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1.
BMC Pediatr ; 24(1): 157, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443865

RESUMO

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.


Assuntos
Displasia Broncopulmonar , Corioamnionite , Lesão Pulmonar , Síndrome do Desconforto Respiratório do Recém-Nascido , Recém-Nascido , Feminino , Gravidez , Lactente , Humanos , Corioamnionite/epidemiologia , Recém-Nascido Prematuro , Inflamação , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/etiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia
2.
Anticancer Drugs ; 33(1): e434-e443, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34459459

RESUMO

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used to treat non-small cell lung cancer. However, its off-targets are obscure, and systematic analysis of off-target activities remains to be performed. Here, we identified the off-targets of osimertinib using PharmMapper and DRAR-CPI and analyzed the intersected targets using the GeneMANIA and DAVID servers. A drug-target-pathway network was constructed to visualize the associations. The results showed that osimertinib is associated with 31 off-targets, 40 Kyoto Encyclopedia of Genes and Genomes pathways, and 9 diseases. Network analysis revealed that the targets were involved in cancer and other physiological processes. In addition to EGFR, molecular docking analysis showed that seven proteins, namely Janus kinase 3, peroxisome proliferator-activated receptor alpha, renin, mitogen-activated protein kinases, lymphocyte-specific protein tyrosine kinase, cell division protein kinase 2 and proto-oncogene tyrosine-protein kinase Src, could also be potential targets of osimertinib. In conclusion, osimertinib is predicted to target multiple proteins and pathways, resulting in the formation of an action network via which it exerts systematic pharmacological effects.


Assuntos
Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Farmacologia em Rede/métodos , Proteínas/efeitos dos fármacos , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas/fisiologia
3.
J Cell Biochem ; 120(1): 658-670, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30203578

RESUMO

Emerging evidence indicated that changes in DNA methylation early in breast cancer (BC) development might be clinically relevant for therapeutic decisions. Through analysis of whole-genome gene expression microarray and DNA methylation microarray, we explored genes with abnormal DNA methylation in BC for early detection. Firstly, human BC tissues and adjacent non-cancerous tissues were collected from nine BC patients. Gene expression microarray sequencing was conducted for identifying differentially expressed genes and DNA methylation microarray sequencing for differentially methylated genes in BC. Differentially expressed genes and methylated genes in BC were further explored using the Cancer Genome Atlas database. The correlation between DNA methylation and gene expression was illustrated by multiple comparisons. In other 60 clinical samples, methylation specific polymerase chain reaction (PCR) and reverse transcription quantitative PCR were applied for the methylation of HOXA4 and IGF1 genes in BC and adjacent non-cancerous tissues. In total, 1680 upregulated genes and 1249 downregulated genes were determined in BC. Chromosome 16 and 17 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in each gene region. Chromosome 19 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in the exoniensis 1, untranslated region-5 and transcriptional start site 200 gene regions. In other 60 clinical samples, HOXA4 and IGF1 in BC tissues presented increased DNA methylation and decreased gene expression in BC. MCF7 cells treated with RG108 showed decreased HOXA4 and IGF1 expressions. It was estimated that HOXA4 and IGF1 were identified with increased DNA methylation and decreased gene expression in BC, which may serve as biomarkers in early BC detection.


Assuntos
Neoplasias da Mama/genética , Metilação de DNA/genética , Detecção Precoce de Câncer , Genoma Humano/genética , Proteínas de Homeodomínio/genética , Fator de Crescimento Insulin-Like I/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Fatores de Transcrição/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , Metilação de DNA/efeitos dos fármacos , Bases de Dados de Ácidos Nucleicos , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Células MCF-7 , Pessoa de Meia-Idade , Ftalimidas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Transcriptoma/genética , Triptofano/análogos & derivados , Triptofano/farmacologia , Regulação para Cima/genética
4.
Int J Vitam Nutr Res ; 89(3-4): 168-175, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30806606

RESUMO

Background: Vitamin E has anti-cancer properties, which was demonstrated mainly due to its antioxidant effect. Several epidemiological studies have investigated the association between vitamin E consumption and the risk of bladder cancer. However, the results were inconsistent. The meta-analysis study aimed to evaluate the association of vitamin E consumption and the risk of bladder cancer. METHODS: We conducted a systematic literature search in the electronic databases, which included MEDLINE, EMBASE and the Cochrane Library till 1 January 2016. The pooled relative risk ratios (RRs) with 95% confidence intervals (CIs) were calculated depending on the heterogeneity among studies. Subgroup analysis and sensitivity analysis were also performed. Publication bias was assessed using Begg's test and Egger's test. RESULTS: A total of 11 prospective studies (3 randomized clinical trials and 8 cohort studies) including 575601 participants were identified to be eligible for our present meta-analysis. The pooled RRs with 95% CI for highest versus lowest vitamin E consumption was 0.89 (0.78-1.00). An inverse linear association between vitamin E consumption and bladder cancer risk was detected in the dose response analysis. The results were also stable in the subgroup analysis and sensitivity analysis. Meanwhile, no obvious publication bias was observed. CONCLUSIONS: Our study indicates that vitamin E consumption was inversely associated with the risk of bladder cancer.


Assuntos
Neoplasias da Bexiga Urinária , Vitamina E , Humanos , Razão de Chances , Estudos Prospectivos
5.
Food Microbiol ; 76: 487-496, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30166178

RESUMO

The objective of this study was to explore the core functional microbiota for the production of volatile flavour during the traditional brewing of Wuyi Hong Qu glutinous rice wine, one of the most typical representatives of rice wine in China. Microbiological analysis based on high-throughput sequencing (HTS) technology demonstrated that bacteria of Lactobacillus, Bacillus, Leuconostoc, Lactococcus, Raoultella, Staphylococcus, Pediococcus, and Weissella, and fungi of Saccharomyces, Saccharomycopsis, Rhizopus, Monascus, Pichia, Wickerhamomyces, Candida, and Aspergillus were the predominant genera during the traditional fermentation process. Principal component analysis (PCA) based on the relative abundance showed that both of bacterial and fungal communities varied significantly in different fermentation phases. Some predominant microbial species or genera (including bacteria of Bacillus spp., Staphylococcus spp., Weissella spp., and P. acidilactici, and fungi of M. purpureus, R. oryzae, R. arrhizus var. arrhizus, and A. niger) were detected at the initial brewing stage, and their populations decreased as the fermentation progressed, while those of Lactobacillus, Gluconacetobacter, Leuconostoc, Pichia, Wickerhamomyces, and Saccharomyces increased to become the predominant genera at the final stage. A total of 79 volatile compounds were identified in traditional fermentation starters and during the traditional brewing process, mainly including esters, alcohols, acids, aldehydes, ketones, and phenols. Heatmaps and PCA also revealed the significant variances in the composition of volatile compounds among different samples. Furthermore, the potential correlations between microbiota succession and volatile flavour dynamics were explored through bidirectional orthogonal partial least squares (O2PLS) based correlation analysis. Three bacterial genera, namely, Gluconacetobacter, Lactobacillus, Lactococcus, and three fungal genera of Pichia, Wickerhamomyces, and Saccharomyces, were determined as the core functional microbiota for production of main volatile compounds in Wuyi Hong Qu glutinous rice wine. To conclude, information provided by this study is valuable to the development of effective strategies for the selection of beneficial bacterial and fungal strains to improve the quality of Wuyi Hong Qu glutinous rice wine.


Assuntos
Bactérias/metabolismo , Aromatizantes/metabolismo , Fungos/metabolismo , Microbiota , Oryza/microbiologia , Compostos Orgânicos Voláteis/metabolismo , Vinho/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Biodiversidade , China , Fermentação , Aromatizantes/química , Fungos/classificação , Fungos/genética , Fungos/isolamento & purificação , Oryza/química , Compostos Orgânicos Voláteis/química , Vinho/análise
6.
Pak J Pharm Sci ; 31(2): 485-489, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29618439

RESUMO

Taxanes, mainly group paclitaxel and docetaxel, are amongst the most promising anticancer agents that are widely used for a variety of tumor types. It is a great challenge to gain a quick overview of the molecular mechanisms of taxanes, owning to the massive amounts of data have been produced. Network pharmacology will be a powerful tool to uncover the drug-targets network of taxanes. In this study, drug-targets network of paclitaxel and docetaxel were constructed via STITCH by database mining, and its topological parameters and important nodes were analyzed. All will provide a systematic understanding for molecular mechanisms of pacltaxel and docetaxel in a quick and visual way.


Assuntos
Mineração de Dados/métodos , Docetaxel/farmacologia , Paclitaxel/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP , Antineoplásicos Fitogênicos/farmacologia , Biologia Computacional/métodos , Citocromo P-450 CYP2C8 , Bases de Dados Factuais , Receptores ErbB , Humanos , Terapia de Alvo Molecular/métodos , Mapeamento de Interação de Proteínas/métodos , Software , Taxoides/farmacologia
7.
Acta Pharmacol Sin ; 38(4): 571-580, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28216622

RESUMO

There is considerable inter-individual variabil¬ity in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiv¬ing the same or similar treatment protocols. In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients. A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled. Genotypes in ER stress pathway genes, including VCP (valosin-containing protein) rs2074549, HSP90B1 rs17034943, CANX (calnexin) rs7566, HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397, CALCR (calcitonin receptor) rs2528521, and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system. The short-term effects of primary tumor and lymph node after radiotherapy were assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) of WHO. And acute radiation-induced toxic reactions were evaluated according to the Radiation Therapy Oncology Group or European Organization for Research and Treatment of Cancer (RTOG/EORTC). The effects of gene polymorphisms on clinical outcomes of chemoradiotherapy were assessed by chi-square test, univariate and multivariate logistic regression analyses. We found that CT and CT+CC genotypes of CANX rs7566 was significantly correlated with primary tumor treatment efficacy at 3 months after chemoradiotherapy and with occurrence of radiation-induced myelosuppression in Chinese NPC patients. CT and CT+CC genotypes of CALCR rs2528521 were significantly correlated with cervical lymph node efficacy at 3 months after chemoradiotherapy. And CC and CT+CC genotypes of VCP rs2074549 were significantly associated with occurrence of myelosuppression. In conclusion, SNPs of VCP rs2074549, CANX rs7566 and CALCR rs2528521 in ER stress pathway genes may serve as predictors for clinical outcomes of chemoradiotherapy in Chinese NPC patients.


Assuntos
Carcinoma/terapia , Estresse do Retículo Endoplasmático/genética , Neoplasias Nasofaríngeas/terapia , Adenosina Trifosfatases/genética , Adulto , Povo Asiático , Calnexina/genética , Carcinoma/metabolismo , Proteínas de Ciclo Celular/genética , Quimiorradioterapia , Chaperona BiP do Retículo Endoplasmático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Polimorfismo Genético , Receptores da Calcitonina/genética , Transdução de Sinais , Proteína com Valosina
8.
Clin Exp Pharmacol Physiol ; 44(5): 539-548, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28199751

RESUMO

The purpose of this paper is to assess the relationship between gene polymorphism in angiogenesis-related genes and radiation responses in nasopharyngeal carcinoma (NPC) patients. The genotypes of 180 NPC patients were analyzed by Sequenom MassARRAY. The response evaluation criteria in solid tumours were used for assessing efficacies, and the criteria of the Radiation Therapy Oncology Group or European Organization for Research & Treatment of Cancer were utilized for evaluating acute toxic reactions in response to radiation. Statistical methods included chi-square test, uni- and multivariate logistic regression analyses. Genotypic carriers of rs1800541 GT were at an elevated risk of developing grade 3+ oral mucositis, and a genetic variant of rs5333 was a predictor for a lower occurring risk of grade 2+ radiation-induced xerostomia. EDN1 rs1800541, rs2071942 and rs5370 variants were associated with a significantly higher risk of severe myelosuppression. SNPs in such angiogenesis-related genes as EDN1 rs1800541, rs2071942 & rs5370 and EDNRA rs5333 may serve as useful biomarkers for predicting the outcomes of NPC patients.


Assuntos
Carcinoma/genética , Carcinoma/radioterapia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Neovascularização Patológica/genética , Neovascularização Patológica/radioterapia , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Endotelina-1/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Polimorfismo de Nucleotídeo Único/efeitos da radiação , Resultado do Tratamento , Adulto Jovem
9.
BMC Urol ; 17(1): 38, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28558682

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common types of cancer in urological system worldwide. Recently, the anticancer role of Glucosamine has been studied in many types of cancer. The aim of this study was to investigate the effects of Glucosamine on RCC. METHODS: The effects of Glucosamine on RCC cell proliferation and apoptosis were investigated by MTT assay and Annexin V-FITC Apoptosis assay, respectively in vitro. Cell cycle was detected by flow cytometry after treatment with Glucosamine. Protein levels of several cell cycle associated markers were examined by Western Blot. RESULTS: Our data showed that Glucosamine significantly inhibited the proliferation of renal cancer 786-O and Caki-1 cells in a dose-dependent manner. Besides, Glucosamine treatment resulted in cell cycle arrest at G0/G1 phase in both cell lines. Meanwhile, the expression of several regulators that contribute to G1/S phased transition, such as Cyclin D1, CDK4 and CDK6, were significantly down-regulated with the up-regulation of cell cycle inhibitors, p21 and p53, after treatment with glucosamine. However, the apoptosis rate of RCC cells was down-regulated when treatment with Glucosamine at 1 mM and 5 mM, while up-regulated at 10 mM. CONCLUSIONS: Our findings indicated that Glucosamine inhibited the proliferation of RCC cells by promoting cell cycle arrest at G0/G1 phase, but not promoting apoptosis. The present results suggested that Glucosamine might be a potential therapeutic agent in RCC treatment in the future.


Assuntos
Carcinoma de Células Renais/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Glucosamina/farmacologia , Neoplasias Renais/patologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Humanos , Células Tumorais Cultivadas
10.
Proc Natl Acad Sci U S A ; 111(36): 13199-204, 2014 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-25146699

RESUMO

Cerebral edema is a potentially life-threatening illness, but knowledge of its underlying mechanisms is limited. Here we report that hypobaric hypoxia induces rat cerebral edema and neuronal apoptosis and increases the expression of corticotrophin releasing factor (CRF), CRF receptor type 1 (CRFR1), aquaporin-4 (AQP4), and endothelin-1 (ET-1) in the cortex. These effects, except for the increased expression of CRF itself, could all be blocked by pretreatment with an antagonist of the CRF receptor CRFR1. We also show that, in cultured primary astrocytes: (i) both CRFR1 and AQP4 are expressed; (ii) exogenous CRF, acting through CRFR1, triggers signaling of cAMP/PKA, intracellular Ca(2+), and PKCε; and (iii) the up-regulated cAMP/PKA signaling contributes to the phosphorylation and expression of AQP4 to enhance water influx into astrocytes and produces an up-regulation of ET-1 expression. Finally, using CHO cells transfected with CRFR1(+) and AQP4(+), we show that transfected CRFR1(+) contributes to edema via transfected AQP4(+). In conclusion, hypoxia triggers cortical release of CRF, which acts on CRFR1 to trigger signaling of cAMP/PKA in cortical astrocytes, leading to activation of AQP4 and cerebral edema.


Assuntos
Aquaporina 4/metabolismo , Edema Encefálico/etiologia , Edema Encefálico/metabolismo , Hipóxia/complicações , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Animais , Apoptose/genética , Aquaporina 4/genética , Astrócitos/metabolismo , Edema Encefálico/patologia , Células CHO , Hormônio Liberador da Corticotropina/metabolismo , Cricetinae , Cricetulus , Endotelina-1/metabolismo , Hipóxia/metabolismo , Hipóxia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Neurônios/metabolismo , Neurônios/patologia , Fosforilação , Ratos Sprague-Dawley , Transdução de Sinais , Transfecção , Regulação para Cima/genética
11.
Molecules ; 22(4)2017 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-28420179

RESUMO

Salvianolic acid A (SAA) is one of the most abundant water-soluble and potent anti-oxidative compounds isolated from Danshen, a traditional Chinese medicine. A systematic overview of its mechanism of action is yet to be performed. In the present study, the druggability of SAA was measured using the TCMSP server, and potential targets of SAA were identified by PharmMapper and DRAR-CPI. Intersecting targets were then assessed by GeneMANIA and GO pathway analysis, and drug-target-pathway networks were constructed to give a visual view. The results showed that SAA has good druggability, and 13 putative protein targets were identified. Network analysis showed that these targets were associated with cancer, metabolism and other physiological processes. In summary, SAA is predicted to target multiple proteins and pathways to form a network that exerts systematic pharmacological effects.


Assuntos
Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Lactatos/química , Lactatos/farmacologia , Modelos Biológicos , Modelos Moleculares , Ligação Proteica , Salvia miltiorrhiza/química , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
12.
Biomed Microdevices ; 18(3): 41, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27165101

RESUMO

The objective of this study was to determine if plasma membrane vesicles (PMVs) could be exploited for efficient transfer of macro-biomolecules and mitochondria. PMVs were derived from mechanical extrusion, and made fusogenic (fPMVs) by incorporating the glycoprotein G of vesicular stomatitis virus (VSV-G). Confocal microscopy examination revealed that cytoplasmic proteins and mitochondria were enclosed in PMVs as evidenced by tracing with cytoplasmically localized and mitochondria-targeted EGFP, respectively. However, no fluorescence signal was detected in PMVs from cells whose nucleus was labeled with an EGFP-tagged histone H2B. Consistently, qRT-PCR measurement showed that mRNA, miRNA and mitochondrial DNA decreased slightly; while nuclear DNA was not measureable. Further, Western blot analysis revealed that cytoplasmic and membrane-bound proteins fell inconspicuously while nuclear proteins were barely detecsle. In addition, fPMVs carrying cytoplamic DsRed proteins transduced about ~40 % of recipient cells. The transfer of protein was further confirmed by using the inducible Cre/loxP system. Mitochondria transfer was found in about 20 % recipient cells after incubation with fPMVs for 5 h. To verify the functionalities of transferred mitochondria, mitochodria-deficient HeLa cells (Rho0) were generated and cultivated with fPMVs. Cell enumeration demonstrated that adding fPMVs into culture media stimulated Rho0 cell growth by 100 % as compared to the control. Lastly, MitoTracker and JC-1 staining showed that transferred mitochondria maintained normal shape and membrane potential in Rho0 cells. This study established a time-saving and efficient approach to delivering proteins and mitochondria by using fPMVs, which would be helpful for finding a cure to mitochondria-associated diseases. Graphical abstract Schematic of the delivery of macro-biomolecules and organelles by fPMVs. VSV-G-expressing cells were extruded through a 3 µm polycarbonate membrane filter to generate fusogenic plasma membrane vesicles (fPMVs), which contain bioactive molecules and organelles but not the nucleus. fPMVs can be endocytosed by target cells, while the cargo is released due to low-pH induced membrane fusion. These nucleus-free fPMVs are efficient at delivery of cytoplasmic proteins and mitochondria, leading to recovery of mitochondrial biogenesis and proliferative ability in mitochondria-deficient cells.


Assuntos
Membrana Celular/metabolismo , Glicoproteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Vesículas Transportadoras/metabolismo , Proteínas do Envelope Viral/metabolismo , Linhagem Celular , Núcleo Celular , DNA Mitocondrial/genética , Genômica , Proteínas de Fluorescência Verde/metabolismo , Células HeLa , Histonas/metabolismo , Humanos , MicroRNAs/genética , Cimento de Policarboxilato/química , RNA Mensageiro/genética , Análise de Sequência de DNA , Vírus da Estomatite Vesicular Indiana
13.
Gen Comp Endocrinol ; 237: 98-108, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27570060

RESUMO

OBJECTIVES: We previously found niacin receptor GPR109A was expressed in murine islet beta-cells, and signaling through GPR109A inhibited glucose stimulated insulin secretion (GSIS). However, the expression of GPR109A in human islets and its functional relevance is still not known. METHODS: The expression of GPR109A was examined by antibody staining and in situ hybridization on pancreatic paraffin sections. GPR109A was cloned and expressed in INS-1 islet beta-cells. Intracellular cAMP and GSIS were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression of GPR109A was confirmed in murine islet beta-cells and further detected in human counterparts by using commercially available polyclonal antibodies. In situ hybridization study detected the transcripts of GPR109A, but not that of closely related GPR109B. Furthermore, GPR109A was significantly reduced in islets from diabetic individuals and animal model of db/db mice as compared to their respective controls. Further, GPR109A levels in insulinoma were also reduced dramatically as compared to islets found in corresponding non-tumor normal tissues. Quantitative RT-PCR analysis demonstrated that GPR109A transcripts were severely down-regulated in rodent insulinoma cell lines as compared to that of freshly isolated islets from mice. Finally, human and murine GPR109A expression cassettes were transfected into INS-1 cells, which resulted in reduced accumulation of cAMP and insulin secretion after incubation with niacin. The effect could be completely abrogated by pretreatment with pertussis toxin. CONCLUSIONS: These results demonstrate that GPR109A is functionally expressed in both human and murine islet beta-cells. However, the role of GPR109A in the prevention of diabetes or insulinoma needs further study.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Regulação para Baixo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Nicotínicos/metabolismo , Idoso , Animais , AMP Cíclico/metabolismo , Regulação para Baixo/efeitos dos fármacos , Feminino , Imunofluorescência , Glucose/farmacologia , Humanos , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Insulinoma/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Nicotínicos/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
14.
Neuro Endocrinol Lett ; 37(6): 461-466, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28315631

RESUMO

OBJECTIVES: Urocortins (Ucns), members of corticotropin releasing factor family, play critical roles in a number of pathological and physiological conditions. Many proteins have been reported to participate in Ucns signaling pathways, which formed complex interaction networks. METHODS: STITCH ('search tool for interactions of chemicals') is an interaction network database that provides exploration of the known and predicted interactions among large sets of chemicals and proteins. RESULTS: In this study, using STITCH, interaction networks of Ucns were constructed by database mining, and then their topological parameters and important nodes were analyzed by network related tools. This may help a quick and thorough overview of the Ucns mechanisms underlying in a visual format.


Assuntos
Transdução de Sinais/fisiologia , Urocortinas/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Bases de Dados Factuais , Humanos , Mapas de Interação de Proteínas , Receptores de Hormônio Liberador da Corticotropina/metabolismo
15.
Zhongguo Zhong Yao Za Zhi ; 41(11): 2124-2130, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28901111

RESUMO

Alkaloids and flavonoids in flowers, flower buds, stems, leaves, and bulbs of Fritillaria thunbergii were identified by LC-LTQ-Orbitrap MSn.Alkaloids were identified by ACQUITY UPLC BEH C18(2.1 mm×50 mm, 1.7 µm ) chromatographic column with a mobile phase of 10 mmol•L⁻¹ ammonium formate-acetonitrile and gradient elution in positive MS scan mode.Meanwhile, flavonoids were analyzed by Agilent-Zorbax SB C18 (4.6 mm×250 mm, 5 µm) chromatographic column with a mobile phase of 0.2% acetic acid-acetonitrile and gradient elution in negative MS scan mode.Combined with literature reports, chemical constituents were identified and determined by accurate molecular weights and fragment ion peaks in the ESI-MS/MS spectra based on high resolution mass spectrometer.In all parts of F.thunbergii, 37 alkaloids including 7 alkaloids (zhebeininoside, peimisine, peimine, peiminine, ebeiedinone/puqiedinone, ebeiedine/ puqiedine, peimisine-N-oxide) were simultaneously analyzed.Moreover, 16 flavonoids including quercetin, kaempferol and their glycosides were identified.The results indicated that the aerial parts had the similar alkaloids as the bulbs on the whole.Meanwhile, it had a series of flavonoids undetected in the bulbs.Our results provided the scientific basis for the development and utilization of aerial parts of F.thunbergii.


Assuntos
Alcaloides/análise , Flavonoides/análise , Fritillaria/química , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos/análise , Espectrometria de Massas em Tandem
16.
Tumour Biol ; 36(4): 2947-55, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25480417

RESUMO

Long noncoding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has recently been identified to be involved in tumorigenesis of several cancers such as lung cancer, pancreatic cancer, and cervical cancer. However, the role of lncRNA MALAT1 in clear cell renal cell carcinoma (ccRCC) remains unclear. Expression levels of lncRNA MALAT1 in ccRCC tissues and renal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR), and its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress MALAT1 expression in renal cancer cells. In vitro assays were conducted to further explore its role in tumor progression. The expression level of MALAT1 was higher in ccRCC tissues and renal cancer cells compared to adjacent non-tumor tissues and normal human proximal tubule epithelial cells HK-2. The ccRCC patients with higher MALAT1 expression had an advanced clinical features and a shorter overall survival time than those with lower MALAT1 expression. And multivariate analysis showed that the status of MALAT1 expression was an independent predictor of overall survival in ccRCC. Additionally, our data indicated that knockdown expression of MALAT1 decreased renal cancer cell proliferation, migration, and invasion. Our data suggested that lncRNA MALAT1 was a novel molecule involved in ccRCC progression, which provided a potential prognostic biomarker and therapeutic target.


Assuntos
Carcinogênese , Carcinoma de Células Renais/genética , Proliferação de Células/genética , RNA Longo não Codificante/biossíntese , Adulto , Idoso , Apoptose/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Prognóstico , RNA Longo não Codificante/genética
17.
Zhong Yao Cai ; 35(12): 1974-7, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23705363

RESUMO

OBJECTIVE: To normalize bacteriostasis and relieving itching external therapeutic function of Kochiae Fructus. METHODS: Itching guinea pig model caused by histamine, itching mice model, eczema guinea pig model caused by OVA, and inhibitory effect on pathogens in vitro were used to observe the itching threshold, symptoms and other related physiological index, as well as the inhibitory effect on the normal skin fungi by water extraction of Kochiae Fructus to evaluate the external therapeutic function of Kochiae Fructus. RESULTS: The itching threshold of guinea pig itching model treated by water extraction of Kochiae Fructus at high, medium and low three dosage level, could be significantly increased when compared with negative control group (P < 0.05 or P < 0.01); Red speckle of OVA guinea pig model treated by water extraction of Kochiae Fructus at high, medium and low three dosage level, could be significantly decreased when compared with negative control group (P < 0.05 or P < 0.01); The number of itching and total time of itching within 30 minutes of mice model caused by R-glycose anhydride treated by water extraction of Kochiae Fructus at high, medium and low three dosage level, could be significantly decreased when compared with negative control group (P < 0.05 or P < 0.01); Several common skin fungi could be significantly inhibited by the water extraction of Kochiae Fructus. MIC of the water extraction of Kochiae Fructus on Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis, Trichophyton violaceum, and Trichophyton schoenleini were 3.12%, 0.78%, 0.78%, 0.78%, 0.78%, respectively. CONCLUSION: Kochiae fructus has the effect of bacteriostasis and relieving itching.


Assuntos
Antibacterianos/farmacologia , Antipruriginosos/farmacologia , Arthrodermataceae/efeitos dos fármacos , Bassia scoparia/química , Medicamentos de Ervas Chinesas/farmacologia , Prurido/tratamento farmacológico , Administração Cutânea , Animais , Antibacterianos/administração & dosagem , Antipruriginosos/administração & dosagem , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/isolamento & purificação , Eczema/induzido quimicamente , Eczema/tratamento farmacológico , Eczema/patologia , Feminino , Frutas/química , Cobaias , Histamina/administração & dosagem , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Microsporum/efeitos dos fármacos , Ovalbumina/administração & dosagem , Prurido/induzido quimicamente , Prurido/patologia , Pele/efeitos dos fármacos , Pele/patologia , Trichophyton/efeitos dos fármacos
18.
Cancer Gene Ther ; 26(11-12): 374-387, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30546116

RESUMO

Breast cancer is ranked as the second leading cause of cancer-related deaths among women. Accumulating evidences have revealed that long non-coding RNAs (lncRNAs) are involved in human tumorigenesis owing to the regulation of essential pathways for tumor initiation and progression. Herein, the current study aimed to explore the regulatory mechanism of lncRNA ZFHX4-AS1 in breast cancer in relation to the Hippo signaling pathway. Initially, microarray analysis was conducted to screen out differentially expressed lncRNAs related to breast cancer. Next, the functional role of lncRNA ZFHX4-AS1 in breast cancer was determined using ectopic expression, knockdown, and reporter assay experiments. Subsequently, lncRNA ZFHX4-AS1, TAF4, TAZ, and YAP expressions were determined, followed by verification of the targeting relationship between lncRNA ZFHX4-AS1 and TAF4. Then cell proliferation, invasion, migration, cell cycle, and apoptosis were measured. Lastly, tumor growth and metastasis were detected by tumor xenograft in nude mice. LncRNA ZFHX4-AS1 was found to be highly expressed while FAT4 was poorly expressed in breast cancer tissues. FAT4 was the target gene of lncRNA ZFHX4-AS1, and lncRNA ZFHX4-AS1 silencing increased FAT4 expressions, while decreased YAP and TAZ expressions. In addition, knockdown of lncRNA ZFHX4-AS1 suppressed breast cancer cell proliferation, migration, and invasion as well as tumor growth, blocked cell cycle entry, while promoted cell apoptosis by inhibiting the Hippo signaling pathway. In conclusion, our findings reveal that lncRNA ZFHX4-AS1 silencing exerts an inhibitory effect on breast cancer development by suppressing the activation of the Hippo signaling pathway via FAT4.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Caderinas/genética , Proteínas de Homeodomínio/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Longo não Codificante , Transdução de Sinais , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Animais , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Caderinas/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Xenoenxertos , Via de Sinalização Hippo , Humanos , Camundongos , Proteínas Supressoras de Tumor/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-29636777

RESUMO

Curcumae Rhizoma, a traditional Chinese medication, is commonly used in both traditional treatment and modern clinical care. Its anticancer effects have attracted a great deal of attention, but the mechanisms of action remain obscure. In this study, we screened for the active compounds of Curcumae Rhizoma using a drug-likeness approach. Candidate protein targets with functions related to cancer were predicted by reverse docking and then checked by manual search of the PubMed database. Potential target genes were uploaded to the GeneMANIA server and DAVID 6.8 database for analysis. Finally, compound-target, target-pathway, and compound-target-pathway networks were constructed using Cytoscape 3.3. The results revealed that the anticancer activity of Curcumae Rhizoma potentially involves 13 active compounds, 33 potential targets, and 31 signaling pathways, thus constituting a "multiple compounds, multiple targets, and multiple pathways" network corresponding to the concept of systematic actions in TCM. These findings provide an overview of the anticancer action of Curcumae Rhizoma from a network perspective, as well as setting an example for future studies of other materials used in TCM.

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