODS: Single neurons from ARC of adult rats with matured feeding function were isolated. [Ca2+]i was measured to monitore their activities. The time course of leptin effects on ghrelin-induced versus orexin-induced [Ca2+]i increases in NPY neurons was studied. RESULTS: Administration of ghrelin or orexin-A at 101~ mol/L increased cytosolic Ca2~ concentration ([Ca2+]~) in NPY neurons isolated from the ARC of adult rats. Upon administration of leptin at 10^-14-10^-12 mol/L, ghrelin-induced [Ca2+]i increases were initially (〈 10 min) inhibited but later restored, exhibiting a transient pattern of inhibition. In contrast, orexin-induced [Ca2+]i increases were inhibited by leptin in a long- lasting manner. Furthermore, a prior administration of leptin inhibited orexin action but not ghrelin action to increase ICa 2+li, CONCLUSION: Leptin counteracted ghrelin effects transiently and orexin effects long-lastingly in NPY neurons. The transient property with which leptin counteracts ghrelin action in NPY neurons may allow the fasting-associated increase in ghrelin levels to activate NPY neurons in the presence of physiological leptin and to stimulate feeding. 展开更多
关键词 LEPTIN GHRELIN OREXIN Arcuate nucleus Neuropeptide Y Ca2 FEEDING Phosphatidylinositol 3-kinase Phosphodiesterase 3 signal transducer and activator of transcription 3
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Structural and biochemical basis of FLS2-mediated signal activation and transduction in rice
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作者 Qiaoqiao Zhao Jinlin Bao +9 位作者 Huailong Li Wei Hu Yanqiong Kong Yifeng Zhong Qiang Fu Guolyu Xu Fenmei Liu Xi Jiao Jian Jin Zhenhua Ming 《Plant Communications》 SCIE CSCD 2024年第3期216-231,共16页
The receptor-like kinase FLAGELLIN-SENSITIVE 2(FLS2)functions as a bacterialflagellin receptor local-ized on the cell membrane of plants.In Arabidopsis,the co-receptor BRI1-ASSOCIATED RECEPTOR KI-NASE 1(BAK1)cooperate... The receptor-like kinase FLAGELLIN-SENSITIVE 2(FLS2)functions as a bacterialflagellin receptor local-ized on the cell membrane of plants.In Arabidopsis,the co-receptor BRI1-ASSOCIATED RECEPTOR KI-NASE 1(BAK1)cooperates with FLS2 to detect theflagellin epitopeflg22,resulting in formation of a signaling complex that triggers plant defense responses.However,the co-receptor responsible for recog-nizing and signaling theflg22 epitope in rice remains to be determined,and the precise structural mecha-nism underlying FLS2-mediated signal activation and transduction has not been claried.This study pre-sents the structural characterization of a kinase-dead mutant of the intracellular kinase domain of OsFLS2(OsFLS2-KDD1013A)in complex with ATP or ADP,resolved at resolutions of 1.98 A˚and 2.09 A˚,respectively.Structural analysis revealed that OsFLS2 can adopt an active conformation in the absence of phosphorylation,although it exhibits only weak basal catalytic activity for autophosphorylation.Subse-quent investigations demonstrated that OsSERK2 effectively phosphorylates OsFLS2,which reciprocally phosphorylates OsSERK2,leading to complete activation of OsSERK2 and rapid phosphorylation of the downstream substrate receptor-like cytoplasmic kinases OsRLCK176 and OsRLCK185.Through mass spectrometry experiments,we successfully identied critical autophosphorylation sites on OsSERK2,as well as sites transphosphorylated by OsFLS2.Furthermore,we demonstrated the interaction between OsSERK2 and OsFLS2,which is enhanced in the presence offlg22.Genetic evidence suggests that OsRLCK176 and OsRLCK185 may function downstream of the OsFLS2-mediated signaling pathway.Our study reveals the molecular mechanism by which OsFLS2 mediates signal transduction pathways in rice and provides a valuable example for understanding RLK-mediated signaling pathways in plants. 展开更多
关键词 FLS2 active conformation kinase activation transphosphorylation signal transduction
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基于Hepcidin和JAK2/STAT3信号通路探讨通痹颗粒 对胶原诱导性关节炎大鼠的影响
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作者 吴伊莹 柳玉佳 +2 位作者 廖亮英 范伏元 郭志华 《湖南中医药大学学报》 CAS 2024年第6期960-966,共7页
目的研究通痹颗粒对胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠铁调素(hepcidin,Hepc)、Janus激酶(janus kinase,JAK)2/信号转导子和转录激活子(signal transduction and activator of transcription,STAT)3信号通路的影响... 目的研究通痹颗粒对胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠铁调素(hepcidin,Hepc)、Janus激酶(janus kinase,JAK)2/信号转导子和转录激活子(signal transduction and activator of transcription,STAT)3信号通路的影响。方法选取36只雌性SD大鼠随机分成空白组、模型组、阳性对照组和通痹颗粒低、中、高剂量组,每组6只。空白组不予处理,其余组用牛Ⅱ型胶原建立CIA模型。造模完成后,空白组、模型组予生理盐水灌胃,其余各组分别以巴瑞替尼片和低、中、高剂量通痹颗粒灌胃。每天1次,连续4周。HE染色行滑膜组织病理学观察;酶联免疫吸附法测定血清Hepc、白细胞介素6(interleukin 6,IL-6)水平;逆转录-聚合酶链反应法测定滑膜中JAK2、STAT3、细胞信号因子传导抑制体(suppressor of cytokine signaling,SOCS)1、SOCS3的mRNA相对表达量;Western blot法检测滑膜中JAK2、p-JAK2、STAT3、p-STAT3、SOCS1、SOCS3的蛋白表达量。结果模型组见滑膜上皮结构缺损,滑膜重度增生,排列紊乱,并有大量炎症细胞浸润和多个血管翳形成;各给药组滑膜炎症均有所减轻,阳性对照组优于通痹颗粒高剂量组,通痹颗粒中、高剂量组优于低剂量组。与模型组相比,各给药组关节炎指数评分、血清Hepc和IL-6水平均显著降低(P<0.01);与阳性对照组相比,通痹颗粒中、低剂量组关节炎指数评分、血清Hepc和IL-6水平均升高(P<0.05)。与模型组比较,阳性对照组和通痹颗粒低、中、高剂量组JAK2、STAT3 mRNA和蛋白以及p-JAK2、p-STAT3的蛋白表达量均降低(P<0.05),而通路抑制因子SOCS1、SOCS3 mRNA和蛋白的表达均升高(P<0.05);与阳性对照组比较,通痹颗粒各剂量组JAK2、STAT3 mRNA和蛋白以及p-JAK2、p-STAT3的蛋白表达量均升高(P<0.05),而SOCS1、SOCS3 mRNA和蛋白的表达均降低(P<0.05)。结论通痹颗粒能够改善CIA大鼠滑膜炎症,其机制可能与抑制JAK2/STAT3信号通路而减少Hepc的表达有关。 展开更多
关键词 类风湿关节炎 胶原诱导性关节炎 中药 通痹颗粒 铁调素 JAK2/STAT3信号通路
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青藤碱调节CXCR4-STAT3轴对卵巢癌A2780细胞增殖、迁移和血管生成拟态的影响
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作者 闫振宇 郭锰 +2 位作者 杨然 苏博 张海燕 《现代肿瘤医学》 CAS 2024年第16期2944-2951,共8页
目的:探讨青藤碱(Sinomenine)对卵巢癌细胞增殖、迁移和血管生成拟态的影响及作用机制。方法:使用不同浓度(0、0.25、0.50、1.0、2.0、4.0、8.0 mmol/L)的青藤碱分别处理A2780细胞24、48 h, CCK-8法检测细胞存活率。将A2780细胞随机分... 目的:探讨青藤碱(Sinomenine)对卵巢癌细胞增殖、迁移和血管生成拟态的影响及作用机制。方法:使用不同浓度(0、0.25、0.50、1.0、2.0、4.0、8.0 mmol/L)的青藤碱分别处理A2780细胞24、48 h, CCK-8法检测细胞存活率。将A2780细胞随机分为对照(Control)组、CXCR4激活剂基质细胞衍生因子-1(SDF-1)(SDF-1,100 ng/mL)组、CXCR4抑制剂普乐沙福(Plerixafor, 500 ng/mL)组、青藤碱(Sinomenine, 1.0 mmol/L)组、Sinomenine+SDF-1(1.0 mmol/L Sinomenine+100 ng/mL SDF-1)组,分别检测A2780细胞增殖、迁移与侵袭,体外血管生成拟态形成实验检测青藤碱对血管生成拟态的影响,Western blot法检测血管内皮生长因子(VEGF)、上皮细胞激酶(EphA2)、基质金属蛋白酶9(MMP-9)、MMP-2、CXC趋化因子受体4(CXCR4)、信号转导与转录激活因子3(STAT3)、磷酸化STAT3(p-STAT3)蛋白表达。结果:青藤碱可有效抑制A2780细胞增殖,且呈浓度依赖性;青藤碱可显著抑制A2780细胞迁移、侵袭及血管生成拟态形成,并下调血管生成拟态标志蛋白VEGF、EphA2、MMP-9、MMP-2表达,抑制CXCR4、p-STAT3表达(P<0.05),青藤碱的这一抑制作用可被CXCR4激活剂减弱。结论:青藤碱可能通过抑制CXCR4-STAT3轴,抑制卵巢癌细胞增殖、迁移、侵袭及血管生成拟态形成。 展开更多
关键词 青藤碱 CXC趋化因子受体4-信号转导与转录激活因子3轴 卵巢癌细胞 增殖 迁移 血管生成拟态
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白藜芦醇通过阻断JAK激酶2/信号转导及转录活化因子3信号通路抑制食管癌细胞增殖和迁移并诱导其凋亡的作用研究
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作者 崔晓佳 谭程 +4 位作者 杨百霞 倪峰 杭达明 沈健 钱霞 《安徽医药》 CAS 2024年第6期1103-1108,共6页
目的探究白藜芦醇对人食管癌细胞增殖、凋亡、迁移及JAK激酶2/信号转导及转录活化因子3(JAK2/STAT3)信号通路的调控作用。方法2021年7月至2022年7月,体外培养人食管癌OE19细胞,将细胞分为对照组(不做干预)和实验组(15、30、60、90和120... 目的探究白藜芦醇对人食管癌细胞增殖、凋亡、迁移及JAK激酶2/信号转导及转录活化因子3(JAK2/STAT3)信号通路的调控作用。方法2021年7月至2022年7月,体外培养人食管癌OE19细胞,将细胞分为对照组(不做干预)和实验组(15、30、60、90和120μmol/L白藜芦醇干预24 h)进行预实验,根据细胞计数试剂盒(CCK-8)预实验结果,筛选有显著作用且细胞活力高于50%的30、60、90μmol/L白藜芦醇进行后续的实验,后续实验又分为对照组(不做干预)、30、60、90μmol/L白藜芦醇组(30、60和90μmol/L白藜芦醇)和30μmol/L白藜芦醇+抑制剂组(30μmol/L白藜芦醇+10μmol/L JAK2/STAT3通路抑制剂AG490),干预24 h。用5-乙炔基-2'脱氧尿嘧啶核苷(EdU)、Hoechst 33258染色、Transwell、实时荧光定量PCR(RT-qPCR)及蛋白质印迹法对细胞增殖率、凋亡情况、迁移数及细胞周期蛋白D1(cyclin D1)、胱天蛋白酶-3(caspase-3)和JAK2/STAT3相关因子表达水平进行分析。结果不同浓度实验组的细胞活力与对照组相比逐渐降低,其中30、60、90和120μmol/L白藜芦醇差异有统计学意义(P<0.05),但120μmol/L白藜芦醇组细胞活力低于50%,所以本研究选择30、60和90μmol/L白藜芦醇继续后续实验;60μmol/L白藜芦醇组细胞增殖率(41.49±5.06)%、迁移细胞数(36.67±2.52)个显著低于对照组(53.34±1.99)%、(58.00±2.00)个,凋亡细胞数(7.67±1.53)个显著高于对照组(2.50±0.71)个,且cyclin D1、p-JAK2和p-STAT3表达量也低于对照组,caspase-3 mRNA和蛋白表达水平高于对照组(P<0.05);30、90μmol/L白藜芦醇组以上各指标与对照组比较同样如此。与30μmol/L白藜芦醇组相比,30μmol/L白藜芦醇+抑制剂组以上各指标变化更显著(P<0.05)。结论白藜芦醇可通过抑制JAK2/STAT3通路抑制人食管癌OE19细胞的增殖和迁移并诱导凋亡。 展开更多
关键词 食管肿瘤 白藜芦醇 JAK激酶2/信号转导及转录活化因子3信号通路 增殖 凋亡 迁移
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基于JAK2/STAT3信号通路探究利咽糖浆对慢性咽炎大鼠咽喉组织损伤及咽黏膜修复的影响
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作者 李勇 沈文明 王文茜 《中国免疫学杂志》 CAS CSCD 北大核心 2024年第1期110-115,共6页
目的:基于Janus激酶2(JAK2)/信号转导和转录激活因子3(STAT3)信号通路探究利咽糖浆对慢性咽炎大鼠咽喉组织损伤及咽黏膜修复的影响。方法:取SD大鼠随机分为对照组、模型组、利咽糖浆组、RO8191(JAK2/STAT3激活剂)组、利咽糖浆+RO8191组... 目的:基于Janus激酶2(JAK2)/信号转导和转录激活因子3(STAT3)信号通路探究利咽糖浆对慢性咽炎大鼠咽喉组织损伤及咽黏膜修复的影响。方法:取SD大鼠随机分为对照组、模型组、利咽糖浆组、RO8191(JAK2/STAT3激活剂)组、利咽糖浆+RO8191组,模型组与药物干预组大鼠采用氨水刺激咽部构建慢性咽炎模型,对照组大鼠咽部注射等剂量生理盐水,经利咽糖浆与RO8191干预后,检测大鼠一般情况及咽部表观状态,并进行咽部表观状态评分;HE染色检测大鼠咽部病理形态变化;流式细胞术检测大鼠外周血T淋巴细胞亚群CD4^(+)T与CD8^(+)T表达、CD4^(+)T/CD8^(+)T;试剂盒检测大鼠血清肿瘤坏死因子-α(TNF-α)、IL-6、IL-10、丙二醛(MDA)、活性氧(ROS)、总抗氧化能力(T-AOC)水平;以免疫印记法检测大鼠咽部组织JAK2/STAT3通路相关蛋白表达。结果:与对照组比较,模型组大鼠咽部组织出现明显病理形态损伤,外周血CD4^(+)T与CD4^(+)T/CD8^(+)T、IL-10、血清T-AOC水平降低(P<0.05),咽部表观状态评分、CD8^(+)T、血清TNF-α、IL-6、MDA与ROS水平、咽部组织p-JAK2/JAK2与p-STAT3/STAT3水平升高(P<0.05);与模型组、利咽糖浆+RO8191组相比,利咽糖浆组大鼠咽部组织病理形态损伤减轻,外周血CD4^(+)T表达与CD4^(+)T/CD8^(+)T、IL-10、血清T-AOC水平均升高(P<0.05),咽部表观状态评分、CD8^(+)T、血清TNF-α、IL-6、MDA与ROS水平、咽部组织p-JAK2/JAK2与p-STAT3/STAT3水平均降低(P<0.05);RO8191组大鼠各指标变化趋势与利咽糖浆组相反。结论:利咽糖浆可通过抑制JAK2/STAT3信号激活减轻炎症及氧化应激,增强抗炎及抗氧化能力,缓解慢性咽炎大鼠咽喉组织损伤,修复咽黏膜。 展开更多
关键词 Janus激酶2/信号转导和转录激活因子3 利咽糖浆 慢性咽炎 咽喉组织 损伤 咽黏膜修复
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谷氨酰胺酶2对肝内胆管细胞癌细胞增殖和侵袭能力的影响及机制
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作者 陈大勇 郭宏志 《新乡医学院学报》 CAS 2024年第9期816-821,共6页
目的探讨谷氨酰胺酶2(GLS2)对肝内胆管细胞癌细胞增殖和侵袭能力的影响及其机制。方法将对数生长期人肝内胆管细胞癌RBE细胞随机分为空白对照组(Con组)、GLS2过表达阴性对照组(pcDNA-NC组)、pcDNA-GLS2组和pcDNA-GLS2+磷酸化蛋白酪氨酸... 目的探讨谷氨酰胺酶2(GLS2)对肝内胆管细胞癌细胞增殖和侵袭能力的影响及其机制。方法将对数生长期人肝内胆管细胞癌RBE细胞随机分为空白对照组(Con组)、GLS2过表达阴性对照组(pcDNA-NC组)、pcDNA-GLS2组和pcDNA-GLS2+磷酸化蛋白酪氨酸激酶(p-JAK)组。Con组RBE细胞不转染任何质粒,pcDNA-NC组RBE细胞转染pcDNA-NC质粒,pcDNA-GLS2组RBE细胞转染pcDNA-GLS2质粒,pcDNA-GLS2+p-JAK组RBE细胞转染pcDNA-GLS2质粒并和p-JAK多肽共培养。采用实时荧光定量聚合酶链反应法检测各组细胞中GLS2 mRNA的相对表达量,细胞计数试剂盒-8检测各组细胞增殖能力,流式细胞术检测各组细胞凋亡情况,Transwell小室实验检测各组细胞侵袭能力,Western blot法检测细胞中蛋白酪氨酸激酶2(JAK2)、p-JAK2、信号转导子与转录激活子3(STAT3)、磷酸化信号转导子与转录激活子3(p-STAT3)蛋白相对表达量。结果pcDNA-GLS2组细胞中GLS2 mRNA的相对表达量显著高于Con组和pcDNA-NC组(P<0.05);pcDNA-GLS2+p-JAK组细胞中GLS2 mRNA的相对表达量显著低于pcDNA-GLS2组(P<0.05)。pcDNA-GLS2组细胞存活率显著低于Con组(P<0.05);与pcDNA-GLS2组相比,pcDNA-GLS2+p-JAK组细胞存活率显著增加(P<0.05)。与Con组相比,pcDNA-GLS2组细胞凋亡率显著增加(P<0.05);pcDNA-GLS2+p-JAK组细胞凋亡率显著低于pcDNA-GLS2组(P<0.05)。pcDNA-GLS2组细胞迁移数显著低于Con组(P<0.05);与pcDNA-GLS2组相比,pcDNA-GLS2+p-JAK组细胞迁移数显著增加(P<0.05)。与Con组相比,pcDNA-GLS2组细胞中p-JAK2/JAK2、p-STAT3/STAT3比值显著降低(P<0.05);pcDNA-GLS2+p-JAK组细胞中p-JAK2/JAK2、p-STAT3/STAT3比值显著高于pcDNA-GLS2组(P<0.05)。结论过表达GLS2可通过抑制JAK2/STAT3信号通路调控肝内胆管癌细胞生物学活性,抑制肝内胆管癌RBE细胞增殖、侵袭、迁移能力,诱导细胞凋亡。 展开更多
关键词 谷氨酰胺酶2 蛋白酪氨酸激酶2/信号转导子与转录激活子3 肝内胆管细胞癌 细胞增殖 细胞侵袭
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冬凌草甲素调节JAK2/STAT3/SOCS-1信号通路对糖耐量异常大鼠胰岛素抵抗的影响
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作者 甘志远 陆济华 +2 位作者 刘岩 陈汝斌 曾志美 《河北医药》 CAS 2024年第6期830-834,共5页
目的探讨冬凌草甲素(Oridonin,Ori)对糖耐量异常(impaired glucose tolerance,IGT)大鼠胰岛素抵抗(insulin resistance,IR)的影响及作用机制。方法采用高脂饮食喂养联合链脲佐菌素注射法构建IGT大鼠IR模型,大鼠分为正常组(CT组)、IGT模... 目的探讨冬凌草甲素(Oridonin,Ori)对糖耐量异常(impaired glucose tolerance,IGT)大鼠胰岛素抵抗(insulin resistance,IR)的影响及作用机制。方法采用高脂饮食喂养联合链脲佐菌素注射法构建IGT大鼠IR模型,大鼠分为正常组(CT组)、IGT模型组(IGT组)、Ori组(10 mg·kg^(-1)·d^(-1))、Ori+Colivelin(COL)组(10 mg·kg^(-1)·d^(-1)Ori+2 mg/kg COL),每组6只。血糖检测仪测定空腹血糖(FPG)、葡萄糖耐量试验(OGTT)2 h血糖(2 hPG),ELISA试剂盒测定空腹胰岛素(FINS)、单核细胞趋化蛋白1(MCP-1)、肿瘤坏死因子α(TNF-α)含量,计算胰岛素抵抗指数(HOMA-IR),血液自动分析仪测定血清胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平,HE染色观察肝脏病理形态,Western blot验证附睾脂肪磷酸化(p)-激活Janus激活激酶2(JAK2)、JAK2、p-信号转导和转录激活因子3(STAT3)、STAT3、p-细胞因子信号传导抑制蛋白1(SOCS-1)、SOCS-1蛋白表达。结果与CT组比较,IGT组大鼠肝脏细胞肿胀,胞浆内可见大量大小不一的脂肪空泡,细胞核被脂肪空泡挤压偏位,且发生炎性细胞浸润,FPG、2hPG、FINS、HOMA-IR、TC、TG、LDL-C、MCP-1、TNF-α以及p-JAK2/JAK2、p-STAT3/STAT3、p-SOCS-1/SOCS-1蛋白表达水平升高,血清HDL-C水平下降(P<0.05);与IGT组相比,Ori组大鼠肝脏细胞胞浆内脂肪滴及空泡数量明显减少,细胞肿胀有所缓解,未见炎性细胞浸润,FPG、2hPG、FINS、HOMA-IR、TC、TG、LDL-C、MCP-1、TNF-α以及p-JAK2/JAK2、p-STAT3/STAT3、p-SOCS-1/SOCS-1蛋白表达水平下降,血清HDL-C水平升高(P<0.05);与Ori组相比,Ori+COL组大鼠肝脏脂肪变状况加剧,细胞肿大,血清FPG、2hPG、FINS、HOMA-IR、TC、TG、LDL-C、MCP-1、TNF-α以及p-JAK2/JAK2、p-STAT3/STAT3、p-SOCS-1/SOCS-1蛋白表达水平升高,血清HDL-C水平下降(P<0.05)。结论Ori对IGT大鼠IR的缓解作用可能与抑制JAK2/STAT3/SOCS-1信号通路激活有关。 展开更多
关键词 糖耐量异常 胰岛素抵抗 冬凌草甲素 Janus激活激酶2 信号转导和转录激活因子3 细胞因子信号传导抑制蛋白1
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PIM1基因对急性髓系白血病U937细胞增殖、凋亡及JAK2/STAT3信号通路的影响
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作者 高鑫 储李婧 颜宗海 《中国实验血液学杂志》 CAS CSCD 北大核心 2024年第3期663-669,共7页
目的:探讨PIM1基因对急性髓系白血病(AML)U937细胞增殖、凋亡的影响,以及对JAK2/STAT3通路的调控作用。方法:收集初诊成人AML患者和单纯缺铁性贫血患者的骨髓单个核细胞,荧光定量PCR检测PIM1 mRNA表达。将AML细胞系U937细胞分为:U937组(... 目的:探讨PIM1基因对急性髓系白血病(AML)U937细胞增殖、凋亡的影响,以及对JAK2/STAT3通路的调控作用。方法:收集初诊成人AML患者和单纯缺铁性贫血患者的骨髓单个核细胞,荧光定量PCR检测PIM1 mRNA表达。将AML细胞系U937细胞分为:U937组(U937细胞正常培养)、Si-PIM1组(U937细胞转染含PIM1 mRNA的低表达腺病毒载体)、Si-NC组(U937细胞转染不含PIM1 mRNA的低表达腺病毒载体)、CoA1组(U937细胞中加入浓度为20μmol/L的JAK2激活剂CoA1)、Si-PIM1+CoA1组(U937细胞转染含PIM1 mRNA低表达的腺病毒载体并加入浓度为20μmol/L的CoA1)。培养24 h。荧光定量PCR和蛋白印迹法检测U937细胞PIM1 mRNA和蛋白、JAK2/STAT3通路、细胞周期、凋亡相关蛋白表达;噻唑蓝法检测细胞增殖活性;流式细胞术检测细胞周期变化及凋亡率。结果:AML患者骨髓单个核细胞中PIM1 mRNA表达水平高于单纯缺铁性贫血患者(P<0.05)。与U937组相比,Si-PIM1组细胞PIM1 mRNA和蛋白、p-JAK2/JAK2、p-STAT3/STAT3、Cyclin D1、CDK2蛋白、细胞增殖活性、S期比例、G2/M期比例降低(均P<0.05),p27、Caspase-3蛋白、G0/G1期、凋亡率升高(均P<0.05),而CoA1组上述指标的变化情况与Si-PIM1组正好相反,CoA1可逆转Si-PIM1对U937细胞的作用效果。U937组、Si-PIM1+CoA1组、Si-NC组U937细胞上述指标差异无统计学意义(P>0.05)。结论:敲低PIM1基因表达可抑制U937细胞增殖、促进凋亡,缓解ALM进程,且上述作用可能与抑制JAK2/STAT3通路活化有关。 展开更多
关键词 丝/苏氨酸激酶家族成员1 急性髓系白血病U937细胞 增殖 凋亡 Janus酪氨酸激酶2/信号转导及转录激活因子3通路
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基于IL-6/JAK2/STAT3信号轴研究阳和平喘颗粒调控哮喘大鼠气道重塑作用机制 被引量:2
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作者 吕川 朱慧志 +4 位作者 刘向国 曹晓梅 夏咏琪 张秋萍 余子奇 《海南医学院学报》 北大核心 2024年第1期15-20,28,共7页
目的:研究阳和平喘颗粒对哮喘大鼠气道重塑及白细胞介素-6(IL-6)/Janus蛋白酪氨酸激酶2(JAK2)/信号转导和转录活化因子3(STAT3)信号轴在其中的作用机制。方法:选取健康雄性SD大鼠42只,随机数字法分为正常对照组7只与造模组35只,造模组... 目的:研究阳和平喘颗粒对哮喘大鼠气道重塑及白细胞介素-6(IL-6)/Janus蛋白酪氨酸激酶2(JAK2)/信号转导和转录活化因子3(STAT3)信号轴在其中的作用机制。方法:选取健康雄性SD大鼠42只,随机数字法分为正常对照组7只与造模组35只,造模组采用卵清蛋白(OVA)联合氢氧化铝腹腔注射2周的方式进行致敏,正常对照组采用等量的生理盐水;2周后将造模组随机分为模型组、阳和平喘高、中、低剂量组和地塞米松组,每组7只;后4周采用OVA雾化+灌胃的方式进行激发和治疗,阳和平喘高中低组每日分别予以15.48、7.74、3.87 g/kg阳和平喘颗粒灌胃,地塞米松组予以0.0625 mg/kg地塞米松进行灌胃,其余组灌胃等量生理盐水。HE、PAS、Masson染色观察大鼠肺组织病理学变化;ELISA检测大鼠血清中IL-6、IL-23、IL-17A水平;Western blot检测肺组织中JAK-2、P-JAK2、STAT3、P-STAT3蛋白表达量;qRT-PCR检测大鼠肺组织中IL-6、JAK2、STAT3的mRNA水平。结果:与正常对照组比较,模型组大鼠肺组织有大量炎性细胞浸润,杯状细胞增生、上皮下胶原纤维沉积、气道上皮增厚较为明显;血清中IL-6、IL-23、IL-17A水平显著升高(P<0.01),肺组织JAK-2、P-JAK2、STAT3、P-STAT3的蛋白表达量和IL-6、JAK2、STAT3的mRNA表达水平显著升高(P<0.01);与模型组比较,各给药组炎性细胞浸润、杯状细胞增生、上皮下胶原纤维沉积、气道上皮增厚程度明显减轻,血清中IL-6、IL-23、IL-17A水平显著降低(P<0.01),肺组织JAK-2、P-JAK2、STAT3、P-STAT3的蛋白表达量和IL-6、JAK2、STAT3的mRNA水平显著降低(P<0.01)。结论:阳和平喘颗粒可明显缓解哮喘大鼠气道重塑,其机制可能是通过抑制IL-6/JAK2/STAT3信号轴发挥作用。 展开更多
关键词 哮喘 阳和平喘颗粒 气道重塑 IL-6/JAK2/STAT3信号轴 机制研究
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基于IL-6/JAK2/STAT3信号通路探讨灰树花提取物对溃疡性结肠炎大鼠结肠组织炎症反应的影响
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作者 金雪 马贤德 +5 位作者 赵卓 徐铭 王建光 杜晗 关洪全 韩晓伟 《中国免疫学杂志》 CAS CSCD 北大核心 2024年第3期456-460,465,共6页
目的:探讨灰树花提取物通过调控白细胞介素6(IL-6)/蛋白酪氨酸激酶2(JAK2)/信号转导和激活因子3(STAT3)信号通路,对溃疡性结肠炎(UC)大鼠结肠组织炎症反应的影响及作用机制。方法:将40只SD大鼠随机分为空白对照组、UC模型组、灰树花治... 目的:探讨灰树花提取物通过调控白细胞介素6(IL-6)/蛋白酪氨酸激酶2(JAK2)/信号转导和激活因子3(STAT3)信号通路,对溃疡性结肠炎(UC)大鼠结肠组织炎症反应的影响及作用机制。方法:将40只SD大鼠随机分为空白对照组、UC模型组、灰树花治疗组、西药治疗组、联合治疗组,每组8只。采用3%DSS自由饮用法7 d建立UC大鼠模型后,治疗组分别灌胃灰树花提取物10 mg/(kg·d)、柳氮磺吡啶0.3 g/(kg·d)及等量两种药物,连续14 d。实验期间观察大鼠一般状态,计算疾病活动指数(DAI)评分;采用HE染色法观察大鼠结肠组织病理改变;Western blot检测大鼠结肠组织IL-6、JAK2、STAT3、pSTAT3蛋白表达水平;ELISA检测大鼠血清中IL-6含量;免疫组化法测定大鼠结肠组织中IL-6R、MPO蛋白含量及表达情况。结果:与空白对照组比较,UC模型组大鼠一般状态欠佳,DAI评分升高,HE染色可见明显的组织黏膜损伤与炎症细胞浸润;结肠组织IL-6、JAK2、STAT3、p-STAT3蛋白表达水平及IL-6R、MPO含量均显著升高(P<0.01);血清中IL-6含量显著升高(P<0.01),差异有统计学意义。与UC模型组比较,各治疗组大鼠的一般状态均有所改善,DAI评分降低,HE染色可见黏膜损伤有不同程度改善,偶见炎症细胞浸润;结肠组织IL-6、JAK2、STAT3、p-STAT3蛋白表达水平显著降低(P<0.01),结肠组织IL-6R和MPO含量及血清中IL-6含量均明显减少(P<0.01或P<0.05),差异有统计学意义。结论:灰树花提取物可通过调控IL-6/JAK2/STAT3信号通路相关因子表达,减轻UC大鼠结肠组织炎症反应。 展开更多
关键词 灰树花提取物 溃疡性结肠炎 白细胞介素6 蛋白酪氨酸激酶2 信号转导及转录激活蛋白3
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STAT1在非小细胞肺癌中的表达及对IL-2抗肿瘤作用的影响
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作者 赵嘉璐 孙蕾 +2 位作者 蓝秀 熊雪芳 李伟文 《浙江医学》 CAS 2024年第12期1239-1244,1279,I0003,共8页
目的探讨信号转导和转录激活因子1(STAT1)在非小细胞肺癌中的表达及对IL-2抗肿瘤作用的影响。方法回顾性选取2018年1月至2020年1月丽水市中心医院20例非小细胞肺癌患者外科手术切除的肺癌组织标本及距离肿瘤组织5 cm以上正常肺组织标本... 目的探讨信号转导和转录激活因子1(STAT1)在非小细胞肺癌中的表达及对IL-2抗肿瘤作用的影响。方法回顾性选取2018年1月至2020年1月丽水市中心医院20例非小细胞肺癌患者外科手术切除的肺癌组织标本及距离肿瘤组织5 cm以上正常肺组织标本,采用Western blot法检测两种标本中STAT1蛋白表达水平。利用慢病毒载体Lenti-增强绿色荧光蛋白(EGFP)或Lenti-STAT1转染非小细胞肺癌SPC-A-1细胞,将细胞分为空白组、Lenti-EGFP对照组和Lenti-STAT1组。采用平板克隆实验观察细胞克隆形成率。不同浓度(0、20、100、500 U/mL)IL-2处理细胞后,采用细胞计数试剂盒法检测细胞增殖活性,Transwell法检测0、100 U/mL IL-2处理后细胞迁移和侵袭能力,流式细胞仪分析0、100 U/mL IL-2处理后细胞凋亡百分比。观察IL-2对3组细胞抗肿瘤作用的影响。采用Western blot法检测3组细胞磷酸化STAT1(p-STAT1)、细胞间黏附分子-1(ICAM-1)及增殖细胞核抗原(PCNA)蛋白表达水平。结果肺癌组织中STAT1蛋白表达水平低于正常组织(P<0.001)。Lenti-STAT1组细胞增殖活性、迁移和侵袭能力均低于Lenti-EGFP对照组,细胞凋亡百分比高于Lenti-EGFP对照组,差异均有统计学意义(均P<0.05)。用20、100、500 U/mL IL-2处理后,Lenti-STAT1组细胞增殖均低于Lenti-EGFP对照组(均P<0.05)。用100 U/mL IL-2处理后,Lenti-STAT1组细胞迁移和侵袭能力均低于Lenti-EGFP对照组,Lenti-STAT1组细胞凋亡百分比高于Lenti-EGFP对照组,差异均有统计学意义(均P<0.05)。此外,IL-2未处理的Lenti-STAT1组细胞p-STAT1蛋白表达水平高于Lenti-EGFP对照组,ICAM-1蛋白表达水平低于Lenti-EGFP对照组,差异均有统计学意义(均P<0.05)。用100 U/mL IL-2处理后,Lenti-STAT1组细胞p-STAT1蛋白表达水平高于Lenti-EGFP对照组,PCNA蛋白表达水平低于Lenti-EGFP对照组,差异均有统计学意义(均P<0.05)。结论STAT1在非小细胞肺癌组织中表达明显下调,可抑制细胞增殖、迁移和侵袭,促进细胞凋亡,增强IL-2在肺癌细胞中的抗肿瘤效应。因此,STAT1与IL-2的联合治疗可能是未来肺癌治疗的一种可行方法。 展开更多
关键词 信号转导和转录激活因子1 SPC-A-1细胞 白细胞介素-2 肺癌
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大柴胡汤含药血清通过JAK2/STAT3信号通路抑制AR42J细胞炎症反应
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作者 赵东颖 王清华 +1 位作者 于艳 姚旭 《吉林中医药》 2024年第8期960-964,共5页
目的探讨大柴胡汤含药血清对胰腺腺泡细胞炎症反应的防治作用及可能机制。方法HPLC法检测大柴胡汤中指标成分含量;采用雨蛙肽处理AR42J细胞复制急性腺泡细胞炎症模型,采用CCK-8方法检测大柴胡汤含药血清对细胞活力的影响;Western blot... 目的探讨大柴胡汤含药血清对胰腺腺泡细胞炎症反应的防治作用及可能机制。方法HPLC法检测大柴胡汤中指标成分含量;采用雨蛙肽处理AR42J细胞复制急性腺泡细胞炎症模型,采用CCK-8方法检测大柴胡汤含药血清对细胞活力的影响;Western blot方法检测细胞内JAK2、STAT3及NFκB磷酸化程度;ELISA法检测IL-6和TNF-α含量。结果大柴胡汤中黄芩苷和芍药苷含量分别为13.02 mg/mL、7.19 mg/mL,大柴胡汤含药血清用量不超过20%;大柴胡汤含药血清降低炎性细胞上清液中TNF-α和IL-6含量,降低细胞内JAK2、STAT3及NFκB磷酸化作用,减轻细胞炎症反应;STAT3抑制剂cucurbitacin可减弱大柴胡汤的炎症抑制作用。结论大柴胡汤含药血清可减轻腺泡细胞急性炎症作用,其机制可能为抑制细胞内JAK2/STAT3信号通路进而降低NFκB活性,减少促炎性细胞因子合成。 展开更多
关键词 大柴胡汤 急性胰腺炎 酪氨酸蛋白激酶2 信号传导与转录激活因子3 白介素-6 核因子ΚB
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基于生物信息学分析探讨羟基红花黄色素A通过JAK2/STAT3信号通路抑制缺血性脑卒中后神经元凋亡的机制
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作者 吴艺舸 殷丽君 +4 位作者 王泽乾 贾思锋 温春丽 宋丽娟 马存根 《中西医结合心脑血管病杂志》 2024年第18期3326-3335,3352,共11页
目的:利用生物信息学技术筛选并鉴定缺血性脑卒中(IS)的关键基因,基于基因富集分析结合相关实验探讨羟基红花黄色素A(HSYA)对脑缺血损伤后神经元凋亡的影响及机制。方法:从GEO数据库获得IS相关的样本数据,进行差异表达基因(DEGs)分析及... 目的:利用生物信息学技术筛选并鉴定缺血性脑卒中(IS)的关键基因,基于基因富集分析结合相关实验探讨羟基红花黄色素A(HSYA)对脑缺血损伤后神经元凋亡的影响及机制。方法:从GEO数据库获得IS相关的样本数据,进行差异表达基因(DEGs)分析及基因富集分析,获得关键基因与关键信号通路,并通过体内外实验进行相关验证。建立Sprague-Dawley大鼠大脑中动脉闭塞再灌注模型(MCAO/R),采用蛋白免疫印迹法(Western Blot)和免疫荧光检测Janus激酶2(JAK2)/信号传导转录激活因子3(STAT3)通路的磷酸化水平及凋亡相关蛋白的表达;线粒体膜电位探针检测线粒体膜电位情况进而明确细胞凋亡水平。利用HT-22海马神经元细胞建立糖氧剥夺/复糖氧模型(OGD/R),使用JAK2/STAT3信号通路抑制剂进一步验证HSYA对神经元凋亡的作用机制。结果:通过生物信息学分析研究GSE22255数据集发现23个显著上调的DEGs和2个显著下调的DEGs。富集分析发现其与脂多糖的反应、细胞凋亡的调控、炎症反应、急性炎症反应调节、分子干预信号通路相关。生物过程方面,通过建立特征基因功能网络发现,特征基因与急性炎症反应、凋亡信号通路的调节、脂多糖介导的反应、稳态分子的反应等功能相关。基因集富集分析显示,肿瘤坏死因子α(TNF-α)介导的核因子κB(NF-κB)信号通路、血红素代谢信号通路、细胞凋亡相关信号通路、JAK/STAT3信号通路、P53信号通路发挥着关键作用。筛选出JAK2/STAT3信号通路和凋亡相关通路为研究重点。与假手术组比较,MCAO/R组大鼠磷酸化JAK2(p-JAK2)、磷酸化STAT3(p-STAT3)和促凋亡相关蛋白表达升高(P<0.001),抑凋亡相关蛋白表达降低(P<0.001)。HSYA干预后可抑制JAK2/STAT3信号通路磷酸化激活和神经元凋亡(P<0.01)。体外实验显示,OGD/R组JAK2/STAT3通路被磷酸化激活,促凋亡相关蛋白表达较Normal组升高(P<0.001),抑凋亡相关蛋白表达低于Normal组(P<0.001);加入抑制剂AG490后JAK2、STAT3磷酸化程度降低(P<0.01)。与Normal组比较,OGD/R组凋亡相关蛋白半胱氨酸蛋白酶3(Cleaved Caspase-3)、Bcl-2关联X蛋白(Bax)表达水平升高(P<0.001),Bcl-2表达降低(P<0.001)。HSYA抑制了神经元的凋亡(P<0.01)。结论:JAK2/STAT3信号通路和凋亡相关信号通路在IS后发挥着关键作用,HSYA可能通过调控JAK2/STAT3信号通路,抑制缺血缺氧后神经元凋亡,从而减轻脑损伤。 展开更多
关键词 缺血性脑卒中 生物信息学分析 羟基红花黄色素A 脑缺血 神经元 Janus激酶2/信号传导转录激活因子3信号通路 凋亡 实验研究
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