排序方式: 共有30条查询结果,搜索用时 15 毫秒
1.
Shashi P. Singh Hitendra S. Chand Sravanthi Gundavarapu Ali Imran Saeed Raymond J. Langley Yohannes Tesfaigzi Neerad C. Mishra Mohan L. Sopori 《PloS one》2015,10(9)
Rationale
Smoking during pregnancy increases the risk of bronchopulmonary dysplasia (BPD) and, in mice, gestational exposure to sidestream cigarette smoke (SS) induces BPD-like condition characterized by alveolar simplification, impaired angiogenesis, and suppressed surfactant protein production. Normal fetal development occurs in a hypoxic environment and nicotinic acetylcholine receptors (nAChRs) regulate the hypoxia-inducible factor (HIF)-1α that controls apoptosis and angiogenesis. To understand SS-induced BPD, we hypothesized that gestational SS affected alveolar development through HIF-1α.Methods
Pregnant BALB/c mice were exposed to air (control) or SS throughout the gestational period and the 7-day-old lungs of the progeny were examined.Results
Gestational SS increased apoptosis of alveolar and airway epithelial cells. This response was associated with increased alveolar volumes, higher levels of proapoptotic factors (FOXO3a, HIPK2, p53, BIM, BIK, and BAX) and the antiangiogenic factor (GAX), and lower levels of antiapoptotic factors (Akt-PI3K, NF-κB, HIF-1α, and Bcl-2) in the lung. Although gestational SS increased the cells containing the proangiogenic bombesin-like-peptide, it markedly decreased the expression of its receptor GRPR in the lung. The effects of SS on apoptosis were attenuated by the nAChR antagonist mecamylamine.Conclusions
Gestational SS-induced BPD is potentially regulated by nAChRs and associated with downregulation of HIF-1α, increased apoptosis of epithelial cells, and increased alveolar volumes. Thus, in mice, exposure to sidestream tobacco smoke during pregnancy promotes BPD-like condition that is potentially mediated through the nAChR/HIF-1α pathway. 相似文献2.
Myocardial remodeling is a major contributor in the development of heart failure (HF) after myocardial infarction (MI). Integrin-linked kinase (ILK), LIM-only adaptor PINCH-1, and α-parvin are essential components of focal adhesions (FAs), which are highly expressed in the heart. ILK binds tightly to PINCH-1 and α-parvin, which regulates FA assembly and promotes cell survival via the activation of the kinase Akt. Mice lacking ILK, PINCH or α-parvin have been shown to develop severe defects in the heart, suggesting that these proteins play a critical role in heart function. Utilizing failing human heart tissues (dilated cardiomyopathy, DCM), we found a 2.27-fold (p<0.001) enhanced expression of PINCH, 4 fold for α-parvin, and 10.5 fold (p<0.001) for ILK as compared to non-failing (NF) counterparts. No significant enhancements were found for the PINCH isoform PINCH-2 and parvin isoform β-parvin. Using a co-immunoprecipitation method, we also found that the PINCH-1-ILK-α-parvin (PIP) complex and Akt activation were significantly up-regulated. These observations were further corroborated with the mouse myocardial infarction (MI) and transaortic constriction (TAC) model. Thymosin beta4 (Tβ4), an effective cell penetrating peptide for treating MI, was found to further enhance the level of PIP components and Akt activation, while substantially suppressing NF-κB activation and collagen expression--the hallmarks of cardiac fibrosis. In the presence of an Akt inhibitor, wortmannin, we show that Tβ4 had a decreased effect in protecting the heart from MI. These data suggest that the PIP complex and activation of Akt play critical roles in HF development. Tβ4 treatment likely improves cardiac function by enhancing PIP mediated Akt activation and suppressing NF-κB activation and collagen-mediated fibrosis. These data provide significant insight into the role of the PIP-Akt pathway and its regulation by Tβ4 treatment in post-MI. 相似文献
3.
CD18 is required for optimal development and function of CD4+CD25+ T regulatory cells 总被引:5,自引:0,他引:5
Marski M Kandula S Turner JR Abraham C 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(12):7889-7897
CD4+CD25+ T regulatory (Treg) cells inhibit immunopathology and autoimmune disease in vivo. CD4+CD25+ Treg cells' capacity to inhibit conventional T cells in vitro is dependent upon cell-cell contact; however, the cell surface molecules mediating this cell:cell contact have not yet been identified. LFA-1 (CD11a/CD18) is an adhesion molecule that plays an established role in T cell-mediated cell contact and in T cell activation. Although expressed at high levels on murine CD4+CD25+ Treg cells, the role of LFA-1 in these cells has not been defined previously. We hypothesized that LFA-1 may play a role in murine CD4+CD25+ Treg function. To evaluate this, we analyzed LFA-1-deficient (CD18-/-) CD4+CD25+ T cells. We show that CD18-/- mice demonstrate a propensity to autoimmunity. Absence of CD18 led to diminished CD4+CD25+ T cell numbers and affected both thymic and peripheral development of these cells. LFA-1-deficient CD4+CD25+ T cells were deficient in mediating suppression in vitro and in mediating protection from colitis induced by the transfer of CD4+CD25- T cells into lymphopenic hosts. Therefore, we define a crucial role for CD18 in optimal CD4+CD25+ Treg development and function. 相似文献
4.
The leukocyte-specific integrin, LFA-1, plays a critical role in trafficking of T cells to both lymphoid and nonlymphoid tissues. However, the role of LFA-1 in T cell activation in vivo has been less well understood. Although there have been reports describing LFA-1-deficient T cell response defects in vivo, due to impaired migration to lymphoid structures and to sites of effector function in the absence of LFA-1, it has been difficult to assess whether T cells also have a specific activation defect in vivo. We examined the role of LFA-1 in CD4(+) T cell activation in vivo by using a system that allows for segregation of the migration and activation defects through the adoptive transfer of LFA-1-deficient (CD18(-/-)) CD4(+) T cells from DO11.10 Ag-specific TCR transgenic mice into wild-type BALB/c mice. We find that in addition to its role in trafficking to peripheral lymph nodes, LFA-1 is required for optimal CD4(+) T cell priming in vivo upon s.c. immunization. CD18(-/-) DO11.10 CD4(+) T cells primed in the lymph nodes demonstrate defects in IL-2 and IFN-gamma production. In addition, recipient mice adoptively transferred with CD18(-/-) DO11.10 CD4(+) T cells demonstrate a defect in OVA-specific IgG2a production after s.c. immunization. The defect in priming of CD18(-/-) CD4(+) T cells persists even in the presence of proliferating CD18(+/-) CD4(+) T cells and in lymphoid structures to which there is no migration defect. Taken together, these results demonstrate that LFA-1 is required for optimal CD4(+) T cell priming in vivo. 相似文献
5.
6.
7.
M. Anil Kumar S. S. Sravanthi Pammi M. S. Sukanya Archana Giri 《In vitro cellular & developmental biology. Plant》2018,54(1):94-103
These studies report the development of an efficient technique for large-scale cultivation of fast-growing hairy root culture systems for production of bioactive isoflavones. Trifolium pratense L. is an important source of pharmaceutically important isoflavones with immense health care applications. Trifolium pratense was transformed using different strains of Agrobacterium rhizogenes for hairy root induction and establishment of hairy root rhizoclones. Selected fast-growing rhizoclones of T. pratense were evaluated for their growth and isoflavone production. This study is the first report of stable production of isoflavones through successive culture passages from transformed hairy-root rhizoclones of T. pratense. One of the fast-growing hairy-root rhizoclones 2364A displayed significantly higher accumulation of all four pharmaceutically important isoflavones, 8.56 mg (gdw)?1 of daidzein, 2.45 mg (gdw)?1 of genistein, 15.23 mg (gdw)?1 of formononetin, and 1.10 mg (gdw)?1 of biochanin A, compared to other rhizoclones. 相似文献
8.
Choong IC Serafimova I Fan J Stockett D Chan E Cheeti S Lu Y Fahr B Pham P Arkin MR Walker DH Hoch U 《Bioorganic & medicinal chemistry letters》2008,18(21):5763-5765
The identification of a selective CDK2, 7, 9 inhibitor 4 with improved permeability is described. Compound 4 exhibits comparable CDK selectivity profile to SNS-032, but shows improved permeability and higher bioavailability in mice. 相似文献
9.
10.
Dhirendra Tripathi Sravanthi Koora K Satyanarayana S Saleem Basha Selvaraj Jayaraman 《Bioinformation》2021,17(6):623
Piper longum (Indian long pepper) is known for its use as an anti inflammatory agent in Indian Ayurvedic System of medicine. Therefore, it is of interest to document the molecular docking analysis of compounds from Piper longum with COX-2 using the Autodock Vina PyRx tool. Molecular docking results show that asarinine, sesamine, fargesin, and piperlonguminine have optimal binding energy of 10, 10, -9.5 and 9.4 Kcal/mol, respectively for further consideration. 相似文献