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排序方式: 共有362条查询结果,搜索用时 140 毫秒
111.
112.
Beimeng Yang Xiuli Dan Yujun Hou JongHyuk Lee Noah Wechter Sudarshan Krishnamurthy Risako Kimura Mansi Babbar Tyler Demarest Ross McDevitt Shiliang Zhang Yongqing Zhang Mark P. Mattson Deborah L. Croteau Vilhelm A. Bohr 《Aging cell》2021,20(4)
Senescence phenotypes and mitochondrial dysfunction are implicated in aging and in premature aging diseases, including ataxia telangiectasia (A‐T). Loss of mitochondrial function can drive age‐related decline in the brain, but little is known about whether improving mitochondrial homeostasis alleviates senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence‐associated secretory phenotype (SASP) occur in A‐T patient fibroblasts, and in ATM‐deficient cells and mice. Senescence is mediated by stimulator of interferon genes (STING) and involves ectopic cytoplasmic DNA. We further show that boosting intracellular NAD+ levels with nicotinamide riboside (NR) prevents senescence and SASP by promoting mitophagy in a PINK1‐dependent manner. NR treatment also prevents neurodegeneration, suppresses senescence and neuroinflammation, and improves motor function in Atm−/− mice. Our findings suggest a central role for mitochondrial dysfunction‐induced senescence in A‐T pathogenesis, and that enhancing mitophagy as a potential therapeutic intervention. 相似文献
113.
Guiju Cai Yuejiao Wang Tahiri Houda Chun Yang Lijuan Wang Muqing Gu Alfred Mueck Stephane Croteau Xiangyan Ruan Pierre Hardy 《Translational oncology》2021,14(6):101068
BackgroundResearch suggests that hormone replacement therapy may increase the risk of breast cancer, and progestins such as norethisterone (NET) play a key role in this phenomenon. We have demonstrated that microRNA-181a (miR-181a) suppresses NET-promoted breast cancer cell survival. Nonetheless, the effects of NET and miR-181a on the tumorigenesis of human breast epithelial cells have not yet been elaborated.MethodsAssays of cell viability, proliferation, migration, apoptosis, and colony formation were performed to investigate the pro-tumorigenesis effect of NET and the effects of miR-181a on human breast epithelial MCF10A cells. The expressions of cell-proliferation-related genes and apoptotic factors were analyzed by quantitative RT-PCR and Western blot in MCF10A cells treated with NET and miR-181a.ResultsNET significantly increased MCF10A cell viability, proliferation, migration, and colony formation, but reduced cellular apoptosis. In addition, NET increased the expression of progesterone receptor membrane component 1 (PGRMC1), EGFR, B-cell lymphoma 2, cyclin D1, and proliferating cell nuclear antigen, but decreased the expression of pro-apoptosis factors, such as Bax, caspase-7, and caspase-9. Overexpression of miR-181a strongly inhibited the effects of NET on MCF10A cells and abrogated NET-stimulated PGRMC1, EGFR, and mTOR expression.ConclusionsActivation of the PGRMC1/EGFR–PI3K/Akt/mTOR signaling pathway is the primary mechanism underlying the pro-tumorigenesis effects of NET on human breast epithelial MCF10A cells. Additionally, miR-181a can suppress the effects of NET on these cells. These data suggest a therapeutic potential for miR-181a in reducing or preventing the risk of breast cancer in hormone replacement therapy using NET. 相似文献
114.
Rhonda C Foley Ling-Ling Gao Andrew Spriggs Lena YC Soo Danica E Goggin Penelope MC Smith Craig A Atkins Karam B Singh 《BMC plant biology》2011,11(1):59
Background
In legumes, seed storage proteins are important for the developing seedling and are an important source of protein for humans and animals. Lupinus angustifolius (L.), also known as narrow-leaf lupin (NLL) is a grain legume crop that is gaining recognition as a potential human health food as the grain is high in protein and dietary fibre, gluten-free and low in fat and starch. 相似文献115.
A cell line of Taxus cuspidata has been transformed with wild-type Agrobacterium rhizogenes ATCC strain 15834 containing binary vector pCAMBIA1301 and, separately, with A. tumefaciens strain EHA105 containing binary vector pCAMBIA1305.2. Additionally, a cell line of T. chinensis has been transformed with wild-type A. rhizogenes ATCC strain 25818 containing binary vector pCAMBIA1301. The two transgenic T. cuspidata cell lines have been maintained in culture for more than 20 months, and the transgenic T. chinensis cell line for more than 9 months, with no loss of reporter gene expression or antibiotic resistance. The introduced genes
had no discernable effect on growth or Taxol production in the transgenic cell lines when compared to the parent control.
The methods for transforming non-embryogenic Taxus suspension cultures are described. 相似文献
116.
The fate of crop nutrients during digestion of swine manure in psychrophilic anaerobic sequencing batch reactors 总被引:1,自引:0,他引:1
The objectives of the study were to measure the levels of manure nutrients retained in psychrophilic anaerobic sequencing batch reactors (PASBRs) digesting swine manure, and to determine the distribution of nutrients in the sludge and supernatant zones of settled bioreactor effluent. Anaerobic digestion reduced the total solids (TS) concentration and the soluble chemical oxygen demand (SCOD) of manure by 71.4% and 79.9%, respectively. The nitrogen, potassium, and sodium fed with the manure to the PASBRs were recovered in the effluent. The bioreactors retained on average 25.5% of the P, 8.7% of the Ca, 41.5% of the Cu, 18.4% of the Zn, and 67.7% of the S fed to the PASBRs. The natural settling of bioreactor effluent allowed further nutrient separation. The supernatant fraction, which represented 71.4% of effluent volume, contained 61.8% of the total N, 67.1% of the NH4-N, and 73.3% of the Na. The settled sludge fraction, which represented 28.6% of the volume, contained 57.6% of the solids, 62.3% of the P, 71.6% of the Ca, 89.6% of the Mg, 76.1% of the Al, 90.0% of the Cu, 74.2% of the Zn, and 52.2% of the S. The N/P ratio was increased from 3.9 in the raw manure to 5.2 in the bioreactor effluent and 9.2 in the supernatant fraction of the settled effluent. The PASBR technology will then substantially decrease the manure management costs of swine operations producing excess phosphorus, by reducing the volume of manure to export outside the farm. The separation of nutrients will also allow land spreading strategies that increase the agronomic value of manure by matching more closely the crop nutrient requirements. 相似文献
117.
AA Bozzo CA Soñez I Monedero Cobeta A Rolando MC Romanini D Cots 《Biotechnic & histochemistry》2014,89(4):296-303
The model of chronic intermittent stress by immobilization during pregnancy may produce alterations in the mechanisms that maintain adrenal gland homeostasis. In earlier investigations using this model, significant variations in plasma prolactin and corticosterone levels, and adrenal gland weights were observed. We hypothesized that chronic stress causes changes in apoptosis in the adrenal glands of pregnant rats. We identified and quantified apoptotic cells in the adrenal cortex and examined their ultrastructural characteristics using transmission electron microscopy. Adrenal glands of pregnant rats at gestation days 12, 17 and 21 were studied for control and experimental (stressed) rats. Immunolabelling techniques, stereological analysis and image quantification of adrenal gland sections were combined to determine differences in apoptosis in the different cell populations of the adrenal cortex. The apoptotic index of the experimental rats showed a significant reduction at gestation day 17, while at days 12 and 21 there were no differences from controls. Moreover, the apoptotic index of the reticular zones in control and experimental animals showed a significant increase compared to the glomerular and fascicular zones at the three gestation times studied. Chronic stress by immobilization reduced the caspase-dependent apoptotic index at gestation day 17, which may be related to variations in plasma concentrations of estrogens and prolactin. 相似文献
118.
119.
Shepherd H. Schurman Christopher A. Dunn Rebecca Greaves Binbing Yu Luigi Ferrucci Deborah L. Croteau Michael M. Seidman Vilhelm A. Bohr 《PloS one》2012,7(9)
The phosphorylated form of histone H2AX (γ-H2AX) forms immunohistochemically detectable foci at DNA double strand breaks. In peripheral blood mononuclear cells (PBMCs) derived from leukapheresis from patients enrolled in the Baltimore Longitudinal Study of Aging, γ-H2AX foci increased in a linear fashion with regards to age, peaking at ∼57 years. The relationship between the frequency of γ-H2AX foci and age-related pathologies was assessed. We found a statistically significant (p = 0.023) 50% increase in foci in PBMCs derived from patients with a known history of vitamin D deficiency. In addition, there were trends toward increased γ-H2AX foci in patients with cataracts (34% increase, p<0.10) and in sleep apnea patients (44%, p<0.10). Among patients ≥57 y/o, we found a significant (p = 0.037) 36% increase in the number of γ-H2AX foci/cell for patients with hypertension compared to non-hypertensive patients. Our results support a role for increased DNA damage in the morbidity of age-related diseases. γ -H2AX may be a biomarker for human morbidity in age-related diseases. 相似文献
120.
A Bureau J Croteau C Mérette A Fournier YC Chagnon MA Roy M Maziade 《Human heredity》2012,73(4):195-207
Objective: To increase power to detect modifier loci conferring susceptibility to specific phenotypes such as disease diagnoses which are part of a broader disorder spectrum by jointly modeling a modifier and a broad susceptibility gene and to identify modifier loci conferring specific susceptibility to schizophrenia (SZ) or to bipolar disorder (BP) using the approach. Methods: We implemented a two-locus linkage analysis model where a gene 1 genotype increases the risk of a broad phenotype and a gene 2 genotype modifies the expression of gene 1 by conferring susceptibility to a specific phenotype. Results: Compared to a single-locus analysis within the broad phenotype, the proposed approach had greater power to detect the modifier gene 2 (0.96 vs. 0.54 under a simulation scenario including heterogeneity). In a sample of 12 mixed SZ and BP Eastern Quebec kindreds, D8S1110 at 8p22 showed the strongest evidence of linkage to a gene determining a specific phenotype (SZ or BP) among subjects susceptible to major psychosis because of putative genes at 10p13 (D10S245, conditional maximized LOD (cMOD) = 4.20, p = 0.0003) and 3q21-q23 (D3S2418, cMOD = 4.09, p = 0.0005). Conclusion: The proposed strategy is useful to detect modifier loci conferring susceptibility to a specific phenotype within a broader phenotype. 相似文献