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1.
Int J Phytoremediation ; : 1-12, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38505937

RESUMO

The improvement of biosorption efficiency for selective dye removal in a multi-dye aqueous system has become an increasingly significant research topic. However, the competitive effects of coexisting dyes and the target dye in such systems remain uncertain due to complex interactions between adsorbent and coexisting dyes. Therefore, in this research, response surface methodology (RSM) model was effectively employed to investigate the competitive effects of allura red (AR) and malachite green (MG) on methylene blue (MB) removal in a ternary dye aqueous system using three different parts of rape straw powders. In the current design of RSM, the initial concentrations of AR and MG dyes ranging from 0 mg·L-1 to 500 mg·L-1 were considered as influencing factors, while the removal rates of MB on adsorbents at an initial concentration of 500 mg·L-1 were established as response values. The RSM models exhibited high correlation coefficients with adjusted R2 values of 0.9908 (pith core), 0.9870 (seedpods), and 0.9902 (shells), respectively, indicating a close fitted between predicted and actual values. The proposed models indicated that the perturbation effects of initial AR and MG concentrations were observed on the removal rates of MB by three types of rape straw powders in a ternary dye aqueous system, resulting in a decrease in MB removal rates, particularly at higher initial AR concentration due to stronger competitive effects compared to initial MG concentration. The structures of rape straw powders, including pith core, seedpods and shell, were analyzed using scanning eletron microscoe (SEM), energy dispersive spectroscopy (EDS), N2 physisorption isotherm, frourier transform infared spectroscopy (FTIR), Zeta potential classes and fluorescence spectrum before and after adsorption of MB in various dye aqueous systems. The characteristics of rape straw powders suggested that similar adsorption mechanisms, such as electrostatic attraction, pore diffusion, and group complex formation for MB, AR, and MG, respectively, occurred on the surfaces of adsorbents during their respective adsorption processes. This leads to significant competitive effects on the removal rates of MB in a ternary dye aqueous system, which are particularly influenced by initial AR concentrations as confirmed through fluorescence spectrum analysis.


Impact of AR and MG on MB removal was analyzed using simple methodologies.Competitive behaviors between AR, MG and MB were understood through RSM.Intense restrain effects on MB removal were revealed by AR concentration.

2.
Mol Carcinog ; 63(4): 629-646, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38226841

RESUMO

Circular RNAs (circRNAs) are key in regulating bladder cancer progression. This study explored the effects of circRNA TATA-box binding protein associated factor 15 (circTAF15) on bladder cancer progression. We enrolled 80 bladder cancer patients to examine the relationship between circTAF15 expression and clinical features. The function of circTAF15 on bladder cancer cell viability, proliferation, migration, invasion, and glycolysis was monitored by cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine experiment, Transwell experiment, and glycolysis analysis. Dual luciferase reporter gene assay, RNA pull-down assay, and RNA immunoprecipitation assay were used to verify the binding between circTAF15 and miR-502-5p or between miR-502-5p and high mobility group box 3 (HMGB3). circTAF15 effect on in vivo growth of bladder cancer was investigated by xenograft tumor experiment. Quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry were implemented to investigate the expression levels of genes. circTAF15 was upregulated in bladder cancer patients, associated with unfavorable outcomes. circTAF15 knockdown attenuated bladder cancer cell viability, proliferation, migration, invasion, epithelial-mesenchymal transition, and glycolysis. circTAF15 suppressed miR-502-5p expression, and miR-502-5p inhibited HMGB3 expression. Low miR-502-5p expression was associated with unfavorable outcomes in bladder cancer patients. miR-502-5p silencing and HMGB3 overexpression counteracted the inhibition of circTAF15 knockdown on the malignant phenotype of bladder cancer cells. circTAF15 knockdown attenuated the in vivo growth of bladder cancer cells. circTAF15 enhanced the progression of bladder cancer through upregulating HMGB3 via suppressing miR-502-5p. circTAF15 may be a novel target to treat bladder cancer in the future.


Assuntos
MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , RNA Circular/genética , Proteína de Ligação a TATA-Box , Oncogenes , Neoplasias da Bexiga Urinária/genética , MicroRNAs/genética , Proliferação de Células/genética , Linhagem Celular Tumoral
3.
J Appl Toxicol ; 44(2): 201-215, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37697829

RESUMO

Huobahua, namely, Tripterygium hypoglaucum (Levl.) Hutch, known as a traditional Chinese herbal medicine, especially its underground parts, has been widely developed into several Tripterygium agents for the treatment of rheumatoid arthritis and other autoimmune diseases. It has sparked wide public concern about its safety, such as multi-organ toxicity. However, the toxic characteristics and damage mechanism of Huobahuagen extract (HBHGE) remain unclear. In the present study, subchronic oral toxicity study of HBHGE (10.0 g crude drug/kg/day for 12 weeks) was performed in male rats. Hematological, serum biochemical, and histopathological parameters, urinalysis, and plasma metabolic profiling were assessed. The single-dose subchronic toxicity results related to HBHGE exhibited obvious toxicity to the testis and epididymis of male rats. Furthermore, plasma metabolomics analysis suggested that a series of metabolic disorders were induced by oral administration of HBHGE, mainly focusing on amino acid (glutamate, phenylalanine, and tryptophan) metabolisms, pyrimidine metabolism, glutathione metabolism, and steroid hormone biosynthesis. Moreover, it appeared that serum testosterone in male rats treated with HBHGE for 12 weeks, decreased significantly, and was susceptible to the toxic effects of HBHGE. Taken together, conventional pathology and plasma metabolomics for preliminarily exploring subchronic toxicity and underlying mechanism can provide useful information about the reduction of toxic risks from HBHGE and new insights into the development of detoxification preparations.


Assuntos
Medicina Tradicional Chinesa , Testículo , Ratos , Masculino , Animais , Metabolômica/métodos , Plasma , Tripterygium/química , Extratos Vegetais/toxicidade , Testes de Toxicidade Subcrônica
4.
Rev Sci Instrum ; 94(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38054833

RESUMO

In this paper, a new 0.15-2 GHz broadband phase shifter with 9-bit phase resolution is presented. This broadband digital adjustable phase shifter is implemented by utilizing the signal vector summation technology. The phase shifter consists of one 90° hybrid coupler, two digital attenuators, two 180° hybrid couplers, two microwave switches, and one combiner. By adjusting the attenuation value of the two digital attenuators, the device creates a minimum 0.7° stepped phase shift. In addition, by switching the two microwave switches, a 360° range of phase shift is achieved while almost keeping the amplitude of the phase shifter constant. The measurement results show that the proposed phase shifter achieves a phase resolution of 0.7° while exhibiting an average insertion loss of 9 ± 2 dB and phase unbalance within ±10°. The calculated RMS phase error of the broadband phase shifter is below 5° from 0.15 to 2 GHz.

5.
Rev Sci Instrum ; 94(9)2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37737695

RESUMO

Stochastic cooling of the high-precision spectrometer ring (SRing) at the High Intensity Heavy-Ion Accelerator Facility (HIAF) project in China, which is used mainly for experiments with radioactive fragment beams, is applied to speed up the cooling process of a stored ion beam. In this article, a new coaxial-type notch filter with an amplitude equalizer in the long branch and an optical-type notch filter with phase-stabilized optical fiber are discussed and evaluated for the SRing stochastic cooling system. Both prototypes of coaxial and optical notch filters are fabricated and tested. The minimum notch depth of coaxial and optical notch filters reaches to 26 and 40 dB, respectively. The performance of both coaxial notch filter and optical fiber notch filter is presented in this work. These developments will be used not only for the longitudinal stochastic cooling system but also have potential for the beam feedback system.

6.
Rev Sci Instrum ; 93(4): 043306, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35489913

RESUMO

A diagonal-cut type beam position monitor (BPM) has been developed for the High Intensity Heavy-Ion Accelerator Facility (HIAF) project at the Institute of Modern Physics. Compared with other types of BPMs, the diagonal-cut type BPM has almost perfect position linearity, i.e., no non-linear correction required, which is advantageous for beams that are transversally large and have a complex charge distribution. The key parameters for the diagonal-cut type BPM have been simulated and optimized in detail and systematically herein. It was found that the crosstalk is improved by ∼10 dB at 160 MHz by insertion of a separate ring between two horizontal or vertical electrodes of the BPM made of stainless steel with vacuum as a dielectric. Furthermore, the longitudinal and transverse numerical simulation to evaluate the beam impedance on the diagonal-cut type BPM has been performed. The results for the crosstalk, position sensitivity, and electrode capacitance to ground obtained from simulations and laboratory measurements agree well. The vacuum of the BPM prototype after baking out at 250 °C for 72 h is better than 1.0 × 10-11 mbar. The simulated and on-line measured BPM output signal magnitude results are consistent with each other. This diagonal-cut type BPM structure will be considered for application to the HIAF project as a priority.

7.
Int J Phytoremediation ; 24(4): 350-363, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34410866

RESUMO

Foxtail millet shell as a raw efficient adsorbent was chosen first to eliminate methylene blue (MB) based on the uneven surface with many micropores, lots of negative charges, various functional groups, and some primary elements. And then the adsorbent-loaded MB was used to remove Pb(II), Cd(II), Cu(II), and Zn(II) from aqueous water for secondary adsorption. The effects of various factors were explored and optimized for removal rates of MB on the surface of the adsorbent using response surface methodology (RSM). After these factors were optimized, the confirmed removal rates of MB by the adsorbents were reached at 92.04, 93.05, and 93.36%, respectively from aqueous water while the solution pH was at 3, 7, and 11, respectively. The behavior of adsorption for MB dye was well-described by Langmuir isotherm (R2 = 0.9951), demonstrating favorable monolayer adsorption of MB on the adsorbent with the maximum capacity of 165.07 mg·L-1 in aqueous water. The data of MB dye removal was better assessed by pseudo-second-order model (R2 ≥ 0.9033), indicating an exchange of electrons has occurred between the adsorbent and MB particles, especially K and Ca ions of the adsorbent. In addition, the adsorbent-loaded MB has still presented better adsorption abilities for Pb(II), Cd(II), Cu(II), and Zn(II), respectively after MB removal in aqueous water. The adsorption mechanisms of adsorption were explored with the characterizations of the adsorbent before and after adsorption for the target pollutants by the methods of TEM, SEM, nitrogen physisorption isotherms, XPS, EDS, IR, and zeta potential classes. In summary, the results presented that the foxtail millet shell could be applied to remove MB dye effectively from aqueous water with the combined effects of electrostatic attraction, ion exchange, functional groups binding, and pore diffusion, but also, the adsorbent loaded with MB can be still applied to eliminate Pb(II), Cd(II), Cu(II), and Zn(II) by effects of electrostatic attraction and functional groups complexation in aqueous water.Novelty Statement In the present work, (a) the raw foxtail millet shell as a new potential adsorbent was used to remove MB dye from aqueous water for the first times, and operational variables of adsorption MB were investigated and optimized using response surface methodology, (b) the foxtail millet shell loaded MB as a disused adsorbent without any chemical reagent added was carried out to remove Pb(II), Cd(II), Cu(II), and Zn(II) ions, respectively in aqueous water for a secondary cycle, (c) adsorption mechanisms of MB removal on the adsorbent and the target heavy metals on the disused adsorbent were explored by the various analytical methods. This work provides evidence for the adsorption of MB on the natural adsorbent and improves the utilization efficiency of the used adsorbent on Pb(II), Cd(II), Cu(II), and Zn(II) removal in aqueous water.


Assuntos
Setaria (Planta) , Poluentes Químicos da Água , Adsorção , Biodegradação Ambiental , Cádmio/análise , Concentração de Íons de Hidrogênio , Cinética , Chumbo , Azul de Metileno/química , Água/química , Poluentes Químicos da Água/química , Zinco
8.
Medicine (Baltimore) ; 100(47): e27960, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34964785

RESUMO

BACKGROUND: Hip synovitis is a common hip disorder in children and a frequent cause of hip or groin pain in children. Its onset is rapid and poses a threat to patient health. Conventional treatment methods have suboptimal efficacy and large side effects. Clinical study surface, the therapeutic effect of traditional Chinese medicine (TCM) on hip synovitis in children is obvious. Therefore, we aimed to systematically review the efficacy and safety of TCM on hip synovitis in children. METHODS: We will search databases including PubMed, Web of Science, EMBASE database, Cochrane Library, MEDLINE, Wanfang Data, Chinese biomedical literature database, China National Knowledge Infrastructure, Chinese science and technology journals database, and World Health Organization International Clinical Trials Registry Platform (since the databases were established). We also searched secondary resources, including the reference lists of studies. Included articles were carefully screened and reviewed by 2 researchers. Statistical analysis was performed using Review Manager 5.3 software. RESULTS: This study will comprehensively evaluate the efficacy and safety of TCM for the treatment of hip synovitis in children. CONCLUSION: This systematic review explores the efficacy and safety of TCM for the treatment of hip synovitis in children and provides an update on its clinical use.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Sinovite/terapia , Criança , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Metanálise como Assunto , Projetos de Pesquisa , Sinovite/tratamento farmacológico , Revisões Sistemáticas como Assunto
9.
Medicine (Baltimore) ; 100(30): e26811, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397740

RESUMO

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common refractory disease in orthopedics. Overdose glucocorticoid application is a common trigger for ONFH. Traditional Chinese medicine (TCM), as a treatment for ONFH, has been shown to be effective in treating steroid-induced ONFH (SONFH). However, a systematic review and meta-analysis of them is lacking. We aim to systematically review the effectiveness and safety of TCM in the treatment of SONFH. METHODS: We will search the following databases: PubMed, Embase, the Cochrane Library, MEDLINE, the Chinese Biomedical Literature Database, China Science and Technology Journal Database, China National Knowledge Infrastructure, and Wanfang Data (since the inception of the databases to the present). In addition, we will look for clinical trial registrations, prospective grey literature, relevant conference papers, and established study reference lists. We will use Review Manager 5.3 software for meta-analysis and heterogeneity assessment. We will evaluate the quality of the evidence using a hierarchy of recommendation assessment, development, and evaluation. RESULTS: This study will systematically evaluate the efficacy and safety of TCM in the treatment of SONFH. CONCLUSION: This systematic review to evaluate the effectiveness and safety of TCM in the treatment of SONFH will provide updated evidence for clinical application. INPLASY REGISTRATION NUMBER: INPLASY202170015.


Assuntos
Necrose da Cabeça do Fêmur/terapia , Medicina Tradicional Chinesa , Necrose da Cabeça do Fêmur/induzido quimicamente , Glucocorticoides/efeitos adversos , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
10.
Medicine (Baltimore) ; 100(9): e24166, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655910

RESUMO

BACKGROUND: The purpose of this meta-analysis was to evaluate the clinical efficacy and safety of HR and PFNA in the treatment of intertrochanteric fractures in the elderly. METHODS: We carried out this review according to the principle of preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline. The clinical randomized controlled trials (RCTs), prospective cohort studies, retrospective cohort studies (RCSs), and case-control studies involving HR and PFNA in the treatment of intertrochanteric fractures in the elderly from 2000 to 2020 were compared by searching Web of Science, Pubmed, the Cochrane Library, and Embase. The quality of the included cohort study (CS) lines was evaluated using the Newcastle-Ottawa Scale (NOS). The quality of the included RCT lines was evaluated using Jadad. Forest plots were drawn by RevMan5.4 software based on the results and the data were analyzed. RESULTS: After screening, a total of 9 articles were included, of which one was a clinical RCT and eight were RCSs with 1374 patients. The operative time of the PFNA group was shorter [WMD = 15.20; 95% CI (13.17, 17.23), P < .05] and the intraoperative blood loss was less [WMD = 178.81; 95% CI (97.24, 260.38), P < .05] than the HR group, while the first weight-bearing time of the HR group was shorter [WMD = -7.70; 95% CI (-10.54, -4.86), P  < .05] than the PFNA group. There was no significant difference in the length of hospital stay, HHS, postoperative orthopedic complications, and postoperative medical complications between the 2 groups. CONCLUSION: With the development of HR technology and minimally invasive technology, the trauma caused by surgery is decreasing. Under the premise of improving perioperative management, such as optimizing the preoperative preparation and postoperative management, shortening the operative time, reducing intraoperative blood loss, and actively managing co-existing diseases, HR has more advantages than PFNA in the treatment of senile intertrochanteric fractures.


Assuntos
Artroplastia de Quadril/estatística & dados numéricos , Pinos Ortopédicos , Fixação Interna de Fraturas/estatística & dados numéricos , Fraturas do Quadril/cirurgia , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do Tratamento
11.
Stem Cells Transl Med ; 9(4): 499-517, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31943851

RESUMO

Mesenchymal stem cells (MSCs) have been used in clinical studies to treat neurological diseases and damage. However, implanted MSCs do not achieve their regenerative effects by differentiating into and replacing neural cells. Instead, MSC secretome components mediate the regenerative effects of MSCs. MSC-derived extracellular vesicles (EVs)/exosomes carry cargo responsible for rescuing brain damage. We previously showed that EP4 antagonist-induced MSC EVs/exosomes have enhanced regenerative potential to rescue hippocampal damage, compared with EVs/exosomes from untreated MSCs. Here we show that EP4 antagonist-induced MSC EVs/exosomes promote neurosphere formation in vitro and increase neurogenesis and neuritogenesis in damaged hippocampi; basal MSC EVs/exosomes do not contribute to these regenerative effects. 2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP) levels in EP4 antagonist-induced MSC EVs/exosomes are 20-fold higher than CNP levels in basal MSC EVs/exosomes. Decreasing elevated exosomal CNP levels in EP4 antagonist-induced MSC EVs/exosomes reduced the efficacy of these EVs/exosomes in promoting ß3-tubulin polymerization and in converting toxic 2',3'-cAMP into neuroprotective adenosine. CNP-depleted EP4 antagonist-induced MSC EVs/exosomes lost the ability to promote neurogenesis and neuritogenesis in damaged hippocampi. Systemic administration of EV/exosomes from EP4 -antagonist derived MSC EVs/exosomes repaired cognition, learning, and memory deficiencies in mice caused by hippocampal damage. In contrast, CNP-depleted EP4 antagonist-induced MSC EVs/exosomes failed to repair this damage. Exosomal CNP contributes to the ability of EP4 antagonist-elicited MSC EVs/exosomes to promote neurogenesis and neuritogenesis in damaged hippocampi and recovery of cognition, memory, and learning. This experimental approach should be generally applicable to identifying the role of EV/exosomal components in eliciting a variety of biological responses.


Assuntos
2',3'-Nucleotídeo Cíclico 3'-Fosfodiesterase/metabolismo , Lesões Encefálicas/terapia , Região CA1 Hipocampal/metabolismo , Cognição , Exossomos/enzimologia , Aprendizagem , Células-Tronco Mesenquimais/enzimologia , Neuritos/metabolismo , Neurogênese , Animais , Lesões Encefálicas/patologia , Cognição/efeitos dos fármacos , AMP Cíclico/metabolismo , Proteínas do Domínio Duplacortina , Exossomos/efeitos dos fármacos , Humanos , Isoindóis/farmacologia , Aprendizagem/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Neuritos/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Neuropeptídeos/metabolismo , Polimerização , Receptores de Prostaglandina E Subtipo EP4/antagonistas & inibidores , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Sulfonamidas/farmacologia , Tubulina (Proteína)/metabolismo
12.
Stem Cells Transl Med ; 8(7): 707-723, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30891948

RESUMO

Adult brains have limited regenerative capacity. Consequently, both brain damage and neurodegenerative diseases often cause functional impairment for patients. Mesenchymal stem cells (MSCs), one type of adult stem cells, can be isolated from various adult tissues. MSCs have been used in clinical trials to treat human diseases and the therapeutic potentials of the MSC-derived secretome and extracellular vesicles (EVs) have been under investigation. We found that blocking the prostaglandin E2 /prostaglandin E2 receptor 4 (PGE2 /EP4 ) signaling pathway in MSCs with EP4 antagonists increased EV release and promoted the sorting of specific proteins, including anti-inflammatory cytokines and factors that modify astrocyte function, blood-brain barrier integrity, and microglial migration into the damaged hippocampus, into the EVs. Systemic administration of EP4 antagonist-elicited MSC EVs repaired deficiencies of cognition, learning and memory, inhibited reactive astrogliosis, attenuated extensive inflammation, reduced microglial infiltration into the damaged hippocampus, and increased blood-brain barrier integrity when administered to mice following hippocampal damage. Stem Cells Translational Medicine 2019.


Assuntos
Barreira Hematoencefálica , Cognição , Vesículas Extracelulares , Hipocampo , Isoindóis/farmacologia , Aprendizagem , Células-Tronco Mesenquimais/metabolismo , Receptores de Prostaglandina E Subtipo EP4/antagonistas & inibidores , Recuperação de Função Fisiológica , Sulfonamidas/farmacologia , Adulto , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/fisiopatologia , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/transplante , Hipocampo/lesões , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Receptores de Prostaglandina E Subtipo EP4/metabolismo
13.
Int J Cancer ; 143(6): 1440-1455, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29658109

RESUMO

Cells expressing mesenchymal/basal phenotypes in tumors have been associated with stem cell properties. Cancer stem cells (CSCs) are often resistant to conventional chemotherapy. We explored overcoming mesenchymal CSC resistance to chemotherapeutic agents. Our goal was to reduce CSC numbers in vivo, in conjunction with chemotherapy, to reduce tumor burden. Analysis of clinical samples demonstrated that COX-2/PGE2 /EP4 signaling is elevated in basal-like and chemoresistant breast carcinoma and is correlated with survival and relapse of breast cancer. EP4 antagonism elicts a striking shift of breast cancer cells from a mesenchymal/CSC state to a more epithelial non-CSC state. The transition was mediated by EP4 antagonist-induced extracellular vesicles [(EVs)/exosomes] which removed CSC markers, mesenchymal markers, integrins, and drug efflux transporters from the CSCs. In addition, EP4 antagonism-induced CSC EVs/exosomes can convert tumor epithelial/non-CSCs to mesenchymal/CSCs able to give rise to tumors and to promote tumor cell dissemination. Because of its ability to induce a CSC-to-non-CSC transition, EP4 antagonist treatment in vivo reduced the numbers of CSCs within tumors and increased tumor chemosensitivity. EP4 antagonist treatment enhances tumor response to chemotherapy by reducing the numbers of chemotherapy-resistant CSCs available to repopulate the tumor. EP4 antagonism can collaborate with conventional chemotherapy to reduce tumor burden.


Assuntos
Neoplasias da Mama/patologia , Ciclo-Oxigenase 2/química , Dinoprostona/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos , Vesículas Extracelulares/patologia , Células-Tronco Neoplásicas/patologia , Receptores de Prostaglandina E Subtipo EP4/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Movimento Celular , Proliferação de Células , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Transição Epitelial-Mesenquimal , Vesículas Extracelulares/efeitos dos fármacos , Vesículas Extracelulares/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Invasividade Neoplásica , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Transdução de Sinais , Carga Tumoral , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Sensors (Basel) ; 17(10)2017 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-28991154

RESUMO

For an electronic nose (E-nose) in wound infection distinguishing, traditional learning methods have always needed large quantities of labeled wound infection samples, which are both limited and expensive; thus, we introduce self-taught learning combined with sparse autoencoder and radial basis function (RBF) into the field. Self-taught learning is a kind of transfer learning that can transfer knowledge from other fields to target fields, can solve such problems that labeled data (target fields) and unlabeled data (other fields) do not share the same class labels, even if they are from entirely different distribution. In our paper, we obtain numerous cheap unlabeled pollutant gas samples (benzene, formaldehyde, acetone and ethylalcohol); however, labeled wound infection samples are hard to gain. Thus, we pose self-taught learning to utilize these gas samples, obtaining a basis vector θ. Then, using the basis vector θ, we reconstruct the new representation of wound infection samples under sparsity constraint, which is the input of classifiers. We compare RBF with partial least squares discriminant analysis (PLSDA), and reach a conclusion that the performance of RBF is superior to others. We also change the dimension of our data set and the quantity of unlabeled data to search the input matrix that produces the highest accuracy.


Assuntos
Nariz Eletrônico , Aprendizado de Máquina , Infecção dos Ferimentos/diagnóstico , Acetona/análise , Benzeno/análise , Equipamentos para Diagnóstico/normas , Análise Discriminante , Etanol/análise , Formaldeído/análise , Reprodutibilidade dos Testes
15.
J Vis Exp ; (124)2017 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-28605392

RESUMO

Cells can communicate via exosomes, ~100-nm extracellular vesicles (EVs) that contain proteins, lipids, and nucleic acids. Non-adherent/mesenchymal mammary epithelial cell (NAMEC)-derived extracellular vesicles can be isolated from NAMEC medium via differential ultracentrifugation. Based on their density, EVs can be purified via ultracentrifugation at 110,000 x g. The EV preparation from ultracentrifugation can be further separated using a continuous density gradient to prevent contamination with soluble proteins. The purified EVs can then be further evaluated using nanoparticle-tracking analysis, which measures the size and number of vesicles in the preparation. The extracellular vesicles with a size ranging from 50 to 150 nm are exosomes. The NAMEC-derived EVs/exosomes can be ingested by mammary epithelial cells, which can be measured by flow cytometry and confocal microscopy. Some mammary stem cell properties (e.g., mammary gland-forming ability) can be transferred from the stem-like NAMECs to mammary epithelial cells via the NAMEC-derived EVs/exosomes. Isolated primary EpCAMhi/CD49flo luminal mammary epithelial cells cannot form mammary glands after being transplanted into mouse fat pads, while EpCAMlo/CD49fhi basal mammary epithelial cells form mammary glands after transplantation. Uptake of NAMEC-derived EVs/exosomes by EpCAMhi/CD49flo luminal mammary epithelial cells allows them to generate mammary glands after being transplanted into fat pads. The EVs/exosomes derived from stem-like mammary epithelial cells transfer mammary gland-forming ability to EpCAMhi/CD49flo luminal mammary epithelial cells.


Assuntos
Comunicação Celular , Exossomos/fisiologia , Vesículas Extracelulares/fisiologia , Glândulas Mamárias Animais/citologia , Animais , Molécula de Adesão da Célula Epitelial/análise , Células Epiteliais/fisiologia , Feminino , Integrina alfa6/análise , Camundongos , Camundongos Endogâmicos C57BL , Ultracentrifugação
16.
Stem Cells ; 35(2): 425-444, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27506158

RESUMO

Prostaglandin E2 (PGE2 )-initiated signaling contributes to stem cell homeostasis and regeneration. However, it is unclear how PGE2 signaling controls cell stemness. This study identifies a previously unknown mechanism by which PGE2 /prostaglandin E receptor 4 (EP4 ) signaling regulates multiple signaling pathways (e.g., PI3K/Akt signaling, TGFß signaling, Wnt signaling, EGFR signaling) which maintain the basal mammary stem cell phenotype. A shift of basal mammary epithelial stem cells (MaSCs) from a mesenchymal/stem cell state to a non-basal-MaSC state occurs in response to prostaglandin E receptor 4 (EP4 ) antagonism. EP4 antagonists elicit release of signaling components, by controlling their trafficking into extracellular vesicles/exosomes in a lipid raft/caveolae-dependent manner. Consequently, EP4 antagonism indirectly inactivates, through induced extracellular vesicle/exosome release, pathways required for mammary epithelial stem cell homeostasis, e.g. canonical/noncanonical Wnt, TGFß and PI3K/Akt pathways. EP4 antagonism causes signaling receptors and signaling components to shift from non-lipid raft fractions to lipid raft fractions, and to then be released in EP4 antagonist-induced extracellular vesicles/exosomes, resulting in the loss of the stem cell state by mammary epithelial stem cells. In contrast, luminal mammary epithelial cells can acquire basal stem cell properties following ingestion of EP4 antagonist-induced stem cell extracellular vesicles/exosomes, and can then form mammary glands. These findings demonstrate that PGE2 /EP4 signaling controls homeostasis of mammary epithelial stem cells through regulating extracellular vesicle/exosome release. Reprogramming of mammary epithelial cells can result from EP4 -mediated stem cell property transfer by extracellular vesicles/exosomes containing caveolae-associated proteins, between mammary basal and luminal epithelial cells. Stem Cells 2017;35:425-444.


Assuntos
Dinoprostona/metabolismo , Vesículas Extracelulares/metabolismo , Glândulas Mamárias Humanas/citologia , Microdomínios da Membrana/metabolismo , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Transdução de Sinais , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Anticorpos Neutralizantes/metabolismo , Biomarcadores/metabolismo , Cavéolas/metabolismo , Adesão Celular , Linhagem Celular , Movimento Celular , Forma Celular , Ciclo-Oxigenase 2/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Vesículas Extracelulares/ultraestrutura , Feminino , Humanos , Integrinas/metabolismo , Microdomínios da Membrana/ultraestrutura , Camundongos Endogâmicos C57BL , Prostaglandina-E Sintases/metabolismo , Receptores de Prostaglandina E Subtipo EP4/antagonistas & inibidores , Esferoides Celulares/citologia , Proteínas rab de Ligação ao GTP/metabolismo
17.
Sensors (Basel) ; 16(9)2016 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-27626420

RESUMO

Electronic nose (E-nose), as a device intended to detect odors or flavors, has been widely used in many fields. Many labeled samples are needed to gain an ideal E-nose classification model. However, the labeled samples are not easy to obtain and there are some cases where the gas samples in the real world are complex and unlabeled. As a result, it is necessary to make an E-nose that cannot only classify unlabeled samples, but also use these samples to modify its classification model. In this paper, we first introduce a semi-supervised learning algorithm called S4VMs and improve its use within a multi-classification algorithm to classify the samples for an E-nose. Then, we enhance its performance by adding the unlabeled samples that it has classified to modify its model and by using an optimization algorithm called quantum-behaved particle swarm optimization (QPSO) to find the optimal parameters for classification. The results of comparing this with other semi-supervised learning algorithms show that our multi-classification algorithm performs well in the classification system of an E-nose after learning from unlabeled samples.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Nariz Eletrônico , Máquina de Vetores de Suporte , Bases de Dados como Assunto
18.
PLoS One ; 8(1): e54187, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23349821

RESUMO

Drosophila melanogaster crammer is a novel cathepsin inhibitor involved in long-term memory formation. A molten globule-to-ordered structure transition is required for cathepsin inhibition. This study reports the use of alanine scanning to probe the critical residues in the two hydrophobic cores and the salt bridges of crammer in the context of disorder-to-order transition and cathepsin inhibition. Alanine substitution of the aromatic residues W9, Y12, F16, Y20, Y32, and W53 within the hydrophobic cores, and charged residues E8, R28, R29, and E67 in the salt bridges considerably decrease the ability of crammer to inhibit Drosophila cathepsin B (CTSB). Far-UV circular dichroism (CD), intrinsic fluorescence, and nuclear magnetic resonance (NMR) spectroscopies show that removing most of the aromatic and charged side-chains substantially reduces thermostability, alters pH-dependent helix formation, and disrupts the molten globule-to-ordered structure transition. Molecular modeling indicates that W53 in the hydrophobic Core 2 is essential for the interaction between crammer and the prosegment binding loop (PBL) of CTSB; the salt bridge between R28 and E67 is critical for the appropriate alignment of the α-helix 4 toward the CTSB active cleft. The results of this study show detailed residue-specific dissection of folding transition and functional contributions of the hydrophobic cores and salt bridges in crammer, which have hitherto not been characterized for cathepsin inhibition by propeptide-like cysteine protease inhibitors. Because of the involvements of cathepsin inhibitors in neurodegenerative diseases, these structural insights can serve as a template for further development of therapeutic inhibitors against human cathepsins.


Assuntos
Alanina/química , Catepsina B/antagonistas & inibidores , Proteínas de Drosophila/química , Proteínas de Drosophila/farmacologia , Alanina/genética , Alanina/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Aminoácidos/química , Aminoácidos/genética , Aminoácidos/metabolismo , Animais , Catepsina B/metabolismo , Dicroísmo Circular , Inibidores de Cisteína Proteinase/química , Inibidores de Cisteína Proteinase/genética , Inibidores de Cisteína Proteinase/farmacologia , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Conformação Proteica , Dobramento de Proteína , Estabilidade Proteica , Estrutura Secundária de Proteína , Homologia de Sequência de Aminoácidos , Temperatura
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