Редактирование: CFB (раздел)

==Publications==

{{medline-entry
|title=Effect of Age on the Efficacy and Safety of Once-Daily Single-Inhaler Triple Therapy Fluticasone Furoate/Umeclidinium/Vilanterol in Patients With Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis of the [[IMPACT]] Trial.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33031829
|abstract=In the [[IMPACT]] trial, single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduced moderate/severe exacerbation rates versus FF/VI and UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations, with a similar safety profile. Research Question Does age have an effect on trial outcomes? [[IMPACT]] was a Phase III, double-blind, 52-week trial. Patients ≥40 years of age with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 mcg, FF/VI 100/25 mcg, or UMEC/VI 62.5/25 mcg. Endpoints assessed by age included annual rate of moderate/severe exacerbations, change from baseline ([[CFB]]) in trough forced expiratory volume in 1 second ([[FEV]] ), proportion of St George's Respiratory Questionnaire (SGRQ) responders (≥4 units decrease from baseline in SGRQ total score) and safety. The intent-to-treat population comprised 10,355 patients; 4724 (46%), 4225 (41%), and 1406 (14%) were ≤64, 65-74, and ≥75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates versus FF/VI (% reduction [95% confidence interval (CI)], ≤64 years: 8% [-1, 16], p=0.070; 65-74 years: 22% [14, 29], p<0.001; ≥75 years 18% [3, 31], p=0.021) and versus UMEC/VI (≤64 years: 16% [7, 25], p=0.002; 65-74 years: 33% [25, 41], p<0.001; ≥75 years 24% [6, 38], p=0.012), with greatest rate reduction seen in the 65-74 and ≥75 years subgroups. Post hoc analyses of [[CFB]] in trough [[FEV]] , and proportion of SGRQ responders at Week 52 were significantly greater with FF/UMEC/VI than FF/VI or UMEC/VI in all subgroups. No new safety signals were identified. FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status versus FF/VI and UMEC/VI irrespective of age for most endpoints, with a similar safety profile. GSK (CTT116855/NCT02164513).

|keywords=* COPD
* aging
* exacerbations
* safety
* single-inhaler triple therapy
|full-text-url=https://sci-hub.do/10.1016/j.chest.2020.09.253
}}
{{medline-entry
|title=The expression of C1 inhibitor (C1INH) in macrophages is upregulated by retinal pigment epithelial cells - implication in subretinal immune privilege in the aging eye.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29905533
|abstract=Age-related para-inflammation in the retina-choroidal interface is featured by low-levels of complement activation and subretinal macrophage accumulation. This study aimed to understand how complement expression in macrophages is regulated by retinal pigment epithelium ([[RPE]]). Bone marrow-derived macrophages (BMDMs) and [[RPE]] cells were cultured from 8-10 weeks old C57BL/6J mice. The BMDMs were co-cultured with normal [[RPE]], or oxidized photoreceptor outer segment (oxPOS) or [[TNF]]-α pre-treated [[RPE]], or apoptotic [[RPE]], or [[RPE]]-choroid eyecups. Macrophages were then isolated and processed for real-time RT-PCR. The expression of complement inhibitor C1INH in BMDMs was significantly upregulated by [[RPE]] and [[RPE]]-choroid eyecups. The eyecups also upregulated [[CFH]], CD59a, and Crry in BMDMs. oxPOS pre-treated [[RPE]] upregulated C1qb but down-regulated [[C3]] expression in BMDMs. [[TNF]]-α pre-treated [[RPE]] enhanced C1INH and [[CFB]] expression. When BMDMs were treated with apoptotic [[RPE]], the expression of C1qb, [[CFH]], and CD59a was reduced, whereas the expression of [[C3]], [[CFB]] and C1INH was increased. Our results suggest that [[RPE]] can modulate macrophages complement expression at the retina-choroidal interface even under aging or oxidative conditions. However, during inflammation, they may promote the alternative pathway of complement activation through down-regulating [[CFH]] and CD59a and upregulating [[CFB]] and [[C3]].
|mesh-terms=* Animals
* Cattle
* Cells, Cultured
* Coculture Techniques
* Complement C1 Inhibitor Protein
* Epithelial Cells
* Macrophages
* Mice
* Photoreceptor Cells, Vertebrate
* Retinal Pigment Epithelium
* Tumor Necrosis Factor-alpha
* Up-Regulation
|keywords=* aging
* complement
* macrophages
* retinal pigment epithelial cells
* subretinal immune privilege
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046230
}}
{{medline-entry
|title=Extended Multiplexing of Tandem Mass Tags (TMT) Labeling Reveals Age and High Fat Diet Specific Proteome Changes in Mouse Epididymal Adipose Tissue.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28325852
|abstract=The lack of high-throughput methods to analyze the adipose tissue protein composition limits our understanding of the protein networks responsible for age and diet related metabolic response. We have developed an approach using multiple-dimension liquid chromatography tandem mass spectrometry and extended multiplexing (24 biological samples) with tandem mass tags (TMT) labeling to analyze proteomes of epididymal adipose tissues isolated from mice fed either low or high fat diet for a short or a long-term, and from mice that aged on low [i]versus[/i] high fat diets. The peripheral metabolic health (as measured by body weight, adiposity, plasma fasting glucose, insulin, triglycerides, total cholesterol levels, and glucose and insulin tolerance tests) deteriorated with diet and advancing age, with long-term high fat diet exposure being the worst. In response to short-term high fat diet, 43 proteins representing lipid metabolism ([i]e.g.[/i] [[AACS]], [[ACOX1]], ACLY) and red-ox pathways ([i]e.g.[/i] CPD2, CYP2E, SOD3) were significantly altered (FDR < 10%). Long-term high fat diet significantly altered 55 proteins associated with immune response ([i]e.g.[/i] IGTB2, [[IFIT3]], LGALS1) and rennin angiotensin system ([i]e.g.[/i] [[ENPEP]], [[CMA1]], [[CPA3]], ANPEP). Age-related changes on low fat diet significantly altered only 18 proteins representing mainly urea cycle ([i]e.g.[/i] [[OTC]], [[ARG1]], CPS1), and amino acid biosynthesis ([i]e.g.[/i] GMT, AKR1C6). Surprisingly, high fat diet driven age-related changes culminated with alterations in 155 proteins involving primarily the urea cycle ([i]e.g.[/i] [[ARG1]], CPS1), immune response/complement activation ([i]e.g.[/i] [[C3]], C4b, C8, [[C9]], [[CFB]], [[CFH]], FGA), extracellular remodeling ([i]e.g.[/i] [[EFEMP1]], [[FBN1]], [[FBN2]], [[LTBP4]], [[FERMT2]], [[ECM1]], [[EMILIN2]], ITIH3) and apoptosis ([i]e.g.[/i] [[YAP1]], [[HIP1]], [[NDRG1]], [[PRKCD]], MUL1) pathways. Using our adipose tissue tailored approach we have identified both age-related and high fat diet specific proteomic signatures highlighting a pronounced involvement of arginine metabolism in response to advancing age, and branched chain amino acid metabolism in early response to high fat feeding. Data are available via ProteomeXchange with identifier PXD005953.
|mesh-terms=* Adipose Tissue
* Aging
* Animals
* Diet, High-Fat
* Epididymis
* Gene Regulatory Networks
* Immunoblotting
* Male
* Mass Spectrometry
* Metabolic Networks and Pathways
* Mice, Inbred C57BL
* Proteome
* Proteomics
* Reproducibility of Results
* Sample Size

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417827
}}
{{medline-entry
|title=Genetic factors associated with the development of age-related macular degeneration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27170480
|abstract=Age-related macular degeneration (AMD) affects the macula and is the leading cause of significant and irreversible central visual loss. It is the most common cause of visual loss in people aged more than 60 years. This disease affects 2.5 million individuals in Europe. AMD is caused by both environmental and genetic factors. Numerous risk factors have been reported, but the pathogenesis of AMD is complex and fairly understood. Age, female gender, obesity, race, education status, family history, hyperopia, iris color, cigarette smoking, previous cataract surgery, history of cardiovascular and cerebrovascular disease, diabetes, sunlight exposure and many other factors have been shown to be associated with AMD development. Scientific evidence shows that genes may play a role in the development of nearly 3 out of 4 cases of this devastating eye disease. The genes that have been shown to be associated with AMD are genes encoding complement system components such as [[CFH]], [[C2]], [[C3]], [[CFB]], and other. 
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Diabetes Complications
* Europe
* Female
* Genetic Predisposition to Disease
* Humans
* Macular Degeneration
* Male
* Middle Aged
* Obesity
* Prevalence
* Risk Factors
|keywords=* Early and late age-related macular degeneration
* Genes
* Risk factors
|full-text-url=https://sci-hub.do/10.1016/j.medici.2016.02.004
}}
{{medline-entry
|title=Gene expression changes in aging retinal microglia: relationship to microglial support functions and regulation of activation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23608111
|abstract=Microglia, the resident immune cells of the central nervous system (CNS), are thought to contribute to the pathogenesis of age-related neurodegenerative disorders. It has been hypothesized that microglia undergo age-related changes in gene expression patterns that give rise to pathogenic phenotypes. We compared the gene expression profiles in microglia isolated ex vivo from the retinas of mice ranging from early adulthood to late senescence. We discovered that microglial gene expression demonstrated progressive change with increasing age, and involved genes that regulate microglial supportive functions and immune activation. Molecular pathways involving immune function and regulation, angiogenesis, and neurotrophin signaling demonstrated age-related change. In particular, expression levels of complement genes, [[C3]] and [[CFB]], previously associated with age-related macular degeneration (AMD), increased with aging, suggesting that senescent microglia may contribute to complement dysregulation during disease pathogenesis. Taken together, senescent microglia demonstrate age-related gene expression changes capable of altering their constitutive support functions and regulation of their activation status in ways relating to neuroinflammation and neurodegeneration in the CNS. 
|mesh-terms=* Aging
* Animals
* Central Nervous System Diseases
* Complement C3c
* Complement Factor B
* Gene Expression Profiling
* Gene Expression Regulation, Developmental
* Immunity
* Inflammation
* Macular Degeneration
* Male
* Mice
* Mice, Inbred C57BL
* Microglia
* Nerve Growth Factors
* Neurodegenerative Diseases
* Retina
* Signal Transduction
|keywords=* Activation
* Aging
* Angiogenesis
* Complement
* Gene expression
* Microarray
* Microglia
* Neurotrophic factors
* Retina
* Senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706521
}}
{{medline-entry
|title=Genetic variation in complement regulators and susceptibility to age-related macular degeneration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22024702
|abstract=Age-related macular degeneration (AMD) is the commonest cause of blindness in Western populations. Risk is influenced by age, genetic and environmental factors. Complement activation appears to be important in the pathogenesis and associations have been found between AMD and genetic variations in complement regulators such as complement factor H. We therefore investigated other complement regulators for association with AMD. We carried out a case-control study to test for association between AMD and single nucleotide polymorphisms (SNPs) spanning the genes encoding complement factor P ([[CFP]], properdin), [[CD46]] (membrane cofactor protein, MCP), [[CD55]] (decay accelerating factor, DAF) and [[CD59]] (protectin). All cases and controls were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status. 20 SNPs were genotyped in 446 cases and 262 controls. For two SNPs with p-values approaching significance additional subjects were genotyped to increase the numbers to 622 cases and 359 controls. There was no evidence of association between AMD and any of the SNPs typed in [[CFP]], [[CD46]], [[CD55]] or [[CD59]]. In a case-control sample that has shown the well established associations between AMD and variants in [[CFH]], [[CFB]] and [[C3]] there was absence of association with SNPs in [[CFP]], [[CD46]], [[CD55]] and [[CD59]]. This suggests that these are not important susceptibility genes for AMD.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* CD55 Antigens
* CD59 Antigens
* Case-Control Studies
* Complement System Proteins
* Female
* Genetic Association Studies
* Genetic Predisposition to Disease
* Genetic Variation
* Genotype
* Humans
* Macular Degeneration
* Male
* Membrane Cofactor Protein
* Polymorphism, Single Nucleotide
* Properdin

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657157
}}
{{medline-entry
|title=Genetic control of the alternative pathway of complement in humans and age-related macular degeneration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19825847
|abstract=Activation of the alternative pathway of complement is implicated in common neurodegenerative diseases including age-related macular degeneration (AMD). We explored the impact of common variation in genes encoding proteins of the alternative pathway on complement activation in human blood and in AMD. Genetic variation across the genes encoding complement factor H ([[CFH]]), factor B ([[CFB]]) and component 3 (C3) was determined. The influence of common haplotypes defining transcriptional and translational units on complement activation in blood was determined in a quantitative genomic association study. Individual haplotypes in [[CFH]] and [[CFB]] were associated with distinct and novel effects on plasma levels of precursors, regulators and activation products of the alternative pathway of complement in human blood. Further, genetic variation in [[CFH]] thought to influence cell surface regulation of complement did not alter plasma complement levels in human blood. Plasma markers of chronic activation (split-products Ba and C3d) and an activating enzyme (factor D) were elevated in AMD subjects. Most of the elevation in AMD was accounted for by the genetic variation controlling complement activation in human blood. Activation of the alternative pathway of complement in blood is under genetic control and increases with age. The genetic variation associated with increased activation of complement in human blood also increased the risk of AMD. Our data are consistent with a disease model in which genetic variation in the complement system increases the risk of AMD by a combination of systemic complement activation and abnormal regulation of complement activation in local tissues.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Case-Control Studies
* Complement Activation
* Complement Pathway, Alternative
* Complement System Proteins
* Female
* Genetic Loci
* Genetic Predisposition to Disease
* Haplotypes
* Humans
* Macular Degeneration
* Male
* Middle Aged
* Models, Genetic
* Sex Characteristics

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792151
}}
{{medline-entry
|title=Up-regulation of complement factor B in retinal pigment epithelial cells is accompanied by complement activation in the aged retina.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18926817
|abstract=Complement activation is involved in the pathogenesis of age-related macular degeneration. How complement is activated in the retina is not known. Previously we have shown that complement factor H ([[CFH]]) is constitutively expressed by retinal pigment epithelial ([[RPE]]) cells and the production of [[CFH]] is negatively regulated by inflammatory cytokines and oxidative insults. Here we investigated the production and regulation of complement factor B ([[CFB]]) in [[RPE]] cells. Immunohistochemistry showed that [[CFB]] is expressed at low levels on the apical portion of the [[RPE]] cells in normal physiological conditions. With age, [[CFB]] expression increases and extends to the basal part of [[RPE]] cells. Confocal microscopy and real-time PCR of [[RPE]] cultures indicated that the production of [[CFB]] by [[RPE]] cells is positively regulated by [[TNF]]-alpha, IFN-gamma and long-term (30 days) photoreceptor outer segments treatments. Increased [[CFB]] expression in [[RPE]] cells in vivo is accompanied by the accumulation of complement [[C3]] and [[C3]]a deposition at the Bruch's membrane and the basal layer of [[RPE]] cells. Our results suggest that [[RPE]] cells play important roles in regulating complement activation in the retina. Increased complement activation in the aged retina may be important for retinal homeostasis in the context of accumulating photoreceptor waste products.
|mesh-terms=* Aging
* Animals
* Cells, Cultured
* Complement Factor B
* Complement Pathway, Alternative
* Inflammation Mediators
* Interleukin-6
* Mice
* Mice, Inbred C57BL
* Microscopy, Confocal
* Phagocytosis
* Retinal Pigment Epithelium
* Reverse Transcriptase Polymerase Chain Reaction
* Rod Cell Outer Segment
* Tumor Necrosis Factor-alpha
* Up-Regulation

|full-text-url=https://sci-hub.do/10.1016/j.exer.2008.09.005
}}
{{medline-entry
|title=[[C2]] and [[CFB]] genes in age-related maculopathy and joint action with [[CFH]] and LOC387715 genes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18493315
|abstract=Age-related maculopathy (ARM) is a common cause of visual impairment in the elderly populations of industrialized countries and significantly affects the quality of life of those suffering from the disease. Variants within two genes, the complement factor H ([[CFH]]) and the poorly characterized LOC387715 (ARMS2), are widely recognized as ARM risk factors. [[CFH]] is important in regulation of the alternative complement pathway suggesting this pathway is involved in ARM pathogenesis. Two other complement pathway genes, the closely linked complement component receptor ([[C2]]) and complement factor B ([[CFB]]), were recently shown to harbor variants associated with ARM. We investigated two SNPs in [[C2]] and two in [[CFB]] in independent case-control and family cohorts of white subjects and found rs547154, an intronic SNP in [[C2]], to be significantly associated with ARM in both our case-control (P-value 0.00007) and family data (P-value 0.00001). Logistic regression analysis suggested that accounting for the effect at this locus significantly (P-value 0.002) improves the fit of a genetic risk model of [[CFH]] and LOC387715 effects only. Modeling with the generalized multifactor dimensionality reduction method showed that adding [[C2]] to the two-factor model of [[CFH]] and LOC387715 increases the sensitivity (from 63% to 73%). However, the balanced accuracy increases only from 71% to 72%, and the specificity decreases from 80% to 72%. [[C2]]/[[CFB]] significantly influences AMD susceptibility and although accounting for effects at this locus does not dramatically increase the overall accuracy of the genetic risk model, the improvement over the [[CFH]]-LOC387715 model is statistically significant.
|mesh-terms=* Aging
* Case-Control Studies
* Complement C2
* Complement Factor B
* Complement Factor H
* Genetic Predisposition to Disease
* Humans
* Macular Degeneration
* Polymorphism, Single Nucleotide

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374901
}}
{{medline-entry
|title=Single-dose pharmacokinetics of ceftibuten (SCH 39720) in infants and children.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/1759830
|abstract=Ceftibuten ([[CFB]]), a new broad-spectrum cephalosporin for oral administration, possesses potent activity in vitro against a wide range of gram-negative and certain gram-positive pathogens frequently encountered in pediatric patients. Its antimicrobial spectrum and dosage formulation suggest a use for [[CFB]] in the treatment of otitis media and upper and lower respiratory and urinary tract infections in infants and children. To assess the pharmacokinetic characteristics of [[CFB]] in pediatric patients, we completed a multicenter investigation of 49 children (26 females) between the ages of 6 months and 17 years who had normal hepatic and renal functions and no evidence of chronic disease. Pharmacokinetic parameters were determined from repeated blood samples (n = 12) and, when possible, quantitative urine collections (n = 7) obtained over a 12- to 24-h period following a single oral [[CFB]] dose of either 4.5 or 9.0 mg/kg of body weight. [[CFB]] was quantitated from plasma and urine samples by using a sensitive, microanalytical high-pressure liquid chromatography method. The drug was rapidly absorbed (mean time to maximum concentration in serum = 140 min) and produced apparent peak concentrations in plasma (Cmax) ranging from 5.0 to 19.0 mg/liter. Average [[CFB]] pharmacokinetic parameters ( /- standard deviations) were as follows: apparent elimination half-life, 2.0  /- 0.5 h; mean residence time, 3.9  /- 1.1 h; apparent steady-state volume of distribution, 0.4  /- 0.2 liter/kg; and apparent total plasma clearance (CL/F), 2.5  /- 0.9 ml/min/kg. No significant differences in any of the pharmacokinetic parameters were observed between the two dosing groups. Significant (P < 0.05) negative correlations were found between patient age and [[CFB]] elimination half-life and CL/F and between the estimated creatinine clearance and renal clearance and CL/F. Apparent age dependence of [[CFB]] disposition was also reflected by a greater CL/F in children from 0.5 to less than or equal 5 years of age (3.1  /- 1.1 ml/min/kg) than in children > 10 years of age (2.0  /- 0.6 ml/min/kg; P < 0.005). The increased CL/f for [[CFB]] (3.0  /- 0.5 ml/min/kg) was corroborated by a validation study performed with 11 infants (1.0  /- 0.5 ml/min/kg) with CL/F for 19 subjects suggested that appreciable nonrenal clearance (1.3  /- 0.6 ml/min/kg) of [[CFB]] occurred in children, a finding different from preliminary data for adults.
|mesh-terms=* Adolescent
* Aging
* Ceftibuten
* Cephalosporins
* Child
* Child, Preschool
* Chromatography, High Pressure Liquid
* Female
* Half-Life
* Humans
* Infant
* Male

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC245329
}}