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排序方式: 共有451条查询结果,搜索用时 31 毫秒
81.
Jim Secka Arpan Pal Francis A. Acquah Blaine H. M. Mooers Anand B. Karki Dania Mahjoub Mohamed K. Fakhr David R. Wallace Takuya Okada Naoki Toyooka Adama Kuta Naga Koduri Deacon Herndon Kenneth P. Roberts Zhiguo Wang Bethany Hileman Nisha Rajagopal Syed R. Hussaini 《RSC advances》2022,12(30):19431
This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides. We plan to use this method to synthesize indolizidine (−)-237D analogs to find α6-selective antismoking agents. Therefore, we also performed in silico α6-nAchRs binding studies of selected products. Compounds with low root-mean-square deviation values showed more favorable binding free energies. We also report preliminary pharmacokinetic data on indolizidine (−)-237D and found it to have weak activity at CYP3A4. In addition, as enamino carbonyl compounds are also known for antimicrobial properties, we screened previously reported and new enamino carbonyl compounds for antibacterial, antimicrobial, and antifungal properties. Eleven compounds showed significant antimicrobial activities.This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides. 相似文献
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Targeted Disruption of NF1 in Osteocytes Increases FGF23 and Osteoid With Osteomalacia‐like Bone Phenotype
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Nobuhiro Kamiya Ryosuke Yamaguchi Olumide Aruwajoye Audrey J Kim Gen Kuroyanagi Matthew Phipps Naga Suresh Adapala Jian Q Feng Harry KW Kim 《Journal of bone and mineral research》2017,32(8):1716-1726
Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations, exhibits multi‐system abnormalities, including skeletal deformities in humans. Osteocytes play critical roles in controlling bone modeling and remodeling. However, the role of neurofibromin, the protein product of the NF1 gene, in osteocytes is largely unknown. This study investigated the role of neurofibromin in osteocytes by disrupting Nf1 under the Dmp1‐promoter. The conditional knockout (Nf1 cKO) mice displayed serum profile of a metabolic bone disorder with an osteomalacia‐like bone phenotype. Serum FGF23 levels were 4 times increased in cKO mice compared with age‐matched controls. In addition, calcium‐phosphorus metabolism was significantly altered (calcium reduced; phosphorus reduced; parathyroid hormone [PTH] increased; 1,25(OH)2D decreased). Bone histomorphometry showed dramatically increased osteoid parameters, including osteoid volume, surface, and thickness. Dynamic bone histomorphometry revealed reduced bone formation rate and mineral apposition rate in the cKO mice. TRAP staining showed a reduced osteoclast number. Micro‐CT demonstrated thinner and porous cortical bones in the cKO mice, in which osteocyte dendrites were disorganized as assessed by electron microscopy. Interestingly, the cKO mice exhibited spontaneous fractures in long bones, as found in NF1 patients. Mechanical testing of femora revealed significantly reduced maximum force and stiffness. Immunohistochemistry showed significantly increased FGF23 protein in the cKO bones. Moreover, primary osteocytes from cKO femora showed about eightfold increase in FGF23 mRNA levels compared with control cells. The upregulation of FGF23 was specifically and significantly inhibited by PI3K inhibitor Ly294002, indicating upregulation of FGF23 through PI3K in Nf1‐deficient osteocytes. Taken together, these results indicate that Nf1 deficiency in osteocytes dramatically increases FGF23 production and causes a mineralization defect (ie, hyperosteoidosis) via the alteration of calcium‐phosphorus metabolism. This study demonstrates critical roles of neurofibromin in osteocytes for osteoid mineralization. © 2017 American Society for Bone and Mineral Research. 相似文献
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Comparative Analysis of Various Electrostatic Potentials on Docking Precision Against Cyclin-Dependent Kinase 2 Protein: A Multiple Docking Approach
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Sunil K. Tripathi Rajendran Naga Soundarya Poonam Singh Sanjeev K. Singh 《Chemical biology & drug design》2015,85(2):107-118
The fundamental of molecular modeling is the interaction and binding to form a complex, because it explains the action of most drugs to a receptor active site. In the present study, different semiempirical (RM1, AM1, PM3, MNDO) and ab intio (HF, DFT) charge models were investigated for their performance in prediction of docking pose against CDK2 proteins with their respective inhibitor. Further, multiple docking approaches and Prime/MM-GBSA calculations were applied to predict the binding mode with respective charge model against CDK2 inhibitors. A reliable docking result was obtained using RRD, which showed significance improvement on ligand binding poses and docking score accuracy to the IFD. The combined use of RRD and Prime/MM-GBSA method could give a high correlation between the predicted binding free energy and experimental biological activity. The preliminary results point out that AM1 could be a precious charge model for design of new drugs with enhanced success rate. As a very similar result was also found for a different system of the protein–ligand binding, the suggested scoring function based on AM1 method seems to be applicable in drug design. The results from this study can provide insights into highest success rate for design of potent and selective CDK2 inhibitors. 相似文献
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Suvashisa Rana Gursinga Lakshman Kumar Naga Seema Durgesh Nandinee 《Diabetes & Metabolic Syndrome: Clinical Research & Reviews》2021,15(1):303-308
Background and aimsNegligence of illness care in terms of non-adherence may give rise to serious health outcomes in patients with type 2 diabetes mellitus. Considering the importance of both chronic illness care and adherence, the primary purpose of the study is to explore the profile of diabetic patients’ chronic illness care and examine its role in their clinical adherence. In addition to this, we have also investigated the major confounding variables in understanding the chronic illness care of diabetic patients.MethodsWe have conducted this study using a simple retrospective design with one group involving the patients primarily diagnosed with type 2 diabetes (N = 200) in India.ResultsThe cluster analysis (k-Means) has yielded three clusters on the basis of five domains of chronic illness care—patient activation, delivery system design, goal setting, problem solving, and follow-up/coordination. The findings further reveal that the profile of chronic illness care plays a significant role in deciding the clinical adherence of patients with type 2 diabetes. The three clusters of diabetes patients, however, are confounded by health risk behaviour.ConclusionsThese initial findings are suggestive of an association between chronic illness care, clinical adherence, and health risk behaviour of patients with type 2 diabetes. More research on this topic, however, needs to be undertaken involving other important dimensions of health care system like patient-provider relationship and quality of life during hospitalisation. The implications and shortcomings are discussed. 相似文献
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Amber R. Slevin Mickey J. Hart Caroline Van Horn Syed Rahman Naga Swetha Samji Aniko Szabo Lisa Rein Shannon Werner Kia Saeian 《Journal of the American Pharmacists Association》2019,59(1):51-56
Objectives
There is a dearth of literature on effects of nonadherence to hepatitis C virus (HCV) direct-acting antiviral (DAA) regimens; thus, the objective of our study was to assess the impact of adherence on sustained virologic response (SVR) and evaluate factors associated with nonadherence, such as race, psychiatric comorbidities, and therapy length.Methods
We conducted a retrospective cohort study of patients completing DAA treatment between January 2014 and May 2016 within an interdisciplinary hepatology clinic. Adherence was defined a priori as 95% or greater of DAA doses taken within the prescribed treatment period. Post hoc analyses were done with adherence thresholds ≥ 90%, ≥ 85%, and ≥ 80% and adherence as a continuous percentage. Patients lost to follow-up before completing therapy or that discontinued therapy early were excluded from analyses. The association between adherence and SVR rates was assessed using Fisher exact test (for adherence thresholds) and the Wilcoxon rank-sum test (for continuous adherence). Factors associated with adherence were assessed similarly using Fisher exact and Wilcoxon rank-sum tests and multivariable logistic regression.Results
Overall adherence was high, with an average of 97.8% of DAA doses taken within the prescribed treatment period. Achievement of SVR was not significantly different in adherent and nonadherent patients, at an adherence threshold of 95% or greater (93.4% vs. 88.5%; P = 0.246) or any of the post hoc adherence thresholds (≥ 90% [93.3% vs. 84.0%; P = 0.098], ≥ 85% [92.8% vs. 91.7%; P = 0.601], ≥ 80% [92.9% vs. 80.0%; P = 0.315], or as a continuous percentage [P = 0.328]). Black patients were significantly more likely to be nonadherent to DAAs than non-black patients at each adherence threshold (P < 0.05). No other factors evaluated were associated with nonadherence.Conclusion
A numerically higher but not statistically significant SVR failure rate was noted in nonadherent patients, although the gold standard definition for adherence remains to be established. Black patients may require additional adherence support. 相似文献89.
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Expression of pp32 gene family members in breast cancer 总被引:4,自引:0,他引:4
ShriHari S. Kadkol Gamal Abou El Naga Jonathan R. Brody Jining Bai Yuri Gusev William C. Dooley Gary R. Pasternack 《Breast cancer research and treatment》2001,68(1):65-73
The pp32 gene family consists of at least three closely related members, pp32, pp32r1 and pp32r2. In spite of a high degree of identity at the nucleotide level, pp32 functionally behaves as a tumor suppressor where as pp32r1 and pp32r2 are pro-oncogenic. The purpose of this pilot study was to determine pp32-related expression and whether alternative gene use among the pp32 family members occurred in human breast cancer. As a first step, in situ hybridization with a riboprobe capable of hybridizing with all the three members showed abundant pp32-related mRNA in benign ducts and acini and in infiltrating ductal carcinomas. A total of 100/102 cases were positive. Further, a detailed molecular analysis by RT-PCR, cloning, and sequencing was performed in five frozen infiltrating breast carcinomas and matched benign breast tissues. Oncogenic pp32r1 (5/5) and pp32r2 (3/5) expression was observed in carcinomas where as benign breast tissues expressed pp32. 4/5 carcinomas continued to express pp32 but one was devoid of pp32 expression. These results suggest that alternative expression of pp32 family members may be common in human breast cancer and the analysis of the profile of pp32-related expression might be helpful in understanding the role of these genes in breast cancer pathogenesis. 相似文献