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1.
Paolo Dametto Asvin K. K. Lakkaraju Claire Bridel Lukas Villiger Tracy O’Connor Uli S. Herrmann Pawel Pelczar Thomas Rülicke Donal McHugh Arlind Adili Adriano Aguzzi 《PloS one》2015,10(2)
The cellular prion protein (PrPC) consists of a flexible N-terminal tail (FT, aa 23–128) hinged to a membrane-anchored globular domain (GD, aa 129–231). Ligation of the GD with antibodies induces rapid neurodegeneration, which is prevented by deletion or functional inactivation of the FT. Therefore, the FT is an allosteric effector of neurotoxicity. To explore its mechanism of action, we generated transgenic mice expressing the FT fused to a GPI anchor, but lacking the GD (PrPΔ141–225, or “FTgpi”). Here we report that FTgpi mice develop a progressive, inexorably lethal neurodegeneration morphologically and biochemically similar to that triggered by anti-GD antibodies. FTgpi was mostly retained in the endoplasmic reticulum, where it triggered a conspicuous unfolded protein response specifically activating the PERK pathway leading to phosphorylation of eIF2α and upregulation of CHOP ultimately leading to neurodegeration similar to what was observed in prion infection. 相似文献
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Endothelial cells are activated by angiopoeitin-1 gene transfer and produce coordinated sprouting in vitro and arteriogenesis in vivo 总被引:3,自引:0,他引:3
Gluzman Z Koren B Preis M Cohen T Tsaba A Cosset FL Shofti R Lewis BS Virmani R Flugelman MY 《Biochemical and biophysical research communications》2007,359(2):263-268
RATIONAL AND OBJECTIVES: Activation of fully differentiated vascular cells using angiogenic genes can lead to phenotypic changes resulting in formation of new blood vessels. We tested whether Ang-1 gene transfer to endothelial cells (EC) activates these cells. METHODS AND RESULTS: EC and SMC were transduced using retroviral or adenoviral vectors to produce Ang-1 or vascular endothelial growth factor (VEGF). EC Tie-2 receptor was phosphorilated by autologous secretion of Ang-1. Transduced EC and SMC sprouting capacity was tested using collagen embedded spheroids assay and capacity to produce arteriogenesis was tested in a hind limb model of ischemia. EC expressing Ang-1 in the presence of SMC expressing VEGF exhibited high levels of sprouting of the two cell types. Flow and numbers of arteries were increased after transduced cells implantation in vivo. CONCLUSIONS: Autologous secretion of Ang-1 by transduced EC resulted in Tie-2 activation and in the presence of SMC expressing VEGF resulted in coordinated sprouting in vitro and increase in flow and number of arteries in vivo. 相似文献
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Fikaris AJ Lewis AE Abulaiti A Tsygankova OM Meinkoth JL 《The Journal of biological chemistry》2006,281(46):34759-34767
Genetic evidence indicates that Ras plays a critical role in the initiation and progression of human thyroid tumors. Paradoxically, acute expression of activated Ras in normal rat thyroid cells induced deregulated cell cycle progression and apoptosis. We investigated whether cell cycle progression was required for Ras-stimulated apoptosis. Ras increased CDK-2 activity following its introduction into quiescent cells. Apoptotic cells exhibited a sustained increase in CDK-2 activity, accompanied by the loss of CDK-2-associated p27. Blockade of Ras-induced CDK-2 activity and S phase entry via overexpression of p27 inhibited apoptosis. Inactivation of the retinoblastoma protein in quiescent cells through expression of HPV-E7 stimulated cell cycle progression and apoptosis, indicating that deregulated cell cycle progression is sufficient to induce apoptosis. Ras failed to induce G1 phase growth arrest in normal rat thyroid cells. Rather, Ras-expressing thyroid cells progressed into S and G2 phases and evoked a checkpoint response characterized by the activation of ATR. Ras-stimulated ATR activity, as evidenced by Chk1 and p53 phosphorylation, was blocked by p27, suggesting that cell cycle progression triggers checkpoint activation, likely as a consequence of replication stress. These data reveal that Ras is capable of inducing a DNA damage response with characteristics similar to those reported in precancerous lesions. Our findings also suggest that the frequent mutational activation of Ras in thyroid tumors reflects the ability of Ras-expressing cells to bypass checkpoints and evade apoptosis rather than to simply increase proliferative potential. 相似文献
4.
Haider A. Alkafaji Ahmed Raji Heshu S. Rahman Angelina O. Zekiy Ali Adili Mohammadmahdi Jalili Tahereh Hojjatipour Angel Cid-Arregui Navid Shomali Saeed Tarzi Rozita Tamjidifar Ramin Heshmati Faroogh Marofi Morteza Akbari Ali Hasanzadeh Mina Deljavanghodrati Mostafa Jarahian Siamak Sandoghchian Shotorbani 《Journal of cellular and molecular medicine》2021,25(14):6864-6873
Melanoma is a kind of skin cancer that is begun by the alteration of melanocytes. miRNAs are small non-coding RNA molecules that regulate a variety of biological processes. KISS1, the metastasis-suppressor gene, encodes kisspeptins which inhibits migration and proliferation of cancers. This study was aimed to determine the role of Let-7i and KISS1 in melanoma cell migration and proliferation. At first, the expression of Let-7i and KISS1 was determined in patients with melanoma. In the in vitro part of the study, Let-7i mimics were transfected and the impact of its restoration on target gene expression, proliferation, migration and apoptosis of SK-MEL-3 melanoma cell line was assessed by real-time PCR and Western blotting, MTT assay, wound-healing assay and flow cytometry, respectively. Besides, KISS1 inhibitor siRNA alone and along with Let-7i was transfected to determine their probable correlation. The results revealed that either Let-7i or KISS1 were down-regulated in patients with melanoma. The results obtained from the in vitro part of the study revealed that restoration of Let-7i reduced the expression of metastasis- and proliferation-related target genes. Moreover, it was revealed that up-regulation of Let-7i attenuated migration and proliferation capability of SK-MEL-3 cells. Besides, it was demonstrated that Let-7i restoration induced apoptosis in melanoma cells. More importantly, the KISS1 inhibitor caused a prominent cell migration and proliferation, attenuated by Let-7i re-expression. To sum up, the present study revealed the impressive role of Let-7i restoration along with its correlation with KISS1 on melanoma carcinogenicity which may be applicable in future in vivo studies. 相似文献
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We represent a successful minimally invasive combined off-pump procedure consisting of a transapical aortic valve implantation and a direct coronary artery bypass grafting in a woman with a severe aortic stenosis and a critical coronary artery disease. Due to her comorbidities, she was classified as a high-risk patient qualifying for a transcatheter procedure. We performed this combined procedure in a hybrid operation room, starting with the coronary bypass to maintain a coronary blood flow during the transapical valve implantation. The operation processed without any complications and she was discharged at the seventh postoperative day into the allocating hospital. 相似文献
6.
Yang Y Shi Z Reheman A Jin JW Li C Wang Y Andrews MC Chen P Zhu G Ling W Ni H 《PloS one》2012,7(5):e37323
Delphinidin-3-glucoside (Dp-3-g) is one of the predominant bioactive compounds of anthocyanins in many plant foods. Although several anthocyanin compounds have been reported to be protective against cardiovascular diseases (CVDs), the direct effect of anthocyanins on platelets, the key players in atherothrombosis, has not been studied. The roles of Dp-3-g in platelet function are completely unknown. The present study investigated the effects of Dp-3-g on platelet activation and several thrombosis models in vitro and in vivo. We found that Dp-3-g significantly inhibited human and murine platelet aggregation in both platelet-rich plasma and purified platelets. It also markedly reduced thrombus growth in human and murine blood in perfusion chambers at both low and high shear rates. Using intravital microscopy, we observed that Dp-3-g decreased platelet deposition, destabilized thrombi, and prolonged the time required for vessel occlusion. Dp-3-g also significantly inhibited thrombus growth in a carotid artery thrombosis model. To elucidate the mechanisms, we examined platelet activation markers via flow cytometry and found that Dp-3-g significantly inhibited the expression of P-selectin, CD63, CD40L, which reflect platelet α- and δ-granule release, and cytosol protein secretion, respectively. We further demonstrated that Dp-3-g downregulated the expression of active integrin αIIbβ3 on platelets, and attenuated fibrinogen binding to platelets following agonist treatment, without interfering with the direct interaction between fibrinogen and integrin αIIbβ3. We found that Dp-3-g reduced phosphorylation of adenosine monophosphate-activated protein kinase, which may contribute to the observed inhibitory effects on platelet activation. Thus, Dp-3-g significantly inhibits platelet activation and attenuates thrombus growth at both arterial and venous shear stresses, which likely contributes to its protective roles against thrombosis and CVDs. 相似文献
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Aslaminabad Ramin Rahimianshahreza Negin Hosseini Seyed Amirhossein Armagan Güliz Khan Ahmad Kashif Özbolat Gülüzar Ahmed Omar Saad Mardi Azar Amir Adili Ali Dağcı Taner Konyalıoğlu Sibel Özgönül Ali Mert 《Molecular biology reports》2022,49(10):9605-9612
Molecular Biology Reports - HCC is among the most common cancer. Ganoderma lucidum (G.lucidum) has been essential in preventing and treating cancer. The Nrf2 signaling cascade is a cell protective... 相似文献
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【目的】明确新疆新发外来入侵生物番茄潜叶蛾幼虫和卵在不同种群密度下的垂直分布、空间分布型和理论抽样数,探索田间易观察的危害症状和幼虫密度的关系,为田间取样和调查提供理论指导。【方法】在察布查尔县连续调查3个大棚同一品种京番502杂交一代上的番茄潜叶蛾的不同种群密度,利用聚集度指标及Iwao回归分析,计算并分析了番茄潜叶蛾卵和幼虫在不同种群密度下的空间分布型、垂直分布和理论抽样数,分析危害叶片数、虫道长度和虫道数与幼虫密度的动态关系。【结果】计算并统计番茄潜叶蛾幼虫和卵的空间分布聚集度指标的均值m、扩散系数C、扩散型指数I、负二项分布值K、平均拥挤度m~*、聚块指数m~*/m、扩散指数CA和种群聚集均数λ。番茄潜叶蛾卵主要集中在上部,占比43.9%~100%。幼虫主要集中在下部,占比53.3%~100%。番茄潜叶蛾幼虫数与虫道数、虫道长度或为害叶片数的比值随为害加剧呈动态变化。番茄潜叶蛾幼虫和卵Iwao直线回归方程拟合公式为m~*=1.9114+1.2055m (R~2=0.9703)和m~*=0.0536+1.4147m (R~2=0.9014)。根据空间分布型参数,在D=0.1、0. 2和0. 3时,幼虫的理论抽样数模型分别为n=1118. 4/x+78. 9、n=279. 6/x+19.7、n=124.3/x+8.8,卵的理论抽样数模型分别为n=404.8/x+159.3、n=101.2/x+39.8、n=45.0/x+17.7,该模型适用于不同虫口密度下的田间抽样。【结论】在京番502杂交一代上,番茄潜叶蛾幼虫为m=0.6头·株~(-1)以上,卵在达到密度最大值前,均呈聚集性分布。番茄潜叶蛾成虫偏好在幼嫩的叶片产卵,随植株被害加剧该偏好略有减弱。当番茄潜叶蛾幼虫的虫口密度为10和30头·株~(-1)时,建议分别取样50和30株;当卵量为10和30粒·株~(-1)时,分别取样50和45株。 相似文献