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排序方式: 共有1734条查询结果,搜索用时 15 毫秒
991.
Natalia anocha-Arendarczyk Karolina Kot Irena Baranowska-Bosiacka Patrycja Kapczuk Aleksandra anocha Danuta Izabela Kosik-Bogacka 《International journal of molecular sciences》2022,23(9)
To date, no studies have addressed the role of neurotrophins (NTs) in Acanthamoeba spp. infections in the brain. Thus, to clarify the role of NTs in the cerebral cortex and hippocampus during experimental acanthamoebiasis in relation to the host immune status, the purpose of this study was to determine whether Acanthamoeba spp. may affect the concentration of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) in brain structures. Our results suggest that at the beginning of infection in immunocompetent hosts, BDNF and NT-3 may reflect an endogenous attempt at neuroprotection against Acanthamoeba spp. infection. We also observed a pro-inflammatory effect of NGF during acanthamoebiasis in immunosuppressed hosts. This may provide important information for understanding the development of cerebral acanthamoebiasis related to the immunological status of the host. However, the pathogenesis of brain acanthamoebiasis is still poorly understood and documented and, therefore, requires further research. 相似文献
992.
Aleksandra Kvetkina Evgeny Pislyagin Ekaterina Menchinskaya Ekaterina Yurchenko Rimma Kalina Sergei Kozlovskiy Leonid Kaluzhskiy Alexander Menshov Natalia Kim Steve Peigneur Jan Tytgat Alexis Ivanov Naira Ayvazyan Elena Leychenko Dmitry Aminin 《International journal of molecular sciences》2022,23(9)
Parkinson’s disease (PD) is a socially significant disease, during the development of which oxidative stress and inflammation play a significant role. Here, we studied the neuroprotective effects of four Kunitz-type peptides from Heteractis crispa and Heteractis magnifica sea anemones against PD inductors. The peptide HCIQ1c9, which was obtained for the first time, inhibited trypsin less than other peptides due to unfavorable interactions of Arg17 with Lys43 in the enzyme. Its activity was reduced by up to 70% over the temperature range of 60–100 °C, while HCIQ2c1, HCIQ4c7, and HMIQ3c1 retained their conformation and stayed active up to 90–100 °C. All studied peptides inhibited paraquat- and rotenone-induced intracellular ROS formation, in particular NO, and scavenged free radicals outside the cells. The peptides did not modulate the TRPV1 channels but they affected the P2X7R, both of which are considered therapeutic targets in Parkinson’s disease. HMIQ3c1 and HCIQ4c7 almost completely inhibited the ATP-induced uptake of YO-PRO-1 dye in Neuro-2a cells through P2X7 ion channels and significantly reduced the stable calcium response in these cells. The complex formation of the peptides with the P2X7R extracellular domain was determined via SPR analysis. Thus, these peptides may be considered promising compounds to protect neuronal cells against PD inductors, which act as ROS production inhibitors and partially act as ATP-induced P2X7R activation inhibitors. 相似文献
993.
Natalia V. Mitiushkina Grigory A. Yanus Ekatherina Sh. Kuligina Tatiana A. Laidus Alexandr A. Romanko Maksim M. Kholmatov Alexandr O. Ivantsov Svetlana N. Aleksakhina Evgeny N. Imyanitov 《International journal of molecular sciences》2022,23(9)
DNA from formalin-fixed paraffin-embedded (FFPE) tissues, which are frequently utilized in cancer research, is significantly affected by chemical degradation. It was suggested that approaches that are based on duplex sequencing can significantly improve the accuracy of mutation detection in FFPE-derived DNA. However, the original duplex sequencing method cannot be utilized for the analysis of formalin-fixed paraffin-embedded (FFPE) tissues, as FFPE DNA contains an excessive number of damaged bases, and these lesions are converted to false double-strand nucleotide substitutions during polymerase-driven DNA end repair process. To resolve this drawback, we replaced DNA polymerase by a single strand-specific nuclease P1. Nuclease P1 was shown to efficiently remove RNA from DNA preparations, to fragment the FFPE-derived DNA and to remove 5′/3′-overhangs. To assess the performance of duplex sequencing-based methods in FFPE-derived DNA, we constructed the Bottleneck Sequencing System (BotSeqS) libraries from five colorectal carcinomas (CRCs) using either DNA polymerase or nuclease P1. As expected, the number of identified mutations was approximately an order of magnitude higher in libraries prepared with DNA polymerase vs. nuclease P1 (626 ± 167/Mb vs. 75 ± 37/Mb, paired t-test p-value 0.003). Furthermore, the use of nuclease P1 but not polymerase-driven DNA end repair allowed a reliable discrimination between CRC tumors with and without hypermutator phenotypes. The utility of newly developed modification was validated in the collection of 17 CRCs and 5 adjacent normal tissues. Nuclease P1 can be recommended for the use in duplex sequencing library preparation from FFPE-derived DNA. 相似文献
994.
Alena D. Gassan Anton A. Ivanov Tatiana N. Pozmogova Ilia V. Eltsov Natalia V. Kuratieva Yuri V. Mironov Michael A. Shestopalov 《International journal of molecular sciences》2022,23(15)
Despite the great potential of octahedral tungsten cluster complexes in fields of biomedical applications such as X-ray computed tomography or angiography, there is only one example of a water-soluble W6Q8-cluster that has been reported in the literature. Herein we present the synthesis and a detailed characterization including X-ray structural analysis, NMR, IR, UV–Vis spectroscopies, HR-MS spectrometry, and the electrochemical behavior of two new cluster complexes of the general formula W6Q8L6 with phosphine ligands containing a hydrophilic carboxylic group, which makes the complexes soluble in an aqueous medium. The hydrolytic stability of the clusters’ aqueous solutions allows us to investigate for the first time the influence of W6-clusters on cell viability. The results obtained clearly demonstrate their very low cytotoxicity, comparable to the least-toxic clusters presented in the literature. 相似文献
995.
996.
Natalia S. Nemeria Balint Nagy Roberto Sanchez Xu Zhang Joo Leandro Attila Ambrus Sander M. Houten Frank Jordan 《International journal of molecular sciences》2022,23(15)
The human 2-oxoadipate dehydrogenase complex (OADHc) in L-lysine catabolism is involved in the oxidative decarboxylation of 2-oxoadipate (OA) to glutaryl-CoA and NADH (+H+). Genetic findings have linked the DHTKD1 encoding 2-oxoadipate dehydrogenase (E1a), the first component of the OADHc, to pathogenesis of AMOXAD, eosinophilic esophagitis (EoE), and several neurodegenerative diseases. A multipronged approach, including circular dichroism spectroscopy, Fourier Transform Mass Spectrometry, and computational approaches, was applied to provide novel insight into the mechanism and functional versatility of the OADHc. The results demonstrate that E1a oxidizes a non-cognate substrate 2-oxopimelate (OP) as well as OA through the decarboxylation step, but the OADHc was 100-times less effective in reactions producing adipoyl-CoA and NADH from the dihydrolipoamide succinyltransferase (E2o) and dihydrolipoamide dehydrogenase (E3). The results revealed that the E2o is capable of producing succinyl-CoA, glutaryl-CoA, and adipoyl-CoA. The important conclusions are the identification of: (i) the functional promiscuity of E1a and (ii) the ability of the E2o to form acyl-CoA products derived from homologous 2-oxo acids with five, six, and even seven carbon atoms. The findings add to our understanding of both the OADHc function in the L-lysine degradative pathway and of the molecular mechanisms leading to the pathogenesis associated with DHTKD1 variants. 相似文献
997.
多模型自适应预报及其在电力规划负荷预报中的应用 总被引:1,自引:0,他引:1
本文提出一种多模型自适应预报方法,预报系统由几个并行的多步预报器组成,最终预报由Bayes决策律决定。本法适用于随机快时变参数动态过程的预报,在我国工业用电量长期预报中应用此法获得了良好的效果。 相似文献
998.
999.
Renato Jos da Silva-Oliveira Izabela Natalia Faria Gomes Luciane Sussuchi da Silva Andr van Helvoort Lengert Ana Carolina Laus Matias Eliseo Melendez Carla Carolina Munari Fernanda de Paula Cury Giovanna Barbarini Longato Rui Manuel Reis 《International journal of molecular sciences》2022,23(14)
Background: EGFR mutations are present in approximately 15–50% of non-small cell lung cancer (NSCLC), which are predictive of anti-EGFR therapies. At variance, NSCLC patients harboring KRAS mutations are resistant to those anti-EGFR approaches. Afatinib and allitinib are second-generation pan-EGFR drugs, yet no predictive biomarkers are known in the NSCLC context. In the present study, we evaluated the efficacy of pan-EGFR inhibitors in a panel of 15 lung cancer cell lines associated with the KRAS mutations phenotype. Methods: KRAS wild-type sensitive NCI-H292 cell line was further transfected with KRAS mutations (p.G12D and p.G12S). The pan-EGFR inhibitors’ activity and biologic effect of KRAS mutations were evaluated by cytotoxicity, MAPK phospho-protein array, colony formation, migration, invasion, and adhesion. In addition, in vivo chicken chorioallantoic membrane assay was performed in KRAS mutant cell lines. The gene expression profile was evaluated by NanoString. Lastly, everolimus and pan-EGFR combinations were performed to determine the combination index. Results: The GI50 score classified two cell lines treated with afatinib and seven treated with allitinib as high-sensitive phenotypes. All KRAS mutant cell lines demonstrated a resistant profile for both therapies (GI50 < 30%). The protein array of KRAS edited cells indicated a significant increase in AKT, CREB, HSP27, JNK, and, importantly, mTOR protein levels compared with KRAS wild-type cells. The colony formation, migration, invasion, adhesion, tumor perimeter, and mesenchymal phenotype were increased in the H292 KRAS mutated cells. Gene expression analysis showed 18 dysregulated genes associated with the focal adhesion-PI3K-Akt-mTOR-signaling correlated in KRAS mutant cell lines. Moreover, mTOR overexpression in KRAS mutant H292 cells was inhibited after everolimus exposure, and sensitivity to afatinib and allitinib was restored. Conclusions: Our results indicate that allitinib was more effective than afatinib in NSCLC cell lines. KRAS mutations increased aggressive behavior through upregulation of the focal adhesion-PI3K-Akt-mTOR-signaling in NSCLC cells. Significantly, everolimus restored sensibility and improved cytotoxicity of EGFR inhibitors in the KRAS mutant NSCLC cell lines. 相似文献
1000.
Evgeniya Yu Zarechnaya Leonid Dubrovinsky Natalia Dubrovinskaia Nobuyoshi Miyajima Yaroslav Filinchuk Dmitry Chernyshov Vladimir Dmitriev 《Science and Technology of Advanced Materials》2008,9(4)
The densest boron phase (2.52 g cm-3) was produced as a result of the synthesis under pressures above 9 GPa and temperatures up to ∼1800 °C. The x-ray powder diffraction pattern and the Raman spectra of the new material do not correspond to those of any known boron phases. A new high-pressure high-temperature boron phase was defined to have an orthorhombic symmetry (Pnnm (No. 58)) and 28 atoms per unit cell. 相似文献