146 research outputs found
Bioinformatics-based investigation on the genetic influence between SARS-CoV-2 infections and idiopathic pulmonary fibrosis (IPF) diseases, and drug repurposing
No full textSome recent studies showed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and idiopathic pulmonary fibrosis (IPF) disease might stimulate each other through the shared genes. Therefore, in this study, an attempt was made to explore common genomic biomarkers for SARS-CoV-2 infections and IPF disease highlighting their functions, pathways, regulators and associated drug molecules. At first, we identified 32 statistically significant common differentially expressed genes (cDEGs) between disease (SARS-CoV-2 and IPF) and control samples of RNA-Seq profiles by using a statistical r-package (edgeR). Then we detected 10 cDEGs (CXCR4, TNFAIP3, VCAM1, NLRP3, TNFAIP6, SELE, MX2, IRF4, UBD and CH25H) out of 32 as the common hub genes (cHubGs) by the protein–protein interaction (PPI) network analysis. The cHubGs regulatory network analysis detected few key TFs-proteins and miRNAs as the transcriptional and post-transcriptional regulators of cHubGs. The cDEGs-set enrichment analysis identified some crucial SARS-CoV-2 and IPF causing common molecular mechanisms including biological processes, molecular functions, cellular components and signaling pathways. Then, we suggested the cHubGs-guided top-ranked 10 candidate drug molecules (Tegobuvir, Nilotinib, Digoxin, Proscillaridin, Simeprevir, Sorafenib, Torin 2, Rapamycin, Vancomycin and Hesperidin) for the treatment against SARS-CoV-2 infections with IFP diseases as comorbidity. Finally, we investigated the resistance performance of our proposed drug molecules compare to the already published molecules, against the state-of-the-art alternatives publicly available top-ranked independent receptors by molecular docking analysis. Molecular docking results suggested that our proposed drug molecules would be more effective compare to the already published drug molecules. Thus, the findings of this study might be played a vital role for diagnosis and therapies of SARS-CoV-2 infections with IPF disease as comorbidity risk. © 2023, The Author(s)
Recommended from our members
Predictors of death or lung transplant after a diagnosis of idiopathic pulmonary fibrosis: insights from the IPF-PRO Registry
No full textIdiopathic pulmonary fibrosis (IPF) is a progressive disease with a variable clinical course and high mortality. We used data from a large national US registry of patients with IPF to investigate relationships between patient characteristics, including markers of disease severity, and mortality.
The analysis cohort comprised patients enrolled in the IPF-PRO Registry from its inception on 5 June 2014 to 26 October 2017. The primary criterion for inclusion in this registry is that patients must be diagnosed or confirmed with IPF at the enrolling centre within 6 months. Associations between patient characteristics and markers of disease severity at enrolment and mortality outcomes were investigated using univariable, multivariable and adjustment models.
Among 662 patients enrolled, 111 patients died or had a lung transplant over a follow-up period of 30 months. The probability of being free of both events at month 30 was 50.6% (95% CI: 40.0, 60.2). When patient characteristics and markers of disease severity were jointly examined in a multivariable analysis, oxygen use at rest (hazard ratio [HR] 2.44 [95% CI: 1.45, 4.10]), lower forced vital capacity (FVC) % predicted (HR 1.28 [95% CI: 1.10, 1.49] per 10% decrease) and diffusion capacity for carbon monoxide (DLco) % predicted (HR 1.25 [95% CI: 1.04, 1.51] per 10% decrease) were significantly associated with increased risk of death or lung transplant. The risk of death or lung transplant increased with increasing age in patients ≥62 years old (HR 1.18 [95% CI: 0.99, 1.40] per 5-year increase), and decreased with increasing age in patients <62 years old (HR 0.60 [95% CI: 0.39, 0.92] per 5-year increase).
In an observational US registry of patients with IPF, oxygen use at rest, lower FVC % predicted, and lower DLco % predicted were associated with risk of death or lung transplant. An audio podcast of the lead author discussing these data can be downloaded from: http://www.usscicomms.com/respiratory/snyder/IPF-PROsurvival1/ .
ClinicalTrials.gov number: NCT01915511
Areas of normal pulmonary parenchyma on HRCT exhibit increased FDG PET signal in IPF patients
No full textPurpose: Patients with idiopathic pulmonary fibrosis (IPF) show increased PET signal at sites of morphological abnormality on high-resolution computed tomography (HRCT). The purpose of this investigation was to investigate the PET signal at sites of normal-appearing lung on HRCT in IPF. Methods: Consecutive IPF patients (22 men, 3 women) were prospectively recruited. The patients underwent 18F-FDG PET/HRCT. The pulmonary imaging findings in the IPF patients were compared to the findings in a control population. Pulmonary uptake of 18F-FDG (mean SUV) was quantified at sites of morphologically normal parenchyma on HRCT. SUVs were also corrected for tissue fraction (TF). The mean SUV in IPF patients was compared with that in 25 controls (patients with lymphoma in remission or suspected paraneoplastic syndrome with normal PET/CT appearances). Results: The pulmonary SUV (mean ± SD) uncorrected for TF in the controls was 0.48 ± 0.14 and 0.78 ± 0.24 taken from normal lung regions in IPF patients (p < 0.001). The TF-corrected mean SUV in the controls was 2.24 ± 0.29 and 3.24 ± 0.84 in IPF patients (p < 0.001). Conclusion: IPF patients have increased pulmonary uptake of 18F-FDG on PET in areas of lung with a normal morphological appearance on HRCT. This may have implications for determining disease mechanisms and treatment monitoring. © 2013 The Author(s).</p
Areas of normal pulmonary parenchyma on HRCT exhibit increased FDG PET signal in IPF patients
No full textPurpose: Patients with idiopathic pulmonary fibrosis (IPF) show increased PET signal at sites of morphological abnormality on high-resolution computed tomography (HRCT). The purpose of this investigation was to investigate the PET signal at sites of normal-appearing lung on HRCT in IPF. Methods: Consecutive IPF patients (22 men, 3 women) were prospectively recruited. The patients underwent 18F-FDG PET/HRCT. The pulmonary imaging findings in the IPF patients were compared to the findings in a control population. Pulmonary uptake of 18F-FDG (mean SUV) was quantified at sites of morphologically normal parenchyma on HRCT. SUVs were also corrected for tissue fraction (TF). The mean SUV in IPF patients was compared with that in 25 controls (patients with lymphoma in remission or suspected paraneoplastic syndrome with normal PET/CT appearances). Results: The pulmonary SUV (mean ± SD) uncorrected for TF in the controls was 0.48 ± 0.14 and 0.78 ± 0.24 taken from normal lung regions in IPF patients (p < 0.001). The TF-corrected mean SUV in the controls was 2.24 ± 0.29 and 3.24 ± 0.84 in IPF patients (p < 0.001). Conclusion: IPF patients have increased pulmonary uptake of 18F-FDG on PET in areas of lung with a normal morphological appearance on HRCT. This may have implications for determining disease mechanisms and treatment monitoring. © 2013 The Author(s).</p
IPF and CPFE — the two different entities or two different presentations of the same disease?
No full textIn this article the co-existence of pulmonary emphysema with lung fibrosis of typical pattern and distribution for usual interstitialpneumonia (UIP) was compared with idiopathic pulmonary fibrosis (IPF) alone. Author discusses the etiopathogenesis of thesediseases, differences in signaling pathways and the role of senescent cells. Moreover, clinical course, pulmonary function testsas well as main complications are reviewed. However, the lack of well-established diagnostic criteria for CPFE along with mainlyretrospective character of the studies make current knowledge about this entity rather deficient
Shared genetic etiology between idiopathic pulmonary fibrosis and COVID-19 severity
No full textBackground: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease, characterized by progressive lung scarring. Severe COVID-19 is associated with substantial pneumonitis and has a number of shared major risk factors with IPF. This study aimed to determine the genetic correlation between IPF and severe COVID-19 and assess a potential causal role of genetically increased risk of IPF on COVID-19 severity. Methods: The genetic correlation between IPF and COVID-19 severity was estimated with linkage disequilib-rium (LD) score regression. We performed a Mendelian randomization (MR) study for IPF causality in COVID-19. Genetic variants associated with IPF susceptibility (P Findings: We detected a positive genetic correlation of IPF with COVID-19 severity (rg=0.31 [95% CI 0.04-0.57], P = 0.023). The MR estimates for severe COVID-19 did not reveal any genetic association (OR 1.05, [95% CI 0.92-1.20], P = 0.43). However, outlier analysis revealed that the IPF risk allele rs35705950 at MUC5B had a dif-ferent effect compared with the other variants. When rs35705950 was excluded, MR results provided evidence that genetically increased risk of IPF has a causal effect on COVID-19 severity (OR 1.21, [95% CI 1.06-1.38], P = 4.24 x 10(-3)). Furthermore, the IPF risk-allele at MUC5B showed an apparent protective effect against COVID-19 hospitalization only in older adults (OR 0.86, [95% CI 0.73-1.00], P = 2.99 x 10(-2)) . Interpretation: The strongest genetic determinant of IPF, rs35705950 at MUC5B, seems to confer protection against COVID-19, whereas the combined effect of all other IPF risk loci seem to confer risk of COVID-19 severity. The observed effect of rs35705950 could either be due to protective effects of mucin over-produc-tion on the airways or a consequence of selection bias due to (1) a patient group that is heavily enriched for the rs35705950 T undertaking strict self-isolation and/or (2) due to survival bias of the rs35705950 non-IPF risk allele carriers. Due to the diverse impact of IPF causal variants on SARS-CoV-2 infection, with a possible selection bias as an explanation, further investigation is needed to address this apparent paradox between variance at MUC5B and other IPF genetic risk factors. (C) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe
Analyses of idiopathic pulmonary fibrosis (IPF) inpatients in the United States
No full textIdiopathic pulmonary fibrosis (IPF) is a rapidly progressive immune mediated lung disorder that leads to death in the majority of patients, regardless of treatment, within 3-5 years of diagnosis. 1-3 Pulmonary fibrosis is often the final common pathway of many known causes of interstitial lung disease, such as sarcoidosis, silicosis, drug reactions, infections and collagen vascular diseases. The overall goal of the project is to identify the factors and costs associated with IPF patients in terms of mortality, length of stay and costs in different types of clinical settings across the United States. We used data rom the Nationwide Inpatient Sample (NIS) for calendar years 2007-2012 to perform a series of analyses to identify any factors and costs associated with IPF patients, particularly those pertaining to mortality, length of stay (LOS), and costs across the various clinical settings in the US. A series of parametric and non-parametric methods were used. Parametric methods included linear regression models, correlation analysis using Pearson correlation coefficients, paired and unpaired t-tests, and one-way ANOVA. A series of non-parametric methods were also used including: Wilcoxon rank sum tests, Mann-Whitney tests, Spearman correlations, and Kruskal-Wallis tests. Descriptive analyses were employed to compute sample mean, median, standard deviation, and interquartile ranges for study variables. Finally, binary outcomes and categorical variables were examined using the following: logistic regression models, chi-square tests, contingency coefficients, and McNemar’s test. We found a mean expenditure per IPF patient of 16,4049), with a median of 4,162,849, which is approximately six times as high as the 99th percentile total charge of and 147 times as high as the median. These results indicate that the distribution of total costs are skewed heavily by a relative few patients with extremely high bills. LOS also varied wildly with the mean stay being 7.84 days with a standard deviation of 13.60 days. LOS ranged from zero days to 1158 days, which corroborates our conclusion about the distribution of total costs. The patient who stayed 1158 days was hospitalized for 858 days more than any other patient. The next highest LOS values were 300 days, 250 days, 196 days, and 160 days, which further plays to our notion of the extremely expensive few. LOS varied in a statistically significant way between white and black patients (p<0.05). Only 11.2% of all patients in the data set died during the study period (11.2% of whites, 9.5% of blacks, 11.2% Hispanics, 12.2% of Asian/Pacific Islander, 13.0% of Native Americans). Finally, only 12% of all IPF patients passed away, while slightly more (13.8%) of all IIP patients died during the study period.Ph.D.Includes bibliographical referencesby Christopher Policell
Transcriptome analysis of IPF fibroblastic foci identifies key pathways involved in fibrogenesis
No full text\ua9 Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Introduction Fibroblastic foci represent the cardinal pathogenic lesion in idiopathic pulmonary fibrosis (IPF) and comprise activated fibroblasts and myofibroblasts, the key effector cells responsible for dysregulated extracellular matrix deposition in multiple fibrotic conditions. The aim of this study was to define the major transcriptional programmes involved in fibrogenesis in IPF by profiling unmanipulated myofibroblasts within fibrotic foci in situ by laser capture microdissection. Methods The challenges associated with deriving gene calls from low amounts of RNA and the absence of a meaningful comparator cell type were overcome by adopting novel data mining strategies and by using weighted gene co-expression network analysis (WGCNA), as well as an eigengene-based approach to identify transcriptional signatures, which correlate with fibrillar collagen gene expression. Results WGCNA identified prominent clusters of genes associated with cell cycle, inflammation/differentiation, translation and cytoskeleton/cell adhesion. Collagen eigengene analysis revealed that transforming growth factor β1 (TGF-β1), RhoA kinase and the TSC2/RHEB axis formed major signalling clusters associated with collagen gene expression. Functional studies using CRISPR-Cas9 gene-edited cells demonstrated a key role for the TSC2/ RHEB axis in regulating TGF-β1-induced mechanistic target of rapamycin complex 1 activation and collagen I deposition in mesenchymal cells reflecting IPF and other disease settings, including cancer-associated fibroblasts. Conclusion These data provide strong support for the human tissue-based and bioinformatics approaches adopted to identify critical transcriptional nodes associated with the key pathogenic cell responsible for fibrogenesis in situ and further identify the TSC2/ RHEB axis as a potential novel target for interfering with excessive matrix deposition in IPF and other fibrotic conditions
IPF and CPFE—The Two Different Entities or Two Different Presentations of the Same Disease?
No full textIn this article the co-existence of pulmonary emphysema with lung fibrosis of typical pattern and distribution for usual interstitial pneumonia (UIP) was compared with idiopathic pulmonary fibrosis (IPF) alone. Author discusses the etiopathogenesis of these diseases, differences in signaling pathways and the role of senescent cells. Moreover, clinical course, pulmonary function tests as well as main complications are reviewed. However, the lack of well-established diagnostic criteria for CPFE along with mainly retrospective character of the studies make current knowledge about this entity rather deficient.</jats:p
The role of viral and bacterial infections in the pathogenesis of IPF: a systematic review and meta-analysis
No full textBackground: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. Several risk factors such as smoking, air pollution, inhaled toxins, high body mass index and infectious agents are involved in the pathogenesis of IPF. In the present study, this meta-analysis study investigates the prevalence of viral and bacterial infections in the IPF patients and any possible association between these infections with pathogenesis of IPF. Methods: The authors carried out this systematic literature review from different reliable databases such as PubMed, ISI Web of Science, Scopus and Google Scholar to December 2020.Keywords used were the following �Idiopathic pulmonary fibrosis�, �Infection�, �Bacterial Infection� and �Viral Infection�, alone or combined together with the Boolean operators "OR�, �AND� and �NOT� in the Title/Abstract/Keywords field. Pooled proportion and its 95 CI were used to assess the prevalence of viral and bacterial infections in the IPF patients. Results: In this systematic review and meta-analyses, 32 studies were selected based on the exclusion/inclusion criteria. Geographical distribution of included studies was: eight studies in American people, 8; in European people, 15 in Asians, and one in Africans. The pooled prevalence for viral and bacterial infections w ere 53.72 (95 CI 38.1�69.1) and 31.21 (95 CI 19.9�43.7), respectively. The highest and lowest prevalence of viral infections was HSV (77.7 95 CI 38.48�99.32), EBV (72.02, 95 CI 44.65�90.79) and Influenza A (7.3, 95 CI 2.66�42.45), respectively. Whereas the highest and lowest prevalence in bacterial infections were related to Streptococcus sp. (99.49, 95 CI 96.44�99.9) and Raoultella (1.2, 95 CI 0.2�3.08), respectively. Conclusions: The results of this review were confirmed that the presence of viral and bacterial infections are the risk factors in the pathogenesis of IPF. In further analyses, which have never been shown in the previous studies, we revealed the geographic variations in the association strengths and emphasized other methodological parameters (e.g., detection method). Also, our study supports the hypothesis that respiratory infection could play a key role in the pathogenesis of IP. © 2021, The Author(s)
- …
