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1.
Signal Transduct Target Ther ; 6(1): 329, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087

RESUMO

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

2.
Medicine (Baltimore) ; 100(21): e25981, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032711

RESUMO

BACKGROUND: Ovarian carcinoma (OC) is considered among the most prevalent triggers of cancer-related deaths in women. Many studies have demonstrated that human epididymis protein 4 (HE-4) as well as cancer antigen 125 (CA-125) are over-expressed in various malignant tumors, such as lung, liver, endometrial, gastric, breast, as well as ovarian cancers. Nonetheless, the overall diagnostic value of serum HE-4, in addition to CA-125 n patients experiencing OC, is still largely undetermined. Therefore, the current study intends to investigate the general diagnostic significance of HE-4 along with CA-125 in patients with OC. METHODS: We aim to systematically search retrospective or prospective study for potential eligible studies from electronic databases, such as MEDLINE, EMBASE, Cochrane Library, Web of Science, as well as Chinese National Knowledge Infrastructure. We will relevant articles evaluating the general diagnostic significance of HE-4 and CA-125 in patients with OC from these databases. We will define our search in English and Chinese. Likewise, we will use 2 independent authors to extract the required data, using the Quality Assessment of Diagnostic Accuracy Studies-2 tool to evaluate he procedural quality of all included literature. We will use the appropriate statistical method to complete data analyses. RESULTS: The present study aims to investigate the general diagnostic significance of HE-4 and CA-125 in patients suffering from OC. CONCLUSION: The present study will systematically summarise current evidence of HE-4 in combination with CA-125 in relation to diagnosing OC. ETHICS AND DISSEMINATION: Ethical approval will not be required. PROTOCOL REGISTRATION NUMBER: DOI 10.17605/OSF.IO/YQPC7 (https://osf.io/yqpc7/).


Assuntos
Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Carcinoma/diagnóstico , Proteínas de Membrana/sangue , Neoplasias Ovarianas/diagnóstico , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análise , Carcinoma/sangue , Feminino , Humanos , Metanálise como Assunto , Neoplasias Ovarianas/sangue , Estudos Prospectivos , Estudos Retrospectivos , Revisões Sistemáticas como Assunto
3.
Aging (Albany NY) ; 12(22): 22759-22775, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33202380

RESUMO

Melanoma is a skin malignancy with a high mutation frequency of genetic alterations. MicroRNA (miR)-200b-3p is involved in various cancers, while in melanoma its bio-function remains unknown. In this study, we found that miR-200b-3p was down-regulated in melanoma tissues and cell lines compared to benign nevus cells. Overexpression of miR-200b-3p significantly inhibited the proliferation and invasion of melanoma cells. According to bioinformatics analysis and sequencing data, we supposed that SMAD family member 2 (SMAD2) was the target gene and nuclear enriched abundant transcript 1 (NEAT1) was the upstream long non-coding RNA (lncRNA) of miR-200b-3p. These predictions were verified by western blotting and quantitative real-time reverse transcription PCR (RT-qPCR). Luciferase reporter assays revealed that NEAT1 up-regulated SMAD2 by directly sponging miR-200b-3p. In vitro and in vivo, we demonstrated that both NEAT1 and SMAD2 could promote the proliferation and invasion of melanoma cells, and these effects were reversed by up-regulating miR-200b-3p. In addition, NEAT1/miR-200b-3p/SMAD2 axis promoted melanoma progression by activating EMT signaling pathway and immune responses. Taken together, the NEAT1/miR-200b-3p/SMAD2 signaling pathway promotes melanoma via activation of EMT, cell invasion and is related with immune responses, which provides new insights into the molecular mechanisms and therapeutic targets for melanoma.


Assuntos
Melanoma/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias Cutâneas/metabolismo , Proteína Smad2/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Bases de Dados Genéticas , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/genética , Melanoma/mortalidade , Melanoma/patologia , MicroRNAs/genética , Invasividade Neoplásica , RNA Longo não Codificante/genética , Transdução de Sinais , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Proteína Smad2/genética
4.
Eur J Clin Pharmacol ; 72(10): 1205-1213, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27439448

RESUMO

AIM: To investigate whether single-nucleotide polymorphisms (SNPs) in the P450 oxidoreductase (POR) gene were correlated with interindividual variations in cytochrome P450 (CYP) 2B6 activity. METHODS: Thirty-six healthy volunteers who tested CYP2B6 and POR polymorphisms were enrolled in the study. CYP2B6 activity was measured by bupropion hydroxylation with LC/MS/MS. The ratio of hydroxybupropion versus bupropion (AUC_hyd/AUC_bup) in terms of area under the time-concentration curve (AUC) was used to represent the CYP2B6 activity. RESULTS: The volunteers carrying CYP2B6*1/*1 showed a significantly higher mean AUC_hyd/ AUC_bup than those CYP2B6*1/*6 and CYP2B6*6/*6 variants (15.66 ± 1.65 vs. 9.25 ± 1.92, P = 0.008 and 15.66 ± 1.65 vs. 8.21 ± 1.74, P = 0.006, respectively). POR rs2868177 (6593 A > G) AA homozygotes showed a significantly lower mean AUC_hyd/ AUC_bup than that of POR rs2868177 AG heterozygotes or GG homozygotes (8.13 ± 1.37 vs. 12.15 ± 2.97, P = 0.005 and 8.13 ± 1.37 vs. 17.59 ± 3.25, P = 0.001, respectively). Moreover, POR rs2868177 AG heterozygotes and GG homozygotes showed a significantly increased mean AUC_hyd/AUC_bup than AA homozygotes in the CYP2B6*1/*1 and CYP2B6*6 carriers (16.40 ± 2.01 vs. 12.40 ± 1.45, P = 0.006 and 10.65 ± 1.47 vs. 6.54 ± 1.25, P = 0.004, respectively). Meanwhile, a strong correlation between the genetic variations (POR rs2868177 and CYP2B6*6) and AUC_hyd/ AUC_bup was found (P = 0.009 and P = 0.001, respectively). There was no significant difference in the mean AUC_hyd/AUC_bup among different POR *28 genotypes (P > 0.05). CONCLUSION: POR rs2868177 and CYP2B6*6 variants contribute to the interindividual variability in human CYP2B6 activity, which may affect the disposition and interaction of other CYP2B6 substrate drugs.


Assuntos
Citocromo P-450 CYP2B6/genética , Citocromo P-450 CYP2B6/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Adulto , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático/genética , Bupropiona/análogos & derivados , Bupropiona/sangue , Bupropiona/farmacocinética , Frequência do Gene , Genótipo , Voluntários Saudáveis , Humanos , Hidroxilação , Masculino , Polimorfismo de Nucleotídeo Único , Adulto Jovem
5.
J Dermatol ; 39(8): 705-10, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22512708

RESUMO

Hyperpigmentation frequently occurs in human skin autografts resulting in an unsatisfactory appearance. This study aimed to elucidate the role of melanocortin-1 receptor in the hyperpigmentation process of skin autografts by analyzing the expression of melanocortin-1 receptor. The data were correlated with the amount of melanin in autografted human skin and normal skin determined in a previous study. Immunohistochemistry, western blotting and quantitative real-time polymerase chain reaction were carried out to detect the expression and distribution of melanocortin-1 receptor in skin autografts including full-thickness skin autografts, split-thickness skin autografts and normal full-thickness skin. Fontana-Masson stain was used to detect melanin in all types of skin specimens. The expression level of melanocortin-1 receptor in autografted skin was much higher than that in control normal skin, and thinner split-thickness skin autografts had higher levels of expression of melanocortin-1 receptor than thicker grafts. The amount of melanin in skin autografts was significantly increased compared with normal skin. The expression of melanocortin-1 receptor correlated well with the amount of melanin in the epidermis of skin autografts. These results indicate that melanogenesis is dramatically enhanced in skin autografts by the melanocortin-1 receptor, and suggest that overexpression of melanocortin-1 receptor may play an important role in the hyperpigmented process of skin autografts. This study provides a novel mechanism for hyperpigmentation in skin autografts.


Assuntos
Hiperpigmentação/metabolismo , Receptor Tipo 1 de Melanocortina/biossíntese , Transplante de Pele , Humanos , Hiperpigmentação/patologia , Imuno-Histoquímica , Melaninas/análise , Melanócitos/metabolismo , Pele/química , Pele/patologia , Transplante Autólogo
6.
Aesthetic Plast Surg ; 36(3): 611-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22274802

RESUMO

BACKGROUND: This report aims to describe a paranasal flap technique for reconstruction of lower eyelid retraction and ectropion. METHODS: After the contracture of the lower eyelid skin or conjunctiva had been thoroughly released, the ipsilateral upper pedicle paranasal flap was designed according to the size of the lower eyelid skin wound. After dissection of the flap, the subcutaneous tissue of the flap was trimmed according to the depth of the wound, the flap was rotated to cover the defect, and an anchor was fixed to the distal aspect of the outer canthus. The secondary defect of the donor area was sutured directly. RESULTS: In this study, 67 patients with lower eyelid defects resulting from correction of eyelid retraction and ectropion were reconstructed using paranasal flaps between April 2004 and October 2009. The sizes of the paranasal flaps ranged from 0.6×2.2 to 1.5×3.5 cm. At the follow-up assessment, the patients could close their eyes easily and completely without lagophthalmos, and neither the upper lips or the nasal ala showed any anatomic deformities. The features of the paranasal flaps, such as skin color, texture, and contour of the repaired tissue, were a good match with the surrounding skin. The suture lines of the donor areas were sheltered well. CONCLUSIONS: Paranasal flaps were used for effective reconstruction of lower eyelid retraction or ectropion, with achievement of good eyelid function and a good color, contour, and texture match with the surrounding skin. Overall, the functional and cosmetic results were satisfactory. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.


Assuntos
Blefaroplastia/métodos , Ectrópio/cirurgia , Retalhos Cirúrgicos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nariz , Adulto Jovem
7.
Clin Chem ; 52(2): 300-3, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16449211

RESUMO

BACKGROUND: We examined the effect of atorvastatin on the expression of COX-2 in peripheral blood monocytes from patients with early stage of acute myocardial infarction (AMI), and the plasma C-reactive protein (CRP) concentrations were also examined. METHODS: Patients with AMI (n = 40) and with stable coronary heart disease (CHD; n = 18) were registered, and patients with AMI were randomly separated to a group that received routine therapy (group A, n = 20) or to a group that received routine therapy plus atorvastatin at 20 mg/day (group B, n = 20) for a week. Peripheral blood monocytes from patients with AMI both before and after treatment and from patients with stable CHD were isolated and cultured for 24 h. COX-2 mRNA expression was analyzed by reverse transcription-PCR. We measured concentrations of CRP in plasma by ELISA. RESULTS: COX-2 expression was activated in peripheral blood monocytes from patients with AMI [0.92 (0.13)] compared with patients with stable CHD [0.19 (0.08)]; after a week of treatment, COX-2 expression in group B (reduced by 66%) was obviously lower than in group A (reduced by 24%; P <0.05). Plasma concentrations of CRP from patients with AMI [43.3 (14.9) mg/L] were increased compared with those from patients with stable CHD [1.65 (0.78) mg/L; P <0.05]; after a week of treatment, CRP concentrations in group B (reduced by 62%) were lower than in group A (reduced by 35%; P <0.05). COX-2 expression in peripheral blood monocytes from patients with AMI was positively correlated with plasma CRP concentration (r = 0.662; P <0.05). CONCLUSIONS: COX-2 may promote acute inflammatory process after AMI. Atorvastatin may improve the antiinflammatory effects through the COX-2 pathway.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Ciclo-Oxigenase 2/biossíntese , Ácidos Heptanoicos/uso terapêutico , Leucócitos Mononucleares/efeitos dos fármacos , Infarto do Miocárdio/sangue , Pirróis/uso terapêutico , RNA Mensageiro/biossíntese , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Atorvastatina , Feminino , Ácidos Heptanoicos/administração & dosagem , Ácidos Heptanoicos/farmacologia , Humanos , Leucócitos Mononucleares/enzimologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/enzimologia , Proteína C/metabolismo , Pirróis/administração & dosagem , Pirróis/farmacologia , Resultado do Tratamento
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