The effect of respiratory muscle training on children and adolescents with cystic fibrosis: a systematic review and meta-analysis.

BACKGROUND: Cystic fibrosis is a chronic genetic disease that can affect the function of the respiratory system. Previous reviews of the effects of respiratory muscle training in people with cystic fibrosis are uncertain and do not consider the effect of age on disease progression. This systematic review aims to determine the effectiveness of respiratory muscle training in the clinical outcomes of children and adolescents with cystic fibrosis. METHODS: Up to July 2023, electronic databases and clinical trial registries were searched. Controlled clinical trials comparing respiratory muscle training with sham intervention or no intervention in children and adolescents with cystic fibrosis. The primary outcomes were respiratory muscle strength, respiratory muscle endurance, lung function, and cough. Secondary outcomes included exercise capacity, quality of life and adverse events. Two review authors independently extracted data and assessed study quality using the Cochrane Risk of Bias Tool 2. The certainty of the evidence was assessed according to the GRADE approach. Meta-analyses where possible; otherwise, take a qualitative approach. RESULTS: Six studies with a total of 151 participants met the inclusion criteria for this review. Two of the six included studies were published in abstract form only, limiting the available information. Four studies were parallel studies and two were cross-over designs. There were significant differences in the methods and quality of the methodology included in the studies. The pooled data showed no difference in respiratory muscle strength, lung function, and exercise capacity between the treatment and control groups. However, subgroup analyses suggest that inspiratory muscle training is beneficial in increasing maximal inspiratory pressure, and qualitative analyses suggest that respiratory muscle training may benefit respiratory muscle endurance without any adverse effects. CONCLUSIONS: This systematic review and meta-analysis indicate that although the level of evidence indicating the benefits of respiratory muscle training is low, its clinical significance suggests that we further study the methodological quality to determine the effectiveness of training. TRIAL REGISTRATION: The protocol for this review was recorded in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023441829.

Quantitative Proteomics Analysis of Differentially Expressed Proteins in Serum of Former Uranium Miners by Isobaric Tags for the Relative and Absolute Quantitation.

The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. However, there is a lack of early warning indicators for radon radiation damage. In this study, mixed serum samples of 3 groups were collected from 27 underground uranium miners and seven aboveground miners according to the radiation exposure dose. The differentially expressed proteins in the serum were identified using the isobaric tags for the relative and absolute quantitation (iTRAQ)-based method. Some differentially expressed proteins were validated by enzyme-linked immunosorbent assay (ELISA) in 84 underground and 32 aboveground miners. A total of 25 co-differentially expressed proteins in 2 underground miner groups were screened, of which 9 were downregulated and 13 were upregulated. Biological process analysis of these proteins using Metascape showed that 5 GO terms were enriched, such as negative regulation of very-low-density lipoprotein particle clearance, endocytosis, and regulated exocytosis. The results of the ELISA for the expression levels of GCN1, CIP2A, and IGHV1-24 in the serum of 116 miners' serum showed that the levels of GCN1 and CIP2A were consistent with the iTRAQ results. In conclusion, APOC1, APOC2, APOC3, ORM1, ORM2, ANTXR1, GCN1, and CIP2A may be potential early markers of radon radiation damage.

MicroRNA profiling in BEAS-2B cells exposed to alpha radiation reveals potential biomarkers for malignant cellular transformation.

The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. The risk of lung cancer from radon exposure is due to the continuous radioactive decay of this gas and subsequent emission of high-energy alpha decay particles. And the bronchial epithelial cells are the main targets of radon exposure. However, there is a lack of early warning indicators of lung cancer caused by radon in the physical examination of populations involved in occupations with higher exposure to radon. To assess the potential of a molecular-based marker approach for the early detection of human lung cancer induced by radon, human bronchial epithelial cell injury models induced by alpha-particle irradiation were constructed. The results of transwell migration assay, transwell invasion assay, and the expression of the epithelial-mesenchymal transition-related proteins showed that malignant cell transformation could be triggered by alpha irradiation. Potential microRNAs (miRNAs) (hsa-miR-3907, hsa-miR-6732-3p, hsa-miR-4788, hsa-miR-5001-5p, and hsa-miR-4257) were screened using miRNA chips in cell models. The pathway analyses of miRNAs selected using DIANA-miRPath v3.0 showed that miRNAs involved in malignant cell transformation were associated with cell adhesion molecules, extracellular matrix receptor interaction, and proteoglycans in cancer, among others, which are closely related to the occurrence and development of carcinogenesis. Reverse Transcription Quantitative Real-Time PCR (RT-qPCR) assay showed that five screened miRNAs were up-regulated in five lung cancer tissue samples. In conclusion, the results indicated that hsa-miR-3907, hsa-miR-6732-3p, hsa-miR-4788, hsa-miR-5001-5p, and hsa-miR-4257 may be potential early markers of the malignant transformation of bronchial epithelial cells induced by alpha-particle irradiation.

Comparison of transcriptional profiles in human lymphocyte cells irradiated with 12C ion beams at 0-2.0 Gy.

OBJECTIVE: Heavy ions have contributed to tumor site-specific radiotherapy and are a major health risk for astronauts. The purpose of this study was to investigate the changes in gene expression in peripheral lymphocytes of cancer patients and astronauts exposed to 12C ions, and identify suitable molecular biomarkers for health monitoring. We also aimed to observe the effects of treatment and the level of damage, by comparing the transcriptional profiles of human lymphocyte cell lines exposed to 12C ion beams at doses of 0-2.0 Gy. MATERIALS AND METHODS: A human lymphocyte cell line was irradiated with 12C ion beams at 0, 0.1, 0.5, and 2.0 Gy and transcriptional profiles were evaluated using the Agilent human gene expression microarray at 24 hours after irradiation. Differentially expressed genes were identified using a fold change of ≥2.0. Representative genes were further validated by RT-PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to determine the roles of differentially expressed mRNAs. RESULTS: Based on the microarray assays, 1,113 genes were upregulated and 853 genes were downregulated in human lymphocyte cells irradiated with 0.1 Gy 12C ion beams compared with the control group, 1,095 genes were upregulated and 1,220 genes were downregulated in cells irradiated with 0.5 Gy 12C ion beams, and 1,055 genes were upregulated and 1,356 genes were downregulated in cells irradiated with 2.0 Gy. A total of 504 genes were differentially expressed in all irradiated groups, of which 88 genes were upregulated and 416 genes downregulated. Most of these altered genes were related to the cell cycle, apoptosis, signal transduction, DNA transcription, repair, and replication. The expression differences were further confirmed by RT-PCR for a subset of differentially expressed genes. CONCLUSION: Differentially expressed genes between treatment and control groups at 24 hours post-irradiation increased as the radiation dose increased; upregulated genes gradually decreased and downregulated genes increased. Our data indicated that 12C ion beams could repress a number of genes in a dose-dependent manner, which might lead to the failure of multiple cellular biological functions.

Genomic instability induced by ionizing radiation in human hepatocytes.

The aim of this study was to characterize genomic instability induced by ionizing radiation (IR) in human hepatocytes as reflected by alterations in cloning efficiency, micronucleus (MN) frequency, and apoptosis. The human normal liver 7702 cell line (HL7702) was subjected to initial irradiation of (60)Co-γ ray at doses of 0 (control group), 2, 4, 6, 8, or 10 Gy in each group. Progeny of surviving cells from a second irradiation at dose of 2 Gy were cultured for 15 passages until they were transferred. The cloning efficiency, MN frequency, and apoptotic rate were measured after the initial irradiation, and repeated at passage 15 before and after the second irradiation. The initial irradiation resulted in a dose-dependent decline in cloning efficiency and an increase in MN frequency and apoptotic rate. At passage 15 in progeny of initially irradiated cells, cloning efficiency, MN frequency returned to control levels while apoptotic rate rose. After the second irradiation, cloning efficiency fell while a rise in MN frequency and apoptosis occurred. Our results show that the second irradiation may further enhance cell progeny injury induced by initial irradiation, such that genomic instability that may be difficult to detect after one irradiation is more apparent with subsequent irradiation.

Proteomic alterations in progeny of irradiated human liver cells.

This study was designed to characterize the differential protein expression in the progeny of human liver cells surviving exposure to ionizing radiation. The progeny of irradiated cells were derived from a human liver cell line exposed to 0, 2, 4, or 6 Gy of (60)Co gamma-irradiation. Total protein of the cells was extracted by two-dimensional electrophoresis (2-DE) and analyzed with ImageMaster 2D Platinum software. In total, 42 differentially expressed proteins from the progeny of irradiated cells were screened, of which 17 were identified by matrix assistant laser desorption ion-top flight-mass spectrometry (MALDI-TOF-MS) analysis. There were 4 upregulated and 13 downregulated proteins detected. The upregulated expression of two proteins, mitochondrial heat-shock 60-kD protein (HSP60) and globin transcription factor 1 (GATA-1), was further confirmed by immunoblotting. Database search revealed that these differentially expressed proteins may function in cell cycle regulation, cytoskeleton maintenance, stress response, and tumor metastasis, indicating an effect of radiation-induced genomic instability (RIGI) in the progeny of irradiated cells. Analysis on functional roles of the screened proteins may provide insight into further mechanistic investigations underlying molecular events induced by RIGI.