Literature Watch
[EXPERIMENTAL MODEL AND CURRENCY OF EXPERIMENT OF DISTANT RESULTS OF LEAD EXPOSITION].
[EXPERIMENTAL MODEL AND CURRENCY OF EXPERIMENT OF DISTANT RESULTS OF LEAD EXPOSITION].
Georgian Med News. 2017 Feb;(263):125-129
Authors: Pataraia G, Bagashvili T, Andronikashvili G, Gurashvili T, Gogeshvili K, Avalishvili M
Abstract
In order to explore the distant results of exposition of little doses of lead, for the objective of the experiment model we have selected 32 mongral rats, of different age, but aged of both sex. Experimental animals were divided in two groups. During first two month from the beginning of the experiment, together with permissible food, animals were given the water, in which was open Pb(NO3)2 - to first group 1.5 mg on kg/weight and to II group 15 mg on kg/weight during the day and night. Before the beginning of the experiment, in the time of process and after it, observation was conducted, description and collection of photo-video materials about the behavior of animals, physiological parameters, possible change of weight, clear-sighted changes in appearance. During the autopsy of the animal, died during the experiment, it turned out that the reason of the death was acute heart failure caused by septicopyemia, the bilateral abscess pneumonia and right sided purulent pleurisy. The reason of the death of second animal was DIC (disseminated intravascular coagulation) Syndrome and the polyorganic pathology caused by it. We made the Nembutal injection to third animal because there was detected the 50×40×20 sized subcutaneous formation on the right surface of the chest, that turned out to be the breast adenoma with cystic fibrosis. After the completion of the experiment of distant results of lead exposition, surviving rats before autopsy will be dropped to sleep with high dose of drugs in compliance with the "Guidelines of animal care and ethical behavior", taken material will be processed for histopathological (in case of necessity histochemical and imunomorphological) and electronic microscopic researches.
PMID: 28452739 [PubMed - in process]
Respiratory viral detection in the paranasal sinuses of patients with cystic fibrosis.
Respiratory viral detection in the paranasal sinuses of patients with cystic fibrosis.
Am J Rhinol Allergy. 2017 Mar 01;31(2):105-108
Authors: Rowan NR, Wang EW, Kanaan A, Sahu N, Williams JV, Phillips CD, Lee SE
Abstract
BACKGROUND: Pulmonary colonization with antibiotic-resistant organisms in patients with cystic fibrosis (CF) is often preceded by upper-airway infections. Although there is a well-described relationship between pulmonary respiratory viral infections and overall disease progression of CF, the pathogenicity of respiratory viral infections in the paranasal sinuses of patients with CF remains unknown. With recent advances in respiratory virus detection techniques, this study sought to detect the presence of respiratory viruses in the paranasal sinuses of patients with CF in comparison with healthy controls and to correlate the viral presence with clinical measures of sinonasal disease.
METHODS: This prospective individual cohort study compared 24 patients with CF with 14 healthy controls. Basic demographics, clinical measures of disease and respiratory viral screens (commercial multiplex) obtained directly from the paranasal sinuses were compared between the two groups.
RESULTS: Respiratory viruses were detected in 33% of patients with CF (8/24) compared with 0% of the healthy controls (0/14) (p = 0.017). Respiratory viruses were only detected during the winter months, and the most commonly identified were influenza A and human rhinovirus strains. There was no statistical difference in the 22-Item Sino-Nasal Outcome Test (SNOT-22) scores (p = 0.93) or modified Lund-Kennedy scores (p = 0.74) between patients with CF with a positive viral test and those without a positive result.
CONCLUSIONS: Respiratory viral detection is more commonly detected in the paranasal sinuses of patients with CF compared with healthy controls. Although respiratory viral presence did not correlate with a worse clinical severity of sinonasal disease, these findings may provide insight into the pathophysiology of CF and open new avenues for potential targeted therapy.
PMID: 28452706 [PubMed - in process]
Proteomic profiling identifies novel circulating markers associated with bronchiectasis in cystic fibrosis.
Proteomic profiling identifies novel circulating markers associated with bronchiectasis in cystic fibrosis.
Proteomics Clin Appl. 2017 Apr 28;:
Authors: DeBoer EM, Kroehl M, Wagner BD, Accurso F, Harris JK, Lynch DA, Sagel SD, Deterding RR
Abstract
PURPOSE: Evaluate bronchiectasis change over one year in children with cystic fibrosis (CF) and find blood proteins associated with bronchiectasis.
EXPERIMENTAL DESIGN: Pilot study of CF children who had chest computed tomography (CT) scans and blood collected during times of clinical stability. Blood plasma was analyzed for 1129 proteins using SOMAmer(®) , the SOMAscan proteomics platform. Bronchiectasis was measured on two CT scans collected 1 year apart. Spearman's rank estimated the correlations between outcomes. Clinical relevance was defined as |r| > 0.40.
RESULTS: There were 26 children included: mean age 11.3 years (SD 2.4 years), mean Brody Bronchiectasis score 0.65 (SD 0.83), mean airway count 14.3 (SD 5.7) per CT slice. Brody bronchiectasis change over 1 year ranged from -1.0 to 1.9 and airway count change over one year ranged from -7.7 to 13.5 airways per slice. Proteins related to inflammation and extracellular matrix degradation were associated with cross-sectional and longitudinal structural changes.
CONCLUSIONS AND CLINICAL RELEVANCE: Imaging outcomes were more strongly correlated with circulating proteins than age or spirometry values. The unique SOMAscan(TM) proteomic platform identifies several novel proteins in blood that are associated with bronchiectasis and that may serve as clinically useful biomarkers in children with CF. This article is protected by copyright. All rights reserved.
PMID: 28452194 [PubMed - as supplied by publisher]
Computation of ancestry scores with mixed families and unrelated individuals.
Computation of ancestry scores with mixed families and unrelated individuals.
Biometrics. 2017 Apr 27;:
Authors: Zhou YH, Marron JS, Wright FA
Abstract
The issue of robustness to family relationships in computing genotype ancestry scores such as eigenvector projections has received increased attention in genetic association, and is particularly challenging when sets of both unrelated individuals and closely related family members are included. The current standard is to compute loadings (left singular vectors) using unrelated individuals and to compute projected scores for remaining family members. However, projected ancestry scores from this approach suffer from shrinkage toward zero. We consider two main novel strategies: (i) matrix substitution based on decomposition of a target family-orthogonalized covariance matrix, and (ii) using family-averaged data to obtain loadings. We illustrate the performance via simulations, including resampling from 1000 Genomes Project data, and analysis of a cystic fibrosis dataset. The matrix substitution approach has similar performance to the current standard, but is simple and uses only a genotype covariance matrix, while the family-average method shows superior performance. Our approaches are accompanied by novel ancillary approaches that provide considerable insight, including individual-specific eigenvalue scree plots.
PMID: 28452052 [PubMed - as supplied by publisher]
Neutrophil extracellular trap release driven by bacterial motility: Relevance to cystic fibrosis lung disease.
Neutrophil extracellular trap release driven by bacterial motility: Relevance to cystic fibrosis lung disease.
Commun Integr Biol. 2017;10(2):e1296610
Authors: Rada B
Abstract
Neutrophil extracellular trap (NET) formation represents a unique effector function of neutrophils (PMN). The mechanism of NET release in response to bacteria is largely unknown. We studied the process by which Pseudomonas aeruginosa, an opportunistic pathogen, interacts with primary PMNs, and found that flagellar swimming motility of the bacterium is essential for inducing NET extrusion. Cystic fibrosis (CF) lung disease is associated with P. aeruginosa infection and PMN-dominated inflammation. Although NETs are abundant in CF airways, the main factors triggering NET release in CF remain unclear. Our study implicates that motile P. aeruginosa is a strong NET-inducer in CF. In early stages of CF lung disease flagellated, motile isolates of P. aeruginosa are characteristic and their interactions with PMNs could lead to NET formation. In chronic CF, P. aeruginosa down-regulates its flagellum expression to avoid recognition by the immune system and forms biofilms. Flagellated bacteria, however, are released from biofilms and could interact with PMNs to form NETs. Although flagellated forms likely represent only a small fraction of the total P. aeruginosa load in chronic CF, NET release induced by them could have a significant impact on inflammation and lung function since flagellated forms trigger the most robust response of the immune system including PMNs. Overall, we speculate that NET formation driven by motile P. aeruginosa could be a novel, significant contributor to pathogenesis at both, early and late stages of CF lung disease.
PMID: 28451056 [PubMed - in process]
Lessons from the lower airway microbiome in early CF.
Lessons from the lower airway microbiome in early CF.
Thorax. 2017 Apr 27;:
Authors: Hoppe JE, Zemanick ET
PMID: 28450530 [PubMed - as supplied by publisher]
Cystic fibrosis: current therapeutic targets and future approaches.
Cystic fibrosis: current therapeutic targets and future approaches.
J Transl Med. 2017 Apr 27;15(1):84
Authors: Rafeeq MM, Murad HAS
Abstract
OBJECTIVES: Study of currently approved drugs and exploration of future clinical development pipeline therapeutics for cystic fibrosis, and possible limitations in their use.
METHODS: Extensive literature search using individual and a combination of key words related to cystic fibrosis therapeutics.
KEY FINDINGS: Cystic fibrosis is an autosomal recessive disorder due to mutations in CFTR gene leading to abnormality of chloride channels in mucus and sweat producing cells. Respiratory system and GIT are primarily involved but eventually multiple organs are affected leading to life threatening complications. Management requires drug therapy, extensive physiotherapy and nutritional support. Previously, the focus was on symptomatic improvement and complication prevention but recently the protein rectifiers are being studied which are claimed to correct underlying structural and functional abnormalities. Some improvement is observed by the corrector drugs. Other promising approaches are gene therapy, targeting of cellular interactomes, and newer drugs for symptomatic improvement.
CONCLUSIONS: The treatment has a long way to go as most of the existing therapeutics is for older children. Other limiting factors include mutation class, genetic profile, drug interactions, adverse effects, and cost. Novel approaches like gene transfer/gene editing, disease modeling and search for alternative targets are warranted.
PMID: 28449677 [PubMed - in process]
Erratum to: The altered gut microbiota in adults with cystic fibrosis.
Erratum to: The altered gut microbiota in adults with cystic fibrosis.
BMC Microbiol. 2017 Apr 27;17(1):102
Authors: Burke DG, Fouhy F, Harrison MJ, Rea MC, Cotter PD, O'Sullivan O, Stanton C, Hill C, Shanahan F, Plant BJ, Ross RP
PMID: 28449644 [PubMed - in process]
Unusual Pulmonary Arterial Filling Defect caused by Systemic to Pulmonary Shunt in the Setting of Chronic Lung Disease Demonstrated by Dynamic 4D CTA.
Unusual Pulmonary Arterial Filling Defect caused by Systemic to Pulmonary Shunt in the Setting of Chronic Lung Disease Demonstrated by Dynamic 4D CTA.
J Radiol Case Rep. 2015 Nov;9(11):17-23
Authors: Ansari-Gilani K, Gilkeson RC, Hsiao EM, Rajiah P
Abstract
Even though pulmonary embolism is by far the most common cause of filling defect in the pulmonary arterial system, other less common etiologies should be considered especially in the setting of atypical clinical scenario or unusual imaging findings. Unusual pattern of filling defect in the pulmonary artery in the setting of chronic inflammatory/fibrotic parenchymal lung disease should raise the concern for systemic to pulmonary artery shunt. This diagnosis is typically made by conventional angiography. Dynamic 4D CT angiography however can be a safe, noninvasive and effective alternative tool for making such a diagnosis. It has the added value of multiplanar reconstruction capabilities and providing detailed anatomy which can be vital for interventional radiologists when planning their approach for possible intervention. We present 2 cases of such shunts, and illustrate the demonstration of these shunts by using dynamic 4D CT angiography.
PMID: 27252791 [PubMed - indexed for MEDLINE]
Innovative Mental Health Services Research Not Involving Clinical Trials (R01)
Notice of Clarification of Application Due Dates for RFA-OD-17-004 "Intensive Longitudinal Analysis of Health Behaviors: Leveraging New Technologies to Understand Health Behaviors (U01) "
"systems biology"; +37 new citations
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Neuro-symbolic representation learning on biological knowledge graphs.
Neuro-symbolic representation learning on biological knowledge graphs.
Bioinformatics. 2017 Apr 25;:
Authors: Alshahrani M, Khan MA, Maddouri O, Kinjo AR, Queralt-Rosinach N, Hoehndorf R
Abstract
Motivation: Biological data and knowledge bases increasingly rely on Semantic Web technologies and the use of knowledge graphs for data integration, retrieval and federated queries. In the past years, feature learning methods that are applicable to graph-structured data are becoming available, but have not yet widely been applied and evaluated on structured biological knowledge.
Results: We develop a novel method for feature learning on biological knowledge graphs. Our method combines symbolic methods, in particular knowledge representation using symbolic logic and automated reasoning, with neural networks to generate embeddings of nodes that encode for related information within knowledge graphs. Through the use of symbolic logic, these embeddings contain both explicit and implicit information. We apply these embeddings to the prediction of edges in the knowledge graph representing problems of function prediction, finding candidate genes of diseases, protein-protein interactions, or drug target relations, and demonstrate performance that matches and sometimes outperforms traditional approaches based on manually crafted features. Our method can be applied to any biological knowledge graph, and will thereby open up the increasing amount of SemanticWeb based knowledge bases in biology to use in machine learning and data analytics.
Availability and Implementation: https://github.com/bio-ontology-research-group/walking-rdf-and-owl.
Contact: robert.hoehndorf@kaust.edu.sa.
Supplementary information: Supplementary data are available at Bioinformatics online.
PMID: 28449114 [PubMed - as supplied by publisher]
Association Between SLC16A5 Genetic Variation and Cisplatin-Induced Ototoxic Effects in Adult Patients With Testicular Cancer.
Association Between SLC16A5 Genetic Variation and Cisplatin-Induced Ototoxic Effects in Adult Patients With Testicular Cancer.
JAMA Oncol. 2017 Apr 27;:
Authors: Drögemöller BI, Monzon JG, Bhavsar AP, Borrie AE, Brooks B, Wright GEB, Liu G, Renouf DJ, Kollmannsberger CK, Bedard PL, Aminkeng F, Amstutz U, Hildebrand CA, Gunaretnam EP, Critchley C, Chen Z, Brunham LR, Hayden MR, Ross CJD, Gelmon KA, Carleton BC
Abstract
Importance: Cisplatin-induced ototoxic effects are an important complication that affects testicular cancer survivors as a consequence of treatment. The identification of genetic variants associated with this adverse drug reaction will further our mechanistic understanding of its development and potentially lead to strategies to prevent ototoxic effects.
Objective: To identify the genetic variants associated with cisplatin-induced ototoxic effects in adult testicular cancer patients.
Design, Setting, and Participants: This retrospective study was performed by the Canadian Pharmacogenomics Network for Drug Safety using patients recruited from 5 adult oncology treatment centers across Canada. Male patients who were 17 years or older, diagnosed with germ cell testicular cancer, and previously treated with cisplatin-based chemotherapy were recruited from July 2009 to April 2013 using active surveillance methodology. Cisplatin-induced ototoxic effects were independently diagnosed by 2 audiologists. Patients were genotyped for 7907 variants using a custom pharmacogenomic array. Logistic regression was used to identify genetic variants that were significantly associated with ototoxic effects. The validity of these findings was confirmed through independent replication and cell-based functional assays.
Exposures: Cisplatin-based chemotherapy.
Main Outcomes and Measures: Cisplatin-induced ototoxic effects.
Results: After exclusions, 188 patients (median [interquartile range] age, 31 [24-39] years) were enrolled in this study to form the discovery and replication cohorts. Association and fine-mapping analyses identified a protein-coding variant, rs4788863 in SLC16A5, that was associated with protection against cisplatin-induced ototoxic effects in 2 independent cohorts (combined cohort: odds ratio, 0.06; 95% CI, 0.02-0.22; P = 2.17 × 10-7). Functional validation of this transporter gene revealed that in vitro SLC16A5-silencing altered cellular responses to cisplatin treatment, supporting a role for SLC16A5 in the development of cisplatin-induced ototoxic effects. These results were further supported by the literature, which provided confirmatory evidence for the role that SLC16A5 plays in hearing.
Conclusions and Relevance: This study has identified a novel association between protein-coding variation in SLC16A5 and cisplatin-induced ototoxic effects. These findings have provided insight into the molecular mechanisms of this adverse drug reaction in adult patients with germ cell testicular cancer. Given that previous studies have shown that cimetidine, an SLC16A5-inhibitor, prevents murine cisplatin-induced ototoxic effects, the findings from this study have important implications for otoprotectant strategies in humans.
PMID: 28448657 [PubMed - as supplied by publisher]
Together into the future...Pharmacogenomics and documentation.
Together into the future...Pharmacogenomics and documentation.
Nurs Manage. 2017 May;48(5):32-40
Authors: McCormick KA
Abstract
New partnerships target optimal care quality and outcomes.
PMID: 28448287 [PubMed - in process]
Together into the future... Pharmacogenomics and documentation.
Together into the future... Pharmacogenomics and documentation.
Nurs Manage. 2017 May;48(5):1
Authors:
PMID: 28448279 [PubMed - in process]
Paclitaxel-induced sensory peripheral neuropathy is associated with an ABCB1 single nucleotide polymorphism and older age in Japanese.
Paclitaxel-induced sensory peripheral neuropathy is associated with an ABCB1 single nucleotide polymorphism and older age in Japanese.
Cancer Chemother Pharmacol. 2017 Apr 26;:
Authors: Tanabe Y, Shimizu C, Hamada A, Hashimoto K, Ikeda K, Nishizawa D, Hasegawa J, Shimomura A, Ozaki Y, Tamura N, Yamamoto H, Yunokawa M, Yonemori K, Takano T, Kawabata H, Tamura K, Fujiwara Y
Abstract
PURPOSE: Whether age and inter-individual variability of pharmacogenetics are risk factors for paclitaxel-induced peripheral neuropathy (PIPN) is inconclusive. This study was conducted to evaluate the influence of previously investigated single nucleotide polymorphisms (SNPs) and age, using genotype data from a prospective study of paclitaxel-related toxicity in Japanese patients with breast cancer.
METHODS: Peripheral blood mononuclear cells from 127 Japanese women with breast cancer who received weekly adjuvant paclitaxel were used to genotypes SLCO1B3 T334G (rs4149117), CYP2C8 A1196G (rs10509681), ABCB1 C1236T (rs1128503), ABCB1 G2677T/A (rs2032582), and ABCB1 C3435T (rs1045642). Genotypic and clinical factors were investigated for associations with PIPN.
RESULTS: Of the five SNPs evaluated, no SNPs were significantly associated with grade 2 or higher PIPN. However, ABCB1 1236 TT showed a trend to associate with grade 2 or higher PIPN compared to ABCB1 CT/CC (odds ratio 2.1, 95% CI 0.991-4.548, p = 0.051). In subgroup analysis, patients ≥60 years old with an ABCB1 1236 TT had a higher incidence of ≥grade 2 PIPN compared to patients with CT or CC genotype (p = 0.027). On multivariable analysis, age ≥60 years and the ABCB1 1236 TT showed a significant association with ≥grade 2 PIPN (p = 0.005 and p = 0.034, respectively).
CONCLUSIONS: ABCB1 1236 TT genotype and older age might be a predictor of PIPN, which diminishes quality of life of cancer survivors.
PMID: 28447211 [PubMed - as supplied by publisher]
STAT3 regulates glycolysis via targeting hexokinase 2 in hepatocellular carcinoma cells.
STAT3 regulates glycolysis via targeting hexokinase 2 in hepatocellular carcinoma cells.
Oncotarget. 2017 Apr 11;8(15):24777-24784
Authors: Li M, Jin R, Wang W, Zhang T, Sang J, Li N, Han Q, Zhao W, Li C, Liu Z
Abstract
Signal transducer and activator of transcription 3 (STAT3) and hexokinase 2 (HK2) are involved in hepatocellular carcinoma (HCC). Deregulation of cellular energetics involving an increase in glycolysis is a characteristic of HCC. This study examined whether STAT3 regulates HCC glycolysis through the HK2 pathway in HCC cells. Human HCC cell lines HepG2 and Hep3B cells were transfected with pcDNA3.1(+)-EGFP-STAT3, STAT3 siRNA and HK2 siRNA, respectively, or treated with rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), and the effects on STAT3 and HK2 expression and cell glycolysis were determined. STAT3 and HK2 expressions were evaluated by real-time polymerase chain reaction and Western blotting. The level of glycolysis metabolism was assessed by the determination of glucose consumption and lactate production.The results showed that transfection of HepG2 and Hep3B cells with pcDNA3.1(+)-EGFP-STAT3 significantly increased STAT3 mRNA and protein expression, glucose consumption and lactate production, and HK2 mRNA and protein expression. However, transfection of HepG2 and Hep3B cells with STAT3 siRNA significantly decreased glucose consumption and lactate production and HK2 mRNA and protein expression. Transfection of HepG2 and Hep3B cells with HK2 siRNA significantly decreased glucose consumption and lactate production. Treatment of HepG2 and Hep3B cells with rapamycin significantly reduced HK2 mRNA and protein expression and glucose consumption and lactate production. These results suggest that mTOR-STAT3-HK2 pathway is involved in the glycolysis of HCC cells and STAT3 may regulate HCC glycolysis through HK2 pathway, providing potential multiple therapeutic targets through intervention of glycolysis for the treatment of HCC.
PMID: 28445971 [PubMed - in process]
Research Review: Childhood chronic physical illness and adult emotional health - a systematic review and meta-analysis.
Research Review: Childhood chronic physical illness and adult emotional health - a systematic review and meta-analysis.
J Child Psychol Psychiatry. 2017 Apr 27;:
Authors: Secinti E, Thompson EJ, Richards M, Gaysina D
Abstract
BACKGROUND: Childhood chronic physical illness is associated with a greater vulnerability for emotional problems (i.e. depression and anxiety) in childhood. However, little is known about life-long effects of childhood chronic physical illness on mental health. The present study aims to systematically review evidence for associations between eight chronic physical illnesses with childhood onset (arthritis, asthma, cancer, chronic renal failure, congenital heart disease, cystic fibrosis, type 1 diabetes, and epilepsy) and adult emotional problems.
METHODS: A database search of MEDLINE, PsycARTICLES, PsycINFO, and ScienceDirect was undertaken, and random effects meta-analyses were used to synthesise evidence from eligible studies.
RESULTS: In total, 37 studies were eligible for the systematic review (n = 45,733) and of these, 34 studies were included in the meta-analyses (n = 45,358). There were overall associations between childhood chronic physical illness and adult depression (OR = 1.31; 95% CI [1.12, 1.54]) and anxiety (OR = 1.47; 95% CI [1.13, 1.92]). Separate meta-analyses for childhood asthma, type 1 diabetes and cancer were also conducted, with cancer being significantly associated with adult depression (OR = 1.19; 95% CI [1.00, 1.42]).
CONCLUSIONS: The effects of childhood chronic physical illness on the risk of emotional problems persist beyond childhood and adolescence. Mental health prevention and intervention strategies targeting children with chronic physical illnesses can have long-term benefits.
PMID: 28449285 [PubMed - as supplied by publisher]
Combination of Correctors Rescues CFTR Transmembrane-Domain Mutants by Mitigating their Interactions with Proteostasis.
Combination of Correctors Rescues CFTR Transmembrane-Domain Mutants by Mitigating their Interactions with Proteostasis.
Cell Physiol Biochem. 2017 Apr 25;41(6):2194-2210
Authors: Lopes-Pacheco M, Boinot C, Sabirzhanova I, Rapino D, Cebotaru L
Abstract
BACKGROUND/AIMS: Premature degradation of mutated cystic fibrosis transmembrane conductance regulator (CFTR) protein causes cystic fibrosis (CF), the commonest Mendelian disease in Caucasians. Despite recent advances in precision medicines for CF patients, many CFTR mutants have not been characterized and the effects of these new therapeutic approaches are still unclear for those mutants.
METHODS: Cells transfected or stably expressing four CFTR transmembrane-domain mutants (G85E, E92K, L1077P, and M1101K) were used to: 1) characterize the mutants according to their protein expression, thermal sensitivity, and degradation pathways; 2) evaluate the effects of correctors in rescuing them; and 3) explore the effects of correctors on CFTR interactions with proteostasis components.
RESULTS: All four mutants exhibited lower protein expression than did wild type-CFTR, and they were degraded by proteasomes and aggresomes. At low temperature, only cells expressing the mutants L1077P and M1101K exhibited increased CFTR maturation. Co-administration of C4 and C18 showed the greatest effect, restoring functional expression and partial stability of CFTR bearing E92K, L1077P, or M1101K at the cell surface. However, this treatment was inefficient in rectifying the defect of CFTR bearing G85E. Correctors rescued CFTR mutants by reducing their interactions with proteostasis components associated with protein retention in the endoplasmic reticulum and ubiquitination.
CONCLUSION: Co-administration of C4 and C18 rescued CFTR transmembrane-domain mutants by remodeling the CFTR interactome.
PMID: 28448979 [PubMed - as supplied by publisher]
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