115 research outputs found
Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients
Background: Emerging data indicates that extracellular traps (ETs), structures formed by various immune cell types,
may contribute to the pathology of noninfectious infammatory diseases. Histone hypercitrullination is an important
step in ETs formation and citrullinated histone H3 (H3cit) is considered a novel and specifc biomarker of that process.
In the present study we have evaluated circulating H3cit in stable asthmatics and investigated its relationship with
asthma severity, pulmonary function and selected blood and bronchoalveolar lavage (BAL) biomarkers.
Methods: In 60 white adult stable asthmatics and 50 well-matched controls we measured serum levels of H3cit. In
asthmatics we also performed bronchoscopy with BAL. We analyzed blood and BAL biomarkers, including interleukin
(IL)-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A and interferon Îł. For statistical analysis, Mann-Whitney U-test, Ï2
test, one-way
ANCOVA, ROC curve analysis and univariate linear regression were applied. Independent determinants of H3cit were
established in a multiple linear regression model.
Results: Asthma was characterized by elevated circulating H3cit (17.49 [11.25â22.58] vs. 13.66 [8.66â18.87] ng/ml,
p=0.03). In asthmatics positive associations were demonstrated between serum H3cit and lung function variables,
including total lung capacity (TLC) (ÎČ=0.37 [95% CI 0.24-0.50]) and residual volume (ÎČ=0.38 [95% CI 0.25â0.51]).
H3cit was increased in asthma patients receiving systemic steroids (p=0.02), as well as in subjects with BAL eosinoâ
philia above 144 cells/ml (p=0.02). In asthmatics, but not in controls, circulating H3cit correlated well with number
of neutrophils (ÎČ=0.31 [95% CI 0.19â0.44]) and monocytes (ÎČ=0.42 [95% CI 0.29â0.55]) in peripheral blood. Furtherâ
more, BAL macrophages, BAL neutrophils, TLC, high-sensitivity C-reactive protein, Il-12p70 and bronchial obstruction
degree were independent determinants of H3cit in a multivariate linear regression model.
Conclusions: Asthma is characterized by increased circulating H3cit likely related to the enhanced lung ETs formaâ
tion. Inhibition of ETs might be a therapeutic option in selected asthma phenotypes, such as neutrophilic asthma
Increased oxidative stress in asthma - relation to inflammatory blood and lung biomarkers and airway remodeling indices
Airway inflammation in asthma is related to increased reactive oxygen species generation, potentially leading to tissue injury and subsequent airway remodeling. We evaluated oxidative stress in peripheral blood from asthmatic subjects (n = 74) and matched controls (n = 65), using recently developed real-time monitoring of the protein hydroperoxide (HP) formation by the coumarin boronic acid (CBA) assay. We also investigated the relation of the systemic oxidative stress response in asthma to disease severity, lung function, airway remodeling indices (lung computed tomography and histology), and blood and bronchoalveolar lavage fluid (BAL) inflammatory biomarkers. We documented enhanced systemic oxidative stress in asthma, reflected by 35% faster and 58% higher cumulative fluorescent product generation in the CBA assay (p < 0.001 for both). The dynamics of HP generation correlated inversely with lung function but not with asthma severity or histological measures of airway remodeling. HP generation was associated positively with inflammatory indices in the blood (e.g., C-reactive protein) and BAL (e.g., interleukin [IL]-6, IL-12p70, and neutrophil count). Bronchial obstruction, thicker airway walls, increased BAL IL-6, and citrullinated histone 3 in systemic circulation independently determined increased HP formation. In conclusion, a real-time CBA assay showed increased systemic HP generation in asthma. In addition, it was associated with inflammatory biomarkers, suggesting that proper disease control can also lead to a decrease in oxidative stress
Reticular basement membrane thickness is associated with growth : and fibrosis-promoting airway transcriptome profile-study in asthma patients
Airway remodeling in asthma is characterized by reticular basement membrane (RBM) thickening, likely related to epithelial structural and functional changes. Gene expression profiling of the airway epithelium might identify genes involved in bronchial structural alterations. We analyzed bronchial wall geometry (computed tomography (CT)), RBM thickness (histology), and the bronchial epithelium transcriptome profile (gene expression array) in moderate to severe persistent (n = 21) vs. no persistent (n = 19) airflow limitation asthmatics. RBM thickness was similar in the two studied subgroups. Among the genes associated with increased RBM thickness, the most essential were those engaged in cell activation, proliferation, and growth (e.g., CDK20, TACC2, ORC5, and NEK5) and inhibiting apoptosis (e.g., higher mRNA expression of RFN34, BIRC3, NAA16, and lower of RNF13, MRPL37, CACNA1G). Additionally, RBM thickness correlated with the expression of genes encoding extracellular matrix (ECM) components (LAMA3, USH2A), involved in ECM remodeling (LTBP1), neovascularization (FGD5, HPRT1), nerve functioning (TPH1, PCDHGC4), oxidative stress adaptation (RIT1, HSP90AB1), epigenetic modifications (OLMALINC, DNMT3A), and the innate immune response (STAP1, OAS2). Cluster analysis revealed that genes linked with RBM thickness were also related to thicker bronchial walls in CT. Our study suggests that the pro-fibrotic profile in the airway epithelial cell transcriptome is associated with a thicker RBM, and thus, may contribute to asthma airway remodeling
ĐĐœĐ°ŃĐ”ĐœĐžĐ” плаŃŃĐžĐșĐž Đ»ĐŸŃĐșŃŃĐŸĐŒ ĐœĐ° ĐČŃĐ”ĐŒĐ”ĐœĐœĐŸĐč пОŃĐ°ŃŃĐ”Đč ĐœĐŸĐ¶ĐșĐ” ĐČ Đ·Đ°ĐŒĐ”ŃĐ”ĐœĐžĐž ŃĐ°ĐœĐ”ĐČŃŃ ĐŽĐ”ŃĐ”ĐșŃĐŸĐČ
Đ ĐĐĐ« РйРĐĐĐĐ« /Đ„ĐĐ ĐĐĐРйРĐĐĐĄĐĐĐĐĐąĐĐŠĐĐŻĐĐĐ ĐĐĄĐĐĐĐ ĐĐĐĐĐĐĐ ĐĐĐąĐĐĐĐĐĄĐąĐĐĐĐĐĐĄĐУйЫЄĐĐ ĐŁĐ ĐĐЧĐĐĄĐĐĐ ĐĐĐĄĐУйЫЄĐĐ ĐŁĐ ĐĐЧĐĐĄĐĐĐ ĐĐĐĐ ĐĐŠĐĐ ĐĐĐĄĐĄĐąĐĐĐĐĐĐąĐĐĐŹĐĐ«Đ /ĐĐĐąĐĐĐ«ĐĐąĐĐĐŹĐŻĐĐĄĐĐĐŻ ĐĐĐĐĄĐąĐĐĐĐĐĐĐĄĐąĐĐĐ ĐĐąĐĐĐŹĐŻĐĐĄĐĐĐŻĐ ĐĐĐĐĐ«Đ ĐĐĐĐ Đ«ĐąĐЯЊДлŃ. ĐŃĐŸĐČĐ”ŃŃĐž ĐșĐŸĐŒĐżĐ»Đ”ĐșŃĐœŃĐč Đ°ĐœĐ°Đ»ĐžĐ· ĐČĐŸĐ·ĐŒĐŸĐ¶ĐœĐŸŃŃĐ”Đč, ŃĐ”Ń
ĐœĐžŃĐ”ŃĐșĐžŃ
ĐŸŃĐŸĐ±Đ”ĐœĐœĐŸŃŃĐ”Đč Đž ĐœĐ”ĐŽĐŸŃŃĐ°ŃĐșĐŸĐČ ĐŒĐ”ŃĐŸĐŽĐžĐșĐž плаŃŃĐžĐșĐž ŃĐ°Đœ пДŃĐ”ĐŒĐ”ŃĐ”ĐœĐœŃĐŒ Оз ĐŸŃĐŽĐ°Đ»Đ”ĐœĐœŃŃ
ĐŸĐ±Đ»Đ°ŃŃĐ”Đč ŃĐ»ĐŸĐ¶ĐœĐŸŃĐŸŃŃĐ°ĐČĐœŃĐŒ ĐșĐŸĐ¶ĐœŃĐŒ Đ»ĐŸŃĐșŃŃĐŸĐŒ ĐœĐ° ĐČŃĐ”ĐŒĐ”ĐœĐœĐŸĐč пОŃĐ°ŃŃĐ”Đč ĐœĐŸĐ¶ĐșĐ” ĐżŃĐž Đ·Đ°ĐșŃŃŃОО ŃĐ°ĐœĐ”ĐČŃŃ
ĐŽĐ”ŃĐ”ĐșŃĐŸĐČ ĐșĐŸĐœĐ”ŃĐœĐŸŃŃĐ”Đč. ĐĐ°ŃĐ”ŃОал Đž ĐŒĐ”ŃĐŸĐŽŃ. Đ ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžĐ” ĐČĐșĐ»ŃŃĐ”ĐœĐŸ 14 паŃĐžĐ”ĐœŃĐŸĐČ Ń ŃĐ°ĐœĐ”ĐČŃĐŒĐž ĐŽĐ”ŃĐ”ĐșŃĐ°ĐŒĐž ĐșĐŸĐœĐ”ŃĐœĐŸŃŃĐ”Đč ŃазлОŃĐœĐŸĐłĐŸ ĐżŃĐŸĐžŃŃ
ĐŸĐ¶ĐŽĐ”ĐœĐžŃ, ĐșĐŸŃĐŸŃŃĐŒ ĐœĐ° ĐČĐŸŃŃŃĐ°ĐœĐŸĐČĐžŃДлŃĐœĐŸĐŒ ŃŃапД лДŃĐ”ĐœĐžŃ ĐżŃĐžĐŒĐ”ĐœĐ”Đœ ĐŒĐ”ŃĐŸĐŽ плаŃŃĐžĐșĐž пДŃĐ”ĐŒĐ”ŃĐ”ĐœĐœŃĐŒ Оз ĐŸŃĐŽĐ°Đ»Đ”ĐœĐœŃŃ
ĐŸĐ±Đ»Đ°ŃŃĐ”Đč ŃĐ»ĐŸĐ¶ĐœĐŸŃĐŸŃŃĐ°ĐČĐœŃĐŒ ĐșĐŸĐ¶ĐœŃĐŒ Đ»ĐŸŃĐșŃŃĐŸĐŒ ĐœĐ° ĐČŃĐ”ĐŒĐ”ĐœĐœĐŸĐč пОŃĐ°ŃŃĐ”Đč ĐœĐŸĐ¶ĐșĐ”. Đ Đ°ĐœĐ”ĐČŃĐ” ĐŽĐ”ŃĐ”ĐșŃŃ ĐžĐŒĐ”Đ»Đž ŃазлОŃĐœĐŸĐ” ĐżŃĐŸĐžŃŃ
ĐŸĐ¶ĐŽĐ”ĐœĐžĐ” (глŃĐ±ĐŸĐșОД ĐŸŃĐŒĐŸŃĐŸĐ¶Đ”ĐœĐžŃ, Ń
ŃĐŸĐœĐžŃĐ”ŃĐșĐžĐč ĐŸŃŃĐ”ĐŸĐŒĐžĐ”Đ»ĐžŃ, ĐœĐ”ĐčŃĐŸŃŃĐŸŃĐžŃĐ”ŃĐșОД ĐœĐ°ŃŃŃĐ”ĐœĐžŃ), Đ»ĐŸĐșалОзаŃĐžŃ Đž ĐżĐ»ĐŸŃĐ°ĐŽŃ. ĐĐŸĐșĐ°Đ·Đ°ĐœĐžĐ”ĐŒ Đș ĐŽĐ°ĐœĐœĐŸĐŒŃ ĐČĐžĐŽŃ ĐżĐŸĐ»ĐœĐŸŃĐ»ĐŸĐčĐœĐŸĐč плаŃŃĐžĐșĐž ŃĐ»ŃжОла ĐœĐ”ĐŸĐ±Ń
ĐŸĐŽĐžĐŒĐŸŃŃŃ Đ·Đ°ĐșŃŃŃĐžŃ ŃĐ°ĐœŃ ĐČ ŃŃĐœĐșŃĐžĐŸĐœĐ°Đ»ŃĐœĐŸ Đ·ĐœĐ°ŃĐžĐŒĐŸĐč Đ·ĐŸĐœĐ” Đž ĐœĐ”ĐČĐŸĐ·ĐŒĐŸĐ¶ĐœĐŸŃŃŃ ĐżŃĐžĐŒĐ”ĐœĐ”ĐœĐžŃ ĐŽŃŃгОŃ
, Đ±ĐŸĐ»Đ”Đ” ĐżŃĐŸŃŃŃŃ
ĐŒĐ”ŃĐŸĐŽĐŸĐČ ĐșĐŸĐ¶ĐœĐŸĐč плаŃŃĐžĐșĐž. РДзŃĐ»ŃŃĐ°ŃŃ. ĐĐŸĐ»ĐŸĐ¶ĐžŃДлŃĐœŃĐč блОжаĐčŃĐžĐč ŃДзŃĐ»ŃŃĐ°Ń Đ»Đ”ŃĐ”ĐœĐžŃ ĐżĐŸĐ»ŃŃĐ”Đœ ĐČĐŸ ĐČŃĐ”Ń
14 ŃĐ»ŃŃĐ°ŃŃ
пДŃĐ”ĐŒĐ”ŃĐ”ĐœĐžŃ ĐżĐŸĐ»ĐœĐŸŃĐ»ĐŸĐčĐœŃŃ
ĐșĐŸĐ¶ĐœŃŃ
Đ»ĐŸŃĐșŃŃĐŸĐČ ĐžĐ· ĐŸŃĐŽĐ°Đ»Đ”ĐœĐœŃŃ
ŃĐ°ŃŃĐ”Đč ŃДла. Đ 3 ŃĐ»ŃŃĐ°ŃŃ
ĐČ ŃĐ°ĐœĐœĐ”ĐŒ ĐżĐŸŃĐ»Đ”ĐŸĐżĐ”ŃĐ°ŃĐžĐŸĐœĐœĐŸĐŒ пДŃĐžĐŸĐŽĐ” ĐŸŃĐŒĐ”ŃĐ”ĐœĐŸ ŃĐ°Đ·ĐČĐžŃОД ĐŸŃĐ»ĐŸĐ¶ĐœĐ”ĐœĐžĐč (ĐșŃĐžŃĐžŃĐ”ŃĐșĐžĐč пДŃДгОб ĐœĐŸĐ¶ĐșĐž Đ»ĐŸŃĐșŃŃĐ°, ĐżĐŸĐŽĐ»ĐŸŃĐșŃŃĐœĐ°Ń ĐłĐ”ĐŒĐ°ŃĐŸĐŒĐ°, ĐșŃĐ°Đ”ĐČĐŸĐč ĐœĐ”ĐșŃĐŸĐ· Đ»ĐŸŃĐșŃŃĐ°), ĐœĐ” ĐżĐŸĐČлОŃĐČŃĐžŃ
ŃŃŃĐ”ŃŃĐČĐ”ĐœĐœĐŸ ĐœĐ° блОжаĐčŃĐžĐč ŃДзŃĐ»ŃŃĐ°Ń ĐŸĐżĐ”ŃĐ°ŃОО. ĐŃĐŽĐ°Đ»Đ”ĐœĐœŃĐ” ŃДзŃĐ»ŃŃĐ°ŃŃ Đ»Đ”ŃĐ”ĐœĐžŃ ĐŸŃĐ”ĐœĐ”ĐœŃ Ń 8 паŃĐžĐ”ĐœŃĐŸĐČ ĐČ ŃŃĐŸĐșĐž ĐŸŃ 1 ĐŽĐŸ 22 Đ»Đ”Ń ĐżĐŸŃлД ĐŸĐżĐ”ŃĐ°ŃОО. ĐĐ»ŃŃĐ”ĐČŃĐŒ ĐŒĐŸĐŒĐ”ĐœŃĐŸĐŒ, ĐŸĐżŃДЎДлŃŃŃĐžĐŒ ĐŸŃĐŽĐ°Đ»Đ”ĐœĐœŃĐč ŃДзŃĐ»ŃŃĐ°Ń Đ»Đ”ŃĐ”ĐœĐžŃ, ŃŃала ĐșĐŸĐŒĐżĐ»Đ°Đ”ĐœŃĐœĐŸŃŃŃ ĐżĐ°ŃĐžĐ”ĐœŃĐ° ĐČ ŃŃĐ»ĐŸĐČĐžŃŃ
ĐŽĐ”ĐœĐ”ŃĐČĐ°ŃОО Đ»ĐŸŃĐșŃŃĐ° Đž Đ·Đ°ĐșŃŃŃĐžŃ ŃĐ°Đœ ĐČ ŃŃĐœĐșŃĐžĐŸĐœĐ°Đ»ŃĐœĐŸ Đ·ĐœĐ°ŃĐžĐŒŃŃ
ĐŸĐ±Đ»Đ°ŃŃŃŃ
. Đ ĐŽĐČŃŃ
ŃĐ»ŃŃĐ°ŃŃ
Ń ĐżĐ°ŃĐžĐ”ĐœŃĐŸĐČ, ĐœĐ” ŃĐŸĐ±Đ»ŃĐŽĐ°ŃŃĐžŃ
ŃĐ”ĐșĐŸĐŒĐ”ĐœĐŽĐ°ŃОО, ĐżŃĐŸĐžĐ·ĐŸŃДл ĐœĐ”ĐșŃĐŸĐ· Đ»ĐŸŃĐșŃŃĐ° ĐČ Đ·ĐŸĐœĐ” ĐŸĐżĐŸŃĐœĐŸĐč ĐżĐŸĐČĐ”ŃŃ
ĐœĐŸŃŃĐž ŃŃĐŸĐżŃ. Đ ĐŸŃŃĐ°Đ»ŃĐœŃŃ
ĐœĐ°Đ±Đ»ŃĐŽĐ”ĐœĐžŃŃ
ĐżĐŸĐ»ŃŃĐ”Đœ ŃŃĐŸĐčĐșĐžĐč ĐżĐŸĐ»ĐŸĐ¶ĐžŃДлŃĐœŃĐč ŃДзŃĐ»ŃŃĐ°Ń. ĐĐ°ĐșĐ»ŃŃĐ”ĐœĐžĐ”. ĐлаŃŃĐžĐșĐ° ŃĐ°Đœ пДŃĐ”ĐŒĐ”ŃĐ”ĐœĐœŃĐŒ Оз ĐŸŃĐŽĐ°Đ»Đ”ĐœĐœŃŃ
ĐŸĐ±Đ»Đ°ŃŃĐ”Đč ŃĐ»ĐŸĐ¶ĐœĐŸŃĐŸŃŃĐ°ĐČĐœŃĐŒ ĐșĐŸĐ¶ĐœŃĐŒ Đ»ĐŸŃĐșŃŃĐŸĐŒ ŃĐČĐ»ŃĐ”ŃŃŃ ŃŃŃĐ”ĐșŃĐžĐČĐœŃĐŒ ĐŒĐ”ŃĐŸĐŽĐŸĐŒ ŃĐ”ĐșĐŸĐœŃŃŃŃĐșŃОО ĐČ ŃŃĐœĐșŃĐžĐŸĐœĐ°Đ»ŃĐœĐŸ Đ·ĐœĐ°ŃĐžĐŒŃŃ
ĐŸĐ±Đ»Đ°ŃŃŃŃ
ĐČ ŃŃĐ»ĐŸĐČĐžŃŃ
ĐŸĐłŃĐ°ĐœĐžŃĐ”ĐœĐœŃŃ
плаŃŃĐžŃĐ”ŃĐșĐžŃ
ŃДзДŃĐČĐŸĐČ ĐŸĐșŃŃжаŃŃĐ”Đč ĐșĐŸĐ¶Đž. ĐĐ”ĐœĐ”ŃĐČĐ°ŃĐžŃ ŃĐ°ĐșĐžŃ
Đ»ĐŸŃĐșŃŃĐŸĐČ ĐżŃДЎŃŃĐČĐ»ŃĐ”Ń ĐŽĐŸĐżĐŸĐ»ĐœĐžŃДлŃĐœŃĐ” ŃŃĐ”Đ±ĐŸĐČĐ°ĐœĐžŃ Đș паŃĐžĐ”ĐœŃĐ°ĐŒ ĐČ ĐżĐ»Đ°ĐœĐ” ŃĐŸĐ±Đ»ŃĐŽĐ”ĐœĐžŃ ŃĐ”ĐșĐŸĐŒĐ”ĐœĐŽĐ°ŃĐžĐč. ĐŁŃпДŃ
ĐŸĐżĐ”ŃĐ°ŃОО ĐČ ĐŸŃĐŽĐ°Đ»Đ”ĐœĐœŃĐ” ŃŃĐŸĐșĐž ĐČĐŸ ĐŒĐœĐŸĐłĐŸĐŒ ĐŸĐżŃДЎДлŃĐ”ŃŃŃ ĐșĐŸĐŒĐżĐ»Đ°Đ”ĐœŃĐœĐŸŃŃŃŃ ĐżĐ°ŃĐžĐ”ĐœŃĐ°.Objective. Comprehensive analysis of opportunities, technical features and disadvantages of wound plasty with distant pedicled flap closing wound defects of the limbs was performed. Methods. The study included 14 patients with limb wounds of different origin, who were treated using distant pedicled flaps grafting. Wounds were of different origin (deep frostbites, chronic osteomyelitis, neurotrophic disorders), diverse localization and perimeter. The indication for this type of full-layer plastics was the need to treat the wound in a functionally significant zone and the impossibility of using other, less complex methods of skin grafting. Results. A positive immediate result of treatment was obtained in all 14 cases of distant flaps grafting. The development of complications (critical bend of the pedicle of the flap, sub-flap hematoma, the flapâs edge necrosis) was registered in 3 cases in the early postoperative period, those complications did not significantly affect the immediate outcome of the operation. Long-term outcomes of treatment were evaluated in 8 patients in terms from 1 to 22 years after the operation. The key point determining the long-term treatment outcome was the patientâs compliance in the conditions of denervation of the flap and closure of wounds in functionally important areas. A flap necrosis in the plantar area occurred in two cases in patients, who did not follow the recommendations. In the remaining observations a stable positive result was obtained. Conclusions. The distant pedicled flaps grafting is an effective method of reconstruction in functionally important areas under the conditions of limited plastic reserves of the surrounding skin. Denervation of such flaps exposes additional requirements to patients in terms of compliance with recommendations. The success of the operation in the long term period is largely determined by the patientâs compliance
Experimental and theoretical studies of nanofluid thermal conductivity enhancement: a review
Nanofluids, i.e., well-dispersed (metallic) nanoparticles at low- volume fractions in liquids, may enhance the mixture's thermal conductivity, knf, over the base-fluid values. Thus, they are potentially useful for advanced cooling of micro-systems. Focusing mainly on dilute suspensions of well-dispersed spherical nanoparticles in water or ethylene glycol, recent experimental observations, associated measurement techniques, and new theories as well as useful correlations have been reviewed
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field
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