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1.
Exp Physiol ; 105(1): 160-173, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31553078

RESUMO

NEW FINDINGS: What is the central question of this study? The aim was to identify abdominal aortic aneurysm (AAA)-associated microRNAs and their target genes in AAA using microarray analysis. What is the main finding and its importance? The main finding was that miR-145 and miR-30c-2* were found to be downregulated microRNAs in AAA, which could exert suppressive effects on AAA progression, and that miR-145 might target RAC2, whereas miR-30c-2* might target PIK3CD, IL1B and RAC2. The findings obtained from the study provide an enhanced understanding of microRNA as a therapeutic target to limit AAA. ABSTRACT: The aim of the study was to identify abdominal aortic aneurysm (AAA)-associated microRNAs (miRNAs) and genes potentially contributing to AAA. Differential analysis was performed to screen out differentially expressed genes (DEGs) and miRNAs in expression datasets of AAA-related miRNAs [GSE51226 (mouse)] and genes [GSE51227 (mouse) and GSE7084 (human)]. Then, gene ontology (GO) enrichment analysis of DEGs was compared with aneurysm-related GO to screen out DEGs related to the disease. The target genes of differential miRNAs were predicted and used to construct a miRNA-DEG regulatory network, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of target genes. Moreover, the protein-protein interaction network of target genes of miRNAs in the core position (hub-miRNA) with AAA-related genes was constructed to screen out hub genes. Finally, the target relationship between hub-miRNAs and their target genes was verified. There were 20 upregulated miRNAs and 20 downregulated miRNAs in AAA screened from the GSE51226 dataset (mouse). In addition, there were 1154 upregulated genes and 821 downregulated genes in the GSE51227 dataset (mouse), of which 246 DEGs were enriched in aneurysm-related GO entries in AAA. miR-145 and miR-30c-2* were the key miRNAs of AAA, both of which were downregulated in AAA and influenced pathways so as to affect AAA by regulating their respective target genes. The disease-related gene ACTA2 was downregulated, whereas DEGs including PIK3CD, IL1B, RAC2 and SELL were upregulated in AAA. Finally, it was proved that miR-145 targeted RAC2 and SELL, whereas miR-30c-2* targeted PIK3CD, IL1B and RAC2. Taken together, miR-145 and miR-30c-2*, downregulated in AAA, could potentially affect AAA, and miR-145 might target RAC2, whereas miR-30c-2* might target PIK3CD, IL1B and RAC2.

2.
Redox Biol ; 28: 101356, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31704583

RESUMO

Airway remodeling is one of the characteristics for chronic obstructive pulmonary disease (COPD). The mechanism underlying airway remodeling is associated with epithelial-mesenchymal transition (EMT) in the small airways of smokers and patients with COPD. Sirtuin 1 (SIRT1) is able to reduce oxidative stress, and to modulate EMT. Here, we investigated the effects and mechanisms of hydrogen sulfide (H2S) on pulmonary EMT in vitro and in vivo. We found that H2S donor NaHS inhibited cigarette smoke (CS)-induced airway remodeling, EMT and collagen deposition in mouse lungs. In human bronchial epithelial 16HBE cells, NaHS treatment also reduced CS extract (CSE)-induced EMT, collagen deposition and oxidative stress. Mechanistically, NaHS upregulated SIRT1 expression, but inhibited activation of TGF-ß1/Smad3 signaling in vivo and in vitro. SIRT1 inhibition by a specific inhibitor EX527 significantly attenuated or abolished the ability of NaHS to reverse the CSE-induced oxidative stress. SIRT1 inhibition also abolished the protection of NaHS against CSE-induced EMT. Moreover, SIRT1 activation attenuated CSE-induced EMT by modifying TGF-ß1-mediated Smad3 transactivation. In conclusion, H2S prevented CS-induced airway remodeling in mice by reversing oxidative stress and EMT, which was partially ameliorated by SIRT1 activation. These findings suggest that H2S may have therapeutic potential for the prevention and treatment of COPD.

3.
Aging (Albany NY) ; 11(24): 11844-11864, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31881011

RESUMO

Hydrogen sulfide (H2S), an endogenous gaseous signal molecule, regulates many pathologies related to aging. Sirtuin 1 (SIRT1) has been shown to protect against mitochondrial dysfunction and other pathological processes, including premature senescence. This study was aimed to investigate whether and how H2S attenuates senescence and apoptosis of alveolar epithelial cells via a SIRT1-dependent mechanism. Our results showed that treatment with sodium hydrosulfide (NaHS), a donor of H2S, attenuated cigarette smoke extract (CSE)-induced oxidative stress, mitochondrial dysfunction, cellular senescence and apoptosis in A549 cells. This was associated with SIRT1 upregulation. SIRT1 activation by a pharmacological activator, SRT1720, attenuated CSE-induced oxidative stress and mitochondrial dysfunction in A549 cells. While SIRT1 inhibition by EX 527 or silencing by siRNA transfection significantly attenuated or abolished the ability of NaHS to reverse the CSE-induced oxidative stress, mitochondrial dysfunction and the imbalance of mitochondrial fusion and fission. Also, SIRT1 inhibition or silencing abolished the protection of NaHS against CSE-induced cellular senescence and apoptosis. In conclusion, H2S attenuates CSE-induced cellular senescence and apoptosis by improving mitochondrial function and reducing oxidative stress in alveolar epithelial cells in a SIRT1-dependent manner. These findings provide novel mechanisms underlying the protection of H2S against cigarette smoke-induced COPD.

4.
Int Immunopharmacol ; : 105979, 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31771816

RESUMO

Chronic obstructive pulmonary fibrosis (COPD) is a chronic and fatal lung disease with few treatment options. Sodium hydrosulfide (NaHS), a donor of hydrogen sulfide (H2S), was found to alleviate cigarette smoke (CS)-induced emphysema in mice, however, the underlying mechanisms have not yet been clarified. In this study, we investigated its effects on COPD in a CS-induced mouse model in vivo and in cigarette smoke extract (CSE)-stimulated alveolar epithelial A549 cells in vitro. The results showed that NaHS not only relieved emphysema, but also improved pulmonary function in CS-exposed mice. NaHS significantly increased the expressions of tight junction proteins (i.e., ZO-1, Occludin and claudin-1), and reduced apoptosis and secretion of pro-inflammatory cytokines (i.e., TNF-α, IL-6 and IL-1ß) in CS-exposed mouse lungs and CSE-incubated A549 cells, indicating H2S inhibits CS-induced inflammation, injury and apoptosis in alveolar epithelial cells. NaHS also upregulated prolyl hydroxylase (PHD)2, and suppressed hypoxia-inducible factor (HIF)-1α expression in vivo and in vitro, suggesting H2S inhibits CS-induced activation of PHD2/HIF-1α axis. Moreover, NaHS inhibited CS-induced phosphorylation of ERK, JNK and p38 MAPK in vivo and in vitro, and treatment with their inhibitors reversed CSE-induced ZO-1 expression and inflammation in A549 cells. These results suggest that NaHS may prevent emphysema via the suppression of PHD2/HIF-1α/MAPK signaling pathway, and subsequently inhibition of inflammation, epithelial cell injury and apoptosis, and may be a novel strategy for the treatment of COPD.

5.
Neurol Res ; 41(4): 369-377, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30735101

RESUMO

BACKGROUND AND PURPOSE: Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in the impairment of learning and memory. Bax inhibitor-1 (BI-1) has been reported to be involved in the pathological mechanisms for neurodegenerative disorders including depression. Here, we aimed to investigate the role of BI-1 in regulating depression-like behavior induced by olfactory bulbectomy (OB) in rats and the possible mechanism. METHODS: Adeno-associated virus vectors expressing BI-1 (AAV-BI-1) were bilaterally microinjected into the prelimbic cortex (PFC-PL) to establish a BI-1 overexpression model in the PFC-PL of rats. TUNEL staining was used to evaluate the cellular apoptosis rate in the PFC-PL. Western blot analysis was performed to examine the expressions of apoptotic and inflammatory signals. RESULTS: BI-1 overexpression significantly attenuated the OB-induced behavioral abnormalities, including the decreased hyperactivity in the open field, decreased immobility time in the forced swimming test, as well as the increased sucrose consumption. BI-1 overexpression significantly inhibited cellular apoptosis in the PFC-PL of OB rats. The expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, B-cell lymphoma (Bcl)-2 associated X protein (Bax), and caspase-3 in the PFC-PL of OB rats were significantly increased as compared with the sham rats, but the Bcl-2 and IL-10 expressions were decreased, whereas BI-1 overexpression significantly suppressed the changes of these proteins in the PFC-PL of OB rats. CONCLUSION: These results indicated that BI-1 may play an anti-depression function with concurrent regulation of apoptotic and inflammatory signals.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/fisiologia , Citocinas/metabolismo , Transtorno Depressivo/etiologia , Regulação da Expressão Gênica/fisiologia , Proteínas de Membrana/metabolismo , Bulbo Olfatório/lesões , Córtex Pré-Frontal/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas de Ligação ao Cálcio/metabolismo , Citocinas/genética , Transtorno Depressivo/patologia , Modelos Animais de Doenças , Comportamento Exploratório , Preferências Alimentares , Marcação In Situ das Extremidades Cortadas , Masculino , Proteínas de Membrana/genética , Proteínas dos Microfilamentos/metabolismo , Ratos , Ratos Sprague-Dawley , Sacarose/administração & dosagem , Natação/psicologia , Transdução Genética/métodos
6.
Front Pharmacol ; 9: 263, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29765317

RESUMO

Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, can mediate its effect through inhibiting HIF-1α-induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice. STS reduced CS- and cigarette smoke extract (CSE)-induced upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in the lungs and macrophages. STS also inhibited CSE-induced reactive oxygen species (ROS) production, as well as the upregulation of heme oxygenase (HO)-1, NOX1 and matrix metalloproteinase (MMP)-9 in macrophages. In addition, STS suppressed HIF-1α expression in vivo and in vitro, and pretreatment with HIF-1α siRNA reduced CSE-induced elevation of TNF-α, IL-1ß, and HO-1 content in the macrophages. Moreover, we found that STS inhibited CSE-induced the phosphorylation of ERK, p38 MAPK and JNK in macrophages, and inhibition of these signaling molecules significantly repressed CSE-induced HIF-1α expression. It indicated that STS inhibits CSE-induced HIF-1α expression likely by blocking MAPK signaling. Furthermore, STS also promoted HIF-1α protein degradation in CSE-stimulated macrophages. Taken together, these results suggest that STS prevents COPD development possibly through the inhibition of HIF-1α signaling, and may be a novel strategy for the treatment of COPD.

7.
Biomed Pharmacother ; 102: 531-538, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29587239

RESUMO

Serine/Arginine-Rich Protein-Specific Kinase-2 (SRSF protein kinase-2, SRPK2) is up-regulated in multiple human tumors. However, the expression, function and clinical significance of SRPK2 in prostate cancer (PCa) has not yet been understood. We therefore aimed to determine the association of SRPK2 with tumor progression and metastasis in PCa patients in our present study. The expression of SRPK2 was detected by some public datasets and validated using a clinical tissue microarray (TMA) by immunohistochemistry. The association of SRPK2 expression with various clinicopathological characteristics of PCa patients was subsequently statistically analyzed based on the The Cancer Genome Atlas (TCGA) dataset and clinical TMA. The effects of SRPK2 on cancer cell proliferation, migration, invasion, cell cycle progression, apoptosis and tumor growth were then respectively investigated using in vitro and in vivo experiments. First, public datasets showed that SRPK2 expression was greater in PCa tissues when compared with non-cancerous tissues. Statistical analysis demonstrated that high expression of SRPK2 was significantly correlated with a higher Gleason Score, advanced pathological stage and the presence of tumor metastasis in the TCGA Dataset (all P < 0.01). Similar correlations between SRPK2 and a higher Gleason Score or advanced pathological stage were also identified in the TMA (P < 0.05). Kaplan-Meier curve analyses showed that the biochemical recurrence (BCR)-free time of PCa patients with SRPK2 high expression was shorter than for those with SRPK2 low expression (P < 0.05). Second, cell function experiments in PCa cell lines revealed that enhanced SRPK2 expression could promote cell proliferation, migration, invasion and cell cycle progression but suppress tumor cell apoptosis in vitro. Xenograft experiments showed that SRPK2 promoted tumor growth in vivo. In conclusion, our data demonstrated that SRPK2 may play an important role in the progression and metastasis of PCa, which suggests that it might be a potential therapeutic target for PCa clinical therapy.


Assuntos
Progressão da Doença , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Idoso , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Análise Serial de Tecidos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Huan Jing Ke Xue ; 37(10): 3864-3869, 2016 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964420

RESUMO

The odorants in simulated micro-polluted source water were removed by the Biological Powdered Activated Carbon-Ultrafiltration (BPAC-UF) combined process, and variations of microorganisms in the combined process were discussed. Compared with the conventional process of coagulation and sedimentation, BPAC-UF combined process had better performance in controlling odorants in micro-polluted source water. The average removal rates of dimethyl trisulfide, 2-methylisoborneol and ß-ionone reached up to 77.51%, 65.86% and 98.43%, respectively. The process was more adaptable to raw water shock load. The carbon tank which had much more microbial biomass than other areas was determined to be the main unit for removing odorants. The biomass changed smoothly in the carbon tank, while the removal of odorants in raw water was stable in the process.


Assuntos
Carvão Vegetal , Odorantes , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água , Reatores Biológicos , Carbono , Ultrafiltração
9.
Zhonghua Liu Xing Bing Xue Za Zhi ; 28(2): 115-8, 2007 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-17649677

RESUMO

OBJECTIVE: To study the prevalence of snoring and obstructive sleep apnea-hypopnea syndrome (OSAHS) and its high risk factors in Guangxi Zhuang Autonomous Region. METHODS: From January 2003 to March 2005, a total number of 11,163 persons aged > or =14 years Zhuang minority living in Guangxi (from Guinan, Guizhong and Guibei) were surveyed. Questionnaire was administered to draw information. Polysomnography(PSG) and in-home polygraphy were performed on participants being studied and who had reported snoring. RESULTS: Among all the surveyed people, 2940reported snoring with a prevalence of 27.3%. 448 (320 males and 128 females) people reported OSAHS with prevalence as 4.3% (5.9% in males and 2.5% in females). From 14 to 60 year olds, the prevalence of snoring and OSAHS increased with age. Among those above 60 years of age, both the prevalencerates ofsnoring and OSAHS werereduced with age. Among all the study population, 260 (21.6%) had habitual OSAHS a nd 188 (10.8%) hadoccasional OSAHS. The high risk factors of OSAHS were: position during sleep, disease of nose, drinking alcohol, smoking, gender, body mass index (BMI) and age. CONCLUSION: The prevalence rates of snoring and OSAHS were 27.3% and 4.3% respectively. From 14 to 60 years of age, the prevalence rates of snoring and OSAHS were increasing with age while from 60 years of age on, the prevalence of snoring and OSAHS reduced with age. The prevalence rates of snoring and OSAHS in males were higher than females. The high risk factors of OSAHS were position during sleep,disease of nose, drinking, smoking,gender, BMI and age.


Assuntos
Apneia Obstrutiva do Sono/epidemiologia , Ronco/epidemiologia , Adolescente , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
10.
Zhonghua Jie He He Hu Xi Za Zhi ; 30(5): 347-51, 2007 May.
Artigo em Chinês | MEDLINE | ID: mdl-17651640

RESUMO

OBJECTIVE: To study the prevalence of snoring, the blood pressure in the snoring population and the correlating between hypertension and snoring in Guangxi. METHODS: From January 2003 to March 2005, people older than 14 from the south, central and north Guangxi were studied for the prevalence of snoring. A questionnaire was administered, and the blood pressure, height and weight of the participants were measured. RESULTS: A total of 2862 families, 11 163 persons (aged 14 - 99 years, mean, 39.6 +/- 17.5 years) were surveyed. The prevalence of snoring was 27.3% (2940/10 758). The systolic blood pressure and the diastolic blood pressure of the non-snoring were 122.73 +/- 21.71 mm Hg and 75.68 +/- 13.17 mm Hg respectively. The systolic blood pressure and the diastolic blood pressure of the snoring were 128.23 +/- 30.85 mm Hg and 79.27 +/- 12.42 mm Hg respectively. The prevalence of hypertension of the two groups was 19.9% and 32.1% respectively. With the increase of age, there was an increasing tendency of snoring rate (tendency chi(2) = 592.613, P = 0.000) and hypertension rate (tendency chi(2) = 1868.277, P = 0.000). The hypertension incidence of the occasional snorers, habitual snorers, mild snorers, moderate snorers, and severe snorers and persons who suffered from sleep apnea was 27.6%, 37.4%, 27.5%, 31.1%, 37.4% and 44.1% respectively. Multiple logistic regression models showed that the risk factors for hypertension were snoring, age, body mass index (BMI), nationality and alcohol consumption. The partial correlation analysis showed that snoring was positively correlated to the diastolic blood pressure but not correlated to the systolic blood pressure. The severity of snoring was positively correlated to both the diastolic and the systolic blood pressures. CONCLUSIONS: The prevalence of snoring was 27.3% in Guangxi. The systolic blood pressure, the diastolic blood pressure and the prevalence of hypertension in snoring subjects were higher than those in non-snoring subjects. The prevalence of hypertension increased with increased severity of snoring. The severity of snoring was positively correlated to the diastolic and the systolic blood pressures. Snoring, age, BMI and alcohol consumption were the risk factors for hypertension.


Assuntos
Hipertensão/epidemiologia , Ronco/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Índice de Massa Corporal , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Adulto Jovem
11.
J Hum Genet ; 51(8): 727-31, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16871364

RESUMO

Brachydactyly type A1 (BDA1) is caused by mutations in the Indian hedgehog gene, IHH, on chromosome 2q35-36. In this study, a large five-generation Chinese family with BDA1 was identified and characterized. All affected family members demonstrated significant homogeneous phenotype and some unique clinical features different from those associated with the reported BDA1 mutations in IHH. Linkage analysis showed that the BDA1 gene in the family was linked to marker D2S126 close to IHH with a LOD score of 4.74 at a recombination fraction of 0. DNA sequence analysis revealed a heterozygous C to T transition at nucleotide 461 of IHH, resulting in a novel T154I substitution. The T154I mutation co-segregated with all affected individuals in the family, and was not present in normal family members or 200 normal controls. These results expand the spectrum of clinical phenotype associated with IHH mutations.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença/genética , Deformidades Congênitas da Mão/genética , Heterozigoto , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mutação/genética , Sequência de Aminoácidos , China , Mapeamento Cromossômico , Feminino , Deformidades Congênitas da Mão/diagnóstico por imagem , Proteínas Hedgehog , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/química , Masculino , Dados de Sequência Molecular , Linhagem , Radiografia
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