Browsing by Subject "Chronic obstructive pulmonary disease"

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    Genotypic frequencies of mutations associated with alpha-1 antitrypsin deficiency in unrelated bone marrow donors from the Murcia Región donor registry in the southeast of Spain
    (MDPI, 2023-09-02) Cuenca, Irene; Botella, Carmen; Moya Quiles, María Rosa; Jiménez Coll, Víctor; Galián, José Antonio; Martínez Banaclocha, Helios; Muro Pérez, Manuel; Minguela, Alfredo; Muro, Manuel; Legaz Pérez, Isabel; Ciencias Sociosanitarias
    Alpha-1 antitrypsin (AAT1) deficiency (AAT1D) is an inherited disease with an increased risk of chronic obstructive pulmonary disease (COPD), liver disease, and skin and blood vessel problems. AAT1D is caused by mutations in the SERPINE1 gene (Serine Protease Inhibitor, group A, member 1). Numerous variants of this gene, the Pi system, have been identified. The most frequent allelic variants are Pi*M, Pi*S, and Pi*Z. The development of COPD requires both a genetic predisposition and the contribution of an environmental factor, smoking being the most important. Studies on this deficiency worldwide are very scarce, and it is currently considered a rare disease because it is underdiagnosed. The aim of this study was to analyze the genotypic frequencies of mutations associated with AAT1 deficiency in unrelated bone marrow donors from the donor registry of the Region of Murcia in southeastern Spain due to the high risk of presenting with different pathologies and underdiagnosis in the population. A total of 112 DNA-healthy voluntary unrelated bone marrow donors from different parts of the Region of Murcia were analyzed retrospectively. AAT1 deficiency patient testing involved an automated biochemical screening routine. The three main variants, Pi*M, Pi*Z, and Pi*S, were analyzed in the SERPINE1 gene. Our results showed a frequency of 3.12% of the Pi*Z (K342) mutation in over 224 alleles tested in the healthy population. The frequency of Pi*S (V264) was 11.1%. The frequency of the haplotype with the most dangerous mutation, EK342 EE264, was 4.46%, and the frequency of EK342 EV264 was 1.78% in the healthy population. Frequencies of other EE342 EV264-mutated haplotypes accounted for 18.7%. As for the EE342 VV264 haplotype, 0.89% of the total healthy population presented heterozygous for the EV264 mutation and one individual presented homozygous for the VV264 mutation. In conclusion, the frequencies of Pi mutations in the healthy population of the Region of Murcia were not remarkably different from the few studies reported in Spain. The genotype and haplotype frequencies followed the usual pattern. Health authorities should be aware of this high prevalence of the Pi*S allelic variant and pathological genotypes such as Pi*MZ and Pi*SZ in the healthy population if they consider screening the smoking population.
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    Identifying COPD patients with poor health status and low exercise tolerance through the five-repetition sit-to-stand test and modified Medical Research Council Dyspnea Score
    (Elsevier, 2024-07-01) Bernabeu Mora, Roberto; Oliveira Sousa, Silvana Loana de; Medina i Mirapeix, Francesc; Gacto Sánchez, Mariano Luis; Fisioterapia
    Background: The objective of this study was to determine whether the concomitant presence of poor health status (COPD Assessment Test, CAT ≥ 10 points) and low exercise tolerance (6-Minute Walking Test, 6MWT < 350 m) is associated with worse clinical characteristics in patients with COPD. In addition, we aimed to develop a readily applicable diagnostic model to discriminate COPD patients with these conditions. Methods: A cross-sectional multicenter study involving 208 stable COPD patients (FEV1/FVC < 0.7, smoking history of at least 10 pack-years, and chronic respiratory symptoms) was carried out. The outcome measures were the 6MWT, CAT score, 5-repetition sit-to-stand test (5STS) and modified Medical Research Council Dyspnea Scale (mMRC). Patients were categorized into three groups: no condition (6MWT ≥ 350 m and CAT < 10 points), one condition (6MWT < 350 m or CAT ≥ 10 points), and both conditions (6MWT < 350 m and CAT ≥ 10 points). Results: A total of 26 patients (12,5%) presented both conditions. These patients experienced a higher degree of dyspnea (p = 0.001), smoking pack-years (p = 0.011), severe obstruction (p = 0.006), and time on 5STS (p = 0.001). The probability of having both conditions directly increased with the time spent on the 5STS (β=0.188; p = 0.010) and the degree of dyspnea (β=1.920; p < 0.001) (R2=0.413). The scoring system, using the 5STS and dyspnea as surrogate measures, demonstrated adequate calibration between the predicted and observed risk (linear R2=0.852). Conclusions: COPD patients with concurrent conditions have worse clinical status. The diagnostic model developed to discriminate these patients shows good internal validation.
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    Telocytes and lung disease
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Song, Dongli; Cretoiu, Dragos; Cretoiu, Sanda M.; Wang, Xiangdong
    Telocytes (TCs) represent a new distinct type of interstitial cells found in many organs, including lungs. TCs are mainly defined by a small cellular body from which arise very long (hundreds of micrometers) extensions named telopodes. During the last years, TCs were characterized in respect with their microRNA profiles, gene features and proteome signatures. Also, the ultrastructural 3D configuration was further elucidated by the aid of the FIB-SEM technology. TCs are able to communicate by homo- and heterocellular contacts with neighboring cells and are also able to transfer genetic information and signaling molecules to influence other cells by means of extracellular vesicle release. However, the exact function of lung TCs remains unclear. Here, we review the potential significance of TCs in the pathogenesis of pulmonary diseases. We will also discuss some future possibilities for targeting TCs as a potential therapeutic strategy.
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    The BRD4 inhibitor JQ1 protects against chronic obstructive pulmonary disease in mice by suppressing NF-κB activation
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2021) Liu, Yan; Huang, Zhi Zhen; Min, Li; Li, Zhi Feng; Chen, Kui
    Objective. To examine the effect of the BRD4 inhibitor JQ1 on mice with chronic obstructive pulmonary disease (COPD) via NF-κB. Methods. COPD models constructed by exposure to cigarette smoke and intratracheal instillation of lipopolysaccharides (LPS) in mice were treated with JQ1 (15, 25 or 50 mg/kg). HE staining was performed to observe histopathological changes in the lung tissues. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the levels of IL-10, IFN-γ, IL-17, IL1β, IL-6, TNF-α, MMP-2, MMP-9, MDA, SOD, T-AOC and HO-1, and gelatin zymography assays were used to examine MMP-2 and MMP-9 activity. A TransAMTM NF-κB p65 detection kit was used to test NF-κB p65/DNA binding activity. Western blotting was conducted to analyze NF-κB p65 in the nucleus and its acetylation. Results. JQ1 dose-dependently improved the histopathological changes in the lung tissues and decreased the mean linear intercept (MLI), destructive index and inflammatory score of the mice with COPD. The mice with COPD showed increased levels of MMP2, MMP-9, IFN-γ, IL-17, IL-1β, IL-6 and TNF-α with decreased IL-10 level; these changes were reversed by JQ1 in a dose-dependent manner. In addition, JQ1 reduced the MDA level and increased the SOD, HO-1 and T-AOC levels in mice with COPD, with suppression of NF-κB p65 expression in the nucleus, NF-κB/p65 (Lys310) acetylation and NF-κB p65/DNA binding activity in the lung tissues. Conclusion. The BRD4 inhibitor JQ1 can downregulate MMP-2 and MMP-9 expression, reduce inflammatory responses, and alleviate oxidative stress in mice with COPD, and this mechanism might be related to the inhibition of NF-κB.