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1.
Bioengineered ; 12(1): 6240-6250, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34486477

RESUMO

Although the mechanism of osteoarthritis (OA) has been widely studied and the use of quercetin for OA therapy is well documented, the relevant characteristics of the microbiome and metabolism remain unclear. This study reports changes in the gut microbiota and metabolism during quercetin therapy for OA in a rat model and provides an integrative analysis of the biomechanism. In this study, the rats were categorized into 3 different groups: the OA model, quercetin treatment, and control groups. The OA rats was conducted using a monoiodoacetate (MIA) injection protocol. The rats in the quercetin group received daily intragastric administration of quercetin from day 1 to day 28. Stool samples were collected, and DNA was extracted. We used an integrated approach that combined the sequencing of whole 16S rRNA, short-chain fatty acid (SCFA) measurements and metabolomics analysis by mass spectrometry (MS) to characterize the functional impact of quercetin on the gut microbiota and metabolism in a rat model of OA. The use of quercetin partially abrogated intestinal flora disorder and reversed fecal metabolite abnormalities. Compared with the control rats, the OA rats showed differences at both the class level (Clostridia, Bacteroidia, and Bacilli) and the genus level (Lactobacillus and unidentified Ruminococcaceae). Acetic acid, propionic acid and 24 metabolites were significantly altered among the three groups. However, the changes were significantly abrogated in quercetin-treated OA rats. Consequently, this study provided important evidence regarding perturbations of the gut microbiome and the function of these changes in a potential new mechanism of quercetin treatment.

2.
Biomed Res Int ; 2021: 9984112, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337069

RESUMO

Background: Baicalin is an extract from the traditional Chinese herb Scutellaria baicalensis and has the potential to treat osteosarcoma (OS). However, the transcriptome-level mechanism of baicalin-mediated antitumor effects in OS has not yet been investigated. The aim of this study was to analyze the competitive endogenous RNA (ceRNA) regulatory network involved in baicalin-induced apoptosis of OS cells. Methods: In this study, CCK-8 and flow cytometry assays were used to detect the antitumor effects of baicalin on human OS MG63 cells. Furthermore, transcriptome sequencing was employed to establish the long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA profiles. Results: Baicalin inhibited MG63 cell proliferation and induced apoptosis. Totals of 58 lncRNAs, 31 miRNAs, and 2136 mRNAs in the baicalin-treated MG63 cells were identified as differentially expressed RNAs compared to those in control cells. Of these, 2 lncRNAs, 3 miRNAs, and 18 mRNAs were included in the ceRNA regulatory network. The differentially expressed RNAs were confirmed by quantitative real-time PCR (qRT-PCR). Conclusions: By identifying the ceRNA network, our results provide new information about the possible molecular basis of baicalin, which has potential applications in OS treatment.


Assuntos
Apoptose/genética , Flavonoides/farmacologia , Redes Reguladoras de Genes , Osteossarcoma/genética , Osteossarcoma/patologia , RNA Neoplásico/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Mapas de Interação de Proteínas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Reprodutibilidade dos Testes
3.
Biomed Res Int ; 2021: 5521058, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337018

RESUMO

Background: Gastric cancer (GC) is the most common type of cancer. It is highly malignant and is characterized by rapid and uncontrolled growth. The antitumour activity of Baicalin was studied in multiple cancers. However, its mechanism of action has not been fully elucidated. We provided a systematic understanding of the mechanism of action of baicalin against GC using a transcriptome analysis of RNA-seq. Methods: Human GC cells (SGC-7901) were exposed to 200 µg/ml baicalin for 24 h. RNA-seq with a transcriptome, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the antitumour effects of baicalin on SGC-7901 cells in vitro. A protein-protein interaction (PPI) network of differentially expressed genes (DEGs) was constructed. A competitive endogenous RNA (ceRNA) network was constructed and further analysed after validation using qRT-PCR. Results: A total of 68 lncRNAs, 20 miRNAs, and 1648 mRNAs were differentially expressed in baicalin-treated SGC-7901 GC cells. Three lncRNAs, 6 miRNAs, and 7 mRNAs were included in the ceRNA regulatory network. GO analysis revealed that the main DEGs were involved in the biological processes of the cell cycle and cell death. KEGG pathway analysis further suggested that the p53 signalling pathway was involved in the baicalin-induced antitumour effect on SGC-7901 cells. Further confirmation using qPCR indicated that baicalin induced an antitumour effect on SGC-7901 cells, which is consistent with the results of the sequencing data. Conclusions: In summary, the mechanism of baicalin against GC involves multiple targets and signalling pathways. These results provide new insight into the antitumour mechanism of baicalin and help the development of new strategies to cure GC.


Assuntos
Flavonoides/uso terapêutico , Perfilação da Expressão Gênica , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Mapas de Interação de Proteínas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes
4.
Bioengineered ; 12(1): 5173-5183, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34405758

RESUMO

The gut microbiota is widely considered to be involved in several diseases, including atherosclerosis, obesity, chronic obstructive pulmonary disease (COPD) and pulmonary arterial hypertension (PAH). This study aimed to determine if changes in the gut microbiome and metabolome play a major role in the early pathogenesis of PAH. Male Wistar rats were injected with monocrotaline (MCT) (55 mg/kg) at day 1 and injected with calcium-sensing receptor (CaSR) antagonist NPS2143 (4.5 mg/kg/d) from days 1 to 21. Fecal samples were obtained. The gut microbiota and metabolome were analyzed by 16S rRNA gene sequencing and mass spectrometry-based analysis to investigate the effect of PAH in this rat model. MCT injection had a marked effect on the composition of the gut microbiota. This finding was further confirmed by metabolomic analysis with identification of several metabolites relevant to the gut microflora. However, NPS2143 partially abrogated this intestinal flora disorder and reversed fecal metabolite abnormalities. In conclusion, our study shows correlations between changes in the gut microbiome and the metabolome in PAH, which are affected by NPS2143.

5.
J Ethnopharmacol ; 279: 114368, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34197960

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease influenced by diverse endogenous and exogenous factors. It is characterized by cartilage and bone destruction. The current conventional allopathic therapy is expensive and carries adverse side effects. Recently, there were some ethnopharmacological studies on RA including anti-RA effects and therapeutic targets of distinct dosage forms of traditional herbal medicines (THMs). AIM OF THE REVIEW: This review provides a brief overview of the current understanding of the potential pharmacological mechanisms of THMs (active constituents, extracts and prescriptions) in RA. This study is intended to provide comprehensive information and reference for exploring new therapeutic strategies of THMs in the RA treatment. MATERIALS AND METHODS: This review captured scientific literatures invivo and vitro experiments on effects of anti-RA THMs published between 2016 and 2021 from journals and electronic databases (e.g. PubMed, Elsevier, Science Direct, Web of Science and Google Scholar). Relevant literatures were searched and analyzed by using keywords such as 'rheumatoid arthritis AND traditional herbal medicines', 'rheumatoid arthritis AND immune cells', 'rheumatoid arthritis AND inflammation', 'rheumatoid arthritis AND miRNA', 'rheumatoid arthritis AND Angiogenesis', 'rheumatoid arthritis AND oxidative stress', 'rheumatoid arthritis AND osteoclasts', 'rheumatoid arthritis AND CIA model', 'rheumatoid arthritis AND AA model' AND 'rheumatoid arthritis herbal prescription'. RESULTS: Experiments in vitro and in vivo jointly demonstrated the potential of THMs in the RA treatment. There are plentiful therapeutic targets in RA. THMs and active ingredients could alleviate RA symptoms through different therapeutic targets, such as immunoregulation, inflammation, fibroblast-like synoviocytes (FLSs), microRNAs (miRNAs), angiogenesis, oxidative stress, osteoclasts and multiple targets interaction. Anti-RA THMs, active ingredients and prescriptions through corresponding therapeutic targets were summarized and classified. CONCLUSIONS: Flavonoids, phenolic acids, alkaloids and triterpenes of THMs are identified as the main components to ameliorate RA. Regulation of different and multiple related therapeutic targets by THMs and their active ingredients were associated with greater therapeutic benefits, among which inflammation is the main therapeutic target. Nonetheless, further studies are required to unravel the complexities and in-depth mechanisms of THMs in alleviating RA.

6.
Clin Transl Med ; 11(7): e479, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34323408

RESUMO

Chronic obstructive pulmonary disease is a complex condition with multiple etiologies, including inflammation. We identified a novel long noncoding RNA (lncRNA), interleukin 6 antisense RNA 1 (IL6-AS1), which is upregulated in this disease and is associated with airway inflammation. We found that IL6-AS1 promotes the expression of inflammatory factors, especially interleukin (IL) 6. Mechanistically, cytoplasmic IL6-AS1 acts as an endogenous sponge by competitively binding to the microRNA miR-149-5p to stabilize IL-6 mRNA. Nuclear IL6-AS1 promotes IL-6 transcription by recruiting early B-cell factor 1 to the IL-6 promoter, which increases the methylation of the H3K4 histone and acetylation of the H3K27 histone. We propose a model of lncRNA expression in both the nucleus and cytoplasm that exerts similar effects through differing mechanisms, and IL6-AS1 probably increases inflammation via multiple pathways.

7.
J Ethnopharmacol ; 269: 113724, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33359003

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As a classic prescription of Traditional Chinese Medicine in Correction on the Errors of Medical Works, Buyang Huanwu Decoction (BYHWD) has a good curative effect on prevention of atherosclerosis (AS). AIM OF THE STUDY: This study aims to elucidate the anti-atherosclerosis mechanism of BYHWD, which may promote the differentiation of regulatory T cells by regulating the TGF-ß/Smad2 pathway. MATERIALS AND METHODS: ApoE-/- mice were fed a high-fat diet for 12 weeks, then drugs group were given BYHWD with intragastric administration once a day for 4 weeks. The effect of BYHWD on lipid content in peripheral blood and plaque was evaluated by blood lipid test and oil red O staining. The number of Tregs in peripheral blood was tested by flow cytometry, and that in the spleen was evaluated by immunohistochemistry methods. Gene and protein expression relating with Tregs differentiation pathway in mice were checked by RT-PCR and Western blot experiments. CD4+T cells were isolated and interfered by BYHWD drug-loaded serum. The proportion of Tregs was evaluated by flow cytometry. The chemical compositions of BYHWD and rat drug-loaded serum were analyzed by ultra-high performance liquid chromatograph and liquid chromatography-tandem mass spectrometry. RESULTS: BYHWD significantly reduced plaque area and cholesterol accumulation, increased the number of Tregs in spleen and peripheral blood of ApoE-/- AS mice, raised the proportion of Tregs in CD4+T cells, and regulated the levels of inflammatory factors. It also increased the TGF-ß and Smad2 mRNA and protein levels relating with Tregs differentiation pathway in vivo. The mRNA levels of Foxp3/TGF-ß/Smad2 were enhanced via BYHWD in vitro. CONCLUSIONS: BYHWD regulates TGF-ß/Smad2 signaling pathway to promotes the peripheral differentiation of Tregs, increases the number of Tregs, restores the immune balance between CD4+T cells, regulates lipid metabolism, inhibits inflammatory reaction and possesses the potential of enhancing plaque stability.


Assuntos
Aterosclerose/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Aterosclerose/patologia , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Fatores de Transcrição Forkhead/efeitos dos fármacos , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Lipídeos/sangue , Masculino , Medicina Tradicional Chinesa , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Placa Aterosclerótica/induzido quimicamente , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/patologia , Ratos Sprague-Dawley , Soro/química , Proteína Smad2/genética , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/efeitos dos fármacos , Fator de Crescimento Transformador beta/genética , Regulação para Cima/efeitos dos fármacos
8.
Electrophoresis ; 41(16-17): 1469-1481, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32524626

RESUMO

A few advancing technologies for natural product analysis have been widely proposed, which focus on decreasing energy consumption and developing an environmentally sustainable manner. These green sample pretreatment and analysis methods following the green Analytical Chemistry (GAC) criteria have the advantage of improving the strategy of chemical analyses, promoting sustainable development to analytical laboratories, and reducing the negative effects of analysis experiments on the environment. A few minimized extraction methodologies have been proposed for replacing the traditional methods in the quality evaluation of natural products, mainly including solid-phase microextraction (SPME) and liquid phase microextraction (LPME). These procedures not only have no need for large numbers of samples and toxic reagent, but also spend a small amount of extraction and analytical time. This overview aims to list out the main green strategies on the application of quality evaluation and control for natural products in the past 3 years.


Assuntos
Produtos Biológicos , Química Verde , Microextração em Fase Líquida , Microextração em Fase Sólida , Produtos Biológicos/análise , Produtos Biológicos/química , Produtos Biológicos/normas , Controle de Qualidade
9.
Medicine (Baltimore) ; 98(44): e17463, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689750

RESUMO

RATIONALE: Malignant peripheral nerve sheath tumor (MPNST) is a very rare sarcoma of the heart, and few cases have been reported. Herein, we retrospectively reviewed clinical manifestations, imaging features and management of our patient and other reported cases. PATIENT CONCERNS: A 32-year-old woman was referred to the emergency department of our institution with expiratory dyspnea, edema of face for a month. DIAGNOSIS: The patient was initially diagnosed with asthma at a local hospital based on a history of fatigue, cough and expiratory dyspnea, as well as negative electroencephalogram (ECG) and chest radiography. Based on computed tomography (CT) and cardiac magnetic resonance imaging (CMRI) in our hospital, she was found to have a malignant tumor involving right atrium. The tumor was diagnosed as MPNST according to histopathological results. INTERVENTIONS: The tumor was deemed unresectable during the surgery. Then, the patient was referred for chemotherapy and radiotherapy. OUTCOMES: The patient deteriorated and died 4 months later. LESSONS: Cardiac MPNST is very uncommon with nonspecific clinical and imaging characteristics according to limited cased reported. CMR, due to the high tissue resolution and multiple sequence imaging advantages, is useful for the detection, location and evaluation whether there is involvement of adjacent structures, and may help better clinical decision-making.


Assuntos
Neoplasias Cardíacas/diagnóstico , Neurofibrossarcoma/diagnóstico , Adulto , Feminino , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/terapia , Humanos , Imageamento por Ressonância Magnética , Neurofibrossarcoma/diagnóstico por imagem , Neurofibrossarcoma/terapia , Tomografia Computadorizada por Raios X
10.
Am J Respir Cell Mol Biol ; 61(5): 584-596, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31050548

RESUMO

Abnormal expression of long noncoding RNAs (lncRNAs) has been confirmed to be associated with many diseases, including chronic obstructive pulmonary disease (COPD). To gain better understanding of the mechanism of COPD, we investigated the lncRNA and mRNA profiles in the lung tissue of patients with COPD. According to the analysis, one of the significantly different lncRNAs, COPDA1, might participate in the occurrence and development of COPD. Lung tissues were collected from nonsmokers, smokers, or smokers with COPD for RNA sequencing. Bioinformatic analysis and cell experiments were used to define the function of COPDA1, and the effects of COPDA1 on intracellular Ca2+ concentration and cell proliferation were examined after knockdown or overexpression of COPDA1. A number of variations of lncRNAs were found in the comparison of nonsmokers, smokers, and smokers with COPD. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses indicated that smoking was involved in the activation of cytokines and the cell cycle, which is associated with COPD. According to the lncRNA-mRNA-coexpressing network and enrichment analysis, COPDAz1 and one of its target genes, MS4A1 (membrane-spanning 4-domains family, subfamily A) were investigated, and we discovered that the expression of MS4A1 was closely associated with lncRNA COPDA1 expression in human bronchial smooth muscle cells (HBSMCs). Further study showed that lncRNA COPDA1 upregulated the expression of MS4A1 to increase store-operated calcium entry in the HBSMCs, resulting in the promotion of the proliferation of smooth muscle cells as well as of airway remodeling. COPDA1 might be involved in the regulation of certain signaling pathways in COPD, might promote the proliferation of HBSMCs, and might also be involved in facilitating airway remodeling.


Assuntos
Remodelação das Vias Aéreas/genética , Proliferação de Células/genética , Doença Pulmonar Obstrutiva Crônica/genética , RNA Longo não Codificante/genética , Proliferação de Células/efeitos dos fármacos , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Pulmão/metabolismo , Masculino , Miócitos de Músculo Liso/metabolismo , Fumar/metabolismo
11.
Respir Res ; 19(1): 37, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29499705

RESUMO

BACKGROUND: The contribution of airway remodeling in chronic obstructive pulmonary disease (COPD) has been well documented, with airway smooth muscle cell proliferation and migration playing a role in the remodeling process. Here, we aimed to verify the effects of fine particulate matter (PM2.5) on human bronchial smooth muscle cell (HBSMC) migration and to explore the underlying signaling pathways. METHODS: HBSMC apoptosis, proliferation and migration were measured using flow cytometry, cell counting and transwell migration assays, respectively. The role of the hedgehog pathway in cell migration was assessed by western blotting to measure the expression of Sonic hedgehog (Shh), Gli1 and Snail. Furthermore, siRNA was used to knock down Gli1 or Snail expression. RESULTS: PM2.5 induced HBSMC apoptosis in a dose-dependent manner, although certain concentrations of PM2.5 did not induce HBSMC proliferation or apoptosis. Interestingly, cell migration was stimulated by PM2.5 doses far below those that induced apoptosis. Additional experiments revealed that these PM2.5 doses enhanced the expression of Shh, Gli1 and Snail in HBSMCs. Furthermore, PM2.5-induced cell migration and protein expression were enhanced by recombinant Shh and attenuated by cyclopamine. Similar results were obtained by knocking down Gli1 or Snail. CONCLUSIONS: These findings suggest that PM2.5, which may exert its effects through the Shh signaling pathway, is necessary for the migration of HBSMCs. These data define a novel role for PM2.5 in airway remodeling in COPD.


Assuntos
Brônquios/metabolismo , Movimento Celular/fisiologia , Proteínas Hedgehog/metabolismo , Miócitos de Músculo Liso/metabolismo , Material Particulado/toxicidade , Transdução de Sinais/fisiologia , Brônquios/efeitos dos fármacos , Brônquios/patologia , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Miócitos de Músculo Liso/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
12.
Cell Physiol Biochem ; 43(3): 986-1002, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28957813

RESUMO

BACKGROUND/AIMS: The proliferation of human bronchial smooth muscle cells (HBSMCs) is a key pathophysiological component of airway remodeling in chronic obstructive pulmonary disease (COPD) for which pharmacotherapy is limited, and only slight improvements in survival have been achieved in recent decades. Cigarette smoke is a well-recognized risk factor for COPD; however, the pathogenesis of cigarette smoke-induced COPD remains incompletely understood. This study aimed to investigate the mechanisms by which nicotine affects HBSMC proliferation. METHODS: Cell viability was assessed with a CCK-8 assay. Proliferation was measured by cell counting and EdU immunostaining. Fluorescence calcium imaging was performed to measure intracellular Ca2+ concentration ([Ca2+]i). RESULTS: The results showed that nicotine promotes HBSMC proliferation, which is accompanied by elevated store-operated calcium entry (SOCE), receptor-operated calcium entry (ROCE) and basal [Ca2+]i in HBSMCs. Moreover, we also confirmed that canonical transient receptor potential protein 6 (TRPC6) and α7 nicotinic acetylcholine receptor (α7 nAChR) are involved in nicotine-induced upregulation of cell proliferation. Furthermore, we verified that activation of the PI3K/Akt signaling pathway plays a pivotal role in nicotine-enhanced proliferation and calcium influx in HBSMCs. Inhibition of α7 nAChR significantly decreased Akt phosphorylation levels, and LY294002 inhibited the protein expression levels of TRPC6. CONCLUSION: Herein, these data provide compelling evidence that calcium entry via the α7 nAChR-PI3K/Akt-TRPC6 signaling pathway plays an important role in the physiological regulation of airway smooth muscle cell proliferation, representing an important target for augmenting airway remodeling.


Assuntos
Cálcio/metabolismo , Proliferação de Células/efeitos dos fármacos , Nicotina/toxicidade , Canal de Cátion TRPC6/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromonas/farmacologia , Diglicerídeos/farmacologia , Humanos , Morfolinas/farmacologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Imagem Óptica , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Canal de Cátion TRPC6/antagonistas & inibidores , Canal de Cátion TRPC6/genética , Regulação para Cima/efeitos dos fármacos , Receptor Nicotínico de Acetilcolina alfa7/antagonistas & inibidores , Receptor Nicotínico de Acetilcolina alfa7/genética
13.
Int J Chron Obstruct Pulmon Dis ; 12: 1447-1455, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28553097

RESUMO

Quantitative computed tomography (CT) measures of emphysema have been shown to be associated with increased mortality in humans, but genetic variants affecting the quantitative parameters of chest CT that measure degree of emphysema have not yet been examined. In this study, using available chest CT data from a total of 344 emphysema patients, we assessed the correlations between five chronic obstructive pulmonary disease (COPD) susceptibility variants in the cholinergic receptor nicotinic (CHRN) genes and the degree of emphysema and chest CT manifestations. We verified that most of the parameters were significantly correlated with the degree of emphysema. Compared to rs76071148AA and TT genotype carriers, the rs76071148AT genotype carriers exhibited a decreased probability of having severe emphysema (odds ratio [OR] =0.63, 95% confidence interval [CI] =0.40-0.99), whereas the variant rs8040868C allele was negatively correlated with the emphysema index (P=0.002). Interestingly, further stratification analysis grouped by spirometry-diagnosed COPD status revealed that the variant rs8040868C (CT + CC) genotypes exerted a protective effect against severe emphysema with borderline significance (OR =0.41, 95% CI =0.16-1.05) and affected the mean lung density, emphysema index, ratio of airway wall thickness to airway dimensions (AWT/AD), and AWT grade in spirometry-diagnosed non-COPD subjects. The rs76071148 variant was also significantly associated with AWT/AD and AWT grade in those individuals. In summary, we determined that rs8040868 and rs76071148 are promising indicators of the degree of emphysema and chest CT manifestations, especially in spirometry-diagnosed non-COPD subjects.


Assuntos
Variação Genética , Pulmão/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/genética , Receptores Nicotínicos/genética , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Distribuição de Qui-Quadrado , China/epidemiologia , Estudos Transversais , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Valor Preditivo dos Testes , Fatores de Proteção , Doença Pulmonar Obstrutiva Crônica/etnologia , Enfisema Pulmonar/etnologia , Fatores de Risco , Espirometria
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