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1.
Nanoscale ; 11(24): 11789-11807, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31184642

RESUMO

Autophagy may represent a common cellular response to nanomaterials. In the present study, it was demonstrated that zinc oxide nanoparticle (ZON)-elicited autophagy contributes to tumor cell killing by accelerating the intracellular dissolution of ZONs and reactive oxygen species (ROS) generation. In particular, ZONs could promote Atg5-regulated autophagy flux without the impairment of autophagosome-lysosome fusion, which is responsible for ZON-elicited cell death in cancer cells. On the other hand, a further study revealed that a significant free zinc ion release in lysosomal acid compartments and sequential ROS generation in cells treated with ZONs were also associated with tumor cytotoxicity. Intriguingly, the colocalization between FITC-labeled ZONs and autophagic vacuoles indicates that the intracellular fate of ZONs is associated with autophagy. Moreover, the chemical or genetic inhibition of autophagy significantly reduced the level of intracellular zinc ion release and ROS generation separately, demonstrating that ZON-induced autophagy contributed toward cancer cell death by accelerating zinc ion release and sequentially increasing intracellular ROS generation. The modulation of autophagy holds great promise for improving the efficacy of tumor chemotherapy. Herein, ZONs were verified to enhance chemotherapy in both normal and drug-resistant cancer cells via synergistic autophagy elicitation. Further, this elicitation resulted in tremendous zinc ion release and ROS generation, which accounted for enhancing the tumor chemotherapy and overcoming drug resistance. No obvious changes in the expression level of P-gp proteins or the amount of doxorubicin uptake induced by ZONs in MCF-7/ADR cells also indicated that the increased zinc ion release and ROS generation via synergistic autophagy induction were responsible for overcoming the drug resistance. Finally, in vivo experiments involving animal models of 4T1 tumor cells revealed that the antitumor therapeutic effect of a combinatory administration obviously outperformed those of ZONs or free doxorubicin treatment alone at the same dose, which could be attenuated by the autophagy inhibitor wortmannin or ion-chelating agent EDTA. Taken together, our results reveal the mechanism wherein the autophagy induction by ZONs potentiates cancer cell death and a novel biological application for ZONs in adjunct chemotherapy in which autophagy reinforces zinc ion release and ROS generation.


Assuntos
Antineoplásicos , Doxorrubicina , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanopartículas , Neoplasias Experimentais/tratamento farmacológico , Óxido de Zinco , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Feminino , Células HeLa , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Espécies Reativas de Oxigênio/metabolismo , Óxido de Zinco/química , Óxido de Zinco/farmacologia
2.
Am J Transl Res ; 10(5): 1273-1283, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29887944

RESUMO

The goal of this study was to assess the ability of quercetin (Qu) to protect against myocardial ischemia-reperfusion injury. Cardiac injury was assessed in the context of global ischemia of isolated hearts, coronary artery ligated rats, and H9C2 cells. Qu was shown to significantly inhibit inflammatory cytokine production in coronary artery occlusion-induced rats, isolated hearts, and H9C2 cells. Electrocardiographic analysis revealed a restoration of the ST segment to normal levels following treatment of Qu. Triphenyltetrazolium chloride (TTC) staining and pathological analysis showed that Qu could significantly alleviate myocardial injury in vivo. Furthermore, ex vivo analyses showed improved recovery of heart function in response to Qu, characterized by enhanced myocardial contractility and coronary flow in isolated hearts. From a mechanistic standpoint, these effects appeared to be mediated through the HMGB1-related pathway, with expression of downstream targets significantly downregulated in rats, isolated hearts, and H9C2 cells following Qu treatment. Taken together, these data demonstrate the protective effects of Qu against myocardial injury via inhibition of the HMGB1 pathway in a myocardial ischemia-reperfusion injury (I/R) model.

3.
Arch Microbiol ; 200(3): 423-429, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29184975

RESUMO

A novel Gram-staining positive, moderately halophilic, endospore-forming, motile, rod-shaped and strictly aerobic strain, designated YIM 93565T, was isolated from a salt lake in Xinjiang province of China and subjected to a polyphasic taxonomic study. Strain YIM 93565T grew in the range of pH 6.0-9.0 (optimum pH 7.0), 10-45 °C (optimum 35-40 °C) and at salinities of 2-24% (w/v) NaCl (optimum 7-10%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain YIM 93565T clustered with members of the genera Gracilibacillus and form a clade with Gracilibacillus bigeumensis KCTC 13130T (95.6% similarity) and Gracilibacillus halophilus DSM 17856T (94.9%), which was well separated from others. The DNA G + C content of this novel strain was 36.8 mol%. The major fatty acids were anteiso-C15:0, iso-C15:0, C16:0 and anteiso-C17:0 and its polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, one unidentified glycolipid and two unidentified phospholipids. The predominant menaquinone was MK-7. The cell-wall peptidoglycan was based on meso-diaminopimelic acid. Based on the results of phylogenetic, physiological and chemotaxonomic comparative analyses, the isolate is assigned to a novel species of the genus Gracilibacillus, for which the name Gracilibacillus eburneus sp. nov. is proposed, with the type strain YIM 93565T (= DSM 23710T = CCTCC AB 2013249T).


Assuntos
Bacillaceae/classificação , Bacillaceae/genética , Bacillaceae/isolamento & purificação , Composição de Bases , Parede Celular/química , China , DNA Bacteriano/genética , Ácido Diaminopimélico/análise , Ácido Diaminopimélico/química , Ácidos Graxos/análise , Ácidos Graxos/química , Lagos/microbiologia , Tipagem Molecular , Fosfolipídeos/análise , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Tolerância ao Sal , Microbiologia da Água
4.
Cancer Cell Int ; 17: 9, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28070171

RESUMO

BACKGROUND: Casticin, the flavonoid extracted from Vitex rotundifolia L, exerts various biological effects, including anti-inflammatory and anti-cancer activity. The aim of this study is to investigate the effects and mechanisms of casticin in human gallbladder cancer cells. METHODS: Human NOZ and SGC996 cells were used to perform the experiments. CCK-8 assay and colony formation assay were performed to evaluate cell viability. Cell cycle analyses and annexin V/PI staining assay for apoptosis were measured using flow cytometry. Western blot analysis was used to evaluate the changes in protein expression, and the effect of casticin treatment in vivo was experimented with xenografted tumors. RESULTS: In this study, we found that casticin significantly inhibited gallbladder cancer cell proliferation in a dose- and time-dependent manner. Casticin also induced G0/G1 arrest and mitochondrial-related apoptosis by upregulating Bax, cleaved caspase-3, cleaved caspase-9 and cleaved poly ADP-ribose polymerase expression, and by downregulating Bcl-2 expression. Moreover, casticin induced cycle arrest and apoptosis by upregulating p27 and downregulating cyclinD1/cyclin-dependent kinase4 and phosphorylated protein kinase B. In vivo, casticin inhibited tumor growth. CONCLUSION: Casticin induces G0/G1 arrest and apoptosis in gallbladder cancer, suggesting that casticin might represent a novel and effective agent against gallbladder cancer.

5.
Small ; 13(7)2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27925395

RESUMO

The diverse biological effects of nanomaterials form the basis for their applications in biomedicine but also cause safety issues. Induction of autophagy is a cellular response after nanoparticles exposure. It may be beneficial in some circumstances, yet autophagy-mediated toxicity raises an alarming concern. Previously, it has been reported that upconversion nanoparticles (UCNs) elicit liver damage, with autophagy contributing most of this toxicity. However, the detailed mechanism is unclear. This study reveals persistent presence of enlarged autolysosomes in hepatocytes after exposure to UCNs and SiO2 nanoparticles both in vitro and in vivo. This phenomenon is due to anomaly in the autophagy termination process named autophagic lysosome reformation (ALR). Phosphatidylinositol 4-phosphate (PI(4)P) relocates onto autolysosome membrane, which is a key event of ALR. PI(4)P is then converted into phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 ) by phosphatidylinositol-4-phosphate 5-kinase. Clathrin is subsequently recruited by PI(4,5)P2 and leads to tubule budding of ALR. Yet it is observed that PI(4)P cannot be converted in nanoparticle-treated hepatocytes cells. Exogenous supplement of PI(4,5)P2 suppresses the enlarged autolysosomes in vitro. Abolishment of these enlarged autolysosomes by autophagy inhibitor relieves the hepatotoxicity of UCNs in vivo. The results provide evidence for disrupted ALR in nanoparticle-treated hepatocytes, suggesting that the termination of nanoparticle-induced autophagy is of equal importance as the initiation.


Assuntos
Autofagia , Hepatócitos/citologia , Hepatócitos/metabolismo , Lisossomos/metabolismo , Nanopartículas/química , Animais , Autofagia/efeitos dos fármacos , Células Cultivadas , Hepatócitos/efeitos dos fármacos , Fígado/metabolismo , Lisossomos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Nanopartículas/toxicidade , Fosfatos de Fosfatidilinositol/metabolismo
6.
Opt Express ; 24(25): 28519-28528, 2016 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-27958496

RESUMO

We realized a polarization-independent split-ratio-tunable optical beam splitter supporting two input and output ports through a stable interferometer. By adjusting the angle of a half-wave plate in the interferometer, we can tune the beam splitter reflectivities for both input ports from 0 to 1, regardless of the input light polarization. High-fidelity polarization-preserving transmission from input to output ports was verified by complete quantum process tomography. Nearly optimal interference effects at the beam splitter with various split ratios were observed by two-photon Hong-Ou-Mandel interference for different input polarization states. Such a beam splitter could find a variety of applications in classical and quantum optical technologies.

7.
Trials ; 17(1): 512, 2016 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-27769284

RESUMO

BACKGROUND: Although Traditional Chinese Medicine (TCM) has been widely used in clinical settings, a major challenge that remains in TCM is to evaluate its efficacy scientifically. This randomized controlled trial aims to evaluate the efficacy and safety of berberine in the treatment of patients with polycystic ovary syndrome. In order to improve the transparency and research quality of this clinical trial, we prepared this statistical analysis plan (SAP). METHODS: The trial design, primary and secondary outcomes, and safety outcomes were declared to reduce selection biases in data analysis and result reporting. We specified detailed methods for data management and statistical analyses. Statistics in corresponding tables, listings, and graphs were outlined. DISCUSSION: The SAP provided more detailed information than trial protocol on data management and statistical analysis methods. Any post hoc analyses could be identified via referring to this SAP, and the possible selection bias and performance bias will be reduced in the trial. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov, NCT01138930 , registered on 7 June 2010.


Assuntos
Berberina/uso terapêutico , Interpretação Estatística de Dados , Medicamentos de Ervas Chinesas/uso terapêutico , Resistência à Insulina , Síndrome do Ovário Policístico/tratamento farmacológico , Adolescente , Adulto , Berberina/efeitos adversos , Protocolos Clínicos , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Modelos Estatísticos , Síndrome do Ovário Policístico/diagnóstico , Projetos de Pesquisa , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Small ; 12(41): 5759-5768, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27593892

RESUMO

Many nanomaterials are reported to disrupt lysosomal function and homeostasis, but how cells sense and then respond to nanomaterial-elicited lysosome stress is poorly understood. Nucleus translocation of transcription factor EB (TFEB) plays critical roles in lysosome biogenesis following lysosome stress induced by starvation. The authors previously reported massive cellular vacuolization, along with autophagy induction, in cells treated with rare earth oxide (REO) nanoparticles. Here, the authors identify these giant cellular vacuoles as abnormally enlarged and alkalinized endo/lysosomes whose formation is dependent on macropinocytosis. This vacuolization causes deactivation of mammalian target of rapamycin (mTOR), a TFEB-interacting kinase that resides on the lysosome membrane. Subsequently, TFEB is dephosphorylated at serine 142 and translocated into cell nucleus. This nucleus translocation of TFEB is observed only in vacuolated cells and it is critical for maintaining lysosome homeostasis after REO nanoparticle treatment, as knock-down of TFEB gene significantly compromises lysosome function and enhances cell death in nanoparticle-treated cells. Our results reveal that cellular vacuolization, which is commonly observed in cells treated with REOs and other nanomaterials, represents a condition of profound lysosome stress, and cells sense and respond to this stress by facilitating mTOR-dependent TFEB nucleus translocation in an effort to restore lysosome homeostasis.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Núcleo Celular/metabolismo , Lisossomos/metabolismo , Metais Terras Raras/química , Nanopartículas/química , Óxidos/química , Serina-Treonina Quinases TOR/metabolismo , Vacúolos/metabolismo , Álcalis/química , Sobrevivência Celular , Endossomos/metabolismo , Células HeLa , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Modelos Biológicos , Pinocitose , Transporte Proteico
9.
Biomaterials ; 103: 44-55, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27376558

RESUMO

Cancer stem cells (CSCs) have garnered increasing attention over the past decade, as they are believed to play a crucial role in tumor initiation, progression and metastasis, relapse and drug resistance. Therapeutic strategies which simultaneously exterminate both bulk tumor cells and the rare CSC subpopulation may produce striking response and result in long-term tumor remission. Accumulating evidence provides insight into the function of autophagy in maintenance, plasticity and survival of CSCs. The role of autophagy in the susceptibility of breast CSCs to chemotherapeutics was investigated in the present work, reduced 'stemness' and increased susceptibility to chemotherapy drugs (doxorubicin, DOX and docetaxel, DTXL) were observed after chloroquine (CQ)-mediated autophagy inhibition in sorted ALDH(hi) cells of breast cancer cell line MDA-MB-231. We further proved that nanoparticle-mediated autophagy inhibition promoted the efficacy of chemotherapeutics against ALDH(hi) MDA-MB-231 cells in vitro. Administration of drug delivery systems significantly prolonged the circulation half-life and augmented enrichment of two different drugs in tumor tissues and ALDH(hi) cells. More importantly, compared with single treatment, the combined delivery systems NPCQ/NPDOX and NPCQ/DOX (NPCQ/NPDTXL and NPCQ/DTXL) showed most effective and persistent tumor growth inhibitory effect by eliminating bulk tumor cells as well as CSCs (p < 0.01) in an MDA-MB-231 orthotopic tumor murine model. Therefore, our research provides new insights into the nanoparticle-facilitated combination of autophagy inhibition and chemotherapy for effective therapy of breast cancer.


Assuntos
Antineoplásicos/administração & dosagem , Autofagia/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Nanopartículas/administração & dosagem , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Animais , Linhagem Celular Tumoral , Quimioterapia Combinada/métodos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos ICR , Camundongos SCID , Resultado do Tratamento
10.
BMC Complement Altern Med ; 16: 201, 2016 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-27402016

RESUMO

BACKGROUND: Qili Qiangxin capsule is a standardized Chinese herbal treatment that is commonly used in China for heart failure (HF) alongside conventional medical care. In 2014, Chinese guidelines for the treatment of chronic HF highlighted Qili Qiangxin capsules as a potentially effective medicine. However, there is at present no high quality review to evaluate the effects and safety of Qili Qiangxin for patients with HF. METHODS: We conducted a systematic review and meta-analysis and followed methods described in our registered protocol [PROSPERO registration: CRD42013006106]. We searched 6 electronic databases to identify randomized clinical trials (RCTs) irrespective of blinding or placebo control of Qili Qiangxin used as an adjuvant treatment for HF. RESULTS: We included a total of 129 RCTs published between 2005 and 2015, involving 11,547 patients, aged 18 to 98 years. Meta-analysis showed no significant difference between Qili Qiangxin plus conventional treatment and conventional treatment alone for mortality (RR 0.53, 95 % CI 0.27 to 1.07). However, compared with conventional treatment alone, Qili Qiangxin plus conventional treatment demonstrated a significant reduction in major cardiovascular events (RR 0.46, 95 % CI 0.34 to 0.64) and a significant reduction in re-hospitalization rate due to HF (RR 0.49, 95 % CI 0.38 to 0.64). Qili Qiangxin also showed significant improvement in cardiac function measured by the New York Heart Association scale (RR 1.38, 95 % CI 1.29 to 1.48) and quality of life as measured by Minnesota Living with Heart Failure Questionnaire (MD -8.48 scores, 95 % CI -9.56 to -7.39). There were no reports of serious adverse events relating to Qili Qiangxin administration. The majority of included trials were of poor methodological quality. CONCLUSIONS: When compared with conventional treatment alone, Qili Qiangxin combined with conventional treatment demonstrated a significant effect in reducing cardiovascular events and re-hospitalization rate, though not in mortality. It appeared to significantly improve quality of life in patients with HF and data from RCTs suggested that Qili Qiangxin is likely safe. This data was drawn from low quality trials and the results of this review must therefore be interpreted with caution. Further research is warranted, ideally involving large, prospective, rigorous trials, in order to confirm these findings.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
12.
Biomaterials ; 73: 160-74, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26409001

RESUMO

Accelerating the clearance of intracellular protein aggregates through elevation of autophagy represents a viable approach for the treatment of neurodegenerative diseases. In our earlier report, we have demonstrated the enhanced degradation of mutant huntingtin protein aggregates through autophagy process induced by europium hydroxide nanorods [EHNs: Eu(III)(OH)3], but the underlying molecular mechanism of EHNs mediated autophagy was unclear. The present report reveals that EHNs induced autophagy does not follow the classical AKT-mTOR and AMPK signaling pathways. The inhibition of ERK1/2 phosphorylation using the specific MEK inhibitor U0126 partially abrogates the autophagy as well as the clearance of mutant huntingtin protein aggregates mediated by EHNs suggesting that nanorods stimulate the activation of MEK/ERK1/2 signaling pathway during autophagy process. In contrast, another mTOR-independent autophagy inducer trehalose has been found to induce autophagy without activating ERK1/2 signaling pathway. Interestingly, the combined treatment of EHNs and trehalose leads to more degradation of mutant huntingtin protein aggregates than that obtained with single treatment of either nanorods or trehalose. Our results demonstrate the rational that further enhanced clearance of intracellular protein aggregates, needed for diverse neurodegenerative diseases, may be achieved through the combined treatment of two or more autophagy inducers, which stimulate autophagy through different signaling pathways.


Assuntos
Európio/química , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hidróxidos/química , Nanotubos/química , Proteínas do Tecido Nervoso/química , Trealose/química , Adenina/análogos & derivados , Adenina/química , Androstadienos/química , Animais , Autofagia , Proteína 5 Relacionada à Autofagia , Butadienos/química , Linhagem Celular Tumoral , Sobrevivência Celular , Cloroquina/química , Proteínas de Fluorescência Verde/metabolismo , Células HeLa , Humanos , Proteína Huntingtina , Lisossomos/metabolismo , Macrolídeos/química , Camundongos , Microscopia de Fluorescência , Proteínas Associadas aos Microtúbulos/metabolismo , Doenças Neurodegenerativas/embriologia , Doenças Neurodegenerativas/metabolismo , Nitrilos/química , Fagossomos/química , Fosforilação , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Wortmanina
13.
Antonie Van Leeuwenhoek ; 108(3): 611-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26122886

RESUMO

A Gram-positive, facultative anaerobe microorganism, designated YIM 93067(T), was isolated from a salt lake in Xinjiang Province of China and subjected to a polyphasic taxonomic study. Strain YIM 93067(T) grew at 5-40 °C, 0-8.0 % (w/v) NaCl and pH 7.0-9.0. Phylogenetic analyses based on 16S rRNA gene sequences revealed that the organism belongs to the genus Jonesia and exhibited a sequence similarity of 98.8 % to the closely related type strain Jonesia quinghaiensis DSM 15701(T). The predominant menaquinone was MK-9 and the major fatty acids were anteiso-C15:0 and C16:0. The polar lipids consisted of diphosphatidylglycerol, glycolipid, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside and one unidentified phospholipid. The G+C content of the genomic DNA was 57.4 mol%. Based on the results of phylogenetic, physiological and chemotaxonomic comparative analyses, the isolate is assigned to a novel species of the genus Jonesia, for which the name Jonesia luteola sp. nov. is proposed, with the type strain YIM 93067(T) (=DSM 21367(T) = CCTCC AB 2014350(T)).


Assuntos
Actinobacteria/classificação , Actinobacteria/isolamento & purificação , Actinobacteria/genética , Actinobacteria/fisiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , Análise por Conglomerados , Citosol/química , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Glicolipídeos/análise , Microscopia Eletrônica de Transmissão , Dados de Sequência Molecular , Fosfolipídeos/análise , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Cloreto de Sódio/metabolismo , Temperatura Ambiente , Vitamina K 2/análise
14.
Antonie Van Leeuwenhoek ; 108(3): 627-32, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26122888

RESUMO

A Gram-negative, pink-coloured, rod-shaped, motile bacterium, designated YIM 93097(T), was isolated from the desert soil collected from Xinjiang province of China. Strain YIM 93097(T) was found to grow at 20-45 °C (optimum 28-37 °C), pH 5.0-7.0 (optimum pH 7.0) and 0-8 % (w/v) NaCl (optimum 1 %, w/v). Based on 16S rRNA gene sequence similarity studies, it belongs to the genus Skermanella. The 16S rRNA gene sequence similarity was identified to be 98.7 % to Skermanella xinjiangensis CCTCC AB 207153(T) while the DNA-DNA hybridization value was found to be only 48.1 %. The predominant isoprenoid quinone was determined to be Q-10. The major fatty acids were identified to be C16:0, C18:1 ω7c and summed feature 4 (consisting of C17:1 anteiso B/iso I). The major polar lipids were identified as phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, two unidentified phospholipids and one unidentified aminolipid. The DNA G+C content was found to be 67.2 mol %. The analysis of the genotypic and phenotypic data indicated that strain YIM 93097(T) belongs to a novel species of the genus Skermanella, for which the name Skermanella rubra sp. nov. is proposed. The type strain is YIM 93097(T) (=DSM 21389(T)=CCTCC AB 2015161(T)).


Assuntos
Rhodospirillaceae/classificação , Rhodospirillaceae/isolamento & purificação , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , China , Análise por Conglomerados , Citosol/química , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Clima Desértico , Ácidos Graxos/análise , Concentração de Íons de Hidrogênio , Locomoção , Hibridização de Ácido Nucleico , Fosfolipídeos/análise , Filogenia , Pigmentos Biológicos/metabolismo , Quinonas/análise , RNA Ribossômico 16S/genética , Rhodospirillaceae/genética , Rhodospirillaceae/fisiologia , Análise de Sequência de DNA , Cloreto de Sódio/metabolismo , Temperatura Ambiente
15.
Mol Cell Biochem ; 406(1-2): 131-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25971370

RESUMO

To investigate the involvement of transforming growth factor-ß1 (TGF-ß1) and tissue inhibitor of metalloproteinase 4 (TIMP-4) in influencing the severity of atrial fibrosis in rheumatic heart disease (RHD) patients with atrial fibrillation (AF). The degree of myocardial fibrosis was evaluated using Masson staining. The expression levels of TGF-ß1, TIMP-4, matrix metalloproteinase-2 (MMP-2), type I collagen, and type III collagen were estimated by Western blot analysis. Additionally, TGF-ß1 and TIMP-4 mRNA levels were quantified by qRT-PCR. The effect of TGF-ß1 stimulation on TIMP-4 expression was assessed by in vitro stimulation of freshly isolated human atrial fibroblasts with recombinant human TGF-ß1, followed by Western blot analysis to detect changes in TIMP-4 levels. Masson stain revealed that the left atrial diameter and collagen volume fraction were obviously increased in AF patients, compared to sinus rhythm (SR) controls (both P < 0.05). Western blot analysis showed significantly elevated levels of the AF markers MMP-2, type I collagen, and type III collagen in the AF group, in comparison to the SR controls (all P < 0.05). In the AF group, TGF-ß1 expression was relatively higher, while TIMP-4 expression was apparently lower than the SR group (all P < 0.05). TIMP-4 expression level showed a negative association with TGF-ß1 expression level (r = -0.98, P < 0.01) and TGF-ß1 stimulation of atrial fibroblasts led to a sharp decrease in TIMP-4 protein level. Increased TGF-ß1 expression and decreased TIMP-4 expression correlated with atrial fibrosis and ECM changes in the atria of RHD patients with AF. Notably, TGF-ß1 suppressed TIMP-4 expression, suggesting that selective TGF-ß1 inhibitors may be useful therapeutic agents.


Assuntos
Fibrilação Atrial/metabolismo , Átrios do Coração/patologia , Cardiopatia Reumática/metabolismo , Inibidores Teciduais de Metaloproteinases/fisiologia , Fator de Crescimento Transformador beta1/fisiologia , Adulto , Idoso , Fibrilação Atrial/etiologia , Feminino , Fibrose , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Cardiopatia Reumática/complicações
16.
Exp Mol Pathol ; 98(3): 486-90, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25796343

RESUMO

BACKGROUND: Transient receptor potential (TRP) family plays important roles in cardiovascular system. We investigated the relationship between transient receptor potential channel subfamily M6 (TRPM6) and atrial fibrosis in rheumatic heart disease patients with atrial fibrillation (AF). METHODS: The right atrial tissue samples were obtained from 64 patients with rheumatic heart diseases who underwent heart valve replacement surgery, and composed of 34 sinus rhythm (SR) patients and 30 AF patients. Hematoxylin and Eosin (HE) staining was used to observe cross-sectional area (CSA) of myocardial cell. Masson staining and measurement of connective tissue growth factor (CTGF), transforming growth factor beta 1 (TGF-ß 1), and collagen type I/III (Collagen I/III) were performed to determine atrial fibrosis. The mRNA and protein levels of TRPM6 were detected by real-time quantitative polymerase chain reaction (RT-PCR) and western blotting, respectively. RESULTS: Marked increases were observed in CSA of myocardial cell and myocardial collagen volume fraction in AF group compared with the SR group (all P<0.05). The mRNA levels of myocardial fibrosis markers (CTGF, TGF-beta 1, Collagen I/III) in AF group increased significantly compared to the SR group (all P<0.05). TRPM6 mRNA and protein levels in AF group were elevated markedly in comparison with SR group (P<0.01). CONCLUSION: These findings revealed that increased TRPM6 mRNA and protein levels may contribute to atrial fibrosis, and suggested that TRPM6 might be involved in AF development by promoting fibrogenesis.


Assuntos
Arritmia Sinusal/metabolismo , Fibrilação Atrial/metabolismo , Cardiopatia Reumática/metabolismo , Canais de Cátion TRPM/genética , Adulto , Idoso , Arritmia Sinusal/genética , Fibrilação Atrial/genética , Estudos de Casos e Controles , Colágeno/genética , Colágeno/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Feminino , Fibrose/genética , Fibrose/metabolismo , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Cardiopatia Reumática/genética , Canais de Cátion TRPM/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
17.
Int J Syst Evol Microbiol ; 64(Pt 7): 2210-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24699066

RESUMO

A Gram-negative, moderately halophilic, strictly aerobic strain, designated YIM 95345(T), was isolated from a soil sample of a hypersaline mine in Yunnan province, PR China, and subjected to a polyphasic taxonomic study. Strain YIM 95345(T) grew at 15-45 °C (optimum 30-35 °C), 3.0-23.0% (w/v) NaCl (optimum 10.0-11.0%, w/v) and pH 6.0-9.0 (optimum pH 7.0-8.0). Phylogenetic analyses based on 16S rRNA gene sequences revealed that the organism belongs to the genus Aquisalimonas and exhibited sequence similarity of 96.6% to the sole type strain Aquisalimonas asiatica CG12(T). The predominant isoprenoid quinone was Q-8 and the major fatty acids were C16 : 0, C19 : 0 cyclo ω8c and C18 : 1ω7c. The polar lipids consisted of diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, three aminolipids and three unidentified phospholipids. The G+C content of the genomic DNA was 59.4 mol%. Based on the results of our comparative phylogenetic, chemotaxonomic and physiological analyses, the new isolate is assigned to a novel species of the genus Aquisalimonas, for which the name Aquisalimonas halophila sp. nov. is proposed, with the type strain YIM 95345(T) ( = DSM 25902(T) = CCTCC AB 2012043(T)).


Assuntos
Gammaproteobacteria/classificação , Mineração , Filogenia , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Gammaproteobacteria/genética , Gammaproteobacteria/isolamento & purificação , Dados de Sequência Molecular , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Salinidade , Análise de Sequência de DNA , Ubiquinona/química
18.
Biomaterials ; 35(3): 899-907, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24169003

RESUMO

Autophagy is one of the well-known pathways to accelerate the clearance of protein aggregates, which contributes to the therapy of neurodegenerative diseases. Although there are numerous reports that demonstrate the induction of autophagy with small molecules including rapamycin, trehalose and lithium, however, there are few reports mentioning the clearance of aggregate-prone proteins through autophagy induction by nanoparticles. In the present article, we have demonstrated that europium hydroxide [Eu(III)(OH)3] nanorods can reduce huntingtin protein aggregation (EGFP-tagged huntingtin protein with 74 polyQ repeats), responsible for neurodegenerative diseases. Again, we have found that these nanorods induce authentic autophagy flux in different cell lines (Neuro 2a, PC12 and HeLa cells) through the expression of higher levels of characteristic autophagy marker protein LC3-II and degradation of selective autophagy substrate/cargo receptor p62/SQSTM1. Furthermore, depression of protein aggregation clearance through the autophagy blockade has also been observed by using specific inhibitors (wortmannin and chloroquine), indicating that autophagy is involved in the degradation of huntingtin protein aggregation. Since [Eu(III)(OH)3] nanorods can enhance the degradation of huntingtin protein aggregation via autophagy induction, we strongly believe that these nanorods would be useful for the development of therapeutic treatment strategies for various neurodegenerative diseases in near future using nanomedicine approach.


Assuntos
Autofagia/efeitos dos fármacos , Európio/farmacologia , Hidróxidos/farmacologia , Nanotubos/química , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Linhagem Celular , Európio/química , Humanos , Proteína Huntingtina , Hidróxidos/química , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutação , Nanotubos/ultraestrutura
19.
Eur J Med Chem ; 62: 405-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23385091

RESUMO

Peptide chaperon TD1 was discovered to facilitate several proteins' transdermal delivery via topical co-administration. To design a practical, safe system for advanced transdermal peptide, a novel method was carried out. Human epidermal growth factor (hEGF) was selected as the model biological agent and a fusion protein: TD1-hEGF was designed. Study showed that TD1-hEGF not only had the similar bioactivity with native hEGF, but also possessed considerable higher transdermal ability than hEGF and a co-administration of TD1 and hEGF. These results provided convincing evidence for the advantages of TD1-hEGF in cosmetic and medical applications. Moreover, the fusion pattern between the cargoes and TD1 offered a new approach to facilitate other hydrophilic drugs' transdermal delivery for therapeutic application.


Assuntos
Sistemas de Liberação de Medicamentos , Fator de Crescimento Epidérmico/química , Chaperonas Moleculares/química , Oligopeptídeos/química , Pele/metabolismo , Administração Cutânea , Animais , Células 3T3 BALB , Proliferação de Células , Células Cultivadas , Fator de Crescimento Epidérmico/administração & dosagem , Fator de Crescimento Epidérmico/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Chaperonas Moleculares/administração & dosagem , Chaperonas Moleculares/metabolismo , Oligopeptídeos/administração & dosagem , Oligopeptídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Absorção Cutânea
20.
Antonie Van Leeuwenhoek ; 103(1): 207-15, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22941247

RESUMO

A Gram-positive, moderately halotolerant, rod-shaped bacterium, designated YIM 94025(T), was isolated from a soil sample from a salt lake in Xinjiang province, north-west China. Strain YIM 94025(T) was observed to grow at 25-45 °C (optimum 37 °C), 0-22 % NaCl (optimum 2-10 %) and pH 6.0-9.0 (optimum pH 8.0). Phylogenetic analyses based on 16S rRNA gene sequences revealed that the organism belongs to the genus Tenuibacillus and exhibited sequence similarity of 98.0 % to the closest type strain, Tenuibacillus multivorans AS 1.3442(T). The predominant menaquinone was found to be MK-7; the cell-wall peptidoglycan diamino acid was meso-diaminopimelic acid; the polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, an unidentified phospholipid and an unknown lipid; and the major fatty acids were found to contain iso-C(15:0), anteiso-C(15:0) and iso-C(16:0). The chemotaxonomic characteristics of strain YIM 94025(T) are consistent with those of the genus Tenuibacillus. The level of DNA-DNA relatedness value between YIM 94025(T) and T. multivorans AS 1.3442(T) was 36.6 ± 4.5 %. The G+C content of the strain YIM 94025(T) was determined to be 38.5 %. Based on the comparative analysis of physiological, biochemical and chemotaxonomic data, as well as DNA-DNA hybridization results, the isolate is considered to represent a novel species of the genus Tenuibacillus, for which the name Tenuibacillus halotolerans sp. nov., is proposed, with the type strain of YIM 94025(T) (=CCTCC AB 2012860(T) = KCTC 33046(T)).


Assuntos
Bacillaceae/classificação , Bacillaceae/isolamento & purificação , Microbiologia do Solo , Bacillaceae/genética , Bacillaceae/fisiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácido Diaminopimélico/análise , Ácidos Graxos/análise , Concentração de Íons de Hidrogênio , Microscopia Eletrônica , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Fosfolipídeos/análise , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Cloreto de Sódio/metabolismo , Temperatura Ambiente , Vitamina K 2/análise
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