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排序方式: 共有1146条查询结果,搜索用时 15 毫秒
91.
Jaime L. Schneider Joan Villarroya Antonio Diaz‐Carretero Bindi Patel Aleksandra M. Urbanska Mia M. Thi Francesc Villarroya Laura Santambrogio Ana Maria Cuervo 《Aging cell》2015,14(2):249-264
Chaperone‐mediated autophagy (CMA), a cellular process that contributes to protein quality control through targeting of a subset of cytosolic proteins to lysosomes for degradation, undergoes a functional decline with age. We have used a mouse model with liver‐specific defective CMA to identify changes in proteostasis attributable to reduced CMA activity in this organ with age. We have found that other proteolytic systems compensate for CMA loss in young mice which helps to preserve proteostasis. However, these compensatory responses are not sufficient for protection against proteotoxicity induced by stress (oxidative stress, lipid challenges) or associated with aging. Livers from old mice with CMA blockage exhibit altered protein homeostasis, enhanced susceptibility to oxidative stress and hepatic dysfunction manifested by a diminished ability to metabolize drugs, and a worsening of the metabolic dysregulation identified in young mice. Our study reveals that while the regulatory function of CMA cannot be compensated for in young organisms, its contribution to protein homeostasis can be handled by other proteolytic systems. However, the decline in the compensatory ability identified with age explains the more severe consequences of CMA impairment in older organisms and the contribution of CMA malfunction to the gradual decline in proteostasis and stress resistance observed during aging. 相似文献
92.
The pleiotropic effects of creatine (Cr) are based mostly on the functions of the enzyme creatine kinase (CK) and its high-energy
product phosphocreatine (PCr). Multidisciplinary studies have established molecular, cellular, organ and somatic functions
of the CK/PCr system, in particular for cells and tissues with high and intermittent energy fluctuations. These studies include
tissue-specific expression and subcellular localization of CK isoforms, high-resolution molecular structures and structure–function
relationships, transgenic CK abrogation and reverse genetic approaches. Three energy-related physiological principles emerge,
namely that the CK/PCr systems functions as (a) an immediately available temporal energy buffer, (b) a spatial energy buffer
or intracellular energy transport system (the CK/PCr energy shuttle or circuit) and (c) a metabolic regulator. The CK/PCr
energy shuttle connects sites of ATP production (glycolysis and mitochondrial oxidative phosphorylation) with subcellular
sites of ATP utilization (ATPases). Thus, diffusion limitations of ADP and ATP are overcome by PCr/Cr shuttling, as most clearly
seen in polar cells such as spermatozoa, retina photoreceptor cells and sensory hair bundles of the inner ear. The CK/PCr
system relies on the close exchange of substrates and products between CK isoforms and ATP-generating or -consuming processes.
Mitochondrial CK in the mitochondrial outer compartment, for example, is tightly coupled to ATP export via adenine nucleotide
transporter or carrier (ANT) and thus ATP-synthesis and respiratory chain activity, releasing PCr into the cytosol. This coupling
also reduces formation of reactive oxygen species (ROS) and inhibits mitochondrial permeability transition, an early event
in apoptosis. Cr itself may also act as a direct and/or indirect anti-oxidant, while PCr can interact with and protect cellular
membranes. Collectively, these factors may well explain the beneficial effects of Cr supplementation. The stimulating effects
of Cr for muscle and bone growth and maintenance, and especially in neuroprotection, are now recognized and the first clinical
studies are underway. Novel socio-economically relevant applications of Cr supplementation are emerging, e.g. for senior people,
intensive care units and dialysis patients, who are notoriously Cr-depleted. Also, Cr will likely be beneficial for the healthy
development of premature infants, who after separation from the placenta depend on external Cr. Cr supplementation of pregnant
and lactating women, as well as of babies and infants are likely to be of benefit for child development. Last but not least,
Cr harbours a global ecological potential as an additive for animal feed, replacing meat- and fish meal for animal (poultry
and swine) and fish aqua farming. This may help to alleviate human starvation and at the same time prevent over-fishing of
oceans. 相似文献
93.
Satoh M Krzyszczak ME Li Y Ceribelli A Ross SJ Chan EK Segal MS Bubb MR Sobel ES Reeves WH 《Arthritis research & therapy》2011,13(3):R73
Introduction
The presence of anti-topoisomerase I (topo I) antibodies is a classic scleroderma (SSc) marker presumably associated with a unique clinical subset. Here the clinical association of anti-topo I was reevaluated in unselected patients seen in a rheumatology clinic setting. 相似文献94.
Miller M Dreisbach A Otto A Becher D Bernhardt J Hecker M Peppelenbosch MP van Dijl JM 《Journal of proteome research》2011,10(9):4018-4032
Staphylococcus aureus is a dangerous opportunistic human pathogen that causes serious invasive diseases when it reaches the bloodstream. Recent studies have shown that S. aureus is highly resistant to killing by professional phagocytes and that such cells even provide a favorable environment for intracellular survival of S. aureus. Importantly, the reciprocal interactions between phagocytes and S. aureus have remained largely elusive. Here we have employed kinase profiling to define the nature and time resolution of the human THP-1 macrophage response toward S. aureus and proteomics to identify the response of S. aureus toward macrophages. The results of these studies reveal major macrophage signaling pathways triggered by S. aureus and proteomic signatures of the responses of S. aureus to macrophages. We also identify human proteins bound to S. aureus that have potential roles in bacterial killing and internalization. Most noticeably, our observations challenge the classical concept that macrophage responses are mainly mediated through Toll-like receptor 2 and NF-κB signaling and highlight the important role of the stress-activated MAP kinase signaling in orchestrating the host defense. 相似文献
95.
Malgorzata Monika Stanczyk 《Reports of Practical Oncology and Radiotherapy》2011,16(5):170-172
The purpose of this paper is to show some aspects of music therapy application in cancer care and to present the integration of music therapy program into a continuous supportive cancer care for inpatients. A cancer diagnosis is one of the most feared and serious life events that causes stress in individuals and families. Cancer disrupts social, physical and emotional well-being and results in a range of emotions, including anger, fear, sadness, guilt, embarrassment and shame. Music therapy is a part of a complementary medicine program in supportive cancer care which accompanies medical treatment. There are many benefits of music therapy for cancer patients—interactive music therapy techniques (instrumental improvisation, singing) as well as receptive music therapy techniques (listening to recorded or live music, music and imaginary) can be used to improve mood, decrease stress, pain, anxiety level and enhance relaxation. Music therapy is an effective form of supporting cancer care for patients during the treatment process. It may be also basic for planning effective programs of rehabilitation to promote wellness, improve physical and emotional well-being and the quality of life. 相似文献
96.
Olszowy P Szultka M Nowaczyk J Buszewski B 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2011,879(25):2542-2548
The polypyrrole (PPy) and polythiophene (PTh) solid phase microextraction (SPME) coatings were obtained with the use of the electropolymerisation and linear sweep voltammetry. Such fibers were modified by an ozone treatment in a gaseous phase in the concentration of 2.1 ± 0.2 × 10(-5) mol dm(-3). Both kinds of fibers were applied in the microextraction of linezolid from standard solutions to compare the extraction efficiencies displayed by these sorption phases. In these investigations a better adsorption capacity was obtained for polypyrrole fibers and hence only these kinds of fibers were utilized in the measurements from human plasma. In all measurements the concentrations of the drugs were in the range from 1 to 20 μg ml(-1) (standard solutions) and 1 to 15 μg ml(-1) (human plasma). Before the measurements, an optimization of the desorption solution experiments was performed. The correlation coefficients (R) obtained in the standard solution and human plasma were in the range from 0.8399 to 0.9970. The relative standard deviations (RSDs) were in the range of 0.1-7.6%. 相似文献
97.
This is a review of the growing scientific interest in the developmental plasticity and therapeutic potential of stromal cells
isolated from adipose tissue. Adipose-derived stem/stromal cells (ASCs) are multipotent somatic stem cells that are abundant
in fat tissue. It has been shown that ASCs can differentiate into several lineages, including adipose cells, chondrocytes,
osteoblasts, neuronal cells, endothelial cells, and cardiomyocytes. At the same time, adipose tissue can be harvested by a
minimally invasive procedure, which makes it a promising source of adult stem cells. Therefore, it is believed that ASCs may
become an alternative to the currently available adult stem cells (e.g. bone marrow stromal cells) for potential use in regenerative
medicine. In this review, we present the basic information about the field of adipose-derived stem cells and their potential
use in various applications. 相似文献
98.
Parczewski M Bander D Leszczyszyn-Pynka M Urbanska A Kaczmarczyk M Ciechanowicz A Boron-Kaczmarska A 《PloS one》2011,6(7):e22215
Objective
Investigation of the interplay between the CCR5 Δ32/wt genotype and demographic, epidemiological, clinical and immunological factors associated with mortality in the cART era.Design
Longitudinal data from 507 HIV-infected patients following the Δ32 allele detection were analyzed.Methods
Cumulative 15 years mortality was calculated using Kaplan-Meyer methodology. Hazard ratios were estimated using univariate Cox models. Basing on Akakie information criteria and statistical significance multivariate Cox model was constructed and effect plots presenting adjusted hazard ratio time-dependency were drawn. Analysis of the association of all-cause mortality and CCR5 Δ32/wt genotype prior to the antiretroviral treatment (cART) initiation (n = 507) and on the therapy (n = 422) was also performed.Results
A mortality rate of 2.66 (CI 2.57–3.19) per 100 person-years was observed. Univariate analysis factors modifying the risk of death included the CCR5 genotype, gender, history of cART, AIDS diagnosis and also CD4 lymphocyte nadir, zenith, the latest CD4 count and stable levels >500 cells/µl. For multivariate analysis the following predictors were selected: CCR5 genotype (HR for wt/wt 2.53, CI 1.16–5.53, p = 0.02), gender (HR for males 1.91, 95%CI 1.1–3.36, p = 0.023), introduction of combined antiretroviral treatment (HR 4.85, CI 3.0–7.89, if untreated or treated <1 month, p<0.0001) CD4 count of 500 cells/µl for six months or more (HR 4.16, CI 1.95–8.88 if not achieved, p = 0.028), the latest CD4 count (HR 5.44, CI 3.39–8.74 for <100 cells/µl, p<0.0001) and history of AIDS (HR 1.69, CI 1.03–2.79, p = 0.039). Among untreated individuals the Δ32/wt genotype was associated with notably better survival (p = 0.026), while among cART treated individuals the Δ32 mutation did not correlate significantly with higher survival rates (p = 0.23).Conclusions
The Δ32 CCR5 allele is associated with a reduction of the risk of all-cause mortality in HIV (+) patients alongside clinical and immunologic predictors such as AIDS, history of cART, lymphocyte CD4 cell count and gender. 相似文献99.
Marta Lydka Ilona Kopera-Sobota Malgorzata Kotula-Balak Katarzyna Chojnacka Dorota Zak Barbara Bilinska 《Acta veterinaria Scandinavica》2011,53(1):12
Background
The dynamic cross-talk between epididymal cells is hormonally regulated and, in part, through direct cell-to-cell interactions. To date, no information is available regarding possible impact of anti-androgens on the proteins involved in the gap junctional communication within the boar epididymis. Thus, a question arised whether prenatal or postnatal exposure to an anti-androgen flutamide alters the expression of gap junction protein - connexin43 (Cx43) and androgen receptor (AR) expression in the caput, corpus and cauda epididymis and leads to delayed effects on morphology and function of adult pig epididymis. 相似文献100.
Joanna Kolodziejczyk Joanna Saluk-Juszczak Malgorzata M. Posmyk Krystyna M. Janas Barbara Wachowicz 《Central European Journal of Biology》2011,6(4):565-574
The present in vitro study was designed to examine the antioxidative activity of red cabbage anthocyanins (ATH) in the protection of blood plasma
proteins and lipids against damage induced by oxidative stress. Fresh leaves of red cabbage were extracted with a mixture
of methanol/distilled water/0.01% HCl (MeOH/H2O/HCl, 50/50/1, v/v/w). Total ATH concentration [μM] was determined with cyanidin 3-glucoside as a standard. Phenolic profiles
in the crude red cabbage extract were determined using the HPLC method. Plasma samples were exposed to 100 μM peroxynitrite
(ONOO−) or 2 mM hydrogen peroxide (H2O2) in the presence/absence of ATH extract (5–15 μM); oxidative alterations were then assessed. Pre-incubation of plasma with
ATH extract partly reduced oxidative stress in plasma proteins and lipids. Dose-dependent reduction of both ONOO− and H2O2-mediated plasma protein carbonylation was observed. ATH extract partly inhibited the nitrative action of ONOO−, and significantly decreased plasma lipid peroxidation caused by ONOO− or H2O2. Our results demonstrate that anthocyanins present in red cabbage have inhibitory effects on ONOO− and H2O2-induced oxidative stress in blood plasma components. We suggest that red cabbage ATH, as dietary antioxidants, should be
considered as potentially usable nutraceuticals in the prevention of oxidative stress-related diseases. 相似文献