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1.
J Control Release ; 320: 337-346, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31931048

RESUMO

BACKGROUND: Drug delivery systems based on electrospun fibers have been under development for many years. However, studies of controllable long-term drug release from electrospun membrane systems and the underlying release mechanisms have seldom been reported. METHODS: In this study, electrospun membrane drug delivery systems consisting of the antibiotic ciprofloxacin hydrochloride and FDA-approved polymers are fabricated. Different second-component polymers are introduced to change the properties of a poly(d,l-lactide-co-glycolide) (PLGA) matrix, thereby altering the drug release behavior. On the basis of observations of morphology, cumulative release profiles, and determinations of release duration, the drug release kinetics and critical characteristics influencing drug release behavior are discussed. RESULTS: It is found that the drug release profiles can be divided into three stages according to the rate of drug release. Stage I is controlled by fiber swelling and diffusion according to Fick's second law. Stage II is controlled by diffusion through a fused membrane structure, which results in very slow drug release. Stage III is controlled by polymer degradation and involves release of the remaining drug. CONCLUSIONS: The results of this study of release mechanisms should provide a basis for adjustments of drug release dosage and duration, thereby contributing to the development of drug delivery systems satisfying clinical requirements.

2.
J Inorg Biochem ; 202: 110857, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669695

RESUMO

Thirteen novel palladium(II) complexes of the general formula [Pd(bipy)(O,O'-dkt)](PF6), (where bipy is 2,2'-bipyridine and O,O'-dkt is ß-diketonate ligand hispolon or its derivative) have been prepared through a metal-ligand coordination method that involves spontaneous formation of the corresponding diketonate scaffold. The obtained palladium(II) complexes have been characterized by NMR spectroscopy, ESI-mass spectrometry as well as elemental analysis. The cytotoxicity analysis indicates that most of the obtained palladium(II) complexes show promising growth inhibition in three human cancer cell lines. Flow cytometry analysis shows complex 3e could promote intracellular reactive oxygen species (ROS) accumulation and lead cancer cell death. And the suppression of ROS accumulation and the rescue of cell viability in HeLa cells by N-acetyl-L-cysteine (NAC) suggest the possible link between the increase in ROS generation and cytotoxicity of complex 3e. Flow cytometry analysis also reveal that complex 3e cause cell cycle arrest in the G2/M phase and collapse of the mitochondrial membrane potential, promote the generation of ROS and lead to tumor cell apoptosis. The interactions of complex 3e with calf thymus DNA (CT-DNA) have been evaluated by UV-Vis spectroscopy, fluorescence quenching experiments and viscosity measurements, which reveal that the complex interact with CT-DNA through minor groove binding and/or electrostatic interactions. Further, the results of fluorescence titration and site marker competitive experiment on bovine serum albumin (BSA) suggest that complex 3e can quench the fluorescence of BSA via a static quenching process and bind to BSA in Sudlow's site II.

3.
Nanoscale ; 11(38): 17782-17790, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31552990

RESUMO

Air pollution is harmful to the functioning of the lungs, heart, and brain even at low concentrations of particle matter (PM) and toxic gases. Purification methods and materials have made tremendous progress to improve the purity of air to adhere to national quality standards. Metal-organic frameworks (MOFs) have an excellent gas adsorption capacity due to their high specific surface area and porous structure, but the intrinsic fragility of MOF crystals limits their application. In this study, we selected appropriate organic ligands to prepare MOF-surface-grown fibrous membranes using an electrospinning technique, which have an excellent ability to adsorb PM and capture toxic gases selectively. The efficiency of the MOF-surface-grown fibrous membranes to remove PM reached 99.99%, even for fine PM. More importantly, under low partial pressure and complex gas composition conditions, the fibrous membrane was able to selectively adsorb SO2. The concentration of SO2 dropped from 7300 ppb to 40 ppb. Interestingly, the MOF-surface-grown fibrous membrane had a higher purification capacity toward O3 than toward SO2. The concentration of O3 rapidly dropped from 3000 ppb to 7 ppb, which was far below national air quality standards (81 ppb). The MOF-surface-grown fibrous membrane was able to adsorb toxic atmospheric gases selectively, while not being influenced by the presence of other gases, such as CO2 and O2. MOF-based fibrous membranes prepared using a simple and inexpensive electrospinning technique have wide potential for practical use in the field of environmental protection and air purification.

4.
ACS Nano ; 13(7): 7556-7567, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31259530

RESUMO

Bone metastasis, a clinical complication of patients with advanced breast cancer, seriously reduces the quality of life. To avoid destruction of the bone matrix, current treatments focus on inhibiting the cancer cell growth and the osteoclast activity through combination therapy. Therefore, it could be beneficial to develop a bone-targeted drug delivery system to treat bone metastasis. Here, a bone-targeted nanoplatform was developed using gold nanorods enclosed inside mesoporous silica nanoparticles (Au@MSNs) which were then conjugated with zoledronic acid (ZOL). The nanoparticles (Au@MSNs-ZOL) not only showed bone-targeting ability in vivo but also inhibited the formation of osteoclast-like cells and promoted osteoblast differentiation in vitro. The combination of Au@MSNs-ZOL and photothermal therapy (PTT), triggered by near-infrared irradiation, inhibited tumor growth both in vitro and in vivo and relieved pain and bone resorption in vivo by inducing apoptosis in cancer cells and improving the bone microenvironment. This single nanoplatform combines ZOL and PTT to provide an exciting strategy for treating breast cancer bone metastasis.

5.
Bioconjug Chem ; 29(10): 3332-3343, 2018 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-30192132

RESUMO

A novel anticancer theranostic prodrug, FDU-DB-NO2, specifically activated by hypoxia for selective two-photon imaging hypoxia status, real-time tracking drug release, and solid tumor therapy was designed. The devised prodrug consists of an anticancer drug floxuridine (FDU), a fluorescence dye precursor 4'-(diethylamino)-1,1'-biphenyl-2-carboxylate (DB), and a hypoxic trigger 4-nitrobenzyl group. In normal cells, FDU-DB-NO2 is "locked". Whereas in tumor cells, the prodrug is "unlocked" by hypoxia and results in fluorescent dye 7-(diethylamino)coumarin (CM) generation along with FDU release. The amounts and rates of CM formation and FDU release were controlled by hypoxic status and increased with the decreasing of the O2 concentration. The hypoxic status, distribution of oxygen, and amount of FDU release in tumor cells, spheroids, and tumor tissue could be visualized by fluorescence. FDU-DB-NO2 showed high cytotoxicity against hypoxic MCF-7 and MCG-803 cell lines and no cytotoxicity against normoxic BRL-3A cells and exhibited effective inhibition on tumor growth of MCF-7-cell-inoculated xenograft nude mice. This strategy may provide a promising platform for selective two-photon imaging hypoxia status, real-time tracking drug release, and personalized solid tumor treatment.


Assuntos
Antineoplásicos/farmacologia , Pró-Fármacos/farmacologia , Animais , Antineoplásicos/farmacocinética , Liberação Controlada de Fármacos , Floxuridina/farmacologia , Corantes Fluorescentes/química , Humanos , Células MCF-7 , Camundongos Nus , Imagem Óptica , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Oncol Lett ; 16(2): 2427-2433, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30013633

RESUMO

DNA-damage regulated autophagy modulator 1 (DRAM1) is known as a target of TP53-mediated autophagy, and has been reported to promote the migration and invasion abilities of glioblastoma stem cells. However, the precise contribution of DRAM1 to cancer cell invasion and migration, and the underlying mechanisms remain unclear. In the present study, small interfering (si)RNA or short hairpin RNA mediated knockdown of DRAM1 was performed in hepatoblastoma cells and the migration and invasion abilities were detected in vitro and in vivo. To investigate the underlying mechanisms, western blotting and immunofluorescence were used to detect the expression of autophagy-associated proteins and epithelial-mesenchymal-transition (EMT)-associated markers. The results showed that DRAM1 knockdown by specific siRNA abrogated cell autophagy, as well as inhibited the migration and invasion of HepG2 cells in Transwell assays, which may be reversed by rapamycin treatment. In addition, DRAM1 knockdown increased the expression of E-Cadherin while decreased the expression of vimentin in HepG2 cells, which was also be reversed by rapamycin treatment. Taken together, these results suggest that DRAM1 is involved in the regulation of the migration and invasion of HepG2 cells via autophagy-EMT pathway.

7.
Int J Syst Evol Microbiol ; 68(7): 2172-2177, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29767617

RESUMO

A Gram-strain-negative, coccoid bacterium, lacking bacteriochlorophyll, designated strain T1lg56T, was isolated from a sediment sample collected from Ximen island mangrove forest, Zhejiang province, China. Cells were halotolerant, and catalase- and oxidase-positive. Growth was observed at 18-42 °C (optimum, 35 °C), at pH 6.0-9.5 (optimum, pH 6.5) and in the presence of 0-15 % (w/v) NaCl (optimum, 2-5 %). The major cellular fatty acids were C18 : 1ω7c and C16 : 0. The polar lipid profile of strain T1lg56T consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylmonomethylethanolamine, two unidentified phospholipids and five unidentified lipids. Ubiquinone-10 was the predominant respiratory quinone. The assimilation of the substrates in the API 20NE kit was positive in strain T1lg56T. The DNA G+C content of strain T1lg56T was 67.2 mol%. 16S rRNA gene sequence analysis indicated that strain T1lg56T was a member of family Rhodobacteraceae and was closely related to Poseidonocella pacifica KMM 9010T, with 95.7 % similarity to the type strain. Phylogenetic analysis showed that strain T1lg56T formed a separate evolutionary branch, and was parallel to other related genera of Rhodobacteraceae. Its phylogenetic distinctiveness and distinguishing phenotypic characteristics supported that strain T1lg56T represents a novel genus of the family Rhodobacteraceae, for which the name Mangrovicoccus ximenensis gen. nov., sp. nov. is proposed. The type strain is T1lg56T (=CCTCC AB 2016238T=KCTC 52623T).


Assuntos
Sedimentos Geológicos/microbiologia , Filogenia , Rhizophoraceae , Rhodobacteraceae/classificação , Áreas Alagadas , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Rhodobacteraceae/genética , Rhodobacteraceae/isolamento & purificação , Análise de Sequência de DNA , Ubiquinona/química
8.
J Biomed Nanotechnol ; 14(1): 179-189, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29463375

RESUMO

The incidence of many diseases is closely related to air pollution. Suspended particulate matter of different sizes represents a major source of environmental pollution. Fine particles, especially ultrafine particles smaller than 2.5 µm, might be more harmful to human health because of their extremely small size, which enables them to penetrate human lungs and bronchi and makes them difficult to filter out. Therefore, the fatal risks associated with PM call for the development of air purification materials with high efficiency and low resistance. In this study, poly(lactic-co-glycolic acid) and polycaprolactone were used to prepare nanofibrous membranes suitable for the efficient capture of particulate matter formed in haze-fog episodes, especially particles smaller than 0.5 µm. The present nanofibrous membranes exhibit superior filtration efficiency for particulate matter, with a much lower pressure drop compared to typical commercial microfiber air filters. Thanks to the combination of small pore size, high porosity, and robust mechanical properties, the poly(lactic-co-glycolic acid)/polycaprolactone (6:4) composite membrane exhibits a high filtration efficiency of 97.81% and a low pressure drop of 181 Pa. These favorable features, combined with the easy availability and biocompatibility of the component materials, highlight the promising potential of the present nanofibrous membranes for the development of personal wearable air purifiers.


Assuntos
Ácido Láctico , Nanofibras , Poliésteres , Ácido Poliglicólico , Filtros de Ar , Glicóis , Humanos , Teste de Materiais , Tamanho da Partícula , Material Particulado , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Dispositivos Eletrônicos Vestíveis
9.
Eur J Med Chem ; 144: 662-671, 2018 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-29289889

RESUMO

Based on the synthesis of curcumin and its derivatives from aromatic aldehydes, a novel series of palladium(II) complexes with curcumin (or its derivatives) and 2,2'-bipyridine have been synthesized through a directed self-assembly approach that involves spontaneous deprotonation of the curcuminoid ligands in H2O/acetone solution. These complexes have been characterized by 1H (13C) NMR, HRMS and elemental analysis. Crystal structure of 3h has been determined by X-ray diffraction analysis. Their cytotoxicity was tested by MTT. The preliminary results showed that complexes 3d, 3f, 3h have significant inhibition on proliferation of three carcinoma cells such as MCF-7, HeLa and A549 cells, which were more active than cisplatin. Further mechanistic studies indicated that the tested complex 3h arrested the cell cycle in the S phase and can disrupted mitochondrial membrane potential and induced tumor cell apoptosis through reactive oxygen species (ROS)-dependent pathway.


Assuntos
Antineoplásicos/farmacologia , Curcumina/farmacologia , Compostos Organometálicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Curcumina/análogos & derivados , Curcumina/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-Atividade
10.
Oncol Res ; 26(5): 795-800, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-28748780

RESUMO

Dysregulation of SUMO-specific protease 1 (SENP1) expression has been reported in several kinds of cancer, including human colorectal and prostate cancers, proposing SENP1 as an oncogene with a critical role in cancer progression. miR-133a-3p has been reported as a tumor suppressor in several malignant neoplasias. However, the precise molecular mechanisms underlying its role in colorectal cancer remain largely unknown. The aim of this work was to investigate the relationship between miR-133a-3p and SENP1 in colorectal cancer cells. We found that miR-133a-3p expression was downregulated in colorectal cancer tissues. In silico analyses indicated that SENP1 is one of the target genes of miR-133a-3p. Overexpression of miR-133a-3p mimics was able to inhibit cell growth with G1 arrest of colorectal cancer cells. Overexpression of miR-133a-3p antisense promoted cell growth of colorectal cancer cells. The luciferase reporter experiments showed that miR-133a-3p regulated the expression of SENP1 by combining with its 3'-UTR and resulted in downregulation of SENP1 and upregulation of CDK inhibitors such as p16, p19, p21, and p27. These results suggest that the miR-133a-3p-SENP1 axis might play a role in cell proliferation and cell cycle regulation of colorectal cancer cells.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Cisteína Endopeptidases/biossíntese , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Ciclo Celular/genética , Proliferação de Células/genética , Cisteína Endopeptidases/genética , Humanos
11.
Am J Cancer Res ; 8(12): 2518-2527, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30662808

RESUMO

Chemotherapy resistance frequently drives tumor progression. However, the underlying molecular mechanisms remain unclear. In this study, we found that the expression level of miR-26b was down-regulated in the human colorectal cancer tissues and the resistant cells strains: HT-29/5-FU and LOVO/5-FU cells. Meanwhile, we showed that miR-26b improved sensibility of colorectal cancer cells to 5-FU in vitro and enhanced the potency of 5-FU in the inhibition of tumor growth in vivo. We further demonstrated that the tumor suppressive role of miR-26b was mediated by negatively regulating P-glycoprotein (Pgp) protein expression. Furthermore, studies of colorectal cancer specimens indicated that the expression of miR-26b and Pgp had inverse correlation. Importantly, we found that CpG islands in the miR-26b promoter region were hypermethylated in 5-FU resistant cells. Our study is the first to identify the tumor suppressive role of over-expressed miR-26b in chemo-sensitivity. Identification of a novel miRNA-mediated pathway that regulates chemo-sensitivity in colorectal cancer will facilitate the development of novel therapeutic strategies in the future.

12.
Sci Rep ; 7(1): 16236, 2017 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-29176652

RESUMO

Nanoparticles provide new fields for life medical science application, including targeted-drug delivery and cancer treatment. To maximize the delivery efficiency of nanoparticle, one must understand the uptake mechanism of nanoparticle in cells, which may determine their ultimate fate and localization in cells. Recently, the proposed-cancer stem cell (CSC) theory has been attracted great attention and regarded as new targets for the new nanodrug developmet and cancer therapies. The interaction between nanoparticles and cancer cells has been extensively studied, but the uptake mechanism of nanoparticles in CSCs has received little attention. Here, we use the pharmacological inhibitors of major endocytic pathways to study the silica nanoparticle (SiNP) uptake mechanisms in the human breast adenocarcinoma cell line (MCF-7) and MCF-7-derived breast cancer stem cells (BCSCs). The results demonstrate that the uptake of SiNPs, particularly amino-functionalized SiNPs, in MCF-7 cells is strongly affected by the actin depolymerization, whereas BCSCs more strongly inhibit the amino-functionalized SiNP uptake after the scavenger receptor disruption. These findings indicate a distinct endocytic mechanism of functionalized SiNPs in BCSCs, which is significant for designing ideal nanosized drug delivery systems and improving the selectivity for CSC-targeted therapy.


Assuntos
Neoplasias da Mama/metabolismo , Endocitose , Nanopartículas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Células MCF-7 , Nanopartículas/química , Dióxido de Silício/química
13.
Int J Nanomedicine ; 12: 7577-7588, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29075116

RESUMO

The development of an artificial bone graft which can promote the regeneration of fractures or diseased bones is currently the most challenging aspect in bone tissue engineering. To achieve the purpose of promoting bone proliferation and differentiation, the artificial graft needs have a similar structure and composition of extracellular matrix. One-step electrospinning method of biocomposite nanofibers containing hydroxyapatite (HA) nanoparticles and collagen (Coll) were developed for potential application in bone tissue engineering. Nanocomposite scaffolds of poly(L-lactide) (PLLA), PLLA/HA, PLLA/Coll, and PLLA/Coll/HA were fabricated by electrospinning. The morphology, diameter, elements, hydrophilicity, and biodegradability of the composite scaffolds have been investigated. The biocompatibility of different nanocomposite scaffolds was assessed using mouse osteoblasts MC3T3-E1 in vitro, and the proliferation, differentiation, and mineralization of cells on different nanofibrous scaffolds were investigated. The results showed that PLLA/Coll/HA nanofiber scaffolds enhanced cell adhesion, spreading, proliferation, differentiation, mineralization, and gene expression of osteogenic markers compared to other scaffolds. In addition, the nanofibrous scaffolds maintained a stable composition at the beginning of the degradation period and morphology wastage and weight loss were observed when incubated for up to 80 days in physiological simulated conditions. The PLLA/Coll/HA composite nanofibrous scaffolds could be a potential material for guided bone regeneration.


Assuntos
Osso e Ossos/citologia , Nanofibras/química , Osteoblastos/citologia , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/química , Osso e Ossos/fisiologia , Adesão Celular , Diferenciação Celular , Linhagem Celular , Colágeno/química , Durapatita/química , Matriz Extracelular/fisiologia , Camundongos , Microscopia Eletrônica de Varredura , Osteoblastos/fisiologia , Osteogênese/fisiologia , Poliésteres/química , Espectroscopia de Infravermelho com Transformada de Fourier , Engenharia Tecidual/métodos
14.
Biomaterials ; 144: 155-165, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28834764

RESUMO

The development of effective therapies to control methicillin-resistant Staphylococcus aureus (MRSA) infections is challenging because antibiotics can be degraded by the production of certain enzymes, for example, ß-lactamases. Additionally, the antibiotics themselves fail to penetrate the full depth of biofilms formed from extracellular polymers. Nanoparticle-based carriers can deliver antibiotics with better biofilm penetration, thus combating bacterial resistance. In this study, we describe a general approach for the construction of ß-lactam antibiotics and ß-lactamase inhibitors co-delivery of nanoantibiotics based on metal-carbenicillin framework-coated mesoporous silica nanoparticles (MSN) to overcome MRSA. Carbenicillin, a ß-lactam antibiotic, was used as an organic ligand that coordinates with Fe3+ to form a metal-carbenicillin framework to block the pores of the MSN. Furthermore, these ß-lactamase inhibitor-loaded nanoantibiotics were stable under physiological conditions and could synchronously release antibiotic molecules and inhibitors at the bacterial infection site to achieve a better elimination of antibiotic resistant bacterial strains and biofilms. We confirmed that these ß-lactamase inhibitor-loaded nanoantibiotics had better penetration depth into biofilms and an obvious effect on the inhibition of MRSA both in vitro and in vivo.


Assuntos
Antibacterianos/uso terapêutico , Carbenicilina/uso terapêutico , Compostos Férricos/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Biofilmes/efeitos dos fármacos , Carbenicilina/administração & dosagem , Carbenicilina/farmacocinética , Preparações de Ação Retardada/química , Feminino , Compostos Férricos/administração & dosagem , Compostos Férricos/farmacocinética , Humanos , Concentração de Íons de Hidrogênio , Estruturas Metalorgânicas/administração & dosagem , Estruturas Metalorgânicas/farmacocinética , Staphylococcus aureus Resistente à Meticilina/fisiologia , Camundongos , Testes de Sensibilidade Microbiana , Nanopartículas/química , Células RAW 264.7 , Dióxido de Silício/química
15.
Sci Rep ; 7(1): 8197, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28811636

RESUMO

Electrospun scaffolds with excellent mechanical properties, high specific surface area and a commendable porous network are widely used in tissue engineering. Improving the hydrophilicity and cell adhesion of hydrophobic substrates is the key point to enhance the effectiveness of electrospun scaffolds. In this study, polycaprolactone (PCL) fibrous membranes with appropriate diameter were selected and coated by mussel-inspired poly norepinephrine (pNE). And norepinephrine is a catecholamine functioning as a hormone and neurotransmitter in the human brain. The membrane with smaller diameter fibers, a relative larger specific surface area and the suitable pNE functionalization provided more suitable microenvironment for cell adhesion and proliferation both in vitro and in vivo. The regenerated muscle layer can be integrated well with fibrous membranes and surrounding tissues at the impaired site and thus the mechanical strength reached the value of native tissue. The underlying molecular mechanism is mediated via inhibiting myostatin expression by PI3K/AKT/mTOR hypertrophy pathway. The properly functionalized fibrous membranes hold the potential for repairing muscle injuries. Our current work also provides an insight for rational design and development of better tissue engineering materials for skeletal muscle regeneration.


Assuntos
Bivalves/química , Norepinefrina/química , Poliésteres/química , Regeneração , Engenharia Tecidual , Animais , Adesão Celular , Proliferação de Células , Células Cultivadas , Humanos , Camundongos , Músculo Esquelético , Polímeros , Tecidos Suporte/química
16.
Glycoconj J ; 34(2): 207-217, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27975161

RESUMO

The present study aimed to characterize the glucan from C. mollissima Blume fruits and its selenium derivative, then investigate their antitumor activity in vitro. A glucan, designated as CPA, was firstly isolated from the fruits of C. mollissima Blume. Structure analysis indicated that CPA was a linear 1,6-α-D-glucan with the average molecular weight about 2.0 × 103 kDa. The selenylation modification derivative of CPA (sCPA), exhibited a stronger antiproliferative effect on tumor cells than CPA in vitro. CPA and sCPA could induce HeLa cells apoptosis and decrease mitochondrial membrane potential. sCPA could also arrest HeLa cells in S phase, promote reactive oxygen species generation and activate caspase-3 activity in HeLa cells. These results manifest that CPA and sCPA inhibit the proliferation of HeLa cells via different mechanisms, which is meaningful for their potential use as antitumor drugs.


Assuntos
Antineoplásicos Fitogênicos , Fagaceae/química , Flores/química , Glucanos , Neoplasias/tratamento farmacológico , Selênio , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Glucanos/química , Glucanos/isolamento & purificação , Glucanos/farmacologia , Células HeLa , Humanos , Células MCF-7 , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Selênio/química , Selênio/farmacologia
17.
Genes (Basel) ; 7(10)2016 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-27706111

RESUMO

Increasing evidence indicates that elevated expression of enhancer of zeste homolog 2 gene (EZH2) in many human malignant tumors acts a significant role in the oncogenic process. However, the underlying molecular mechanism is still unclarified. It is evident that apoptosis and autophagy of tumor cells is crucial for the tumorigenesis and progression of cancer, however, the exact role of EZH2 plays in apoptosis and autophagy has not been fully elucidated in colorectal cancer (CRC). Our previous study found that the expression level of EZH2 was higher in CRC tumor tissues than in the paired normal tissues using immunohistochemical analysis. We also recently found that the autophagy-related gene-related protein Ambra1 plays an important role in the autophagy pathway in CRC cells. In this study, mRNA and protein expression of EZH2 in four CRC cell lines were tested at first and RKO and HCT116 cells showed the highest levels among them. Here we transfected with EZH2-shRNA, or added DZNep (an EZH2 inhibitor) to RKO and HCT116 cells in order to detect the effect of EZH2 on autophagy via determining the change of the protein expression of LC3 and Ambra1. The outcome indicated an obvious decrease of autophagy level in cells transfected with EZH2-shRNA or DZNep. We also found the apoptotic rate of cells was elevated significantly after downregulation of EZH2. In addition, compared to control group, CRC cells transfected with EZH2-shRNA or added DZNep revealed a significantly increased G1 cell cycle rate and an obvious decrease in the G2 cell cycle rate. Further analysis showed that knockdown of EZH2 induced cell-cycle arrest in CRC cells. Meanwhile, downregulation of EZH2 in CRC cells induces autophagy and apoptosis. Taken together, our results suggest that EZH2 plays a critical role in autophagy and apoptosis in the progression of CRC, which potentially facilitates the development of an ideal strategy for combating colorectal cancer.

18.
J Environ Sci (China) ; 47: 63-70, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27593273

RESUMO

A waste paper sludge-derived heterogeneous catalyst (WPS-Fe-350) was synthesized via a facile method and successfully applied for the degradation of Orange II in the presence of oxalic acid under the illumination of ultraviolet light emitting diode (UV-LED) Powder X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electronic microscopy and N2 sorption isotherm analysis indicated the formation of α-Fe2O3 in the mesoporous nanocomposite. The degradation test showed that WPS-Fe-350 exhibited rapid Orange II (OII) degradation and mineralization in the presence of oxalic acid under the illumination of UV-LED. The effects of pH, oxalic acid concentration and dosage of the catalyst on the degradation of OII were evaluated, respectively. Under the optimal conditions (1g/L catalyst dosage, 2mmol/L oxalic acid and pH3.0), the degradation percentage for a solution containing 30mg/L OII reached 83.4% under illumination by UV-LED for 80min. Moreover, five cyclic tests for OII degradation suggested that WPS-Fe-350 exhibited excellent stability of catalytic activity. Hence, this study provides an alternative environmentally friendly way to reuse waste paper sludge and an effective and economically viable method for degradation of azo dyes and other refractory organic pollutants in water.


Assuntos
Compostos Azo/química , Benzenossulfonatos/química , Ácido Oxálico/química , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Compostos Azo/análise , Benzenossulfonatos/análise , Técnicas Eletroquímicas , Lasers Semicondutores , Papel , Fotólise , Raios Ultravioleta , Poluentes Químicos da Água/análise
19.
Chem Commun (Camb) ; 52(60): 9434-7, 2016 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-27379361

RESUMO

A novel anticancer pro-prodrug (GMC-CAE-NO2) with diagnosis and therapy functions based on hypoxia and photo sequential control was designed. It provides a platform for constructing theranostic pro-prodrugs to release active drugs controlled by hypoxic status and UV illumination.


Assuntos
Antineoplásicos/uso terapêutico , Hipóxia/diagnóstico , Hipóxia/tratamento farmacológico , Pró-Fármacos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Humanos , Células MCF-7 , Processos Fotoquímicos , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Nanomedicina Teranóstica
20.
J Biomed Nanotechnol ; 12(1): 1-27, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27301169

RESUMO

For safe and effective therapy, drugs must be delivered efficiently and with minimal systemic side effects. Nanostructured drug carriers enable the delivery of small-molecule drugs as well as nucleic acids and proteins. Inorganic nanomaterials are ideal for drug delivery platforms due to their unique physicochemical properties, such as facile preparation, good storage stability and biocompatibility. Many inorganic nanostructure-based drug delivery platforms have been prepared. Although there are still many obstacles to overcome, significant advances have been made in recent years. This review focuses on the status and development of inorganic nanostructures, including silica, quantum dots, gold, carbon-based and magnetic iron oxide-based nanostructures, as carriers for chemical and biological drugs. We specifically highlight the extensive use of these inorganic drug carriers for cancer therapy. Finally, we discuss the most important areas in the field that urgently require further study.


Assuntos
Compostos Inorgânicos/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Dióxido de Silício/química , Composição de Medicamentos/métodos
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