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This research activated phosphorus tailings to prepare a highphosphorus core (HPC) for multi-species composite slow-release heavy metal soil prophylactic agents (MCP), aiming to extend the slow-release period of MCP and enhance the efficiency of Pb stabilization. During the preparation of HPC, the proportion of non-apatitic inorganic phosphorus (NAIP) and apatite phosphorus (AP) continuously decreased with increasing polymerization temperature. At 400 °C, polyphosphates (PP) began to form, reaching 74.26 % at 600 °C. Initially, the rapidly soluble NAIP remained the major component of HPC, but the proportion of AP increased with higher polymerization temperatures, reaching 40.8 % at 600 °C. After 120 days of cultivation with four MCPs (MCP 300-21, MCP 400-12, MCP 500-14, MCP 600-14), the total soil phosphorus (TSP), soil organic matter (SOM), and Pb stabilization capacity of the cultivated soil showed significant improvements, reaching maximum values of 2.39 mg/g, 38.16 mg/g, and 45.4 mg/g, respectively, which are 9.9, 4.4, and 5.9 times higher than those of the CK soil. KEGG (Kyoto Encyclopedia of Genes and Genomes) functional prediction analysis indicated that MCPs contribute directly or indirectly to the forms and chemical stability of Pb by stimulating soil physiological and biochemical processes. This research proposes a novel approach for using phosphates in soil heavy metal management strategies and provides new insights into the mechanisms of heavy metal stabilization in soil using environmental functional materials.
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Background: Electroacupuncture (EA) exerts beneficial effects on ulcerative colitis. However, its underlying mechanisms remain elusive. In this study, we investigated the impact of high and low-frequency EA at Zusanli (ST36) on the gut microbiota and metabolite profile in the dextran sulfate sodium (DSS)-induced colitis mouse model. Methods: Colitis was established using DSS, and daily electroacupuncture at ST36 with varying frequencies was administered. Changes in body weight and fecal characteristics were monitored. Pro-inflammatory cytokines were detected, and the core molecule of intestinal barrier function were analyzed. The composition of intestinal flora was analyzed using 16S sRNA sequencing, while the changes of metabolites in colon tissue were detected by Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS). Results: Treatment with both high and low frequencies of EA at ST36 significantly ameliorated the symptoms of colitis, while also exerting systemic and local anti-inflammatory effect by downregulating the proinflammatory cytokines, iNOS and MPO. EA at ST36 enhanced the intestinal barrier by upregulating the expression of MUC2 and ZO-1. Furthermore, high-frequency EA at ST36 remarkably restored the gut microbial composition and diversity, as well as modulated the gut microbial metabolism of phenylalanine. Conclusion: Our results suggest that EA treatment may alleviate colitis by reducing colon damage through gut microbiota-phenylalanine metabolism, which provides insight into EA's underlying mechanisms in the treatment of colitis.
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Soil remediation poses significant challenges due to its spatial heterogeneity, surpassing the complexities of atmospheric and water remediation. This study introduces an innovative approach to prevent soil heavy metal pollution by developing three phosphorus slow-release heavy metal soil prophylactic agents (SLPs) - Sap-11, Sap-12, and Sap-21. At a liquid-to-solid ratio of 1:20, the three types of SLPs achieve phosphorus sustained slow release amounts of 1.586 g/L, 4.259 g/L, and 1.444 g/L within 30 days, respectively. Over a cultivation period of 120 days, after amendment with the three SLPs, the surface soil demonstrates stabilization capacities for Pb of 29.56 mg/g, 46.24 mg/g, and 25.77 mg/g, respectively, representing enhancements of 283.64 %, 500.12 %, and 250.74 % compared to the control. Firstly, the direct contribution of P (up to 3.778 mg/g) released from SLPs chemically binding with Pb, and secondly, a significant proportion of the indirect contribution originating from the microbial activity and soil organic matter. In summary, SLP emerges as an effective strategy for soil heavy metal management, stabilizing heavy metals by stimulating the soil's inherent physiological and biochemical reactions. This approach provides a practical solution for the application of P-containing materials and introduces novel perspectives for soil heavy metal management strategies.
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Recuperação e Remediação Ambiental , Chumbo , Fósforo , Microbiologia do Solo , Poluentes do Solo , Solo , Poluentes do Solo/análise , Fósforo/análise , Chumbo/análise , Solo/química , Recuperação e Remediação Ambiental/métodos , Cinética , Metais Pesados/análiseRESUMO
Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is influenced by genetic factors. The genetic signal rs10516526 in the glutathione S-transferase C-terminal domain containing (GSTCD) gene is a highly significant and reproducible signal associated with lung function and COPD on chromosome 4q24. In this study, comprehensive bioinformatics analyses and experimental verifications were detailly implemented to explore the regulation mechanism of rs10516526 and GSTCD in COPD. The results suggested that low expression of GSTCD was associated with COPD (p = 0.010). And C-Jun and CREB1 transcription factors were found to be essential for the regulation of GSTCD by rs80245547 and rs72673891. Moreover, rs80245547T and rs72673891G had a stronger binding ability to these transcription factors, which may promote the allele-specific long-range enhancer-promoter interactions on GSTCD, thus making COPD less susceptible. Our study provides a new insight into the relationship between rs10516526, GSTCD, and COPD.
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PURPOSE: While asthma comorbidities are associated with higher health care utilisation, lower quality of life and poorer asthma control, the impact of asthma comorbidities on hospitalisation for asthma exacerbation (H-AX) remains less recognised. We aim to analyse the impact of asthma comorbidities on H-AX. METHODS: Based on a national survey on asthma control and disease perception (CARN 2015 study), we analysed the impact of comorbidities on annual incidence and frequency of H-AX in China. Information on demographic characteristics, asthma comorbidities and annual incidence and frequency of H-AX were presented in this study. RESULTS: Among 3875 ambulatory asthma patients, 75.9% (2941/3875) had comorbidities, and 26.4% (1017/3858) experienced H-AX during past year. After adjusting for confounding factors such as demographic data, smoking status and asthma control, COPD [OR = 2.189, 95% CI (1.673, 2.863)] and coronary heart disease [OR = 1.387, 95% CI (1.032, 1.864)] were associated with higher annual incidence, while allergic rhinitis [OR = 0.692, 95% CI (0.588, 0.815)] was associated with lower annual incidence, of H-AX. In terms of frequency, allergic rhinitis [OR = 1.630, 95% CI (1.214, 2.187)], COPD [OR = 1.472, 95% CI (1.021, 2.122)] and anxiety [OR = 2.609, 95% CI (1.051, 6.477)] showed statistically significant correlation with frequent H-AX. CONCLUSIONS: COPD and coronary heart disease were associated with higher annual incidence, while allergic rhinitis was associated with lower annual incidence of H-AX. Allergic rhinitis, COPD and anxiety were associated with frequent H-AX. Comorbidities may have an important role in the risk and frequency of annual hospitalisations due to asthma exacerbation. The goal of asthma control should rely on a multi-disciplinary treatment protocol.
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Asma , Doença Pulmonar Obstrutiva Crônica , Rinite Alérgica , Asma/complicações , Asma/epidemiologia , Hospitalização , Humanos , Incidência , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Qualidade de Vida , Rinite Alérgica/epidemiologiaRESUMO
Rapid, non-destructive methods for determining the biochemical composition of straw are crucial in ruminant diets. In this work, ground samples of corn stover (n = 156) and wheat straw (n = 135) were scanned using near-infrared spectroscopy (instrument NIRS DS2500). Samples were divided into two sets, with one set used for calibration (corn stover, n = 126; wheat straw, n = 108) and the remaining set used for validation (corn stover, n = 30; wheat straw, n = 27). Calibration models were developed utilizing modified partial least squares (MPLS) regression with internal cross validation. Concentrations of moisture, crude protein (CP), and neutral detergent fiber (NDF) were successfully predicted in corn stover, and CP and moisture were in wheat straw, but other nutritional components were not predicted accurately when using single-crop samples. All samples were then combined to form new calibration (n = 233) and validation (n = 58) sets comprised of both corn stover and wheat straw. For these combined samples, the CP, NDF, and ADF were predicted successfully; the coefficients of determination for calibration (RSQC) were 0.9625, 0.8349, and 0.8745, with ratios of prediction to deviation (RPD) of 6.872, 2.210, and 2.751, respectively. The acid detergent lignin (ADL) and moisture were classified as moderately useful, with RSQC values of 0.7939 (RPD = 2.259) and 0.8342 (RPD = 1.868), respectively. Although the prediction of hemicellulose was only useful for screening purposes (RSQC = 0.4388, RPD = 1.085), it was concluded that NIRS is a suitable technique to rapidly evaluate the nutritional value of forage crops.
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BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often combined with type 2 diabetes mellitus (T2DM) in clinical, and with poor prognosis. In recent years, research shows that inflammation is a common characteristic of COPD and T2DM. T-helper 17 cell (Th17)/regulatory T-cell (Treg) balance controls inflammation and may be important in the pathogenesis of COPD combined with T2DM patients. This study investigated the characteristics of Th17, Treg and related inflammatory factors in COPD combined with T2DM patients and the potential mechanism. METHODS: Application of flow cytometry technology, real-time fluorescent quantitative PCR and ELISA to detect the changes in peripheral blood of Th17 and Treg number and the expression of key transcription factors and related cytokines in COPD combined T2DM patients were performed. RESULTS: Patients with COPD combined with T2DM revealed significant increase in peripheral Th17, Th17 related cytokines (IL-17A, IL-17F, IL-21, IL-23, IL-6) and transcription factor (RORγt) levels and significant decrease in Treg, Treg-related cytokines (IL-10, TGFß1) and transcription factor (Foxp3) as compared with patients with COPD, T2DM and healthy controls. CONCLUSION: Th17/Treg functional imbalance exists in patients with COPD combined with T2DM, indicating a potential role of Th17/Treg imbalance in the formation and progression of COPD combined with T2DM.
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Diabetes Mellitus Tipo 2 , Doença Pulmonar Obstrutiva Crônica , Citocinas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Linfócitos T Reguladores , Células Th17RESUMO
Nitrogen (N) is one of the major nutrients limiting plant growth in terrestrial ecosystems. To avoid plant-microbe competition, previous studies on plant N uptake preference often used hydroponic experiments on fine roots of seedlings and demonstrated ammonium preference for conifer species; however, we lack information about N uptake and translocation in the field. In this paper, we described a method of in situ paired 15N labeling and reported the rates and time course of N uptake and translocation by mature trees in situ. We added 15N-enriched ammonium or nitrate, together with the nitrification inhibitor dicyandiamide, to paired Larix kaempferi (Lamb.) Carr (larch) trees from 30-, 40- and 50-year-old plantations. Fine roots, coarse roots, leaves and small branches were collected 2, 4, 7, 14 and 30 days after labeling. Nitrate uptake and translocation averaged 1.59 ± 0.16 µg 15N g-1 day-1, which is slightly higher than ammonium (1.08 ± 0.10 µg 15N g-1 day-1), in all tree organs. Nitrate contributed 50-78% to N uptake and translocation, indicating efficient nitrate use by larch in situ. We observed no age effect. We suggest that sampling leaves after 4 days of 15N labeling is sufficient to detect mature tree N uptake preference in situ. Whole-tree 15N-ammonium recovery equaled that of 15N-nitrate 30 days after 15N addition, implying the importance of both ammonium and nitrate to mature larch N use in the long run. We conclude that our method is promising for studying mature tree N uptake preference in situ and can be applied to other conifer and broadleaf species. We suggest using highly enriched 15N tracer to overcome soil dilution and a nitrification inhibitor to minimize ammonium transformation to nitrate. Our study revealed mature tree N preference in situ and demonstrated the strong contribution of nitrate toward mature larch growth on soils rich in nitrate.
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Nitrogênio , Árvores , Ecossistema , Nitrogênio/análise , Isótopos de Nitrogênio , Raízes de Plantas , SoloRESUMO
Conifers are considered to prefer to take up ammonium (NH4+ ) over nitrate (NO3- ). However, this conclusion is mainly based on hydroponic experiments that separate roots from soils. It remains unclear to what extent mature conifers can use nitrate compared to ammonium under field conditions where both roots and soil microbes compete for nitrogen (N). We conducted an in situ whole mature tree nitrogen-15 (15 N) labeling experiment (15 NH4+ vs 15 NO3- ) over 15 d to quantify ammonium and nitrate uptake and assimilation rates in four 40-yr-old monoculture coniferous plantations (Pinus koraiensis, Pinus sylvestris, Picea koraiensis and Larix olgensis, respectively). For the whole tree, 15 NO3- contributed 39% to 90% to total 15 N tracer uptake among four plantations during the study period. At day 3, the 15 NO3- accounted for 77%, 64%, 62% and 59% by Larix olgensis, Pinus koraiensis, Pinus sylvestris and Picea koraiensis, respectively. Our study indicates that mature coniferous trees assimilated nitrate as efficiently as ammonium from soils even at low soil nitrate concentration, in contrast to the results from hydroponic experiments showing that ammonium uptake dominated over nitrate. This implies that mature conifers can adapt to increasing availability of nitrate in soil, for example, under the context of globalization of N deposition and global warming.
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Compostos de Amônio , Traqueófitas , Florestas , Nitratos/análise , Nitrogênio/análise , Solo , ÁrvoresRESUMO
PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients. METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed. RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%). CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.
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Fundamental questions of how plant species within secondary forests and plantations in northeast China partition limited nitrogen (N) resource remain unclear. Here we conducted a 15N tracer greenhouse study to determine glycine, ammonium, and nitrate uptake by the seedlings of two coniferous species, Pinus koraiensis (Pinus) and Larix keampferi (Larix), and two broadleaf species, Quercus mongolica (Quercus) and Juglans mandshurica (Juglans), that are common in natural secondary forests in northeast China. Glycine contributed 43% to total N uptake of Pinus, but only 20, 11, and 21% to N uptake by Larix, Quercus, and Juglans, respectively (whole plant), whereas nitrate uptake was 24, 74, 88, and 68% of total uptake for these four species, respectively. Retention of glycine carbon versus nitrogen in Pinus roots indicated that 36% of glycine uptake was retained intact. Nitrate was preferentially used by Larix, Quercus, and Juglans, with nitrate uptake constituting 68â¼88% of total N use by these three species. These results demonstrated that these dominant tree species in secondary forests in northeast China partitioned limited N resource by varying uptake of glycine, ammonium and nitrate, with all species, except Pinus, using nitrate that are most abundant within these soils. Such N use pattern may also provide potential underlying mechanisms for the higher retention of deposited nitrate than ammonium into aboveground biomass in these secondary forests.
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Ulcerative colitis (UC), a bowel disease with signiï¬cant morbidity, is associated with inflammation. In this study, the effect of Qingchang Huashi granule (QCHS) on UC and its underlying mechanisms were explored using both animal and cell culture experiments. A rat UC model was induced with trinitro-benzene-sulfonic acid (TNBS), concentrations of the cytokines IL-1α, IL-6, IL-8, IL-1ß, and TNF-α were signiï¬cantly up-regulated and the concentrations of IL-4, IL-10, and IL-13 were signiï¬cantly down-regulated compared with the control group (P < 0.05). In contrast, the QCHS and salicylazosulfapyridine (SASP) groups reversed these modulations (P < 0.05). A UC cell model in HT-29 cells was generated using TNF-α combined with lipopolysaccharide treatment. Cells treated with QCHS were used to investigate the possible mechanisms. The expression of apoptosis-related proteins, including Bax/Bcl-2, caspase-3, caspase-9, Fas/Fas-L, and Rafl in the QCHS and SASP groups, were significantly lower than that in the control group in both animal and cell experiments (P < 0.05). In addition, the in vitro results indicate changes in these indicators mediate the MEK/ERK signaling pathways via SGK1. Our results suggested that QCHS could be beneficial in preventing UC progression as an alternative drug for UC treatment.
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Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/enzimologia , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Modelos Biológicos , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Colo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Inativação Gênica , Células HT29 , Humanos , Proteínas Imediatamente Precoces/metabolismo , Lipopolissacarídeos , Masculino , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-DawleyRESUMO
BACKGROUND: Heterogeneity of COPD results in different therapeutic effects for different patients receiving the same treatment. COPD patients need to be individually treated according to their own characteristics. The purpose of this study was to explore the differences in different CT phenotypic COPD by molecular metabolites through the use of metabolomics. METHODS: According to the characteristics of CT imaging, 42 COPD patients were grouped into phenotype E (n=20) or phenotype M (n=24). Each COPD patient received tiotropium bromide powder for inhalation for a therapeutic period of 3 months. All subjects were assigned into phenotype E in pre-therapy (EB, n=20), phenotype E in post-therapy (EA, n=20), phenotype M in pre-therapy (MB, n=22), phenotype M in post-therapy (MA, n=22), or normal control (N, n=24). The method of metabolomics based on 1H nuclear magnetic resonance (1H-NMR) was used to compare the changes in serum metabolites between COPD patients and normal controls and between different phenotypes of COPD patients in pre- and post-therapy. RESULTS: Patients with COPD phenotype E responded better to tiotropium bromide than patients with COPD phenotype M in terms of pulmonary function and COPD assessment test scores. There were differences in metabolites in COPD patients vs normal control people. Differences were also observed between different COPD phenotypic patients receiving the treatment in comparison with those who did not receive treatment. The changes of metabolites involved lactate, phenylalanine, fructose, glycine, asparagine, citric acid, pyruvic acid, proline, acetone, ornithine, lipid, pyridoxine, maltose, betaine, lipoprotein, and so on. These identified metabolites covered the metabolic pathways of amino acids, carbohydrates, lipids, genetic materials, and vitamin. CONCLUSION: The efficacy of tiotropium bromide on COPD phenotype E is better than that of phenotype M. Metabolites detected by 1H-NMR metabolomics have potentialities of differentiation of COPD and healthy people, discrimination of different COPD phenotypes, and giving insight into the individualized treatment of COPD.
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Espectroscopia de Ressonância Magnética/métodos , Metabolômica/métodos , Fenótipo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Brometo de Tiotrópio/administração & dosagem , Administração por Inalação , Adulto , Idoso , Broncodilatadores/administração & dosagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Valores de Referência , Testes de Função Respiratória , Medição de Risco , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
Background: Previous studies have suggested that ß2-adrenergic receptor (ADRB2) is associated with COPD. However, the role of genetic polymorphisms in ADRB2 on COPD has not been evaluated yet. Methods: In this study, SNaPshot genotyping, luciferase assay, chromatin immunoprecipitation and real-time polymerase chain reaction were adopted to investigate the association between ADRB2 genetic polymorphisms and COPD, comprehensively. Results: One single nucleotide polymorphism (rs12654778), located upstream of ADRB2, showed a significant association with COPD by the logistic regression analysis after adjusting for age, sex and smoking history (p=0.04) in 200 COPD patients and 222 controls from southwest Chinese population. Furthermore, the luciferase assay indicated that rs12654778-A allele reduced the relative promoter activity by ~26% compared with rs12654778-G allele (p=0.0034). The chromatin immunoprecipitation analysis demonstrated that rs12654778 modulated the binding affinity of transcription factor neurofibromin 1. In addition, a significantly reduced expression of ADRB2 in COPD patients was observed, compared with normal controls (p=0.017). Conclusion: Our findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on ADRB2 expression to COPD onset, for the first time.
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Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Receptores Adrenérgicos beta 2/genética , Adulto , Idoso , Sítios de Ligação , Estudos de Casos e Controles , Linhagem Celular , Distribuição de Qui-Quadrado , China , Feminino , Volume Expiratório Forçado , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neurofibromina 1/metabolismo , Razão de Chances , Fenótipo , Regiões Promotoras Genéticas , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Receptores Adrenérgicos beta 2/metabolismo , Fatores de Risco , Capacidade VitalRESUMO
BACKGROUND: Metabolomics is the global unbiased analysis of all the small-molecule metabolites within a biological system. Metabolic profiling of different high-resolution computed tomography (HRCT) phenotypes of COPD patients before and after treatment may identify discriminatory metabolites that can serve as biomarkers and therapeutic agents. PATIENTS AND METHODS: 1H nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomics was performed on a discovery set of plasma samples from 50 patients with stable COPD. Patients were assigned into two groups on the basis of HRCT findings including phenotype E (n=22) and phenotype M (n=28). After budesonide-formoterol treatment (160/4.5 µg ×2 inhalations twice daily for 3 months), clinical characteristics and metabolites were then compared between phenotype E pretreatment and posttreatment, phenotype M pretreatment and posttreatment, phenotype E pretreatment and phenotype M pretreatment, and phenotype E posttreatment and phenotype M posttreatment. RESULTS: Inhaled budesonide-formoterol therapy for both phenotype E (emphysema without bronchial wall thickening) and phenotype M (emphysema with bronchial wall thickening) was effective. However, phenotype E and phenotype M were different in response to therapy. Patients with phenotype M in response to therapeutic effects were significantly greater compared with phenotype E. Certain metabolites were identified, which were closely related to the treatment and phenotype. Metabolic changes in phenotype E or phenotype M after treatment may be involved with adenosine diphosphate (ADP), guanosine, choline, malonate, tyrosine, glycine, proline, l-alanine, l-valine, l-threonine leucine, uridine, pyruvic acid, acetone and metabolism disturbance. Metabolic differences between phenotype E and phenotype M in pretreatment and posttreatment covered glycine, d-glucose, pyruvic acid, succinate, lactate, proline, l-valine and leucine. CONCLUSION: Bronchial wall thickening in COPD may be an indicator for predicting the better response to the treatment with bronchodilator and corticosteroid. The identification of metabolic alterations provides new insights into different HRCT phenotypes and therapeutic assessment of COPD.
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Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Pulmão/efeitos dos fármacos , Metabolômica/métodos , Espectroscopia de Prótons por Ressonância Magnética , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tomografia Computadorizada por Raios X , Administração por Inalação , Idoso , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do TratamentoRESUMO
Peripheral muscle dysfunction is an important complication in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to explore the relationship between the levels of peroxisome proliferator-activated receptor α (PPARα) mRNA expression and the respiratory function and ultrastructure of mitochondria in the vastus lateralis of patients with COPD. Vastus lateralis biopsies were performed on 14 patients with COPD and 6 control subjects with normal lung function. PPARα mRNA levels in the muscle tissue were detected by real-time PCR. A Clark oxygen electrode was used to assess mitochondrial respiratory function. Mitochondrial number, fractional area in skeletal muscle cross-sections, and Z-line width were observed via transmission electron microscopy. The PPARα mRNA expression was significantly lower in COPD patients with low body mass index (BMIL) than in both COPD patients with normal body mass index (BMIN) and controls. Mitochondrial respiratory function (assessed by respiratory control ratio) was impaired in COPD patients, particularly in BMIL. Compared with that in the control group, mitochondrial number and fractional area were lower in the BMIL group, but were maintained in the BMIN group. Further, the Z-line became narrow in the BMIL group. PPARα mRNA expression was positively related to mitochondrial respiratory function and volume density. In COPD patients with BMIN, mitochondria volume density was maintained, while respiratory function decreased, whereas both volume density and respiratory function decreased in COPD patients with BMIL. PPARα mRNA expression levels are associated with decreased mitochondrial respiratory function and volume density, which may contribute to muscle dysfunction in COPD patients.
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Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , PPAR alfa/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , RNA Mensageiro/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/genética , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Doença Pulmonar Obstrutiva Crônica/genéticaRESUMO
Pleural effusion is a common clinical manifestation with various causes. Current diagnostic and therapeutic methods have exhibited numerous limitations. By involving the analysis of dynamic changes in low molecular weight catabolites, metabolomics has been widely applied in various types of disease and have provided platforms to distinguish many novel biomarkers. However, to the best of our knowledge, there are few studies regarding the metabolic profiling for pleural effusion. In the current study, 58 pleural effusion samples were collected, among which 20 were malignant pleural effusions, 20 were tuberculous pleural effusions and 18 were transudative pleural effusions. The small molecule metabolite spectrums were obtained by adopting 1H nuclear magnetic resonance technology, and patternrecognition multi-variable statistical analysis was used to screen out different metabolites. Oneway analysis of variance, and StudentNewmanKeuls and the KruskalWallis test were adopted for statistical analysis. Over 400 metabolites were identified in the untargeted metabolomic analysis and 26 metabolites were identified as significantly different among tuberculous, malignant and transudative pleural effusions. These metabolites were predominantly involved in the metabolic pathways of amino acids metabolism, glycometabolism and lipid metabolism. Statistical analysis revealed that eight metabolites contributed to the distinction between the three groups: Tuberculous, malignant and transudative pleural effusion. In the current study, the feasibility of identifying small molecule biochemical profiles in different types of pleural effusion were investigated reveal novel biological insights into the underlying mechanisms. The results provide specific insights into the biology of tubercular, malignant and transudative pleural effusion and may offer novel strategies for the diagnosis and therapy of associated diseases, including tuberculosis, advanced lung cancer and congestive heart failure.
Assuntos
Exsudatos e Transudatos/metabolismo , Metaboloma , Metabolômica/métodos , Derrame Pleural Maligno/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Tuberculose/metabolismo , Biomarcadores/metabolismo , Demografia , Análise Discriminante , Feminino , Humanos , Análise dos Mínimos Quadrados , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung, and HO-1 gene promoter polymorphism has been shown to be associated with the severity and prognosis of COPD patients. N-acetylcysteine (NAC), an antioxidant/mucous modifier, has shown an uncertain benefit in COPD patients. We hypothesized that this polymorphism could be associated with the effectiveness of oral NAC. METHODS: A total of 368 patients with COPD were recruited and the polymorphisms of their HO-1 gene promoter were classified into three subclasses according to the number of (GT)n repeats, as previously reported: class S (<27 (GT)n repeats), class M (27-32 (GT)n repeats), and class L (>32 (GT)n repeats). These subjects were then classified as L+ group (with the L allele: L/L, L/M, L/S) and L- group (without the L allele: M/M, M/S, S/S). All the patients were allocated to standard therapy plus NAC 600 mg bid over a 1-year period and were observed over that year. RESULTS: The L- group saw improvements in forced expiratory volume in 1 second (FEV1) (from 1.44±0.37 to 1.58±0.38, P=0.04) and FEV1% predicted (from 56.6±19.2 to 59.7±17.2, P=0.03). No improvement was found in forced vital capacity of each group and the decline of forced vital capacity in both of the groups was not statistical significant. The number of yearly COPD exacerbations of the L- group was 1.5±0.66 which was lower than the 2.1±0.53 of the L+ group (P<0.01). For the changes of St George's Respiratory Questionnaire (SGRQ) score, only the activity score of the L- group was more significant than that of the L+ group (P=0.02). The improvement of the outcome of 6-minute walking distance test in L- group (from 290.1±44.9 meters to 309.7±46.9 m) was higher than that in the L+ group (from 289.7±46.2 m to 300.3±44.2 m) (P=0.03). CONCLUSION: A 600 mg bid oral NAC treatment for 1-year on COPD patients without the L allele can improve the FEV1, FEV1% predicted, the SGRQ activity score, and the result of 6-minute walking distance test, and the exacerbation rate of the L allele carrier in COPD patients is much higher than in the COPD patients without the L allele.
Assuntos
Acetilcisteína/administração & dosagem , Acetilcisteína/uso terapêutico , Heme Oxigenase-1/genética , Repetições de Microssatélites/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Administração Oral , Idoso , Alelos , DNA/genética , Relação Dose-Resposta a Droga , Feminino , Genótipo , Heme Oxigenase-1/metabolismo , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnósticoRESUMO
To discuss the differences in protein expression among tuberculosis pleural effusion (TBPE), malignant pleural effusion (MPE) and transudative pleural effusion (TSPE). We recruited 50 patients with pleural effusion, including 20 TBPEs, 17 MPEs and 13 TSPEs. Using the two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS), we acquired the peptide mass finger printings (PMFs) of featured proteins. Then, we identified characteristic proteins by searching in the protein databank of the National Center of Biotechnology Information (NCBI) and assessed their diagnostic significance. We found five characteristic proteins: C1-inhibitor (C1-INH), transthyretin (TTR), human complement fragment 3b (C3b), human ceruloplasmin (CP), and Z34c protein fragment Fc (Z34c-Fc). C1-INH shows a high expression in TBPE and a low expression in MPE while TTR and C3 show low expression in TBPE and high expressions in MPE. Z34c-Fc and CP have a higher expression in TBPE than in TSPE. No common characteristic protein was found between MPE and TSPE. Statistic analysis consisted of paired t-tests and the difference between them is significance (P<0.05). C1-inhibitor (C1-INH), transthyretin (TTR), human Complement fragment 3b (C3b), human Ceruloplasmin (CP) and Z34c protein fragment Fc (Z34c-Fc) may provide an additional perspective in the differential diagnosis of PE.