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101.
An expedient synthesis of N‐(1‐(5‐mercapto‐4‐((substituted benzylidene)amino)‐4H‐1,2,4‐triazol‐3‐yl)‐2‐phenylethyl)benzamides as jack bean urease inhibitors and free radical scavengers: Kinetic mechanism and molecular docking studies 下载免费PDF全文
Aamer Saeed Fayaz Ali Larik Pervaiz Ali Channar Haroon Mehfooz Mohammad Haseeb Ashraf Qamar Abbas Mubashir Hassan Sung‐Yum Seo 《Chemical biology & drug design》2017,90(5):764-777
In this study, some new azomethine‐triazole hybrids 5a–5l derived from N‐benzoyl‐L‐phenylalanine were synthesized and characterized. The synthesized compounds showed first‐rate, urease inhibition, and compounds 5c and 5e were found to be most effective inhibitors with 0.0137 ± 0.00082 μm and 0.0183 ± 0.00068 μm , respectively (thiourea 15.151 ± 1.27 μm ). The kinetic mechanism of urease inhibition revealed the compounds 5c and 5e to be non‐competitive inhibitors, whereas compounds 5d and 5j were found to be of mixed‐type inhibitors. Docking studies also indicated better interaction patterns with urease enzyme. The results of enzyme inhibition, kinetic mechanism and molecular docking suggest that these compounds can serve as lead compounds in the design of more effective urease inhibitors. 相似文献
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Hina Qamar Adil Saeed Mohammad Owais Touseef Hussain Kashif Hussain Aziz ur Rahman Sarfraz Ahmed Sachin Kumar Zulfiqar Ahmad Khan 《Materials》2021,14(21)
Worldwide, bacterial resistance to beta-lactam antibiotics is the greatest challenge in public health care. To overcome the issue, metal-based nanoparticles were extensively used as an alternative to traditional antibiotics. However, their unstable nature limits their use. In the present study a very simple, environmentally friendly, one-pot synthesis method that avoids the use of organic solvents has been proposed to design stable, novel nanocomposites. Formulation was done by mixing biogenic copper oxide (CuO) nanomaterial with glycerol and phospholipids isolated from egg yolk in an appropriate ratio at optimum conditions. Characterization was done using dynamic light scattering DLS, Zeta potential, high performance liquid chromatography (HPLC), and transmission electron microscopy (TEM). Further, its antibacterial activity was evaluated against the extended-spectrum beta-lactamase strains based on zone of inhibition and minimal inhibitory concentration (MIC) indices. Results from this study have demonstrated the formulation of stable nanocomposites with a zeta potential of 34.9 mV. TEM results indicated clear dispersed particles with an average of 59.3 ± 5 nm size. Furthermore, HPLC analysis of the egg yolk extract exhibits the presence of phospholipids in the sample and has significance in terms of stability. The newly formed nanocomposite has momentous antibacterial activity with MIC 62.5 μg/mL. The results suggest that it could be a good candidate for drug delivery in terms of bactericidal therapeutic applications. 相似文献
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Habib Kedir Rebecca Miller Faizaan Syed Mohammed Hakim Hina Walia Dmitry Tumin Christopher McKee Joseph D. Tobias 《Journal of pediatric surgery》2019,54(10):2075-2079
BackgroundAlthough preoperative anemia has been suggested to predict postsurgical morbidity and mortality among infants < 1 year of age, the data were drawn from heterogeneous patient cohorts including severely ill infants undergoing complex, high-risk procedures. We aimed to determine whether untreated preoperative anemia was associated with increased risk of postoperative complications in infants < 1 year of age who underwent pyloromyotomy, a common and relatively simple surgery.MethodsInfants < 1 year of age undergoing pyloromyotomy were identified from the American College of Surgeons (ACS) National Surgical Quality Improvement Program-Pediatric database. Preoperative anemia was defined as a hematocrit ≤ 40% for infants 0–30 days of age and ≤ 30% for infants more than 30 days of age. Patients who received pre- or postoperative blood transfusions were excluded.ResultsWe identified 2948 patients who met our inclusion criteria, of whom 843 were anemic (29%). The overall rate of complications in this cohort was 6%. The most common postoperative complications were readmission (97 cases), surgical site infection (43), reoperation (39), prolonged hospital stay (24), urinary tract infection (3), 30-day mortality (3) and cardiac arrest (2). We found no differences in the incidence of complications in anemic versus nonanemic patients on bivariate analysis or multivariable logistic regression (adjusted odds ratio = 1.2; 95% confidence interval: 0.8–1.7; P = 0.319).ConclusionsIn relatively healthy infants undergoing pyloromyotomy, untreated preoperative anemia was not associated with postoperative compilations and should not be considered a significant risk factor.Level of evidence III. 相似文献
106.
Qamar J. Khan Bruce F. Kimler Pavan S. Reddy Priyanka Sharma Jennifer R. Klemp Jennifer L. Nydegger Hung-Wen Yeh Carol J. Fabian 《Breast cancer research and treatment》2017,166(2):491-500
Purpose
Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) frequently occur in women being treated for breast cancer. Prior studies suggest high prevalence of vitamin D deficiency in breast cancer patients with musculoskeletal (MS) pain. We conducted a randomized, placebo-controlled trial to determine if 30,000 IU vitamin D3 per week (VitD3) would prevent worsening of AIMSS in women starting adjuvant letrozole for breast cancer.Methods
Women with stage I–III breast cancer starting adjuvant letrozole and 25(OH)D level ≤40 ng/ml were eligible. All subjects received standard daily supplement of 1200 mg calcium and 600 IU vitamin D3 and were randomized to 30,000 IU oral VitD3/week or placebo. Pain, disability, fatigue, quality of life, 25(OH)D levels, and hand grip strength were assessed at baseline, 12, and 24 weeks. The primary endpoint was incidence of an AIMSS event.Results
Median age of the 160 subjects (80/arm) was 61. Median 25OHD (ng/ml) was 25 at baseline, 32 at 12 weeks, and 31 at 24 weeks in the placebo arm and 22, 53, and 57 in the VitD3 arm. There were no serious adverse events. At week 24, 51% of women assigned to placebo had a protocol defined AIMSS event (worsening of joint pain using a categorical pain intensity scale (CPIS), disability from joint pain using HAQ-II, or discontinuation of letrozole due to MS symptoms) vs. 37% of women assigned to VitD3 (p = 0.069). When the brief pain inventory (BPI) was used instead of CPIS, the difference was statistically significant: 56 vs. 39% (p = 0.024).Conclusions
Although 30,000 IU/week of oral vitamin D3 is safe and effective in achieving adequate vitamin D levels, it was not associated with a decrease in AIMSS events based on the primary endpoint. Post-hoc analysis using a different tool suggests potential benefit of vitamin D3 in reducing AIMSS.107.
Takahiro Kataoka Hina Shuto Shota Naoe Junki Yano Norie Kanzaki Akihiro Sakoda Hiroshi Tanaka Katsumi Hanamoto Fumihiro Mitsunobu Hiroaki Terato Kiyonori Yamaoka 《Journal of radiation research》2021,62(5):861
Radon inhalation decreases the level of lipid peroxide (LPO); this is attributed to the activation of antioxidative functions. This activation contributes to the beneficial effects of radon therapy, but there are no studies on the risks of radon therapy, such as DNA damage. We evaluated the effect of radon inhalation on DNA damage caused by oxidative stress and explored the underlying mechanisms. Mice were exposed to radon inhalation at concentrations of 2 or 20 kBq/m3 (for one, three, or 10 days). The 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels decreased in the brains of mice that inhaled 20 kBq/m3 radon for three days and in the kidneys of mice that inhaled 2 or 20 kBq/m3 radon for one, three or 10 days. The 8-OHdG levels in the small intestine decreased by approximately 20–40% (2 kBq/m3 for three days or 20 kBq/m3 for one, three or 10 days), but there were no significant differences in the 8-OHdG levels between mice that inhaled a sham treatment and those that inhaled radon. There was no significant change in the levels of 8-oxoguanine DNA glycosylase, which plays an important role in DNA repair. However, the level of Mn-superoxide dismutase (SOD) increased by 15–60% and 15–45% in the small intestine and kidney, respectively, following radon inhalation. These results suggest that Mn-SOD probably plays an important role in the inhibition of oxidative DNA damage. 相似文献
108.
Cervical cancer is caused by human papilloma virus (HPV) expressing E6 and E7 oncoproteins, which are known to inactivate tumor suppressor proteins p53 and pRb, respectively. Repression of HPV oncoproteins would therefore result in reactivation of tumor suppressor pathways and cause apoptosis in cancer cells. Withaferin A (WA), the active component of the medicinal plant Withania Somnifera, has exhibited inhibitory effects against several different cancers. We examined the activity of WA on human cervical cancer cells in vitro and in vivo. WA potently inhibited proliferation of the cervical cancer cells, CaSki (IC(50) 0.45 ± 0.05 μM). Mechanistically, WA was found to (i) downregulate expression of HPV E6 and E7 oncoproteins, (ii) induce accumulation of p53, (iii) increase levels of p21(cip1/waf1) and its interaction with proliferating cell nuclear antigen (PCNA), (iv) cause G(2)/M cell cycle arrest, associated with modulation of cyclin B1, p34(cdc2) and PCNA levels, (v) decrease the levels of STAT3 and its phosphorylation at Tyr(705) and Ser(727) and (vi) alter expression levels of p53-mediated apoptotic markers-Bcl2, Bax, caspase-3 and cleaved PARP. In vivo, WA resulted in reduction of nearly 70% of the tumor volume in athymic nude mice with essentially similar trend in the modulation of molecular markers as in vitro. This is the first demonstration indicating that WA significantly downregulates expression of HPV E6/E7 oncogenes and restores the p53 pathway, resulting in apoptosis of cervical cancer cells. Together, our data suggest that WA can be exploited as a potent therapeutic agent for the treatment and prevention of cervical cancer without deleterious effects. 相似文献
109.
Paul E. Gottschall Joanne M. Ajmo Autumn K. Eakin Matthew D. Howell Hina Mehta Lauren A. Bailey 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2010,201(4):885-893
The purpose of this study was to develop ELISAs for key neural proteins, three synaptic and one glial, that exist in different
intracellular compartments, which would be used as a measure of synaptic phenotype. These assays would be valuable to neurologically
phenotype transgenic mouse models of human disease and also human disease itself using minimal amounts of post-mortem tissue.
We showed that supernatant from crude brain tissue homogenates extracted in RIPA buffer containing 0.1% SDS bind to synaptophysin,
synaptosome-associated protein of 25 kDa (SNAP-25), post-synaptic density-95 (PSD-95), and glial fibrillary acidic protein
(GFAP) antibody pairs with high affinity and selectivity. Overall, RIPA + 0.1% SDS were more efficient than RIPA + 2% SDS
or a buffer containing only 1% Triton-X-100. Diluting the brain extracts resulted in dose-dependent binding to the antibody
pairs for each neural protein, with EC50s that varied from 8.6 μg protein for PSD-95 to 0.23 μg for GFAP. The assays were
used to measure synaptic marker protein levels at various times during mouse development and GFAP in a model of disease accompanied
by neuroinflammation. Comparison of ELISAs with Western blots by measuring marker levels in brain extract from developing
mice showed a greater relative difference in values derived from ELISA. These ELISAs should be valuable to phenotype the synapse
in neurological disease and their rodent models. 相似文献
110.