共查询到20条相似文献，搜索用时 0 毫秒
1.
Amada D. Caliz Hyung-Jin Yoo Anastassiia Vertii Ana C. Dolan Cathy Tournier Roger J. Davis John F. Keaney Jr. Shashi Kant 《International journal of molecular sciences》2021,22(17)
Mitogen kinase kinase 4 (MKK4) and mitogen kinase kinase 7 (MKK7) are members of the MAP2K family that can activate downstream mitogen-activated protein kinases (MAPKs). MKK4 has been implicated in the activation of both c-Jun N-terminal kinase (JNK) and p38 MAPK, while MKK7 has been reported to activate only JNK in response to different stimuli. The stimuli, as well as the cell type determine which MAP2K member will mediate a given response. In various cell types, MKK7 contributes to the activation of downstream MAPKs, JNK, which is known to regulate essential cellular processes, such as cell death, differentiation, stress response, and cytokine secretion. Previous studies have also implicated the role of MKK7 in stress signaling pathways and cytokine production. However, little is known about the degree to which MKK4 and MKK7 contribute to innate immune responses in macrophages or during inflammation in vivo. To address this question and to elucidate the role of MKK4 and MKK7 in macrophage and in vivo, we developed MKK4- and MKK7-deficient mouse models with tamoxifen-inducible Rosa26 CreERT. This study reports that MKK7 is required for JNK activation both in vitro and in vivo. Additionally, we demonstrated that MKK7 in macrophages is necessary for lipopolysaccharide (LPS)-induced cytokine production, M1 polarization, and migration, which appear to be a major contributor to the inflammatory response in vivo. Conversely, MKK4 plays a significant, but minor role in cytokine production in vivo. 相似文献
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煤矿井下电缆由于绝缘老化等原因,发生故障是不可避免的,快速地诊断和消除故障,能加快事故后的检修和恢复速度,提高系统运行的安全稳定性。现有的行波故障测距方法,受各种条件制约,测距结果误差较大、可靠性差。针对煤矿井下的特殊条件,提出了一种新的行波故障测距方法。 相似文献
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Autocrine signaling is defined as the production and secretion of an extracellular mediator by a cell followed by the binding of that mediator to receptors on the same cell to initiate signaling. Autocrine stimulation often operates in autocrine loops, a type of interaction, in which a cell produces a mediator, for which it has receptors, that upon activation promotes expression of the same mediator, allowing the cell to repeatedly autostimulate itself (positive feedback) or balance its expression via regulation of a second factor that provides negative feedback. Autocrine signaling loops with positive or negative feedback are an important feature in cancer, where they enable context-dependent cell signaling in the regulation of growth, survival, and cell motility. A growth factor that is intimately involved in tumor development and progression and often produced by the cancer cells in an autocrine manner is transforming growth factor-β (TGF-β). This review surveys the many observations of autocrine TGF-β signaling in tumor biology, including data from cell culture and animal models as well as from patients. We also provide the reader with a critical discussion on the various experimental approaches employed to identify and prove the involvement of autocrine TGF-β in a given cellular response. 相似文献
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Zifen Xu Yushuang Lei Huan Qin Shiyao Zhang Ping Li Kai Yao 《International journal of molecular sciences》2022,23(14)
Retinal degenerative diseases are the major factors leading to severe visual impairment and even irreversible blindness worldwide. The therapeutic approach for retinal degenerative diseases is one extremely urgent and hot spot in science research. The sigma-1 receptor is a novel, multifunctional ligand-mediated molecular chaperone residing in endoplasmic reticulum (ER) membranes and the ER-associated mitochondrial membrane (ER-MAM); it is widely distributed in numerous organs and tissues of various species, providing protective effects on a variety of degenerative diseases. Over three decades, considerable research has manifested the neuroprotective function of sigma-1 receptor in the retina and has attempted to explore the molecular mechanism of action. In the present review, we will discuss neuroprotective effects of the sigma-1 receptor in retinal degenerative diseases, mainly in aspects of the following: the localization in different types of retinal neurons, the interactions of sigma-1 receptors with other molecules, the correlated signaling pathways, the influence of sigma-1 receptors to cellular functions, and the potential therapeutic effects on retinal degenerative diseases. 相似文献
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针对FTU定位方法只能确定到故障区段,无法得到故障点准确位置的不足,提出了FTU与行波法相结合的配电网接地故障定位技术,并用MATLAB仿真验证了本方法的正确性。 相似文献
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Due to global warming and population growth, plants need to rescue themselves, especially in unfavorable environments, to fulfill food requirements because they are sessile organisms. Stress signal sensing is a crucial step that determines the appropriate response which, ultimately, determines the survival of plants. As important signaling modules in eukaryotes, plant mitogen-activated protein kinase (MAPK) cascades play a key role in regulating responses to the following four major environmental stresses: high salinity, drought, extreme temperature and insect and pathogen infections. MAPK cascades are involved in responses to these environmental stresses by regulating the expression of related genes, plant hormone production and crosstalk with other environmental stresses. In this review, we describe recent major studies investigating MAPK-mediated environmental stress responses. We also highlight the diverse function of MAPK cascades in environmental stress. These findings help us understand the regulatory network of MAPKs under environmental stress and provide another strategy to improve stress resistance in crops to ensure food security. 相似文献
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Prajita Pandey Khadiza Zaman Laszlo Prokai Vladimir Shulaev 《International journal of molecular sciences》2021,22(1)
The early signaling events involved in oxidant recognition and triggering of oxidant-specific defense mechanisms to counteract oxidative stress still remain largely elusive. Our discovery driven comparative proteomics analysis revealed unique early signaling response of the yeast Saccharomyces cerevisiae on the proteome level to oxidants with a different mechanism of action as early as 3 min after treatment with four oxidants, namely H2O2, cumene hydroperoxide (CHP), and menadione and diamide, when protein abundances were compared using label-free quantification relying on a high-resolution mass analyzer (Orbitrap). We identified significant regulation of 196 proteins in response to H2O2, 569 proteins in response to CHP, 369 proteins in response to menadione and 207 proteins in response to diamide. Only 17 proteins were common across all treatments, but several more proteins were shared between two or three oxidants. Pathway analyses revealed that each oxidant triggered a unique signaling mechanism associated with cell survival and repair. Signaling pathways mostly regulated by oxidants were Ran, TOR, Rho, and eIF2. Furthermore, each oxidant regulated these pathways in a unique way indicating specificity of response to oxidants having different modes of action. We hypothesize that interplay of these signaling pathways may be important in recognizing different oxidants to trigger different downstream MAPK signaling cascades and to induce specific responses. 相似文献
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Thomas C. Haley Donald A. Drew Richard T. Lahey JR 《Chemical Engineering Communications》1991,106(1):93-117
The eigenvalues and Riemann invariants of a typical two-fluid model of bubbly two-phase flow are analyzed. An analytical procedure for converting this system of conservation equations from Lagrangian to Eulerian (i.e., conservation) form is presented. It is shown that void waves may exhibit both shocks and rarefactions. Moreover, the dependence of the eigenvalues on closure assumptions is demonstrated. 相似文献
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B. S. Seplyarskii G. B. Brauer A. G. Tarasov 《International Journal of Self-Propagating High-Temperature Synthesis》2009,18(1):42-45
Combustion of Cr2O3 + Al powder mixtures in a coflow of inert gas (Ar) was investigated upon variation in green density in the presence/absence of blowing agents (borax, baking soda). The results were rationalized in terms of the convection-conduction theory for combustion in heterogeneous condensed systems. For Part 4, see Int. J. SHS, 2008, vol. 17, no. 3, pp. 199–205. 相似文献
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Birgit Lohberger Heike Kaltenegger Nicole Eck Dietmar Glnzer Patrick Sadoghi Andreas Leithner Rudolf Bauer Nadine Kretschmer Bibiane Steinecker-Frohnwieser 《International journal of molecular sciences》2022,23(6)
Osteoarthritis (OA) is the most common joint disorder and is characterized by the degeneration of articular cartilage. To develop new therapeutic approaches, we investigated the effect of shikonin derivatives on inflammation, MMP expression, and the regulation of MAPK signaling in human healthy (HC) and OA chondrocytes (pCH-OA). Viability was analyzed using the CellTiter-Glo® Assay. Inflammatory processes were investigated using a proteome profiler™ assay. Furthermore, we analyzed the effects of the shikonin derivatives by protein expression analysis of the phosphorylation pattern and the corresponding downstream gene regulation using RT-qPCR. Both HC and pCH-OA showed a dose-dependent decrease in viability after treatment. The strongest effects were found for shikonin with IC50 values of 1.2 ± 0.1 µM. Shikonin counteracts the inflammatory response by massively reducing the expression of the pro-inflammatory mediators. The phosphorylation level of ERK changed slightly. pJNK and pp38 showed a significant increase, and the downstream targets c/EBPs and MEF2c may play a role in the cartilage homeostasis. STAT3 phosphorylation decreased significantly and has a chondroprotective function through the regulation of cyclin D1 and Sox9. Our results demonstrate for the first time that shikonin derivatives have extensive effects on the inflammatory processes, MAPKs, and IL6/STAT3 downstream regulation in healthy and OA chondrocytes. 相似文献
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Yanru Xue Gejing Zhang Shoujie Zhou Shenghang Wang Huanhuan Lv Liangfu Zhou Peng Shang 《International journal of molecular sciences》2021,22(13)
Osteosarcoma is a common malignant bone tumor in clinical orthopedics. Iron chelators have inhibitory effects on many cancers, but their effects and mechanisms in osteosarcoma are still uncertain. Our in vitro results show that deferoxamine (DFO) and deferasirox (DFX), two iron chelators, significantly inhibited the proliferation of osteosarcoma cells (MG-63, MNNG/HOS and K7M2). The viability of osteosarcoma cells was decreased by DFO and DFX in a concentration-dependent manner. DFO and DFX generated reactive oxygen species (ROS), altered iron metabolism and triggered apoptosis in osteosarcoma cells. Iron chelator-induced apoptosis was due to the activation of the MAPK signaling pathway, with increased phosphorylation levels of JNK, p38 and ERK, and ROS generation; in this process, the expression of C-caspase-3 and C-PARP increased. In an orthotopic osteosarcoma transplantation model, iron chelators (20 mg/kg every day, Ip, for 14 days) significantly inhibited the growth of the tumor. Immunohistochemical analysis showed that iron metabolism was altered, apoptosis was promoted, and malignant proliferation was reduced with iron chelators in the tumor tissues. In conclusion, we observed that iron chelators induced apoptosis in osteosarcoma by activating the ROS-related MAPK signaling pathway. Because iron is crucial for cell proliferation, iron chelators may provide a novel therapeutic strategy for osteosarcoma. 相似文献
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Experimental data on acoustic wave propagation through oil shale, summarized in a previous paper1, were used to develop a semi-empirical model. This model predicts the variation of pressure, effective compressional wave velocity, effective density and acoustic impedance with depth for a modified in-situ oil shale retort. Results from computer simulation of a variety of retort conditions establish the possibility of employing seismic propagation and reflection techniques for mapping of pyrolysis fronts in in-situ oil shale process beds. Such techniques are potentially free from uncertainties associated with proximate sensing of temperature profiles in these beds. 相似文献
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B. S. Seplyarskii G. B. Brauer S. V. Kostin 《International Journal of Self-Propagating High-Temperature Synthesis》2008,17(3):199-205
Combustion of bulk density Ti-Si and Zi-Al mixtures an a coflow of argon was studied in the presence/absence of (1) applied pressure difference δP along the direction of wave propagation, (2) thermal treatment of green samples in vacuum, and (3) blowing agent (borax). The data on variation of the burning velocity U c were rationalized in terms of the convection-conduction combustion theory for heterogeneous condensed systems. For Parts 1–3, see Int. J. SHS, 2008, vol. 17, no. 2. 相似文献
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水下爆炸冲击波传播计算由能流密度一时间曲线经验表达式化简。用简单数值积分法解由拉格朗日形式流体动力学方程、Hugoniot方程和能流密度一时间关系式组成的偏微分方程组,不同距离处的冲击波峰值由单点初始数据计算。结果表明,由近似计算方法所得结果与实测数据和相似律结果一致。适当选取起算参数,在5倍装药半径以外的爆炸远场范围计算精度良好。5倍装药半径以内的爆炸近场,冲击波未充分形成,计算方法失效。计算了几种含铝炸药的冲击波传播,表明冲击波能显著影响冲击波传播特性,冲击波能有利于抑制超压衰减。 相似文献
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Liad Segal Sharon Etzion Sigal Elyagon Moran Shahar Hadar Klapper-Goldstein Aviva Levitas Michael S. Kapiloff Ruti Parvari Yoram Etzion 《International journal of molecular sciences》2022,23(17)
Dedicator of cytokinesis 10 (Dock10) is a guanine nucleotide exchange factor for Cdc42 and Rac1 that regulates the JNK (c-Jun N-terminal kinase) and p38 MAPK (mitogen-activated protein kinase) signaling cascades. In this study, we characterized the roles of Dock10 in the myocardium. In vitro: we ablated Dock10 in neonatal mouse floxed Dock10 cardiomyocytes (NMCMs) and cardiofibroblasts (NMCFs) by transduction with an adenovirus expressing Cre-recombinase. In vivo, we studied mice in which the Dock10 gene was constitutively and globally deleted (Dock10 KO) and mice with cardiac myocyte-specific Dock10 KO (Dock10 CKO) at baseline and in response to two weeks of Angiotensin II (Ang II) infusion. In vitro, Dock10 ablation differentially inhibited the α-adrenergic stimulation of p38 and JNK in NMCM and NMCF, respectively. In vivo, the stimulation of both signaling pathways was markedly attenuated in the heart. The Dock10 KO mice had normal body weight and cardiac size. However, echocardiography revealed mildly reduced systolic function, and IonOptix recordings demonstrated reduced contractility and elevated diastolic calcium levels in isolated cardiomyocytes. Remarkably, Dock10 KO, but not Dock10 CKO, exaggerated the pathological response to Ang II infusion. These data suggest that Dock10 regulates cardiac stress-related signaling. Although Dock10 can regulate MAPK signaling in both cardiomyocytes and cardiofibroblasts, the inhibition of pathological cardiac remodeling is not apparently due to the Dock10 signaling in the cardiomyocyte. 相似文献
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Marija Stankovic Katarina Veljovic Nikola Popovic Snezana Kojic Sofija Dunjic Manevski Dragica Radojkovic Natasa Golic 《International journal of molecular sciences》2022,23(10)
Bronchial epithelial cells are exposed to environmental influences, microbiota, and pathogens and also serve as a powerful effector that initiate and propagate inflammation by the release of pro-inflammatory mediators. Recent studies suggested that lung microbiota differ between inflammatory lung diseases and healthy lungs implicating their contribution in the modulation of lung immunity. Lactic acid bacteria (LAB) are natural inhabitants of healthy human lungs and also possess immunomodulatory effects, but so far, there are no studies investigating their anti-inflammatory potential in respiratory cells. In this study, we investigated immunomodulatory features of 21 natural LAB strains in lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Our results show that several LAB strains reduced the expression of pro-inflammatory cytokine and chemokine genes. We also demonstrated that two LAB strains, Lactobacillus brevis BGZLS10-17 and Lb. plantarum BGPKM22, effectively attenuated LPS-induced nuclear factor-κB (NF-κB) nuclear translocation. Moreover, BGZLS10-17 and BGPKM22 reduced the activation of p38, extracellular signal-related kinase (ERK), and c-Jun amino-terminal kinase (JNK) signaling cascade resulting in a reduction of pro-inflammatory mediator expressions in BEAS-2B cells. Collectively, the LAB strains BGZLS10-17 and BGPKM22 exhibited anti-inflammatory effects in BEAS-2B cells and could be employed to balance immune response in lungs and replenish diminished lung microbiota in chronic lung diseases. 相似文献