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81.
Rangaswamy J Kumar HV Harini ST Naik N 《Bioorganic & medicinal chemistry letters》2012,22(14):4773-4777
In search for a new antioxidant and antimicrobial agent with improved potency, we synthesized a series of benzofuran based 1,3,5-substituted pyrazole analogues (5a-l) in five step reaction. Initially, o-alkyl derivative of salicyaldehyde readily furnish corresponding 2-acetyl benzofuran 2 in good yield, on treatment with 1,8-diaza bicyclo[5.4.0]undec-7-ene (DBU) in the presence of molecular sieves. Further, aldol condensation with vanillin, Claisen-Schmidt condensation reaction with hydrazine hydrate followed by coupling of substituted anilines afforded target compounds. The structures of newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR, mass, elemental analysis and further screened for their antioxidant and antimicrobial activities. Among the tested compounds 5d and 5f exhibited good antioxidant property with 50% inhibitory concentration higher than that of reference while compounds 5h and 5l exhibited good antimicrobial activity at concentration 1.0 and 0.5 mg/mL compared with standard, streptomycin and fluconazole respectively. 相似文献
82.
Purpose
Dry eye syndrome is a multifactorial chronic disabling disease mainly caused by the functional disruptions in the lacrimal gland. The treatment involves palliation like ocular surface lubrication and rehydration. Cell therapy involving replacement of the gland is a promising alternative for providing long-term relief to patients. This study aimed to establish functionally competent lacrimal gland cultures in–vitro and explore the presence of stem cells in the native gland and the established in-vitro cultures.Methods
Fresh human lacrimal gland from patients undergoing exenteration was harvested for cultures after IRB approval. The freshly isolated cells were evaluated by flow cytometry for expression of stem cell markers ABCG2, high ALDH1 levels and c-kit. Cultures were established on Matrigel, collagen and HAM and the cultured cells evaluated for the presence of stem cell markers and differentiating markers of epithelial (E-cadherin, EpCAM), mesenchymal (Vimentin, CD90) and myofibroblastic (α-SMA, S-100) origin by flow cytometry and immunocytochemistry. The conditioned media was tested for secretory proteins (scIgA, lactoferrin, lysozyme) post carbachol (100 µM) stimulation by ELISA.Results
Native human lacrimal gland expressed ABCG2 (mean±SEM: 3.1±0.61%), high ALDH1 (3.8±1.26%) and c-kit (6.7±2.0%). Lacrimal gland cultures formed a monolayer, in order of preference on Matrigel, collagen and HAM within 15–20 days, containing a heterogeneous population of stem-like and differentiated cells. The epithelial cells formed ‘spherules’ with duct like connections, suggestive of ductal origin. The levels of scIgA (47.43 to 61.56 ng/ml), lysozyme (24.36 to 144.74 ng/ml) and lactoferrin (32.45 to 40.31 ng/ml) in the conditioned media were significantly higher than the negative controls (p<0.05 for all comparisons).Conclusion
The study reports the novel finding of establishing functionally competent human lacrimal gland cultures in-vitro. It also provides preliminary data on the presence of stem cells and duct-like cells in the fresh and in-vitro cultured human lacrimal gland. These significant findings could pave way for cell therapy in future. 相似文献83.
Cadmium and cadmium compounds are water soluble, mobile in most soils, bio-available, and tend to bio-accumulate. A pot culture experiment was conducted on contaminated soil to study the influence of lime and organic matter on the mobility of cadmium in spinach and its rhizosphere soil. Application of lime (50% and 100% lime requirement) and organic matter (0.5 and 1% by weight of soil) to soil decreased the availability of Cd to the soil and plant throughout the crop growth. The highest diethylene triamine penta-acetic acid (DTPA) extractable Cd was 10.84 mg kg?1 in the treatment OM0 L0 (No application of organic matter and lime) at 20 days after sowing of spinach. Likewise, the highest Cd concentration in spinach roots and shoots were 19.80 and 17.0 mg kg?1 in the treatment OM0 L0 at 20 days after sowing. The Cd concentration in spinach roots and shoots were decreased by 63.23 and 71.88%, respectively, in the treatment OM1 L100 (application of FYM at 1.0% by weight of soil and lime at 100% lime requirement) after 60 days of growth. The lowest concentrations of Cd in the soil and plant after the harvest of the crop were 2.88 and 4.27 mg kg?1, respectively, in the treatment OM1 L100 and resulted in 65.75 and 71.55% decrease over control (OM0 L0). The highest total chlorophyll content of leaves was 2.19 mg kg?1 of fresh weight in the treatment OM1 L100 at 40 days of crop growth. 相似文献
84.
The goal of the Caltech group is to gain insight into the processes that occur within the primate nervous system during dexterous reaching and grasping and to see whether natural recovery from local brain damage can be accelerated by artificial means. We will create computational models of the nervous system embodying this insight and explain a variety of clinically observed neurological deficits in human subjects using these models. 相似文献
85.
A typical biotech process starts with the vial of the cell bank, ends with the final product and has anywhere from 15 to 30 unit operations in series. The total number of process variables (input and output parameters) and other variables (raw materials) can add up to several hundred variables. As the manufacturing process is widely accepted to have significant impact on the quality of the product, the regulatory agencies require an assessment of process comparability across different phases of manufacturing (Phase I vs. Phase II vs. Phase III vs. Commercial) as well as other key activities during product commercialization (process scale-up, technology transfer, and process improvement). However, assessing comparability for a process with such a large number of variables is nontrivial and often companies resort to qualitative comparisons. In this article, we present a quantitative approach for assessing process comparability via use of chemometrics. To our knowledge this is the first time that such an approach has been published for biotech processing. The approach has been applied to an industrial case study involving evaluation of two processes that are being used for commercial manufacturing of a major biosimilar product. It has been demonstrated that the proposed approach is able to successfully identify the unit operations in the two processes that are operating differently. We expect this approach, which can also be applied toward assessing product comparability, to be of great use to both the regulators and the industry which otherwise struggle to assess comparability. 相似文献
86.
The thermoalkalophilic Bacillus halodurans JB 99 cells known for production of novel thermostable alkaline keratinolytic protease were immobilized in calcium alginate
matrix. Batch and repeated batch cultivation using calcium alginate immobilized cells were studied for alkaline protease production
in submerged fermentation. Immobilized cells with 2.5% alginate and 350 beads/flask of initial cell loading showed enhanced
production of alkaline protease by 23.2% (5,275 ± 39.4 U/ml) as compared to free cells (4,280 ± 35.4 U/ml) after 24 h. In
the semicontinuous mode of cultivation, immobilized cells under optimized conditions produced an appreciable level of alkaline
protease in up to nine cycles and reached a maximal value of 5,975 U/ml after the seventh cycle. The enzyme produced from
immobilized cells efficiently degraded chicken feathers in the presence of a reducing agent which can help the poultry industry
in the management of keratin-rich waste and obtaining value-added products. 相似文献
87.
We have identified a new class of microtubule-binding compounds—noscapinoids—that alter microtubule dynamics at stoichiometric
concentrations without affecting tubulin polymer mass. Noscapinoids show great promise as chemotherapeutic agents for the
treatment of human cancers. To investigate the structural determinants of noscapinoids responsible for anti-cancer activity,
we tested 36 structurally diverse noscapinoids in human acute lymphoblastic leukemia cells (CEM). The IC50 values of these noscapinoids vary from 1.2 to 56.0 μM. Pharmacophore models of anti-cancer activity were generated that identify
two hydrogen bond acceptors, two aromatic rings, two hydrophobic groups, and one positively charged group as essential structural
features. Additionally, an atom-based quantitative structure–activity relationship (QSAR) model was developed that gave a
statistically satisfying result (R
2 = 0.912, Q
2 = 0.908, Pearson R = 0.951) and effectively predicts the anti-cancer activity of training and test set compounds. The pharmacophore model presented
here is well supported by electronic property analysis using density functional theory at B3LYP/3-21*G level. Molecular electrostatic
potential, particularly localization of negative potential near oxygen atoms of the dimethoxy isobenzofuranone ring of active
compounds, matched the hydrogen bond acceptor feature of the generated pharmacophore. Our results further reveal that all
active compounds have smaller lowest unoccupied molecular orbital (LUMO) energies concentrated over the dimethoxy isobenzofuranone
ring, azido group, and nitro group, which is indicative of the electron acceptor capacity of the compounds. Results obtained
from this study will be useful in the efficient design and development of more active noscapinoids. 相似文献
88.
JA Cully ME Armento J Mott MR Nadorff AD Naik MA Stanley KH Sorocco ME Kunik NJ Petersen MR Kauth 《Implementation science : IS》2012,7(1):64
ABSTRACT: BACKGROUND: Despite the availability of evidence-based psychotherapies for depression and anxiety, they are underused in non-mental health specialty settings such as primary care. Hybrid effectiveness-implementation designs have the potential to evaluate clinical and implementation outcomes of evidence-based psychotherapies to improve their translation into routine clinical care practices. METHODS: This protocol article discusses the study methodology and implementation strategies employed in an ongoing, hybrid, type 2 randomized controlled trial with two primary aims: (1) to determine whether a brief, manualized cognitive behavioral therapy administered by Veterans Affairs Primary Care Mental Health Integration program clinicians is effective in treating depression and anxiety in a sample of medically ill (chronic cardiopulmonary diseases) primary care patients and (2) to examine the acceptability, feasibility, and preliminary outcomes of a focused implementation strategy on improving adoption and fidelity of brief cognitive behavioral therapy at two Primary Care-Mental Health Integration clinics. The study uses a hybrid type 2 effectiveness/implementation design to simultaneously test clinical effectiveness and to collect pilot data on a multifaceted implementation strategy that includes an online training program, audit and feedback of session content, and internal and external facilitation. Additionally, the study engages the participation of an advisory council consisting of stakeholders from Primary Care-Mental Health Integration, as well as regional and national mental health leaders within the Veterans Administration. It targets recruitment of 320 participants randomized to brief cognitive behavioral therapy (n = 200) or usual care (n = 120). Both effectiveness and implementation outcomes are being assessed using mixed methods, including quantitative evaluation (e.g., intent-to-treat analyses across multiple time points) and qualitative methods (e.g., focus interviews and surveys from patients and providers). Patient-effectiveness outcomes include measures of depression, anxiety, and physical health functioning using blinded independent evaluators. Implementation outcomes include patient engagement and adherence and clinician brief cognitive behavioral therapy adoption and fidelity. CONCLUSIONS: Hybrid designs are needed to advance clinical effectiveness and implementation knowledge to improve healthcare practices. The current article describes the rationale and challenges associated with the use of a hybrid design for the study of brief cognitive behavioral therapy in primary care. Although trade-offs exist between scientific control and external validity, hybrid designs are part of an emerging approach that has the potential to rapidly advance both science and practice. Trial registration NCT01149772 at http://www.clinicaltrials.gov/ct2/show/NCT01149772. 相似文献
89.
90.
Glucose phosphorylation and mitochondrial binding are required for the protective effects of hexokinases I and II 总被引:3,自引:0,他引:3
Alterations in glucose metabolism have been demonstrated for diverse disorders ranging from heart disease to cancer. The first step in glucose metabolism is carried out by the hexokinase (HK) family of enzymes. HKI and II can bind to mitochondria through their N-terminal hydrophobic regions, and their overexpression in tissue culture protects against cell death. In order to determine the relative contributions of mitochondrial binding and glucose-phosphorylating activities of HKs to their overall protective effects, we expressed full-length HKI and HKII, their truncated proteins lacking the mitochondrial binding domains, and catalytically inactive proteins in tissue culture. The overexpression of full-length proteins resulted in protection against cell death, decreased levels of reactive oxygen species, and possibly inhibited mitochondrial permeability transition in response to H2O2. However, the truncated and mutant proteins exerted only partial effects. Similar results were obtained with primary neonatal rat cardiomyocytes. The HK proteins also resulted in an increase in the phosphorylation of voltage-dependent anion channel (VDAC) through a protein kinase C (PKC)-dependent pathway. These results suggest that both glucose phosphorylation and mitochondrial binding contribute to the protective effects of HKI and HKII, possibly through VDAC phosphorylation by PKC. 相似文献