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1.
Artículo en Inglés | MEDLINE | ID: mdl-39095948

RESUMEN

BACKGROUND: Various bronchoscopic lung volume reduction (BLVR) methods have been developed to treat chronic obstructive pulmonary disease (COPD). The efficacy and safety of these interventions remain unclear. This study assessed the efficacy and safety of various BLVR interventions in COPD patients. METHODS: PubMed and Embase were searched from inception to 21 October 2023. The primary outcomes assessed included the 6-min walking distance (6MWD), St. George Respiratory Questionnaire (SGRQ) score, lung function, and adverse events (AE). A frequentist approach with a random-effects model was used for a network meta-analysis. RESULTS: Twelve randomized controlled trials (RCTs) with 1646 patients were included in this meta-analysis. Patients treated with an endobronchial valve (EBV) achieved a minimum clinically important difference (MCID) in 6MWD and SGRQ at 6 months. Patients treated with coils achieved MCID in the SGRQ score at 12 months. Patients with aspiration valve system and bronchoscopic thermal vapor ablation (BTVA) achieved MCID in the SGRQ score at 6 months. CONCLUSIONS: In COPD patients, EBV should be considered first, while being wary of pneumothorax. Coil and BTVA are potential therapeutic alternatives. Although BTVA demonstrates a safer procedural profile than coils, additional studies are imperative to clarify its efficacy.

2.
Int J Biol Macromol ; 275(Pt 2): 133741, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38986985

RESUMEN

BACKGROUND: Sarcopenia, characterized by progressive muscle dysfunction, is a common complication of chronic obstructive pulmonary disease (COPD). Our previous study revealed serum Lipoprotein-associated phospholipaseA2 (Lp-PLA2) level significantly increased in COPD and associated with exercise tolerance. This study further investigated the functions and target potential of Lp-PLA2 for sarcopenia in COPD. METHODS: The circulating Lp-PLA2 level/enzyme activity in COPD patients and age-matched healthy volunteers were measured. Clinical parameters on skeletal muscle were measured and their correlations with Lp-PLA2 were analyzed. We explored the involvement of Lp-PLA2 in vivo and treatment effectiveness of darapladib (a specific Lp-PLA2 inhibitor) in CS-induced muscle dysfunction models. RESULTS: Circulating Lp-PLA2 level/enzyme activity was elevated in COPD patients compared with healthy controls, negatively associated with skeletal muscle mass and function. In CS-induced muscle dysfunction murine models, up-regulated serum Lp-PLA2 level/enzyme activity was verified again. In CS-exposed mouse models, darapladib treatment reversed muscle mass loss and muscle dysfunction, meanwhile rescued upregulation of MuRF1 and atrogin-1, and activation of inflammatory factors, oxidant enzymes and NF-κB signaling. CONCLUSIONS: Lp-PLA2 could be a potential indicator for sarcopenia in COPD. Darapladib, a Lp-PLA2 inhibitor, can alleviate CS-induced skeletal muscle dysfunction and represents a potential therapeutic for sarcopenia in COPD.

3.
Respiration ; : 1-4, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38952129

RESUMEN

INTRODUCTION: Subglottic stenosis, manifested by granulation tissue hyperplasia, is challenging and requires multiple repeated treatments and stent maintenance at times. Corticosteroids prevent severe subglottic stenosis development owing to their antifibrotic and anti-inflammatory properties. Submucosal injection of glucocorticoids, a useful adjuvant therapeutic method, improves the mean interval between endoscopic procedures and reduces airway restenosis risks. CASE PRESENTATION: We report a rare case of a man with complex subglottic stenosis who underwent balloon dilatation combined with cryotherapy, stent placement, and adjuvant submucosal triamcinolone injection. The drug was injected efficiently and safely into the submucosal layer under percutaneous ultrasound guidance, and subglottic stenosis was well-controlled at a low cost. CONCLUSION: POCUS-guided medication injections may be a useful adjuvant medical therapy for subglottic stenosis.

4.
Respiration ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39079503

RESUMEN

Introduction: Endobronchial ultrasound-guided (EBUS) transbronchial mediastinal cryobiopsy (TBMC) is increasingly used to diagnose mediastinal lymphadenopathy. Various methods have been used to create a tunnel between the airway wall and the lesions for this procedure, such as electrocautery and penetration with the sheath of the needle for EBUS-transbronchial fine needle aspiration. However, those methods are complex. Case Presentation: We developed a new technique called EBUS-TBMC via a tunnel, and we used it in four cases of mediastinal and/or hilar lymphadenopathy. We used a puncture dilation catheter to create a tunnel between the airway wall and the target lymph node. The cryoprobe was introduced to the target lymph node and cooled with liquid carbon dioxide for 5-9 seconds. The probe was subsequently pulled out with the samples to complete the EBUS-TBMC via a tunnel. A definite diagnosis was made based on pathological examination of the samples obtained in all four cases. After the procedure, none of the patients experienced moderate to severe bleeding, pneumothorax, pneumomediastinum, or other adverse events. Conclusion: EBUS-TBMC via a tunnel is a feasible and convenient procedure for the performance of TBMC. Further studies are required to evaluate the safety and efficacy of EBUS-TBMC via a tunnel.

5.
Lung ; 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38910197

RESUMEN

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is increasingly used to diagnose interstitial lung disease (ILD). The 1.1-mm cryoprobe has recently been available in clinical practice. The diagnostic yield and safety of TBLC using a 1.1-mm cryoprobe need to be confirmed. METHODS: A prospective, randomized controlled trial was conducted in patients with suspected ILD and randomly assigned to 1.1-mm and 1.9-mm cryoprobe groups. The primary outcome was the diagnostic yield of multidisciplinary discussion. Secondary outcomes were sample quality and incidence of complications. The tension and stress effects during TBLC onto the target lobe caused by 1.1-mm and 1.9-mm cryoprobes were also evaluated using finite element analysis. RESULTS: A total of 224 patients were enrolled. No significant differences were observed in the diagnostic yield (80.4% vs. 79.5%, p = 0.845) and sample quality scores (5.73 ± 0.64 vs. 5.66 ± 0.77; p = 0.324) between the 1.9-mm cryoprobe group and 1.1-mm cryoprobe group. The average surface areas of samples in 1.1-mm cryoprobe group were smaller, while no difference in sample weights was observed. A decreased incidence of moderate bleeding was found in the 1.1-mm cryoprobe group (17.0% vs. 6.2%, p = 0.027), while there was no difference in the incidence of the pneumothorax, there was a trend to higher rate of pneumothorax in 1.1-mm group. In finite element analysis, the 1.1-mm cryoprobe required the largest tension and produced the largest stress. CONCLUSION: Compared with a 1.9-mm cryoprobe, there was no difference in specimen quality or diagnostic rate but smaller sample size with a 1.1-mm cryoprobe. There was a decreased risk of moderate bleeding, but a trend towards increased risk for pneumothorax with 1.1-mm cryoprobe. TRAIL REGISTRATION: Clinicaltrials.gov identifier NCT04047667; registered August 4, 2019.

6.
Redox Biol ; 75: 103237, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38879894

RESUMEN

Silicosis is the most common type of pneumoconiosis, having a high incidence in workers chronically exposed to crystalline silica (CS). No specific medication exists for this condition. GHK, a tripeptide naturally occurring in human blood and urine, has antioxidant effects. We aimed to investigate the therapeutic effect of GHK-Cu on silicosis and its potential underlying molecular mechanism. An experimental silicosis mouse model was established to observe the effects of GHK-Cu on lung inflammation and fibrosis. Moreover, the effects of GHK-Cu on the alveolar macrophages (AM) were examined using the RAW264.7 cell line. Its molecular target, peroxiredoxin 6 (PRDX6), has been identified, and GHK-Cu can bind to PRDX6, thus attenuating lung inflammation and fibrosis in silicosis mice without significant systemic toxicity. These effects were partly related to the inhibition of the CS-induced oxidative stress in AM induced by GHK-Cu. Thus, our results suggest that GHK-Cu acts as a potential drug by attenuating alveolar macrophage oxidative stress. This, in turn, attenuates the progression of pulmonary inflammation and fibrosis, which provides a reference for the treatment of silicosis.

7.
Eur J Med Res ; 29(1): 268, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702744

RESUMEN

RATIONALE AND OBJECTIVES: Bleeding is a major complication of transbronchial lung cryobiopsy (TBLC), and pre-placing a bronchial balloon is one of the clinical practices used to prevent it, but with very weak evidence, which should be confirmed. This study aimed to conduct whether pre-placing a bronchial balloon in TBLC for diagnosing interstitial lung disease (ILD) is more safety. MATERIALS AND METHODS: In this prospective, single-center, randomized controlled trial, patients with suspected ILD were enrolled and randomly assigned to pre-placed balloon and none-pre-placed balloon groups. The primary outcome was incidence of moderate bleeding in each group. The secondary endpoints were the incidence of severe bleeding, pneumothorax, and other procedural complications. RESULTS: Exactly 250 patients were enrolled between August 2019 and March 2022, with 125 in each group. There were no significant differences in severe bleeding between the none-pre-placed balloon group and pre-placed balloon group (1.6% vs. 0.8%; adjusted p = 0.520), while more moderate bleeding occurred in the none-pre-placed balloon group (26.4% vs. 6.4%, adjusted p = 0.001), as well as more use of hemostatic drug (28.0% vs. 6.4%, adjusted p = 0.001). Three patients in the none-pre-placed balloon group used the bronchial balloon. More samples could be acquired in the pre-placed balloon group than in the none-pre-placed balloon group (3.8 ± 0.9 vs. 3.1 ± 0.9, p < 0.001). There were no significant differences in multidisciplinary discussion (MDD) between the two groups (89.6% vs. 91.2%, adjusted p = 0.182). CONCLUSION: A pre-placed bronchial balloon can reduce the incidence of moderate bleeding and increase the confidence of the bronchoscopists. However, it had no effect on increasing the diagnostic rate of MDD and reducing severe bleeding. REGISTRATION NUMBER: NCT04047667 ( www. CLINICALTRIALS: gov identifier).


Asunto(s)
Broncoscopía , Criocirugía , Enfermedades Pulmonares Intersticiales , Humanos , Masculino , Femenino , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/patología , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Broncoscopía/métodos , Broncoscopía/efectos adversos , Criocirugía/métodos , Criocirugía/efectos adversos , Biopsia/métodos , Biopsia/efectos adversos , Hemorragia/etiología , Hemorragia/diagnóstico , Hemorragia/prevención & control , Pulmón/patología , Bronquios/patología
9.
BMC Pulm Med ; 23(1): 476, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38017474

RESUMEN

BACKGROUND: Acute heart failure (AHF) is often associated with diffuse insufficiency and arterial hypoxemia, requiring respiratory support for rapid and effective correction. We aimed to compare the effects of high-flow nasal cannula(HFNC) with those of conventional oxygen therapy(COT) or non-invasive ventilation(NIV) on the prognosis of patients with AHF. METHODS: We performed the search using PubMed, Embase, Web of Science, MEDLINE, the Cochrane Library, CNKI, Wanfang, and VIP databases from the inception to August 31, 2023 for relevant studies in English and Chinese. We included controlled studies comparing HFNC with COT or NIV in patients with AHF. Primary outcomes included the intubation rate, respiratory rate (RR), heart rate (HR), and oxygenation status. RESULTS: From the 1288 original papers identified, 16 studies met the inclusion criteria, and 1333 patients were included. Compared with COT, HFNC reduced the intubation rate (odds ratio [OR]: 0.29, 95% CI: 0.14-0.58, P = 0.0005), RR (standardized mean difference [SMD]: -0.73 95% CI: -0.99 - -0.47, P < 0.00001) and HR (SMD: -0.88, 95% CI: -1.07 - -0.69, P < 0.00001), and hospital stay (SMD: -0.94, 95% CI: -1.76 - -0.12, P = 0.03), and increase arterial oxygen partial pressure (PaO2), (SMD: 0.88, 95% CI: 0.70-1.06, P < 0.00001) and oxygen saturation (SpO2 [%], SMD: 0.70, 95% CI: 0.34-1.06, P = 0.0001). CONCLUSIONS: There were no significant differences in intubation rate, RR, HR, arterial blood gas parameters, and dyspnea scores between the HFNC and NIV groups. Compared with COT, HFNC effectively reduced the intubation rate and provided greater clinical benefits to patients with AHF. However, there was no significant difference in the clinical prognosis of patients with AHF between the HFNC and NIV groups. TRIAL REGISTRATION: PROSPERO (identifier: CRD42022365611).


Asunto(s)
Insuficiencia Cardíaca , Ventilación no Invasiva , Insuficiencia Respiratoria , Humanos , Cánula , Oxígeno , Terapia por Inhalación de Oxígeno/efectos adversos , Hipoxia/terapia , Hipoxia/etiología , Insuficiencia Cardíaca/terapia , Insuficiencia Respiratoria/etiología
10.
BMC Pulm Med ; 23(1): 394, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37853348

RESUMEN

BACKGROUND: Sarcopenia and obesity are two abnormal body composition phenotypes, and sarcopenic obesity (SO) is characterized by both low skeletal muscle mass (sarcopenia) and high adiposity (obesity). SO negatively influences the clinical status of patients with chronic obstructive pulmonary disease (COPD). However, the studies exploring the prevalence and clinical effects of SO in COPD patients are limited. Our study aimed to elucidate the prevalence and impact of SO on COPD patients. METHODS: In this cross-sectional study, the pulmonary function, St. George's Respiratory Questionnaire, exercise tolerance, body composition, and serum levels of resistin and TNF-α were assessed in 198 COPD patients. The clinical value of serum resistin and TNF-α for predicting SO in patients with COPD was evaluated. RESULTS: In the 198 patients with COPD, the prevalence rates of sarcopenia, obesity, and SO in COPD patients were 27.27%, 29.8%, and 9.6%, respectively. Patients with SO experienced more severe symptoms of dyspnea and worse health related quality of life. The expression of resistin increased in patients with SO compared to other patients. The AUC value of serum resistin level for predicting SO was 0.870 (95% CI: 0.799-0.940). BMI (OR: 1.474, 95% CI: 1.124-1.934) and resistin (OR: 1.001, 95% CI: 1.000-1.002) levels were independent risk factors of SO in patients with COPD in Multivariate analysis. CONCLUSION: The prevalence rates of SO in COPD patients was 9.6%. COPD accompanied by SO is significantly associated with worse pulmonary function and poor physical performance. Serum resistin may be a potential adjunct for predicting SO in COPD patients.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Sarcopenia , Humanos , Sarcopenia/complicaciones , Estudios Transversales , Resistina , Calidad de Vida , Factor de Necrosis Tumoral alfa , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Obesidad/complicaciones , Obesidad/epidemiología
11.
Eur J Med Res ; 28(1): 277, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37559150

RESUMEN

BACKGROUND: Preeclampsia is a unique multisystem disorder that affects 5-8% of pregnancies. A high level of soluble fms-like tyrosine kinase-1 (sFlt-1) is a hallmark of preeclampsia that causes endothelial dysfunction. Exosomes derived from mesenchymal stem cells (MSCs) have been indicated to improve endothelial performances by transporting signals to target cells. We hypothesized that exosomes derived from MSCs have potential effects against preeclampsia. METHODS: We collected human umbilical cord MSC-derived exosomes (HUCMSC-exos) by ultracentrifugation. The size and morphology of the exosomes were examined using a transmission electron microscope and nanoparticle tracking analysis. Pregnant mice were injected with murine sFlt-1 adenovirus to build the preeclampsia-like mouse model and then treated with HUCMSC-exos. Human umbilical vein endothelial cells (HUVECs) were infected with lentiviruses expressing tet-on-sFlt-1 to obtain cells overexpressing sFlt-1. Cell proliferation and migration assays were used to measure the endothelial functions. The exosomes enriched proteins underlying mechanisms were explored by proteomic analysis. RESULTS: In the current study, we successfully collected the cup-shaped HUCMSC-exos with diameters of 30-150 nm. In the sFlt-1-induced preeclampsia mouse model, HUCMSC-exos exhibited beneficial effects on adverse birth events by decreasing blood pressure and improving fetal birth weight. In addition, preeclamptic dams that were injected with HUCMSC-exos had rebuilt dense placental vascular networks. Furthermore, we observed that HUCMSC-exos partially rescued sFlt-1-induced HUVECs dysfunction in vitro. Proteomics analysis of HUCMSC-exos displayed functional enrichment in biological processes related to vesicle-mediated transport, cell communication, cell migration, and angiogenesis. CONCLUSION: We propose that exosomes derived from HUCMSCs contain abundant Versican and play beneficial roles in the birth outcomes of sFlt-1-induced preeclamptic mice by promoting angiogenesis.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , Preeclampsia , Humanos , Ratones , Femenino , Embarazo , Animales , Preeclampsia/terapia , Preeclampsia/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Exosomas/genética , Exosomas/metabolismo , Proteómica , Placenta/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Cordón Umbilical
12.
J Transl Int Med ; 11(1): 70-80, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37533845

RESUMEN

Background and Objectives: Transcutaneous point-of-care ultrasound (POCUS) is a good tool to monitor the trachea in many clinical practices. The aim of our study is to verify the feasibility of POCUS-guided submucosal injection as a potential drug delivery method for the treatment of tracheal stenosis. Materials and methods: The inner wall of the trachea was monitored via a bronchoscope during the POCUS-guided submucosal injection of methylene blue in fresh ex vivo porcine trachea to evaluate the distribution of methylene blue. The feasibility and eficacy of POCUS-guided submucosal injection were evaluated in a tracheal stenosis rabbit model. Animals were divided into sham group, tracheal stenosis group, and treatment group. Ten days after the scraping of the tracheal mucosa or sham operation, POCUS-guided submucosal injection of paclitaxel or saline was performed. Seven days after the submucosal injection, the trachea was assessed by cervical computed tomography (CT) scan and ultrasound. Results: The distribution of methylene blue in trachea proved the technical feasibility of POCUS-guided submucosal injection. CT evaluation revealed that the tracheal stenosis index and the degree of tracheal stenosis increased significantly in the stenosis group, while POCUS-guided submucosal injection of paclitaxel partially reversed the tracheal stenosis. POCUS-guided submucosal injection of paclitaxel also decreased the lamina propria thickness and collagen deposition in the stenosed trachea. Conclusion: POCUS-guided submucosal paclitaxel injection alleviated tracheal stenosis induced by scraping of the tracheal mucosa. POCUS-guided submucosal injection might be a potential method for the treatment of tracheal stenosis.

13.
Front Med (Lausanne) ; 10: 1187760, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37359000

RESUMEN

Background: Sarcopenia often occurs as a comorbidity in many diseases which ultimately affects patient prognosis. However, it has received little attention in patients with idiopathic pulmonary fibrosis (IPF). This systematic review and meta-analysis aimed at determining the prevalence and risk factors of sarcopenia in patients with IPF. Methods: Embase, MEDLINE, Web of Science, and Cochrane databases were searched using relevant MeSH terms until December 31, 2022. The Newcastle-Ottawa Scale (NOS) was used for quality assessment and data analysis were performed using Stata MP 17.0 (Texas, USA). A random effects model was adopted to account for differences between articles, and the I2 statistic was used to describe statistical heterogeneities. Overall pooled estimates obtained from a random effects model were estimated using the metan command. Forest plots were generated to graphically represent the data of the meta-analysis. Meta-regression analysis was used for count or continuous variables. Egger test was used to evaluate publication bias and, if publication bias was observed, the trim and fill method was used. Main results: The search results showed 154 studies, and five studies (three cross-section and two cohort studies) with 477 participants were finally included. No significant heterogeneity was observed among studies included in the meta-analysis (I2 = 16.00%) and our study's publication bias is low (Egger test, p = 0.266). The prevalence of sarcopenia in patients with IPF was 26% (95% CI, 0.22-0.31). The risk factors for sarcopenia in patients with IPF were age (p = 0.0131), BMI (p = 0.001), FVC% (p < 0.001), FEV1% (p = 0.006), DLco% (p ≤ 0.001), and GAP score (p = 0.003). Conclusions: The pooled prevalence of sarcopenia in patients with IPF was 26%. The risk factors for sarcopenia in IPF patients were age, BMI, FVC%, FEV1%, DLco%, and GAP score. It is important to identify these risk factors as early as possible to improve the life quality of patients with IPF.

14.
Clin Nutr ; 42(6): 848-858, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37084471

RESUMEN

BACKGROUND: Malnutrition is a significant comorbidity among chronic obstructive pulmonary disease (COPD), but it has been often ignored. To date, the prevalence of malnutrition and its association with clinical parameters in the patients with COPD have not been well described. We aimed to investigate the prevalence of malnutrition and the prevalence of at-risk for malnutrition among COPD and the clinical impact of malnutrition on patients with COPD in a systematic review and meta-analysis. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched for articles describing the prevalence of malnutrition and/or at-risk for malnutrition from January 2010 to December 2021. Eligibility screening, data extraction, and quality assessment of the retrieved articles were conducted independently by two reviewers. Meta-analyses were performed to determine the prevalence of malnutrition and at-risk for malnutrition and the clinical impact of malnutrition on patients with COPD. Meta-regression and subgroup analyses were performed to explore the sources of heterogeneity. Comparisons were made between individuals with and without malnutrition according to pulmonary function, degree of dyspnea, exercise capacity, and mortality risk. RESULTS: Out of the 4156 references identified, 101 were read full-text, of which 36 studies were included. The total number of involved patients included in this meta-analysis was 5289. The prevalence of malnutrition was 30.0% (95% CI 20.3 to 40.6), compared with an at-risk prevalence of 50.0% (95% CI 40.8 to 59.2). Both prevalences were associated with regions and measurement tools. The prevalence of malnutrition was associated with COPD phase (acute exacerbations and stable). COPD with malnutrition showed lower forced expiratory volume 1 s % predicted (mean difference (MD) -7.19, 95% CI -11.86 to -2.52), higher modified Medical Research Council dyspnea scores (MD 0.38, 95% CI 0.12 to 0.64), poorer exercise tolerance (standardized mean difference -0.29, 95% CI -0.54 to -0.05), and higher mortality risk (hazard ratio 2.24, 95% CI 1.23 to 4.06) compared to COPD without malnutrition. CONCLUSION: Malnutrition and at-risk for malnutrition are common among COPD. Malnutrition negatively impacts important clinical outcomes of COPD.


Asunto(s)
Desnutrición , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Prevalencia , Calidad de Vida , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Disnea/epidemiología , Desnutrición/epidemiología
15.
J Cachexia Sarcopenia Muscle ; 14(3): 1365-1380, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36905132

RESUMEN

BACKGROUND: Skeletal muscle dysfunction is an important co-morbidity in patients with chronic obstructive pulmonary disease (COPD) and is significantly associated with increased mortality. Oxidative stress has been demonstrated an important trigger for COPD-related skeletal muscle dysfunction. Glycine-histidine-lysine (GHK) is an active tripeptide, which is a normal component of human plasma, saliva, and urine; promotes tissue regeneration; and acts as an anti-inflammatory and antioxidant properties. The purpose of this study was to determine whether GHK is involved in COPD-related skeletal muscle dysfunction. METHODS: The plasma GHK level in patients with COPD (n = 9) and age-paired healthy subjects (n = 11) were detected using reversed-phase high-performance liquid chromatography. The complex GHK with Cu (GHK-Cu) was used in in vitro (C2C12 myotubes) and in vivo experiments (cigarette smoking [CS]-exposure mouse model) to explore the involvement of GHK in CS-induced skeletal muscle dysfunction. RESULTS: Compared with healthy control, plasma GHK levels were decreased in patients with COPD (70.27 ± 38.87 ng/mL vs. 133.0 ± 54.54 ng/mL, P = 0.009). And plasma GHK levels in patients with COPD were associated with pectoralis muscle area (R = 0.684, P = 0.042), inflammatory factor TNF-α (R = -0.696, P = 0.037), and antioxidative stress factor SOD2 (R = 0.721, P = 0.029). GHK-Cu was found to rescue CSE-induced skeletal muscle dysfunction in C2C12 myotubes, as evidenced by increased expression of myosin heavy chain, reduced expression of MuRF1 and atrogin-1, elevated mitochondrial content, and enhanced resistance to oxidative stress. In CS-induced muscle dysfunction C57BL/6 mice, GHK-Cu treatment (0.2 and 2 mg/kg) reduces CS-induced muscle mass loss (skeletal muscle weight (1.19 ± 0.09% vs. 1.29 ± 0.06%, 1.40 ± 0.05%; P < 0.05) and muscle cross-sectional area elevated (1055 ± 552.4 µm2 vs. 1797 ± 620.9 µm2 , 2252 ± 534.0 µm2 ; P < 0.001), and also rescues CS-induced muscle weakness, indicated by improved grip strength (175.5 ± 36.15 g vs. 257.6 ± 37.98 g, 339.1 ± 72.22 g; P < 0.01). Mechanistically, GHK-Cu directly binds and activates SIRT1(the binding energy was -6.1 kcal/mol). Through activating SIRT1 deacetylation, GHK-Cu inhibits FoxO3a transcriptional activity to reduce protein degradation, deacetylates Nrf2 and contribute to its action of reducing oxidative stress by generation of anti-oxidant enzymes, increases PGC-1α expression to promote mitochondrial function. Finally, GHK-Cu could protect mice against CS-induced skeletal muscle dysfunction via SIRT1. CONCLUSIONS: Plasma glycyl-l-histidyl-l-lysine level in patients with chronic obstructive pulmonary disease was significantly decreased and was significantly associated with skeletal muscle mass. Exogenous administration of glycyl-l-histidyl-l-lysine-Cu2+ could protect against cigarette smoking-induced skeletal muscle dysfunction via sirtuin 1.


Asunto(s)
Fumar Cigarrillos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Ratones , Animales , Lisina/metabolismo , Sirtuina 1/metabolismo , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo
16.
Front Med (Lausanne) ; 10: 1061447, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36968822

RESUMEN

Background: Airway complications seriously affect the clinical outcomes and long-term prognosis of lung-transplantation patients. Airway stenting provides effective palliation for patients with airway stenosis. However, a lack of consensus regarding the efficacy and safety of airway stents in airway stenosis after lung transplantation. This study critically evaluated all available evidence regarding this concern. Methods: We retrieved studies from EMBASE, PubMed, and Cochrane Library databases. Studies were included if they reported baseline characteristics of airway complications after lung transplantation, stenting for airway stenosis, or prognosis. Results: In total, 279 papers were screened and 17 papers were included in final analysis. The short-term efficacy of airway stenting was assessed in almost all studies, with immediate palliation in symptom and improved pulmonary function reported. Eleven of the included studies evaluated the long-term efficacy of stent therapy, with no distinct lung function. The median overall survival time was 1,124 (95% confidence interval 415-1,833) days in stented patients only. Stent-related complications are common regardless of the material; However, serious complications are rare and can be improved with routine management. Conclusion: We demonstrated that airway stenting is a safe and effective method to treat airway stenosis after lung transplantation. The short-term effect was significant, while the long-term efficacy on survival rate needed further investigations. Systematic review registration: www.crd.york.ac.uk/prospero/, identifier: CRD42022364427.

17.
Biomed Pharmacother ; 159: 114230, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36696799

RESUMEN

Oxidative stress and chronic inflammation play key roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). Astaxanthin (AXT) is a keto-carotenoid with a variety of biological functions, including antioxidant and anti-inflammatory effects This study aimed to explore the protective role and underlying mechanism of AXT in the pathogenesis of COPD. In this study, we found AXT alleviated pulmonary emphysema in a CS-exposed mouse model and regulated the expression of MMP-9/TIMP-1. And, AXT attenuates CSE-induced small airway fibrosis. Meanwhile, AXT inhibited Nrf2-modulated oxidative stress and the p65 NF-κB-regulated inflammatory pathway in both the mouse model and CSE-treated HBE cells. Mechanistically, AXT could directly bind to SIRT1 (the binding energy of the complex was -8.8 kcal/mol) and regulate the deacetylation activity of SIRT1. Finally, by activating SIRT1 deacetylation, AXT deacetylated Nrf2 and contributed to its action of reducing oxidative stress by generating antioxidant enzymes, and inhibiting p65 NF-κB transcriptional activity to suppress the inflammatory response. Our results show that treatment with AXT significantly reverses the oxidative stress and inflammation induced by cigarette smoke both in vivo and in vitro in a sirtuin 1-dependent manner.


Asunto(s)
Fumar Cigarrillos , Enfermedad Pulmonar Obstructiva Crónica , Ratones , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Sirtuina 1/metabolismo , FN-kappa B/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Inflamación/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Nicotiana , Modelos Animales de Enfermedad
18.
Front Cell Infect Microbiol ; 12: 937811, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36111237

RESUMEN

Tuberculous pleurisy (TP) is a common type of extrapulmonary tuberculosis (EPTB). With the development of research and changes in TP patient characteristics, an increasing number of studies have revealed the prevalence, risk factors, and novel diagnosis techniques. Thus, this bibliometric analysis was performed to identify global scientific output characteristics and research hotspots and frontiers for TP over the past 15 years. We searched the Web of Science Core Collection (WoSCC) Science Citation Index Expanded (SCI-expanded) for literature published between 2007 and 2021 and recorded their information. The Bibliometrix software package was used for bibliometric indicator analysis, and VOSviewer was used to visualize the trends of and hotspots in TP research. A total of 1,464 original articles were reviewed, and the results indicated that the annual number of publications (Np) focusing on TP has increased over the past 15 years. China had the largest number of papers and the highest H-index, and the United States ranked first for number of citations (Nc). EGYPTIAN KNOWLEDGE BANK and PLOS ONE were the most prolific unit and journal, respectively. The use of the Xpert assay and immune-related biomarker detection to diagnose TP appears to be a recent research hotspot. This bibliometric study demonstrated that the number of publications related to TP have tended to increase. China is a major producer, and the United States is an influential country in this field. Research in the past 15 years has been predominantly clinical research. The diagnosis of TP was the focus of research, and the exploration of novel diagnostic techniques, verification of diagnostic markers, and combination of diagnostic methods have been recent research hotspots. Immune-related biomarkers should be given more attention in the field of TP diagnosis.


Asunto(s)
Tuberculosis Pleural , Bibliometría , Biomarcadores , Humanos , Prevalencia , Factores de Riesgo , Tuberculosis Pleural/diagnóstico , Tuberculosis Pleural/epidemiología , Estados Unidos
19.
Front Nutr ; 9: 897097, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35845807

RESUMEN

Purpose: Sarcopenia is an important factor contributing to comorbidities in patients with chronic obstructive pulmonary disease (COPD) and is an independent risk factor for increased mortality. The diagnostic process for sarcopenia requires specific equipment and specialized training and is difficult procedurally. A previous study found that GDF15 levels are associated with skeletal muscle mass and function in patients with COPD. However, whether circulating GDF15 levels can be used for the prediction of sarcopenia in patients with COPD is unknown. Methods: This study included 235 patients with stable COPD who were divided into a development set (n = 117) and a validation set (n = 118), and we followed the definition of sarcopenia as defined by the guidelines from the Asian Working Group for Sarcopenia. Serum concentrations of GDF15 were measured using an enzyme-linked immunosorbent assay (ELISA), and construction of a nomogram and decision curve analysis were performed using the R package "rms." Results: In this study, serum GDF15 levels were negatively associated with skeletal muscle mass (r = -0.204, p = 0.031), handgrip strength (r = -0.274, p = 0.004), quadriceps strength (r = -0.269, p = 0.029), and the thickness (r = -0.338, p < 0.001) and area (r = -0.335, p < 0.001) of the rectus femoris muscle in patients with COPD. Furthermore, the serum levels of GDF15 in patients with sarcopenia were significantly higher than those in controls. Importantly, serum levels of GDF15 could effectively predict sarcopenia in patients with COPD based on the development set (AUC = 0.827) and validation set (AUC = 0.801). Finally, a nomogram model based on serum GDF15 levels and clinical features showed good predictive ability (AUC > 0.89) in the development and validation sets. Conclusion: Serum GDF15 levels could be used to accurately and easily evaluate sarcopenia in patients with COPD.

20.
Front Immunol ; 12: 604222, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34040601

RESUMEN

Background: Antiphospholipid syndrome (APS) is a systemic autoimmune disease that can lead to thrombosis and/or pregnancy complications. Exosomes, membrane-encapsulated vesicles that are released into the extracellular environment by many types of cells, can carry signals to recipient cells to affect angiogenesis, apoptosis, and inflammation. There is increasing evidence suggesting that exosomes play critical roles in pregnancy. However, the contribution of exosomes to APS is still unknown. Methods: Peripheral plasma was collected from healthy early pregnancy patients (NC-exos) and early pregnancy patients with APS (APS-exos) for exosome extraction and characterization. The effect of exosomes from different sources on pregnancy outcomes was determined by establishing a mouse pregnancy model. Following the coincubation of exosomes and human umbilical vein endothelial cells (HUVECs), functional tests examined the features of APS-exos. The APS-exos and NC-exos were analyzed by quantitative proteomics of whole protein tandem mass tag (TMT) markers to explore the different compositions and identify key proteins. After incubation with HUVECs, functional tests investigated the characteristics of key exosomal proteins. Western blot analysis was used to identify the key pathways. Results: In the mouse model, APS-exos caused an APS-like birth outcome. In vitro experiments showed that APS-exos inhibited the migration and tube formation of HUVECs. Quantitative proteomics analysis identified 27 upregulated proteins and 9 downregulated proteins in APS-exos versus NC-exos. We hypothesized that apolipoprotein H (APOH) may be a core protein, and the analysis of clinical samples was consistent with finding from the proteomic TMT analysis. APOH-exos led to APS-like birth outcomes. APOH-exos directly enter HUVECs and may play a role through the phospho-extracellular signal-regulated kinase pathway. Conclusions: Our study suggests that both APS-exos and APOH-exos impair vascular development and lead to pregnancy complications. APOH-exos may be key actors in the pathogenesis of APS. This study provides new insights into the pathogenesis of APS and potential new targets for therapeutic intervention.


Asunto(s)
Síndrome Antifosfolípido/etiología , Síndrome Antifosfolípido/metabolismo , Susceptibilidad a Enfermedades , Exosomas/metabolismo , beta 2 Glicoproteína I/metabolismo , Animales , Síndrome Antifosfolípido/patología , Transporte Biológico , Biomarcadores , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Ratones , Fenotipo , Fosforilación , Embarazo , Proteoma , Proteómica/métodos
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