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991.
992.
Dong Ha Kim Hyojeong Park Yun Jung Choi Myoung-Hee Kang Tae-Keun Kim Chan-Gi Pack Chang-Min Choi Jae Cheol Lee Jin Kyung Rho 《Cell death & disease》2021,12(8)
Tumor-derived exosomes (TEXs) contain enriched miRNAs, and exosomal miRNAs can affect tumor growth, including cell proliferation, metastasis, and drug resistance through cell-to-cell communication. We investigated the role of exosomal miR-1260b derived from non-small cell lung cancer (NSCLC) in tumor progression. Exosomal miR-1260b induced angiogenesis by targeting homeodomain-interacting protein kinase-2 (HIPK2) in human umbilical vein endothelial cells (HUVECs). Furthermore, exosomal miR-1260b or suppression of HIPK2 led to enhanced cellular mobility and cisplatin resistance in NSCLC cells. In patients with NSCLC, the level of HIPK2 was significantly lower in tumor tissues than in normal lung tissues, while that of miR-1260b was higher in tumor tissues. HIPK2 and miR-1260b expression showed an inverse correlation, and this correlation was strong in distant metastasis. Finally, the expression level of exosomal miR-1260b in plasma was higher in patients with NSCLC than in healthy individuals, and higher levels of exosomal miR-1260b were associated with high-grade disease, metastasis, and poor survival. In conclusion, exosomal miR-1260b can promote angiogenesis in HUVECs and metastasis of NSCLC by regulating HIPK2 and may serve as a prognostic marker for lung cancers.Subject terms: Non-small-cell lung cancer, Metastasis, miRNAs 相似文献
993.
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling 总被引:2,自引:0,他引:2
Randall J. Platt Sidi Chen Yang Zhou Michael J. Yim Lukasz Swiech Hannah R. Kempton James E. Dahlman Oren Parnas Thomas M. Eisenhaure Marko Jovanovic Daniel B. Graham Siddharth Jhunjhunwala Matthias Heidenreich Ramnik J. Xavier Robert Langer Daniel G. Anderson Nir Hacohen Aviv Regev Guoping Feng Phillip A. Sharp Feng Zhang 《Cell》2014
994.
995.
Myung-Soon Yang Jin-Su Hong Seong-Tae Kim Ki-Young Lee Kye Won Park Suk-Tae Kwon Dae-Hyuk Kweon Young Ho Koh Nicholas Gaiano Keejung Yoon 《Biochemical and biophysical research communications》2011,(1):133
Notch signaling pathway enhances neural stem cell characters and regulates cell fate decisions during neural development. Interestingly, besides Notch, other γ-secretase substrates such as APP, LRP2, and ErbB4 have also proven to have biological functions in neural development. We designed a unique experimental setting, combining gain-of- (expression of Notch intracellular domain, NICD) and loss-of-function (γ-secretase inhibition) methods, and were able to examine the function of Notch alone by excluding the activity of other γ-secretase substrates. Here, we show that the frequency and size of neurospheres generated from embryonic neural stem cells (NSCs) significantly decreased by 62.7% and 37.2%, respectively, in the presence of γ-secretase inhibitor even when NICD was expressed. Under the condition of differentiation, however, the γ-secretase inhibitor treatment did not influence the promotion of astrogenesis at the expense of neurogenesis by NICD. These results indicate that other γ-secretase substrate(s) along with Notch are important in the maintenance of the stemness of NSCs, but that Notch alone can sufficiently inhibit neurogenesis without the action of the other γ-secretase substrates during differentiation. 相似文献
996.
997.
Sohn EJ Kim DW Kim YN Kim SM Lim SS Kang TC Kwon HY Kim DS Cho SW Han KH Park J Eum WS Hwang HS Choi SY 《Biochemical and biophysical research communications》2011,(3):336-340
The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1β, and tumor necrosis factor-α induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases. 相似文献
998.
Jeong YI Kim SH Ju JW Cho SH Lee WJ Park JW Park YM Lee SE 《Biochemical and biophysical research communications》2011,407(4):245-800
Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4+CD25+Foxp3+ regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naïve T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical relationship between the allergic immune response and helminth infection. 相似文献
999.
Jang WG Kim EJ Lee KN Son HJ Koh JT 《Biochemical and biophysical research communications》2011,(4):243-1009
This study examined the role of AMPK activation in osteoblast differentiation and the underlining mechanism. An AMPK activator (AICAR or metformin) stimulated osteoblast differentiation with increases in ALP and OC protein production as well as the induction of AMPK phosphorylation in MC3T3E1 cells. In addition, metformin induced the phosphorylation of Smad1/5/8 and expression of Dlx5 and Runx2, whereas compound C or dominant negative AMPK inhibited these effects. Transient transfection studies also showed that metformin increased the BRE-Luc and Runx2-Luc activities, which were inhibited by DN-AMPK or compound C. Down-regulation of Dlx5 expression by siRNA suppressed metformin-induced Runx2 expression. These results suggest that the activation of AMPK stimulates osteoblast differentiation via the regulation of Smad1/5/8-Dlx5-Runx2 signaling pathway. 相似文献
1000.
Mycobacterium tuberculosis NmtR is a Ni(II)/Co(II)-sensing metalloregulatory protein from the extensively studied ArsR/SmtB family. Two Ni(II) ions bind to the NmtR dimer to form octahedral coordination complexes with the following stepwise binding affinities: K(Ni1) = (1.2 ± 0.1) × 10(10) M(-1), and K(Ni2) = (0.7 ± 0.4) × 10(10) M(-1) (pH 7.0). A glutamine scanning mutagenesis approach reveals that Asp91, His93, His104, and His107, all contained within the C-terminal α5 helix, and His3 as part of the conserved α-NH(2)-Gly2-His3-Gly4 motif at the N-terminus make significant contributions to the magnitude of K(Ni). In contrast, substitution of residues from the C-terminal region, His109, Asp114, and His116, previously implicated in Ni(II) binding and metalloregulation in cells, gives rise to wild-type K(Ni) and Ni(II)-dependent allosteric coupling free energies. Interestingly, deletion of residues 112-120 from the C-terminal region (Δ111 NmtR) reduces the Ni(II) binding stoichiometry to one per dimer and greatly reduces Ni(II) responsiveness. H3Q and Δ111 NmtRs also show clear perturbations in the rank order of metal responsiveness to Ni(II), Co(II), and Zn(II) that is distinct from that of wild-type NmtR. (15)N relaxation experiments with apo-NmtR reveal that both N-terminal (residues 2-14) and C- terminal (residues 110-120) regions are unstructured in solution, and this property likely dictates the metal specificity profile characteristic of the Ni(II) sensor NmtR relative to other ArsR family regulators. 相似文献