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排序方式: 共有625条查询结果,搜索用时 15 毫秒
91.
K. Madhumathi K.T. Shalumon V.V. Divya Rani H. Tamura T. Furuike N. Selvamurugan S.V. Nair R. Jayakumar 《International journal of biological macromolecules》2009,45(1):12-15
Chitosan, a deacetylated derivative of chitin is a commonly studied biomaterial for tissue-engineering applications due to its biocompatibility, biodegradability, low toxicity, antibacterial activity, wound healing ability and haemostatic properties. However, chitosan has poor mechanical strength due to which its applications in orthopedics are limited. Hydroxyapatite (HAp) is a natural inorganic component of bone and teeth and has mechanical strength and osteoconductive property. In this work, HAp was deposited on the surface of chitosan hydrogel membranes by a wet chemical synthesis method by alternatively soaking the membranes in CaCl2 (pH 7.4) and Na2HPO4 solutions for different time intervals. These chitosan hydrogel–HAp membranes were characterized using SEM, AFM, EDS, FT-IR and XRD analyses. MTT assay was done to evaluate the biocompatibility of these membranes using MG-63 osteosarcoma cells. The biocompatibility studies suggest that chitosan hydrogel–HAp composite membranes can be useful for tissue-engineering applications. 相似文献
92.
Chuansheng Niu Diane H. Boschelli L. Nathan Tumey Niala Bhagirath Joan Subrath Jaechul Shim Yan Wang Biqi Wu Clark Eid Julie Lee Xiaoke Yang Agnes Brennan Divya Chaudhary 《Bioorganic & medicinal chemistry letters》2009,19(20):5829-5832
A series of 5-vinyl-3-pyridinecarbonitriles were synthesized and evaluated as PKCθ inhibitors. The systematic optimization of 4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-phenylvinyl]-3-pyridinecarbonitrile 3 resulted in the identification of compound 23e as a potent PKCθ inhibitor with good selectivity over PKCδ. 相似文献
93.
Amar S. Prashad Daniel Wang Joan Subrath Biqi Wu Melissa Lin Mei-Yi Zhang Natasha Kagan Julie Lee Xiaoke Yang Agnes Brennan Divya Chaudhary Xin Xu Louis Leung Jack Wang Diane H. Boschelli 《Bioorganic & medicinal chemistry letters》2009,19(19):5799-5802
We previously reported that a 3-pyridinecarbonitrile analog with a furan substituent at C-5 and a 4-methylindol-5-ylamino substituent at C-4, 1, was a potent inhibitor of PKCθ (IC50 = 4.5 nM). Replacement of the C-5 furan ring of 1 with bicyclic heteroaryl rings, led to compounds with significantly improved potency against PKCθ. Analog 6b with a 4-methylindol-5-ylamino group at C-4 and a 5-[(4-methylpiperazin-1-yl)methyl]-1-benzofuran-2-yl group at C-5 had an IC50 value of 0.28 nM for the inhibition of PKCθ. 相似文献
94.
Bojiang Shen Divya Bhargav Aiqun Wei Lisa A Williams Helen Tao David D F Ma Ashish D Diwan 《International journal of biological sciences》2009,5(2):192-200
Bone morphogenetic protein-13 (BMP-13) plays an important role in skeletal development. In the light of a recent report that mutations in the BMP-13 gene are associated with spine vertebral fusion in Klippel-Feil syndrome, we hypothesized that BMP-13 signaling is crucial for regulating embryonic endochondral ossification. In this study, we found that BMP-13 inhibited the osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells (BM MSCs) in vitro. The endogenous BMP-13 gene expression in MSCs was examined under expansion conditions. The MSCs were then induced to differentiate into osteoblasts in osteo-inductive medium containing exogenous BMP-13. Gene expression was analysed by real-time PCR. Alkaline phosphatase (ALP) expression and activity, proteoglycan (PG) synthesis and matrix mineralization were assessed by cytological staining or ALP assay. Results showed that endogenous BMP-13 mRNA expression was higher than BMP-2 or -7 during MSC growth. BMP-13 supplementation strongly inhibited matrix mineralization and ALP activity of osteogenic differentiated MSCs, yet increased PG synthesis under the same conditions. In conclusion, BMP-13 inhibited osteogenic differentiation of MSCs, implying that functional mutations or deficiency of BMP-13 may allow excess bone formation. Our finding provides an insight into the molecular mechanisms and the therapeutic potential of BMP-13 in restricting pathological bone formation. 相似文献
95.
A Genome-wide Association Study Identifies Three Loci Associated with Mean Platelet Volume 总被引:2,自引:0,他引:2
Christa Meisinger Holger Prokisch Christian Gieger Nicole Soranzo Divya Mehta Dieter Rosskopf Peter Lichtner Norman Klopp Jonathan Stephens Nicholas A. Watkins Panos Deloukas Andreas Greinacher Wolfgang Koenig Matthias Nauck Christian Rimmbach Henry Vlzke Annette Peters Thomas Illig Willem H. Ouwehand Thomas Meitinger H.-Erich Wichmann Angela Dring 《American journal of human genetics》2009,84(1):66-71
96.
Aiqun Wei Lisa A Williams Divya Bhargav Bojiang Shen Thomas Kishen Neil Duffy Ashish D Diwan 《International journal of biological sciences》2009,5(5):388-396
Chronic back pain is a global health problem affecting millions of people worldwide and carries significant economic and social morbidities. Intervertebral disc damage and degeneration is a major cause of back pain, characterised by histological and biochemical changes that have been well documented in animal models. Recently there has been intense interest in early intervention in disc degeneration using growth factors or stem cell transplantation, to replenish the diseased tissues. Bone Morphogenetic Proteins (BMPs) have been approved for clinical use in augmenting spinal fusions, and may represent candidate molecules for intervertebral disc regeneration. 相似文献
97.
Melissa Millard Divya Pathania Yumna Shabaik Laleh Taheri Jinxia Deng Nouri Neamati 《PloS one》2010,5(10)
Background
Recently, there has been a surge of interest in developing compounds selectively targeting mitochondria for the treatment of neoplasms. The critical role of mitochondria in cellular metabolism and respiration supports this therapeutic rationale. Dysfunction in the processes of energy production and metabolism contributes to attenuation of response to pro-apoptotic stimuli and increased ROS production both of which are implicated in the initiation and progression of most human cancers.Methodology/Principal Findings
A high-throughput MTT-based screen of over 10,000 drug-like small molecules for anti-proliferative activity identified the phosphonium salts TP187, 197 and 421 as having IC50 concentrations in the submicromolar range. TP treatment induced cell cycle arrest independent of p53 status, as determined by analysis of DNA content in propidium iodide stained cells. In a mouse model of human breast cancer, TP-treated mice showed significantly decreased tumor growth compared to vehicle or paclitaxel treated mice. No toxicities or organ damage were observed following TP treatment. Immunohistochemical staining of tissue sections from TP187-treated tumors demonstrated a decrease in cellular proliferation and increased caspase-3 cleavage. The fluorescent properties of analog TP421 were exploited to assess subcellular uptake of TP compounds, demonstrating mitochondrial localization. Following mitochondrial uptake cells exhibited decreased oxygen consumption and concomittant increase in mitochondrial superoxide production. Proteomics analysis of results from a 600 target antibody microarray demonstrated that TP compounds significantly affected signaling pathways relevant to growth and proliferation.Conclusions/Significance
Through our continued interest in designing compounds targeting cancer-cell metabolism, the Warburg effect, and mitochondria we recently discovered a series of novel, small-molecule compounds containing a triphenylphosphine moiety that show remarkable activity in a panel of cancer cell lines as well as in a mouse model of human breast cancer. The mechanism of action includes mitochondrial localization causing decreased oxygen consumption, increased superoxide production and attenuated growth factor signaling. 相似文献98.
Complex biological systems exhibit a property of robustness at all levels of organization. Through different mechanisms, the
system tries to sustain stress such as due to starvation or drug exposure. To explore whether reconfiguration of the metabolic
networks is used as a means to achieve robustness, we have studied possible metabolic adjustments in Mtb upon exposure to
isoniazid (INH), a front-line clinical drug. The redundancy in the genome of M. tuberculosis (Mtb) makes it an attractive system to explore if alternate routes of metabolism exist in the bacterium. While the mechanism
of action of INH is well studied, its effect on the overall metabolism is not well characterized. Using flux balance analysis,
inhibiting the fluxes flowing through the reactions catalyzed by Rv1484, the target of INH, significantly changes the overall
flux profiles. At the pathway level, activation or inactivation of certain pathways distant from the target pathway, are seen.
Metabolites such as NADPH are shown to reduce drastically, while fatty acids tend to accumulate. The overall biomass also
decreases with increasing inhibition levels. Inhibition studies, pathway level clustering and comparison of the flux profiles
with the gene expression data indicate the activation of folate metabolism, ubiquinone metabolism, and metabolism of certain
amino acids. This analysis provides insights useful for target identification and designing strategies for combination therapy.
Insights gained about the role of individual components of a system and their interactions will also provide a basis for reconstruction
of whole systems through synthetic biology approaches. 相似文献
99.
100.
Chapman J Miles PD Ofrecio JM Neels JG Yu JG Resnik JL Wilkes J Talukdar S Thapar D Johnson K Sears DD 《PloS one》2010,5(11):e13959