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41.
Metabolism describes the series of chemical reactions that are concerned with the provision of energy to biological systems. They may be divided into reactions involved in energy yield (catabolism: demand exceeds supply), and energy storage (anabolism: supply exceeds demand). Regulation of these pathways is critical for homeostasis, and derangements in metabolism are seen in a wide variety of pathological processes. Understanding metabolism is key to the treatment of many diseases, notably diabetes, as well as underpinning clinical nutritional support. 相似文献
42.
Matthieu Talagas Nicolas Lebonvallet Franois Berthod Laurent Misery 《Experimental dermatology》2019,28(12):1466-1469
Recent years have brought an enhanced understanding of keratinocyte contribution to cutaneous nociception. While intra‐epidermal nerve endings were classically considered as the exclusive transducers of cutaneous noxious stimuli, it has now been demonstrated that epidermal keratinocytes can initiate nociceptive responses, like Merkel cells do for the innocuous mechanotransduction. In the light of recent in vivo findings, this article outlines this paradigm shift that points to a not yet considered population of sensory epidermal cells. 相似文献
43.
Y.R. Song B. Wu Y.T. Yang J. Chen L.J. Zhang Z.W. Zhang H.Y. Shi C.L. Huang J.X. Pan P. Xie 《Brazilian journal of medical and biological research》2015,48(11):973-982
Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2%
of the general population of different European countries. Unfortunately, there is no
objective laboratory-based test to aid BD diagnosis or monitor its progression, and
little is known about the molecular basis of BD. Here, we performed a comparative
proteomic study to identify differentially expressed plasma proteins in various BD
mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A
total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched
healthy control subjects were recruited. Seven high-abundance proteins were
immunodepleted in plasma samples from the 4 experimental groups, which were then
subjected to proteome-wide expression profiling by two-dimensional electrophoresis
and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem
mass spectrometry. Proteomic results were validated by immunoblotting and
bioinformatically analyzed using MetaCore. From a total of 32 proteins identified
with 1.5-fold changes in expression compared with healthy controls, 16 proteins were
perturbed in BD independent of mood state, while 16 proteins were specifically
associated with particular BD mood states. Two mood-independent differential
proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be
associated with early perturbations in lipid metabolism. Moreover, down-regulation of
one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved
in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be
associated with early perturbations in lipid metabolism that are independent of mood
state, while CA-1 may be involved in the pathophysiology of depressive episodes. 相似文献
44.
《Biomaterials》2015
The human mutT homologue MTH1, a nucleotide pool sanitizing enzyme, represents a vulnerability factor and an attractive target for anticancer therapy. However, there is currently a lack of selective and effective platforms for the detection and inhibition of MTH1 in cells. Here, we demonstrate for the first time a gold nanoparticle (AuNP) flares-capped mesoporous silica nanoparticle (MSN) nanoplatform that is capable of detecting MTH1 mRNA and simultaneously suppressing MTH1 activity. The AuNP flares are made from AuNPs that are functionalized with a dense shell of MTH1 recognition sequences hybridized to short cyanine (Cy5)-labeled reporter sequences and employed to seal the pores of MSN to prevent the premature MTH1 inhibitors (S-crizotinib) release. Just like the pyrotechnic flares that produce brilliant light when activated, the resulting AuNP flares@MSN (S-crizotinib) undergo a significant burst of red fluorescence enhancement upon MTH1 mRNA binding. This hybridization event subsequently induces the opening of the pores and the release of S-crizotinib in an mRNA-dependent manner, leading to significant cytotoxicity in cancer cells and improved therapeutic response in mouse xenograft models. We anticipate that this nanoplatform may be an important step toward the development of MTH1-targeting theranostics and also be a useful tool for cancer phenotypic lethal anticancer therapy. 相似文献
45.
Yang Liu Yanyan Gao Hengliang Liu Qi Chen Jinrui Ji Kailong Jia 《Arquivos brasileiros de cardiologia》2021,116(2):229
BackgroundDual antiplatelet therapy (DAPT) is the cornerstone treatment of acute myocardial infarction (AMI).ObjectiveThe present study aimed to investigate the efficacy and safety of triple antiplatelet therapy (TAPT) in elderly female patients with diabetes and ST segment elevation myocardial infarction (STEMI), who had undergone percutaneous coronary intervention (PCI).MethodsWe designed a randomized, single-blind study. Control group A (97 elderly male patients with diabetes and STEMI, whose CRUSADE scores were < 30) received aspirin, ticagrelor, and tirofiban. A total of 162 elderly female patients with diabetes and STEMI were randomly divided into two groups according to CRUSADE score. Group B (69 patients with CRUSADE score > 31) received aspirin and ticagrelor. Group C (93 patients with CRUSADE score < 30) received aspirin, ticagrelor and tirofiban. P values < 0.05 were considered statistically significant.ResultsCompared to the findings in group A, post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow and TIMI myocardial perfusion grade 3 were significantly less prevalent in group B (p < 0.05). When compared to groups A and C, the incidence of major adverse complications was significantly higher in group B (p < 0.05).ConclusionTAPT could effectively reduce the incidence of major complications in elderly female patients with diabetes and STEMI. However, close attention should be paid to hemorrhage in patients receiving TAPT. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0) 相似文献
46.
Nidogen 1 (NID1) is a glycoprotein found in basement membranes involved in cross-linking collagen IV and laminin. The role of NID in breast cancer has only been evaluated in a small number of studies and the findings of these studies have been inconsistent. Our previous work revealed that highly tumorigenic murine mammary tumor cells express high levels of Nid1 while weakly tumorigenic mammary tumor cells express low levels of Nid1. To investigate Nid1, two stable knockdown lines were created, and Nid1 knockdown was confirmed at both the mRNA and protein level. Nid1 knockdown significantly reduced cell proliferation and migration/invasion and these reductions in proliferation and migration/invasion could be rescued by conditioned media containing NID1 protein. The reduced migration/invasion observed in the Nid1 knockdown cells was not associated with significant alterations in the epithelial gene Cdh1 or the mesenchymal genes Snai1, Snai2, Twist1, Twist2, Zeb1 and Zeb2. Therefore, suppression of Nid1 expression reduces proliferation and migration/invasion in claudin-low murine mammary tumor cells. 相似文献
47.
48.
49.
Osric A. Forrest Daniel M. Chopyk Yael Gernez Milton R. Brown Carol K. Conrad Richard B. Moss Vin Tangpricha Limin Peng Rabindra Tirouvanziam 《Journal of cystic fibrosis》2019,18(1):64-70
Background
Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.Methods
Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.Results
Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).Conclusions
Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF. 相似文献50.
目的 探究醛糖还原酶和晚期糖基化终末产物受体对糖尿病视网膜病变神经元凋亡的影响。方法 Wistar大鼠36只,随机分为对照组、模型组、转染组,后两组建立糖尿病大鼠模型。模型建立成功后,构建含有晚期糖基化终末产物受体siRNA的质粒并利用慢病毒转染入转染组大鼠体内。造模后4周、8周、12周,记录各组大鼠体质量及空腹血糖。造模后9周,禁食6 h,测定口服葡萄糖耐量。造模后12周,处死全部大鼠后,TUNEL法检测各组大鼠视网膜神经元凋亡情况,荧光分光光度计测定醛糖还原酶活性,Western blotting法测定晚期糖基化终末产物受体的表达,RT-PCR检测视网膜中Bcl-2和Bax mRNA相对表达量。结果 造模后4周、8周、12周,转染组和模型组的大鼠体质量均低于对照组(均为P<0.05);造模后12周,转染组大鼠体质量高于模型组(P<0.05)。造模后4周、8周、12周,各组内大鼠空腹血糖水平均无明显变化(均为P>0.05),转染组和模型组大鼠的空腹血糖水平均高于对照组(均为P<0.05)。模型组和转染组大鼠在口服葡萄糖后30 min时,血糖水平均高于对照组(均为P<0.05);在120 min时分别下降至最低,但仍高于对照组(均为P<0.05)。模型组和转染组的视网膜神经元凋亡指数、醛糖还原酶活性、晚期糖基化终末产物受体和Bax mRNA相对表达量均高于对照组(均为P<0.05),且转染组均高于模型组(均为P<0.05)。模型组和转染组的Bcl-2 mRNA相对表达量均低于对照组(均为P<0.05),转染组低于模型组(P<0.05)。结论 晚期糖基化终末产物结合受体后产生大量的氧自由基损伤,可能是导致糖尿病视网膜神经元凋亡,进而导致糖尿病视网膜病变发生的机制之一。 相似文献