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1.
Nat Prod Res ; : 1-6, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38099373

RESUMO

One novel diketopiperazine derivative 8R-methoxy-9R-hydroxyl-fumitremorgin C (1), together with twelve known compounds, was separated from the fungus Aspergillus fumigatus CYH-5 collected from Haima cold seep. The structures of the compounds were identified by NMR, MS, optical rotation, hydrolysis reaction and comparing with literatures. Among them, compounds 10 and 11 exhibited inhibitory effect against bacteria. Compound 11 showed inhibitory activity on α-glucosidase and compound 8 displayed acetylcholinesterase (AchE) inhibitory activity.

2.
Sci Rep ; 13(1): 12607, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37537191

RESUMO

Gastric cancer (GC) remains the third leading cause of cancer-related mortality in the world, and ninety-five percent of GC are stomach adenocarcinomas (STAD). The active ingredients of Croci Stigma, such as Isorhamnetin, Crocin, Crocetin and Kaempferol, all have antitumor activity. However, their chemical and pharmacological profiles remain to be elusive. In this study, network pharmacology was used to characterize the action mechanism of Croci Stigma. All compounds were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database, and active ingredients were selected by their oral bioavailability and drug-likeness index. The targets of Croci Stigma active ingredients were obtained from the traditional Chinese medicine integrated database (TCMID), whereas the related genes of STAD were obtained from DisGeNET platform. Cytoscape was used to undertake visual analyses of the Drug Ingredients-Gene Symbols-Disease (I-G-D) network, and 2 core genes including MAPK14, ERBB3 were obtained, which are the predicted targets of isorhamnetin (IH) and quercetin, respectively. Data analysis from TCGA platform showed that MAPK14 and ERBB3 all upregulated in STAD patients, but only the effect of MAPK14 expression on STAD patients' survival was significant. Molecular docking showed that IH might affect the function of MAPK14 protein, and then the underlying action mechanisms of IH on STAD were experimentally validated using human gastric cancer cell line, HGC-27 cells. The results showed that IH can inhibit cell proliferation, migration, clonal formation, and arrest cell cycle, but promote the apoptosis of HGC-27 cells. qRT-PCR data demonstrated that IH downregulated the MAPK14 mRNA expression and EMT related genes. WB results showed that IH regulates MAPK/mTOR signaling pathway. These findings suggest that IH has the therapeutic potential for the treatment of STAD.


Assuntos
Adenocarcinoma , Medicamentos de Ervas Chinesas , Proteína Quinase 14 Ativada por Mitógeno , Neoplasias Gástricas , Humanos , Quercetina/farmacologia , Simulação de Acoplamento Molecular , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética
3.
Int J Ophthalmol ; 15(6): 924-931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814895

RESUMO

AIM: To investigate the binocular intraocular lens (IOL) power difference in eyes with short, normal, and long axial lengths (AL) using Lenstar LS 900 optical biometry. METHODS: A total of 716 (1432 eyes) participants were included. The groups were categorized into short (group A: AL<22 mm), normal (group B: 22 mm≤AL≤25 mm), and long AL groups (group C: AL>25 mm). The central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), AL, anterior corneal keratometry, white-to-white (WTW), pupil diameter (PD), as well as IOL power calculated using embedded Barrett formula were assessed. Bland-Altman plots were used to test the agreement of the binocular parameters. RESULTS: In group A, the CCT of the right eye was significantly thinner than that of the left eye (P=0.044) with a difference of -2±8 µm [95% limits of agreement (LoA), -17.8 to 13.2 µm]. For group B, the PD and IOL power in the right eye were significantly lower than those of the left eye (P=0.001, <0.001) with a difference of -0.05±0.32 mm (95%LoA, -0.68 to 0.58 mm) and -0.18±1.01 D (95%LoA, -2.2 to 1.8 D). The AL of right eye was longer than that of the left eye (P=0.002) with a difference of 0.04±0.25 mm (95%LoA, -0.45 to 0.52 mm). No significant difference was observed for all the binocular parameters in group C. The percentage of participants with binocular IOL power difference within ±0.5 D were 62% (31/50), 68.3% (339/496), and 38.8% (66/170) in groups A, B, and C, respectively. CONCLUSION: The binocular parameters related to IOL power are in good agreement, but the binocular IOL power difference of more than half of participants with long AL is more than 0.50 D.

4.
Sci Rep ; 12(1): 3388, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35232961

RESUMO

COPD is the fourth leading cause of mortality, and is predicted to be the third leading cause of death worldwide by 2020. But few studies on Tibetan COPD of China. This study identifies distinctive miRNA signatures in Tibetan COPD patients from Tibetan healthy subjects that could serve as diagnostic biomarkers or describe differential molecular mechanisms with potential therapeutic implications. In this study, a total of 210 differentially expressed miRNAs were screened. Analysis of the functions of target genes of differentially expressed miRNAs via GO enrichment analysis revealed that they mainly influenced guanyl-nucleotide exchange factor activity, cell morphogenesis and the positive regulation of GTPase activity. KEGG pathway enrichment analysis showed that these target genes were mainly enriched in signaling by NGF, Axon guidance, developmental biology, ubiquitin mediated proteolysis, and PDGF signaling pathways. MiR-106-5p and miR-486-5p expression was validated in the complete cohort. Age, plasma miR-106-5p, miR-486-5p, SP-D protein levels, and SP-D mRNA level were also determined to be correlated with FEV1%Pred, and may as the risk factors of Tibetan COPD. The combination of plasma miR-106-5p, miR-486-5p and SP-D mRNA expression may be the best model to assist the diagnosis of Tibetan COPD.


Assuntos
MicroRNA Circulante , MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Proteína D Associada a Surfactante Pulmonar , MicroRNA Circulante/sangue , Perfilação da Expressão Gênica , Humanos , MicroRNAs/genética , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/genética , Proteína D Associada a Surfactante Pulmonar/sangue , Proteína D Associada a Surfactante Pulmonar/genética , RNA Mensageiro , Tibet
5.
Mar Drugs ; 20(1)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35049926

RESUMO

Six new α-pyrone meroterpenoid chevalones H-M (1-6), together with six known compounds (7-12), were isolated from the gorgonian coral-derived fungus Aspergillus hiratsukae SCSIO 7S2001 collected from Mischief Reef in the South China Sea. Their structures, including absolute configurations, were elucidated on the basis of spectroscopic analysis and X-ray diffraction data. Compounds 1-5 and 7 showed different degrees of antibacterial activity with MIC values of 6.25-100 µg/mL. Compound 8 exhibited potent cytotoxicity against SF-268, MCF-7, and A549 cell lines with IC50 values of 12.75, 9.29, and 20.11 µM, respectively.


Assuntos
Antozoários , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Aspergillus , Pironas/farmacologia , Animais , Antibacterianos/química , Antineoplásicos/química , Organismos Aquáticos , Linhagem Celular Tumoral , China , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Pironas/química
6.
Front Bioeng Biotechnol ; 9: 746815, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650961

RESUMO

Optoacoustic (photoacoustic) imaging has demonstrated versatile applications in biomedical research, visualizing the disease pathophysiology and monitoring the treatment effect in an animal model, as well as toward applications in the clinical setting. Given the complex disease mechanism, multimodal imaging provides important etiological insights with different molecular, structural, and functional readouts in vivo. Various multimodal optoacoustic molecular imaging approaches have been applied in preclinical brain imaging studies, including optoacoustic/fluorescence imaging, optoacoustic imaging/magnetic resonance imaging (MRI), optoacoustic imaging/MRI/Raman, optoacoustic imaging/positron emission tomography, and optoacoustic/computed tomography. There is a rapid development in molecular imaging contrast agents employing a multimodal imaging strategy for pathological targets involved in brain diseases. Many chemical dyes for optoacoustic imaging have fluorescence properties and have been applied in hybrid optoacoustic/fluorescence imaging. Nanoparticles are widely used as hybrid contrast agents for their capability to incorporate different imaging components, tunable spectrum, and photostability. In this review, we summarize contrast agents including chemical dyes and nanoparticles applied in multimodal optoacoustic brain imaging integrated with other modalities in small animals, and provide outlook for further research.

7.
Mar Drugs ; 19(10)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34677441

RESUMO

To enlarge the chemical diversity of Eurotium sp. SCSIO F452, a talented marine-derived fungus, we further investigated its chemical constituents from a large-scale fermentation with modified culture. Four pairs of new salicylaldehyde derivative enantiomers, euroticins F-I (1-4), as well as a known one eurotirumin (5) were isolated and characterized. Compound 1 features an unprecedented constructed 6/6/6/5 tetracyclic structures, while 2 and 3 represent two new types of 6/6/5 scaffolds. Their structures were established by comprehensive spectroscopic analyses, X-ray diffraction, 13C NMR, and electronic circular dichroism calculations. Selected compounds showed significant inhibitory activity against α-glucosidase and moderate cytotoxic activities against SF-268, MCF-7, HepG2, and A549 cell lines.


Assuntos
Aldeídos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Eurotium , Aldeídos/química , Animais , Antineoplásicos/química , Antioxidantes/química , Organismos Aquáticos , Linhagem Celular Tumoral/efeitos dos fármacos , Humanos , Estrutura Molecular , Estereoisomerismo
8.
Fitoterapia ; 150: 104839, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33513431

RESUMO

Three new tricyclic cyclopiazonic acid (CPA) related alkaloids asperorydines N-P (1-3), together with six known compounds (4-9) were isolated and characterized from the fungus Aspergillus flavus SCSIO F025 derived from the deep-sea sediments of South China Sea. The structures including absolute configurations of 1-3 were deduced from spectroscopic data, X-ray diffraction analysis, and electronic circular dichroism (ECD). All compounds were evaluated for the antioxidative activities against DPPH, cytotoxic activities against four tumor cell lines (SF-268, HepG-2, MCF-7, and A549), and antimicrobial activities. Compound 9 showed significant radical scavenging activities against DPPH with an IC50 value of 62.23 µM and broad-spectrum cytotoxicities against four tumor cell lines with IC50 values ranging from 24.38 to 48.28 µM. Furthermore, compounds 4-9 exhibited weak antimicrobial activities against E scherichia coli, and compound 9 also showed antibacterial activity against Bacillus thuringiensis, Micrococcus lutea, Staphylococcus aureus, Bacillus subtilis, Methicillin resistant Staphylococcus aureus.


Assuntos
Alcaloides/farmacologia , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Aspergillus flavus/química , Indóis/farmacologia , Alcaloides/isolamento & purificação , Antibacterianos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Organismos Aquáticos/química , Bacillus/efeitos dos fármacos , Linhagem Celular Tumoral , China , Escherichia coli/efeitos dos fármacos , Sedimentos Geológicos/microbiologia , Humanos , Indóis/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Micrococcus/efeitos dos fármacos , Estrutura Molecular , Água do Mar/microbiologia
9.
Am J Physiol Cell Physiol ; 319(5): C922-C932, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32936698

RESUMO

The role of hypoxia-inducible factor (HIF)-1 in pancreatic ß-cell response to intermittent hypoxia (IH) was examined. Studies were performed on adult wild-type (WT), HIF-1α heterozygous (HET), ß-cell-specific HIF-1-/- mice and mouse insulinoma (MIN6) cells exposed to IH patterned after blood O2 profiles during obstructive sleep apnea. WT mice treated with IH showed insulin resistance, and pancreatic ß-cell dysfunction manifested as augmented basal insulin secretion, and impaired glucose-stimulated insulin secretion and these effects were absent in HIF-1α HET mice. IH increased HIF-1α expression and elevated reactive oxygen species (ROS) levels in ß-cells of WT mice. The elevated ROS levels were due to transcriptional upregulation of NADPH oxidase (NOX)-4 mRNA, protein and enzymatic activity, and these responses were absent in HIF-1α HET mice as well as in ß-HIF-1-/- mice. IH-evoked ß-cell responses were absent in adult WT mice treated with digoxin, an inhibitor of HIF-1α. MIN6 cells treated with in vitro IH showed enhanced basal insulin release and elevated HIF-1α protein expression, and these effects were abolished with genetic silencing of HIF-1α. IH increased NOX4 mRNA, protein, and enzyme activity in MIN6 cells and disruption of NOX4 function by siRNA or scavenging H2O2 with polyethylene glycol catalase blocked IH-evoked enhanced basal insulin secretion. These results demonstrate that HIF-1-mediated transcriptional activation of NOX4 and the ensuing increase in H2O2 contribute to IH-induced pancreatic ß-cell dysfunction.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Hipóxia/genética , NADPH Oxidase 4/genética , Oxigênio/farmacologia , Apneia Obstrutiva do Sono/genética , Animais , Digoxina/farmacologia , Modelos Animais de Doenças , Glucose/metabolismo , Heterozigoto , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/metabolismo , Hipóxia/metabolismo , Hipóxia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Insulina/metabolismo , Resistência à Insulina/genética , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NADPH Oxidase 4/antagonistas & inibidores , NADPH Oxidase 4/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/patologia , Ativação Transcricional
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(5): 1531-1537, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30295279

RESUMO

OBJECTIVE: To investigate the effects of exosomes derived from miR-486 gene-modified umbilical cord mesenchymal stem cells (UC-MSCs) on biological characteristics of rat cardiomyocytes. METHODS: The human umbilical cord mesenchymal stem cells (UC-MSCs) were isolated and cultured, then the immunophenotypes and ability of osteogenic and adipogenic differentiation of UC-MSC were identified. The structure of exosomes was observed by electron microscopy; the effect of exosomes on cell migration was detected by transwell cell migration test; the miR-486 high expression of UC-MSC was mediated by using recombinant adenovirus vector, moreover the UC-MSC with high expression of miR-486 were identified by qPT-PCR. The exosomes were isolated from cell culture supernatant by ultracentrifugation and the miR-486 expression level of UC MSC exosomes was detected by qRT-PCR. The effect of exosomes on the proliferation of cardiomyocytes was evaluated by Dye670 marking. The H2O2-induced cardiomyocyte apoptosis model was established, and the effect of exosomes on apoptosis of cardiomyocytes was detected by flow cytometry with Annexin V/PI double staining. RESULTS: The exosomes derived from UC-MSCs had the diameter between 40-100 nm and double membrane stracture. The recombinant adenovirus could effectively mediate the expression of miR-486 in UC-MSC, and the expression level of miR-486 in exosomes of miR-486-modified UC-MSC significantly increased. The exosomes with miR-486 high expression possessed the pro-proliferation and pro-migration effects on cardiomyocytes, moreover the preventive effect on apoptosis of cardiomyocytes. CONCLUSION: The exosomes derived from UC-MSC and accompamied by high expression of miR-486 can promote the proliferation and migration of cardio myocytes, yet can prevent the apoptosis of cardiomyocytes.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Animais , Humanos , Peróxido de Hidrogênio , MicroRNAs , Miócitos Cardíacos , Ratos , Cordão Umbilical
11.
Mar Drugs ; 16(4)2018 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-29690501

RESUMO

Three new prenylated indole 2,5-diketopiperazine alkaloids (1⁻3) with nine known ones (5⁻13), one new indole alkaloid (4), and one new bis-benzyl pyrimidine derivative (14) were isolated and characterized from the marine-derived fungus Eurotium sp. SCSIO F452. 1 and 2, occurring as a pair of diastereomers, both presented a hexahydropyrrolo[2,3-b]indole skeleton. Their chemical structures, including absolute configurations, were elucidated by 1D and 2D NMR, HRESIMS, quantum chemical calculations of electronic circular dichroism, and single crystal X-ray diffraction experiments. Most isolated compounds were screened for antioxidative potency. Compounds 3, 5, 6, 7, 9, 10, and 12 showed significant radical scavenging activities against DPPH with IC50 values of 13, 19, 4, 3, 24, 13, and 18 µM, respectively. Five new compounds were evaluated for cytotoxic activities.


Assuntos
Alcaloides/química , Organismos Aquáticos/química , Eurotium/química , Fungos/química , Alcaloides/farmacologia , Antioxidantes/química , Linhagem Celular Tumoral , Dicroísmo Circular/métodos , Cristalografia por Raios X/métodos , Citotoxinas/química , Citotoxinas/farmacologia , Dicetopiperazinas/química , Dicetopiperazinas/farmacologia , Células Hep G2 , Humanos , Espectroscopia de Ressonância Magnética/métodos
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(5): 1283-1288, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29070096

RESUMO

OBJECTIVE: To investigate the effect and mechanism of miR-486 on glycometabolism of hematopoietic cells. METHODS: qRT-PCR was applied to detect the expression of miR-486 or Sirt1 on TF-1 cells under hypoxia. Lentivirus was used to mediate the overexpression or inhibition of miR-486 on TF-1 cells and qRT-PCR was used to detect the expressions of Sirt1, glucose transporter 1(Glut1) and glucose transporter 4(Glut4). Lentivirus-mediated Sirt1-shRNA transduction was used to knockdown Sirt1 expression which was detected by qRT-PCR and Western blot. The expressions of Glut1 and Glut4 were determined by qRT-PCR. RESULTS: Hypoxia promoted the expression of miR-486 and inhibited the expression of Sirt1. MiR-486 overexpression could inhibit the expression of Sirt1 and promote the expressions of Glut1 and Glut4, whereas miR-486 silencing upregulated the sirt1 expression and inhibited the expressions of Glut1 and Glut4. And inhibition of Sirt1 expression increased the expressions of Glut1 and Glut4. CONCLUSION: MiR-486 can regulate the glycometabolism of hematopoietic cells by targeting Sirt1.


Assuntos
Células-Tronco Hematopoéticas/fisiologia , MicroRNAs/fisiologia , RNA Interferente Pequeno , Sirtuína 1/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Lentivirus
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(4): 965-969, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-28823252

RESUMO

OBJECTIVE: To clarify the roles of SPK pathway in the regulation of proliferation, survival and glucose consume of human erythroleukemia TF-1 cells. METHODS: The interfering in SPK expression of TF-1 cells was performed using leutivirus vector-mediated shRNA, the interference efficacy of SPK in TF-1 cells was detected by RT-qPCR and Western blot, the viability of TF-1 cell proliferation was detected by using CCK-8 method, the apoptosis of TF-1 cells was determined by flow cytmetry with Annexin V staining. RESULTS: Hypoxia up-regulated the expression of HIF-1α, HIF-2α, and SPK in TF-1 cells. SPK treatment resulted in reduced proliferation and induced apoptosis in TF-1 cells. Furthermore, knockdown of the SPK significantly reduced utilization and consumption of glucose. CONCLUSION: The SPK is key signalling molecule involved in regulation of hypoxia-induced proliferation and glucose metabolism in TF-1 cells, and plays an important rote in proliferation and energy metabolism of leukemia cells.


Assuntos
Proliferação de Células , Apoptose , Hipóxia Celular , Linhagem Celular Tumoral , Glucose , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Fosfotransferases (Aceptor do Grupo Álcool) , RNA Interferente Pequeno
14.
Exp Cell Res ; 351(1): 74-81, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28043832

RESUMO

MicroRNAs (miRNAs) regulate the hypoxia-induced erythroid differentiation of hematopoietic cells. In this study, we identified that miR-486 was a rapid response miRNA to hypoxia in erythroleukemia TF-1 cells. Hypoxia exposure increased both intracellular and miR-486 levels of TF-1 cells. Ectopic miR-486 expression enhanced the growth and erythroid differentiation of TF-1 cells, whereas miR-486 inhibition suppressed their growth and erythroid differentiation. Treatment of TF-1 and cord blood CD34+ cells with exogenous containing miR-486 resulted in an increase of intracellular miR-486 level and enhanced erythroid differentiation. Furthermore, we identified that Sirt1 is a miR-486 target gene which modulates hypoxia-induced erythroid differentiation of TF-1 cells. Thus we identified a novel miRNA regulatory network that contributes to hypoxia-induced erythroid differentiation of hematopoietic cells.


Assuntos
Células Precursoras Eritroides/citologia , Eritropoese , Leucemia Eritroblástica Aguda/metabolismo , MicroRNAs/genética , Sirtuína 1/genética , Hipóxia Celular , Linhagem Celular Tumoral , Células Cultivadas , Células Precursoras Eritroides/metabolismo , Humanos , Oxigênio/metabolismo , Sirtuína 1/metabolismo
15.
Int J Biochem Cell Biol ; 74: 152-60, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26923291

RESUMO

Angiogenesis is one of the most important components of embryonic organ formation and vessel growth after birth. Sphingosine kinase 1 (Sphk1) and S1P has been confirmed to participate in various cell signaling pathways and physiological processes including neovascularisation. However, the mechanisms that Sphk1/S1P regulates neovascularisation remain unclear. In this study, we elucidated that Sphk1/S1P upregulates sirtuin 1 (SIRT1), a NAD+ dependent deacetylases protease which exerts multiple cellular functions, to regulate the proliferation and migration of endothelial cells. By using CCK8 and Transwell assays, we demonstrated that Sphk1 and SIRT1 knockdown could significantly decrease proliferation and migration of HUVEC cells. Sphk1 inhibition results in SIRT1 downregulation which could be reversed by exogenous S1P in HUVEC cells. Treatment of HUVECs with S1P reverses the impaired proliferation and migration caused by SIRT1 knockdown. Furthermore, Sphk1 knockdown inhibits the phosphorylation of P38 MAPK, ERK and AKT. Treatment of HUVECs with PD98059, SB203580 and Wortmannin, which are the inhibitors of ERK, P38 MAPK and AKT respectively, resulted in decreased SIRT1 expression and reduced migration of HUVEC cells. Thus, we conclude that Sphk1/S1P induces SIRT1 upregulation through multiple pathways including P38 MAPK, ERK and AKT signals. This is the first report to disclose the existence and roles of Sphk1/S1P/SIRT1 axis in regulation of endothelial cell proliferation and migration, which may provide a theoretical basis for angiogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Células Endoteliais/citologia , Sirtuína 1/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Western Blotting , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Células Endoteliais/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Ensaio de Imunoadsorção Enzimática , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Sirtuína 1/genética
16.
Biochem Biophys Res Commun ; 471(4): 459-65, 2016 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-26898802

RESUMO

Hypoxia provokes metabolism misbalance, mitochondrial dysfunction and oxidative stress in both human and animal cells. However, the mechanisms which hypoxia causes mitochondrial dysfunction and energy metabolism misbalance still remain unclear. In this study, we presented evidence that mitochondrial phosphatase Ptpmt1 is a hypoxia response molecule that regulates cell proliferation, survival and glucose metabolism in human erythroleukemia TF-1 cells. Exposure to hypoxia or DFO treatment results in upregulation of HIF1-α, HIF-2α and Ptpmt1. Only inhibition of HIF-2α by shRNA transduction reduces Ptpmt1 expression in TF-1 cells under hypoxia. Ptpmt1 inhibitor suppresses the growth and induces apoptosis of TF-1 cells. Furthermore, we demonstrated that Ptpmt1 inhibition reduces the Glut1 and Glut3 expression and decreases the glucose consumption in TF-1 cells. In additional, Ptpmt1 knockdown also results in the mitochondrial dysfunction determined by JC1 staining. These results delineate a key role for HIF-2α-induced Ptpmt1 upregulation in proliferation, survival and glucose metabolism of erythroleukemia cells. It is indicated that Ptpmt1 plays important roles in hypoxia-induced cell metabolism and mitochondrial dysfunction.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Glucose/metabolismo , Leucemia Eritroblástica Aguda/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Hipóxia Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo/genética , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 3/genética , Transportador de Glucose Tipo 3/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Leucemia Eritroblástica Aguda/patologia , PTEN Fosfo-Hidrolase/genética
17.
Biochem Biophys Res Commun ; 470(3): 670-677, 2016 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-26801559

RESUMO

MicroRNA-486 (miR-486) was first identified from human fetal liver cDNA library and validated as a regulator of hematopoiesis. Its roles in regulating the biological function of bone marrow-derived mesnechymal stem cells (BM-MSCs) under hypoxia have not been explored yet. In this study, we demonstrated that exposure to hypoxia upregulates miR-486 expression in BM-MSCs. Lentivirus-mediated overexpression of miR-486 resulted in increase of hepatocyte growth factor (HGF) and vascular endothelial growth factor(VEGF) in both mRNA and protein levels. MiR-486 expression also promotes proliferation and reduces apoptosis of BM-MSCs. Whereas MiR-486 knockdown downregulated the secretion of HGF and VEGF and induced apoptosis of BM-MSCs. Furthermore, PTEN-PI3K/AKT signaling was validated to be involved in changes of BM-MSC biological functions regulated by miR-486. These results suggested that MiR-486 mediated the hypoxia-induced angiogenic activity and promoted the proliferation and survival of BM-MSCs through regulating PTEN-PI3K/AKT signaling. These findings might provide a novel understanding of effective therapeutic strategy for hypoxic-ischemic diseases.


Assuntos
Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , MicroRNAs/metabolismo , Neovascularização Fisiológica/fisiologia , Proteína Oncogênica v-akt/metabolismo , Oxigênio/metabolismo , Proteínas Angiogênicas/metabolismo , Diferenciação Celular/fisiologia , Hipóxia Celular/fisiologia , Movimento Celular/fisiologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Regulação da Expressão Gênica/fisiologia , Humanos , Transdução de Sinais/fisiologia
18.
Huan Jing Ke Xue ; 36(2): 379-87, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-26031060

RESUMO

The impact of transport pathways on aerosol properties at Shangdianzi (SDZ) background station was analyzed using the back trajectory analysis method with the observation of PM2.5 concentration and aerosol scattering coefficients ( σ(sp)) during 2005-2010. The results showed that the pollutant level at SDZ was influenced by both the direction and motion state of air masses. The southerly transport pathways of air masses had higher PM2.5 concentration and σ(sp) than those of northerly pathways. The air masses with lower moving speed and altitude generally corresponded to higher PM2.5 concentration and σ(sp). Air masses originated from the North China Plain in spring, summer and autumn, and air masses from the north of North China region in winter had a significant contribution to PM2.5 concentration and σ (sp) at SDZ. Dust aerosol appeared frequently in spring, and the mean scattering efficiency (α(sp)) was 0.78 m2 x g(-1). The mean α(sp) of anthropogenic aerosol of four seasons was 4.00 m2 x g(-1) with the highest value in winter and the lowest in spring. The west-northwest, southerly pathways, and the northerly pathways with low moving speed in spring, summer and autumn correspond to higher α(sp) ( > 4.0 m2 x g(-1)). This indicated that these pathways were affected by the emissions form human activities. However, the α(sp) in winter kept at a high level among all pathways, which suggested that the emission effect was relatively uniform in surrounding regions in winter. The other northerly pathways in spring, summer and autumn were affected by anthropogenic pollutants mixed with dust.


Assuntos
Aerossóis/análise , Movimentos do Ar , Poluentes Atmosféricos/análise , Monitoramento Ambiental , China , Poeira , Estações do Ano
19.
Int J Ophthalmol ; 8(2): 385-94, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25938061

RESUMO

AIM: To investigate the association between SERPING1 rs2511989 (G>A) polymorphism and age-related macular degeneration (AMD). METHODS: A number of electronic databases (up to July 15, 2014) were searched independently by two investigators. A Meta-analysis was performed on the association between SERPING1 rs2511989 polymorphism and AMD. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. RESULTS: Eight studies with 16 cohorts consisting of 9163 cases and 6813 controls were included in this Meta-analysis. There was no significant association between rs2511989 polymorphism and AMD under all genetic models in overall estimates (A vs G: OR= 0.938, 95%CI =0.858-1.025; AA vs GG:OR =0.871, 95%CI =0.719-1.056; AG vs GG: OR =0.944, 95%CI =0.845-1.054; AA+AG vs GG: OR =0.927, 95% CI =0.823-1.044; AA vs AG+GG: OR =0.890, 95%CI =0.780-1.034). Cumulative Meta-analyses also showed a trend of no association between rs2511989 polymorphism and AMD as information accumulated by year. Subgroup analysis and Meta-regression analysis indicated that age-matching status was the main source of heterogeneity. Sensitivity analysis found the results in overall comparisons and subgroup comparisons of white subjects under the allele model were found to have significantly statistical differences after studies deviating from Hardy-Weinberg equilibrium (HWE) were excluded (overall: OR=0.918, 95%CI = 0.844-0.999, P =0.049; whites: OR =0.901, 95%CI = 0.817-0.994, P =0.038). However, the results were not sufficiently robust for further sensitivity analysis and statistical differences disappeared on applying Bonferroni correction (with a significance level set at 0.05/25). CONCLUSION: This Meta-analysis indicates that SERPING1 rs2511989 polymorphism and AMD tend to have no association with each other. Age matching status is a big confounding factor, and more studies with subtle designs are warranted in future.

20.
Yao Xue Xue Bao ; 50(9): 1156-60, 2015 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-26757553

RESUMO

Seven guaiane-type sesquiterpenoids, a new compound 6-formyl-5-isopropyl-3-hydroxymethyl-7-methyl-1H-indene (1), a new natural product 5-isopropyl-3, 7-dimethyl-1H-indene-1-one (2), along with five known compounds: guaiazulene (3), 4-formyl-7-isopropyl-10-methylazulene (4), sesquiterpene ketolactone (5), alismoxide (6) and guaia-1 (5), 6-diene (7), were isolated from gorgonian Muriceides collaris collected in South China Sea. Their structures were elucidated on the basis of extensive spectroscopic analysis [MS, IR, 1H NMR, 13C NMR (DEPT), HMQC, HMBC, NOESY] and by comparison of the spectral data with those of the literatures.


Assuntos
Antozoários/química , Sesquiterpenos/química , Animais , Azulenos , China , Sesquiterpenos/isolamento & purificação , Sesquiterpenos de Guaiano
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