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排序方式: 共有1375条查询结果,搜索用时 15 毫秒
51.
Marta Anna Szychlinska Francesca Maria Trovato Michelino Di Rosa Lucia Malaguarnera Lidia Puzzo Rosy Leonardi Paola Castrogiovanni Giuseppe Musumeci 《International journal of molecular sciences》2016,17(3)
Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease. 相似文献
52.
Investigating the Role of Conformational Effects on Laccase Stability and Hyperactivation under Stress Conditions 下载免费PDF全文
Dr. Valerio Ferrario Dr. Alexey Chernykh Federica Fiorindo Dr. Marina Kolomytseva Dr. Loris Sinigoi Dr. Nina Myasoedova Dr. Diana Fattor Prof. Dr. Cynthia Ebert Prof. Dr. Ludmila Golovleva Prof. Dr. Lucia Gardossi 《Chembiochem : a European journal of chemical biology》2015,16(16):2365-2372
Fungal laccase from Steccherinum ochraceum 1833 displays remarkable stability under different harsh conditions: organic/buffer mixtures, thermal treatment, and microwave radiation. The behavior is particularly significant in the light of the sharp inactivation observed for two different fungal laccases. Laccase from S. ochraceum 1833 also displays hyperactivation under mild thermal treatment (60 °C). Molecular dynamics simulations at 80 °C explained how this laccase retains the geometry of the electron transfer pathway, thereby assuring electron transfer through the copper ions and thus maintaining its catalytic activity at high temperature. Spectroscopic studies revealed that the thermal activation corresponds to specific conformational changes in the protein. The results indicate that this laccase is potentially applicable under denaturing conditions that might be beneficial for the biotransformation of recalcitrant substrates. 相似文献
53.
The Phosphoinositide 3‐Kinase Signaling Pathway is Involved in the Control of Modified Low‐Density Lipoprotein Uptake by Human Macrophages 下载免费PDF全文
Daryn R. Michael Thomas S. Davies Lucia Laubertová Hayley Gallagher Dipak P. Ramji 《Lipids》2015,50(3):253-260
The transformation of macrophages into lipid‐loaded foam cells is a critical early event in the pathogenesis of atherosclerosis. Both receptor‐mediated uptake of modified LDL, mediated primarily by scavenger receptors‐A (SR‐A) and CD36 along with other proteins such as lipoprotein lipase (LPL), and macropinocytosis contribute to macrophage foam cell formation. The signaling pathways that are involved in the control of foam cell formation are not fully understood. In this study, we have investigated the role of phosphoinositide 3‐kinase (PI3K) in relation to foam cell formation in human macrophages. The pan PI3K inhibitor LY294002 attenuated the uptake of modified LDL and macropinocytosis, as measured by Lucifer Yellow uptake, by human macrophages. In addition, the expression of SR‐A, CD36 and LPL was attenuated by LY294002. The use of isoform‐selective PI3K inhibitors showed that PI3K‐β, ‐γ and ‐δ were all required for the expression of SR‐A and CD36 whereas only PI3K‐γ was necessary in the case of LPL. These studies reveal a pivotal role of PI3K in the control of macrophage foam cell formation and provide further evidence for their potential as therapeutic target against atherosclerosis. 相似文献
54.
Identification of Aminoimidazole and Aminothiazole Derivatives as Src Family Kinase Inhibitors 下载免费PDF全文
Dr. Cinzia Maria Francini Dr. Anna Lucia Fallacara Dr. Roberto Artusi Dr. Laura Mennuni Dr. Alessia Calgani Dr. Adriano Angelucci Prof. Silvia Schenone Prof. Maurizio Botta 《ChemMedChem》2015,10(12):2027-2041
Src family kinases (SFKs) are a family of non‐receptor tyrosine kinases (TKs) implicated in the regulation of many cellular processes. The aberrant activity of these TKs has been associated with the growth and progression of cancer. In particular, c‐Src is overexpressed or hyperactivated in a variety of solid tumors and is most likely a strong promoting factor for the development of metastasis. Herein, the synthesis of new 4‐aminoimidazole and 2‐aminothiazole derivatives and their in vitro biological evaluation are described for their potential use as SFK inhibitors. Initially, 2‐aminothiazole analogues of dasatinib and 4‐aminoimidazole derivatives were synthesized and tested against the SFKs Src, Fyn, Lyn, and Yes. Five hits were identified as the most promising compounds, with Ki values in the range of 90–480 nm . A combination of molecular docking, homology modeling, and molecular dynamics were then used to investigate the possible binding mode of such compounds within the ATP binding site of the SFKs. Finally, the antiproliferative activities of the best candidates were evaluated against SH‐SY5Y and K562 cell lines. Compound 3 b [2‐(4‐{2‐methyl‐6‐[(5‐phenylthiazol‐2‐yl)amino]pyrimidin‐4‐yl}piperazin‐1‐yl)ethanol] was found to be the most active inhibitor. 相似文献
55.
Lucia Marseglia Sara Manti Gabriella D’Angelo Antonio Nicotera Eleonora Parisi Gabriella Di Rosa Eloisa Gitto Teresa Arrigo 《International journal of molecular sciences》2015,16(1):378-400
Obesity, a social problem worldwide, is characterized by an increase in body weight that results in excessive fat accumulation. Obesity is a major cause of morbidity and mortality and leads to several diseases, including metabolic syndrome, diabetes mellitus, cardiovascular, fatty liver diseases, and cancer. Growing evidence allows us to understand the critical role of adipose tissue in controlling the physic-pathological mechanisms of obesity and related comorbidities. Recently, adipose tissue, especially in the visceral compartment, has been considered not only as a simple energy depository tissue, but also as an active endocrine organ releasing a variety of biologically active molecules known as adipocytokines or adipokines. Based on the complex interplay between adipokines, obesity is also characterized by chronic low grade inflammation with permanently increased oxidative stress (OS). Over-expression of oxidative stress damages cellular structures together with under-production of anti-oxidant mechanisms, leading to the development of obesity-related complications. The aim of this review is to summarize what is known in the relationship between OS in obesity and obesity-related diseases. 相似文献
56.
Catarine Massucato Nishijima Flavia Karina Delella Clenilson Martins Rodrigues Daniel Rinaldo Monica Valdyrce dos Anjos Lopes-Ferreira Lucia Regina Machado da Rocha Wagner Vilegas Sergio Luis Felisbino Clélia Akiko Hiruma-Lima 《International journal of molecular sciences》2015,16(6):12454-12466
Inflammation and haemorrhage are the main characteristics of tissue injury in botropic envenomation. Although some studies have shown that anti-venom prevents systemic reactions, it is not efficient in preventing tissue injury at the site of the bite. Therefore, this work was undertaken to investigate the anti-inflammatory effects of the methanolic extract and fractions from D. elliptica and to evaluate the role of matrix metalloproteinases (MMPs) in this process. Effects of the extract and fractions from D. elliptica were evaluated using a carrageenan-induced paw oedema model in rats, and leukocyte rolling was visualized by intravital. The quantification of MMPs activities (MMP-2 and MMP-9) extracted from the dermis of mice treated with extract and fractions alone or incubated with venom was determined by zymographic analyses. Our results show that intraperitoneal (i.p.) injection of fractions significantly reduced paw oedema after the carrageenan challenge. Treatment with the tannins fraction also resulted in considerable inhibition of the rolling of leukocytes and this fraction was able to decrease the activation of MMP-9. These results confirmed the anti-inflammatory activity of the methanolic extract and tannins fraction of D. elliptica and showed that the dermonecrosis properties of B. jararaca venom might be mediated through the inhibition of MMP-9 activity. 相似文献
57.
Abstract Chlorine dioxide delignification (D0) modifies kraft residual lignin by oxidizing phenolic groups to both quinone and muconic acid structures. Alkaline extraction (E), in addition to removing solubilized lignin, converts quinone moieties to polyphenols. These polyphenols are easily oxidized by oxygen in an (EO) stage or by ClO2 in a D1 stage to hydroxyquinones (~1.8 mmol/g lignin). Pulps treated by D0E consume considerably more ClO2 in the D1 than D0(EO), and have lower bleachability, as was quantified by a simple bleaching model. Both D0E and D0(EO) pulps approach a common brightness ceiling (~83 ISO) when excess ClO2 is applied. Examination of the post‐D1 b* values indicates that D0E and D0(EO) also have similar asymptotic b* values (~6), indicating that both pulps have similar residual chromophores. Hydroxyquinone structures appear to be eliminated in the D1 stage for D0(EO) pulps, and at high ClO2 levels for D0E pulps. 相似文献
58.
The multi-scale Gibbs–Helmholtz constrained (GHC) equation is a new predictive cubic equation of state that constrains the energy parameter in the SRK equation to satisfy the Gibbs–Helmholtz equation. It makes use of internal energies of departure calculated from NTP Monte Carlo simulations at the molecular length scale and a novel up-scaling expression to determine the energy parameter at the bulk phase length scale. 相似文献
59.
60.
Amitesh Maiti William L. Shaw Samantha M. Clarke Christie Fox Lucia A. Ke William N. Cheung Mark A. Burton Graham D. Kosiba Christian D. Grant Richard H. Gee 《Propellants, Explosives, Pyrotechnics》2024,49(2):e202300253
While most performance metrics of high-explosive (HE) based devices like detonation velocity, detonation pressure, and energy output are expected to degrade over time, the evolution of initiation threshold appears less clear, with claims of both increasing and decreasing trends in threshold having been made in the literature. This work analyzes D-optimally designed sequential binary test data for a few thermally conditioned porous-powder and polymer-bonded HE initiator systems using a Bayesian likelihood method employing the probit regression model. We find that in most cases the initiation threshold decreases (i. e., sensitivity increases) upon accelerated thermal conditioning. However, such results are nuanced and influenced by factors like the contact area of initiating stimulus, HE characteristics like density and specific surface area, as well as possible thermally induced changes to other materials and interfaces involved. 相似文献