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1.
Artigo em Inglês | MEDLINE | ID: mdl-31577408

RESUMO

Anticancer nanomedicine-based multimodal imaging and synergistic therapy hold great promise in cancer diagnosis and therapy owing to its abilities to improve therapeutic efficiency and reduce unnecessary side-effects, producing a promising clinical prospects. Herein, we integrated chemotherapeutic drug camptothecin (CPT) and near infrared (NIR) absorbing new indocyanine green (IR820) into a single system by charge interaction, and got a tumor microenvironment (TME)-activatable PCPTSS/IR820 nanoreactor to perform thermal/fluorescence/photoacoustic imaging-guided chemotherapy and photothermal therapy (PTT) simultaneously. Specifically, the generated PCPTSS/IR820 showed excellent therapeutic agent loading content and size stability, and the trials in vitro and in vivo suggested that the smart PCPTSS/IR820 could deeply permeate into tumor tissue due to its suitable micellar size. Upon near infrared laser irradiation, the nanoreactor further produced a terrific synergism of chemo-photo treatment for cancer therapy. Therefore, the PCPTSS/IR820 polyprodrug based nanoreactor hold outstanding promise for multimodal imaging and combined dual-therapy.

2.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(3): 289-295, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31496161

RESUMO

OBJECTIVE: To investigate the effect and mechanism of glucosides of chaenomeles speciosa (GCS) on ischemia/reperfusion-induced brain injury in mouse model. METHODS: Fifty 8-week C57BL/C mice were randomly divided into five groups with 10 in each group:sham group, model group, GCS 30 mg/kg group, GCS 60 mg/kg group and GCS 90 mg/kg group, and the GCS was administrated by gavage (once a day) for 14 d. HE staining was performed to investigate the cell morphology; the Zea-Longa scores were measured for neurological activity; TUNEL staining was performed to investigate the cell apoptosis; ELISA was used to detected the oxidative stress and inflammation; Western Blot was performed to investigate the key pathway and neurological functional molecules. RESULTS: Compared with the sham group, the brain tissues in model group were seriously damaged, presenting severe cell apoptosis, oxidative stress and inflammation, associated with increased NF-κB P65 and TNF-α levels as well as decreased myelin associate glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp)levels (all P<0.01). Compared with the model group, the brain tissues in GCS groups were ameliorated, and cell apoptosis, oxidative stress and inflammation were inhibited, associated with decreased NF-κB P65 and TNF-α levels as well as increased MAG and OMgp levels (all P<0.01), which were more markedly in GCS 60 mg/kg group. CONCLUSIONS: GCS can inhibit the NF-κB P65 and TNF-α, reduce the oxidative stress and inflammation, decrease the cell apoptosis in mouse ischemia/reperfusion-induced brain injury model, and 60 mg/kg GCS may be the optimal dose.


Assuntos
Lesões Encefálicas , Glucosídeos , Rosaceae , Fator de Necrose Tumoral alfa , Animais , Encéfalo/efeitos dos fármacos , Lesões Encefálicas/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Distribuição Aleatória , Rosaceae/química , Fator de Necrose Tumoral alfa/genética
3.
Biomed Res Int ; 2019: 6282635, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531360

RESUMO

Quercetin, a natural flavonol existing in many food resources, has been reported to be an effective antimicrobial and anti-inflammatory agent for restricting the inflammation in periodontitis. In this study, we aimed to investigate the anti-inflammatory effects of quercetin on Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide- (LPS-) stimulated human gingival fibroblasts (HGFs). HGFs were pretreated with quercetin prior to LPS stimulation. Cell viability was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The levels of inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), along with chemokine interleukin-8 (IL-8), were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of IL-1ß, IL-6, IL-8, TNF-α, IκBα, p65 subunit of nuclear factor-kappa B (NF-κB), peroxisome proliferator-activated receptor-γ (PPAR-γ), liver X receptor α (LXRα), and Toll-like receptor 4 (TLR4) were measured by real-time quantitative PCR (RT-qPCR). The protein levels of IκBα, p-IκBα, p65, p-p65, PPAR-γ, LXRα, and TLR4 were characterized by Western blotting. Our results demonstrated that quercetin inhibited the LPS-induced production of IL-1ß, IL-6, IL-8, and TNF-α in a dose-dependent manner. It also suppressed LPS-induced NF-κB activation mediated by TLR4. Moreover, the anti-inflammatory effects of quercetin were reversed by the PPAR-γ antagonist of GW9662. In conclusion, these results suggested that quercetin attenuated the production of IL-1ß, IL-6, IL-8, and TNF-α in P. gingivalis LPS-treated HGFs by activating PPAR-γ which subsequently suppressed the activation of NF-κB.

4.
Theranostics ; 9(21): 6314-6333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534553

RESUMO

Regenerated silk fibroin (SF) is a type of natural biomacromolecules with outstanding biocompatibility and biodegradability. However, stimulus-responsive SF-based nanocomplex has seldom been reported for application in tumor diagnosis and therapy. Methods: As a proof-of-concept study, a multifunctional SF@MnO2 nanoparticle-based platform was strategically synthesized using SF as a reductant and a template via a biomineralization-inspired crystallization process in an extremely facile way. Because of their mesoporous structure and abundant amino and carboxyl terminal residues, SF@MnO2 nanoparticles were co-loaded with a photodynamic agent indocyanine green (ICG) and a chemotherapeutic drug doxorubicin (DOX) to form a SF@MnO2/ICG/DOX (SMID) nanocomplex. Results: The obtained product was highly reactive with endogenous hydrogen peroxide (H2O2) in tumor microenvironment, which was decomposed into O2 to enhance tumor-specific photodynamic therapy (PDT). Moreover, SMID nanocomplex produced a strong and stable photothermal effect upon near-infrared (NIR) irradiation for photothermal therapy (PTT) owing to the distinct photothermal response of SF@MnO2 and stably conjugated ICG. The concurrent NIR fluorescence and magnetic resonance (MR) imaging in vivo both indicated effective tumor-specific enrichment of SMID nanoparticles via enhanced permeability and retention (EPR) effect. Animal studies further verified that SMID nanoparticles remarkably improved tumor inhibitive efficacy through combination PTT/PDT/chemotherapy with minimal systemic toxicity or adverse effect. Conclusion: This study demonstrated the promising potential of SF-based nanomaterial to address some of the key challenges in cancer therapy due to unfavorable tumor microenvironment for drug delivery.

5.
ACS Appl Mater Interfaces ; 11(39): 36130-36140, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31490659

RESUMO

Low delivery efficiency and limited tumor penetration of nanoparticle-based drug delivery systems (DDSs), the two most concerned issues in tumor therapy, have been considered as the "Achilles' heel" for tumor treatment. In this study, we have designed a highly sensitive dual-redox-responsive prodrug-based starlike polymer ß-CD-b-P(CPTGSH-co-CPTROS-co-OEGMA) (CPGR) for synergistic chemotherapy. The high glutathione (GSH) concentration and high reactive oxygen species (ROS) levels are in a dynamic equilibrium in the tumor microenvironment (TME) and could trigger the disintegration of CPGR micelles, which can promote the release of anticancer drug camptothecin (CPT) completely and intelligently. In order to verify the synergistic antitumor mechanism, two corresponding single-responsive ß-CD-b-P(CPTGSH-co-OEGMA) (CPG) and ß-CD-b-P(CPTROS-co-OEGMA) (CPR) were altogether prepared as contrast. Both in vitro and in vivo studies confirmed the enhanced anticancer activity of CPGR micelles in comparison of single responsive micelles. This work contributes to the orchestrated design of dual-redox-responsive DDSs for synergetic antitumor chemotherapy, which provides a good approach for the development of dual-redox-responsive nanomedicine.

6.
Colloids Surf B Biointerfaces ; 183: 110428, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31415956

RESUMO

Tumor microenvironment (TME)-induced drug delivery technology is a promising strategy for improving low drug accumulation efficiency, short blood circulation and weak therapeutic effect. In this work, a dual-responsive (reduction- and pH-responsive) polyprodrug nanoreactor based on ß-cyclodextrin (ß-CD) was constructed for combinational chemotherapy. Specifically, the dual-responsive star polymeric prodrug was synthesized by atom transfer radical polymerization (ATRP) based on a starburst initiator of ß-CD-Br. The obtained polyprodrug contained a hydrophilic chain of poly-(ethylene glycol) methyl ether methacrylate (POEGMA) and a hydrophobic part of camptothecin (CPT) prodrug and poly[2-(diisopropylamino)ethyl methacrylate] (PDPA), denoted as ß-CD-PDPA-POEGMA-PCPT (CCDO for short). The obtained CCDO could form stable unimolecular micelles, which could be efficiently internalized by cancer cells. To enhance the curative effect, the anticancer agent doxorubicin (DOX) could be encapsulated into the hydrophobic cavity of the CCDO by hydrophobic-hydrophobic interaction. In vitro drug release studies showed that the obtained CCDO/DOX micelles controlled the release of active CPT and DOX occurring in a reductive environment and at low pH. In vitro cytotoxicity results suggested that the anticancer efficacy of dual-responsive CCDO/DOX micelles was superior to that of CCDO micelles. In addition, in vivo results verified good blood compatibility of the unimolecular micelles. This integrated dual-responsive drug delivery system may solve the low drug loading and poor controlled release problems found in traditional polymer-based drug carriers, providing an innovative and promising route for cancer therapy.

7.
Nanomedicine (Lond) ; 14(17): 2273-2292, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31414615

RESUMO

Aim: Hollow mesoporous copper sulfide nanocapsules conjugated with poly(ethylene glycol) (PEG), doxorubicin and chlorin e6 (HPDC) were synthesized for fluorescence imaging and multimodal tumor therapy. Materials & methods: HPDC were synthesized by encapsulating chlorin e6 and doxorubicin into PEGylated nanocapsules via a simple precipitation method. The photothermal/photodynamic effects, drug release, cellular uptake, imaging capacities and antitumor effects of the HPDCs were evaluated. Results: This smart nanoplatform is stimulus-responsive toward an acidic microenvironment and near infrared laser irradiation. Moreover, fluorescence imaging-guided and combined photothermal/photodynamic/chemotherapies of tumors were promoted under laser activation and led to efficient tumor ablation, as evidenced by exploring animal models in vivo. Conclusion: HPDCs are expected to serve as potent and reliable nanoagents for achieving superior therapeutic outcomes in cancer management.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31449010

RESUMO

To solve the problem that traditional image registration methods based on continuous optimization for large motion lung 4D CT image sequences are easy to fall into local optimal solutions and lead to serious misregistration, a novel image registration method based on high-order Markov Random Field (MRF) is proposed. By analyzing the effect of the deformation field constraint of the potential functions with different order cliques in MRF model, energy functions with high-order cliques form are designed separately for 2D and 3D images to preserve topology of the deformation field. In order to preserve the topology of the deformation field more effectively, it is necessary to apply a smooth term and a topology preservation term simultaneously in the energy function and use logarithmic function to impose a penalty on the Jacobian matrix with high-order cliques in the topology preservation term. For the complexity of the designed energy function with high-order cliques form, Markov Chain Monte Carlo (MCMC) algorithm is used to solve the optimization problem of the designed energy function. To address the high computational requirements in lung 4D CT image registration, a multi-level processing strategy is adopted to reduce the space complexity of the proposed registration method and promotes the computational efficiency. In the DIR-lab dataset with 4D CT images and the COPD (Chronic Obstructive Pulmonary Disease) dataset with 3D CT images, the average target registration error (TRE) of our proposed method can reach 0.95mm respectively.

9.
Eur J Pharm Sci ; 138: 104990, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302216

RESUMO

The purpose of this study was to solve the plateau phase (the stage in which the drug in the microsphere undergoes a slow release or almost no release after initial release) problem by understanding the effect of polymer blends on the internal pore changes of the microspheres. This study used PLGA 5050 4H (F-1), PLGA 5050 1A: PLGA 5050 4H = 3:7 (F-2) and PLGA 7525 1A: PLGA 5050 4H = 3:7 (F-3) as a carrier, respectively. Microspheres (MS) were obtained by O/W emulsion solvent evaporation technique and characterized by scanning electron microscopy (SEM), particle size, drug loading, fluorescence characteristics, and in vitro and in vivo release. Accelerated tests in vitro showed that the size and number of core pores significantly affected drug release in the first and second phases. After intramuscular administration, F-2 and F-3 showed effective blood concentration levels and their bioavailability was higher than that of the RLD (Sandostatin Lar). In general, our data indicate that pore formation is unevenly distributed throughout PLGA MS prepared using polymer blends, and the use of polymer blends is instructive for the development of sustained smooth release microspheres. Therefore, the octreotide MS described in this study has a good clinical application potential for the treatment of acromegaly.

10.
Curr Gene Ther ; 19(2): 93-99, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31267871

RESUMO

Acute Respiratory Distress Syndrome (ARDS) and its complications remain lifethreatening conditions for critically ill patients. The present therapeutic strategies such as prone positioning ventilation strategies, nitric oxide inhalation, restrictive intravenous fluid management, and extracorporeal membrane oxygenation (ECMO) do not contribute much to improving the mortality of ARDS. The advanced understanding of the pathophysiology of acute respiratory distress syndrome suggests that gene-based therapy may be an innovative method for this disease. Many scientists have made beneficial attempts to regulate the immune response genes of ARDS, maintain the normal functions of alveolar epithelial cells and endothelial cells, and inhibit the fibrosis and proliferation of ARDS. Limitations to effective pulmonary gene therapy still exist, including the security of viral vectors and the pulmonary defense mechanisms against inhaled particles. Here, we summarize and review the mechanism of gene therapy for acute respiratory distress syndrome and its application.

11.
Br J Cancer ; 121(6): 511-512, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31350527

RESUMO

The original version of this article contained an error in Figure 6A. The volumes of the tumour xenografts were incorrectly calculated. The correct figure and figure legend are provided, where the volume has been calculated using V = length × width2×π/6. The interpretation of the data and conclusions are not affected.

12.
Cell Cycle ; 18(18): 2344-2358, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31345099

RESUMO

Objective: Recently, many studies have revealed the effect of microRNAs (miRNAs) in knee osteoarthritis (KOA). This study aims to explore the role of miR-140-5p in protective effects and mechanisms of synovial injury of rats with KOA via regulating the TLR4/Myd88/NF-κB signaling pathway. Methods: The models of KOA Wistar rats were established by operation of anterior cruciate ligament transection. Rats were injected with agomir NC or miR-140-5p agomir. MiR-140-5p expression in KOA synovial tissues and synoviocytes was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The synoviocytes were transfected with mimics NC sequence and miR-140-5p mimics sequence. The expression of TLR4/Myd88/NF-κB signaling pathway-related proteins was measured by RT-qPCR and western blot analysis. The proliferation and apoptosis of synoviocytes in rats with KOA were evaluated by a string of experiments. The expression levels of inflammatory factors in KOA synovial tissues and synoviocytes were detected. Results: MiR-140-5p was down-regulated in KOA synovial tissues and synoviocytes. Upregulation of miR-140-5p could inhibit the inflammation reaction and the apoptosis of synoviocytes as well as promote proliferation of synoviocytes of rats with KOA. Furthermore, upregulated miR-140-5p could inactivate the TLR4/Myd88/NF-κB signaling pathway in rats with KOA. Conclusion: This study suggests that upregulated miR-140-5p could protect synovial injury by restraining inflammation reaction and apoptosis of synoviocytes in KOA rats via TLR4/Myd88/NF-κB signaling pathway inactivation.

13.
Ying Yong Sheng Tai Xue Bao ; 30(6): 1983-1992, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31257771

RESUMO

In this study, the effects of intercropping with alfalfa and nitrogen application on the functional diversity of soil microbial community in mulberry rhizosphere were examined by Biolog-EcoplateTM technique, and principal component and canonical analyses. Compared to monoculture with no nitrogen (N) addition, monoculture with N application and intercropping with alfalfa remarkably reduced soil pH and significantly increased the contents of soil organic matter, soil available N, soil water content, and activities of peroxidase and urease. Monoculture with N application and intercropping with alfalfa (with or without N application) increased the AWCD values, diversity index, and the carbon source utilization ratios of soil microbes. Higher increments of these parameters were detected in the treatment of intercropping plus N application. The results of principal component analysis showed that N application and intercropping changed the capacity of the rhizosphere microbial community for utilizing carbon sources. The utilization of carbon sources highly related to the principal components by the rhizosphere microbial communities was similar in the treatments of monoculture with N application and intercropping without N application. The utilization of itaconic acid and D-glucamaminic acid in the latter was more than 4% and was significantly higher than that in the former. The results from redundancy analysis showed that the soil microbial diversity in mulberry rhizosphere of the treatment of monoculture without N application was positively correlated with polyphenol oxidase activity and negatively correlated with soil water content, whereas that of monoculture with N application and intercropping without N application was significantly positively correlated with soil pH and soil water content and negatively correlated with soil N avalaibility. The diversity of the microbes in the rhizosphere soil of mulberries under the treatment of intercropping with N application showed positive correlation with soil N availability and was significantly negatively correlated with soil pH.


Assuntos
Agricultura/métodos , Microbiota , Morus/microbiologia , Microbiologia do Solo , Fertilizantes , Nitrogênio , Solo
14.
Drug Deliv ; 26(1): 700-707, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31290705

RESUMO

Efficient delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate borneol and lactoferrin co-modified nanoparticles (Lf-BNPs) encapsulated dopamine as a novel drug delivery system to achieve maximum therapeutic efficacy and reduce side effects for PD. Dopamine Lf-BNPs were prepared using the double emulsion solvent evaporation method and evaluated for physicochemical and pharmaceutical properties. In vitro cytotoxicity studies indicated that treatment with dopamine Lf-BNPs has relatively low cytotoxicity in SH-SY5Y and 16HBE cells. Qualitative and quantitative cellular uptake experiments indicated that Lf modification of NPs increased cellular uptake of SH-SY5Y cells and 16HBE cells, and borneol modification can promote the cellular uptake of 16HBE. In vivo pharmacokinetic studies indicated that AUC0-12 h in the rat brain for dopamine Lf-BNPs was significantly higher (p < .05) than that of dopamine nanoparticles. Intranasal administration of dopamine Lf-BNPs effectively alleviated the 6-hydroxydopamine-induced striatum lesion in rats as indicated by the contralateral rotation behavior test and results for striatal monoamine neurotransmitter content detection. Taken together, intranasal administration of dopamine Lf-BNPs may be an effective drug delivery system for Parkinson's disease.

15.
ACS Appl Mater Interfaces ; 11(32): 29330-29340, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31329411

RESUMO

Mitochondria-targeting cancer therapies have achieved unprecedented advances attributed to their superior ability for improving drug delivery efficiency and producing an enhanced therapeutic effect. Herein, we report a mitochondria-targeting camptothecin (CPT) polyprodrug system (MCPS) covalently decorated with a high-proportioned CPT content, which can realize drug release specifically responsive to a tumor microenvironment. The nonlinear structure of MCPS can form water-soluble unimolecular micelles with high micellar stability and improved drug accumulation in tumoral cells/tissues. Furthermore, a classical mitochondria-targeting agent, triphenylphosphonium bromide, was tethered in this prodrug system, which causes mitochondrial membrane potential depolarization and mediates the transport of CPT into mitochondria. The disulfide bond in MCPS can be cleaved by an intracellular reductant such as glutathione, leading to enhanced destruction of mitochondria DNA and cell apoptosis induced by a high level of reactive oxygen species. The systematic analyses both in vitro and in vivo indicated the excellent tumor inhibition effect and biosafety of MCPS, which is believed to be an advantageous nanoplatform for subcellular organelle-specific chemotherapy of cancer.

16.
Nanotechnology ; 30(43): 435403, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31342936

RESUMO

Herein, a carbon membrane and Au nanoparticles were combined to improve the efficiency of photoelectrocatalytic water splitting over a TiO2 nanotube arrays film (TiO2 NTAF). Two different ternary nanostructures were constructed by hydrothermal and photochemical deposition processes. One was carbon membrane bridged Au nanoparticles and TiO2 nanotube arrays (Au/C/TiO2 NTAF), while the other was Au nanoparticles sandwiched between carbon membrane and TiO2 nanotube arrays (C/Au/TiO2 NTAF). The two structures exhibited enhanced visible light harvesting ability, but they showed distinctly different photoelectric properties. The unique microstructure of C/Au/TiO2 NTAF resulted in a much higher reduction of the electron cloud density of Au nanoparticles as carrier recombination centers, which were responsible for its poor photoelectrochemical performance. However, a champion photocurrent of Au/C/TiO2 NTAF was observed (0.984 mA cm-2), indicating superior ability of the photoelectrocatalytic water splitting. The great enhancement was attributed to multiple carriers transport paths, which can efficiently utilize the sensitization of the carbon membrane and the surface plasmon resonance effect of the Au nanoparticles.

17.
Mol Med Rep ; 20(3): 2199-2208, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31257520

RESUMO

Small­cell lung cancer (SCLC) is a type of lung cancer with early metastasis, and high recurrence and mortality rates. The molecular mechanism is still unclear and further research is required. The aim of the present study was to examine the pathogenesis and potential molecular markers of SCLC by comparing the differential expression of mRNA and microRNA (miRNA) between SCLC tissue and normal lung tissue. A transcriptome sequencing dataset (GSE6044) and a non­coding RNA sequence dataset (GSE19945) were downloaded from the Gene Expression Omnibus (GEO) database. In total, 451 differentially expressed genes (DEGs) and 134 differentially expressed miRNAs (DEMs) were identified using the R limma software package and the GEO2R tool of the GEO, respectively. The Gene Ontology function was significantly enriched for 28 terms, and the Kyoto Encyclopedia of Genes and Genomes database had 19 enrichment pathways, mainly related to 'cell cycle', 'DNA replication' and 'oocyte meiosis mismatch repair'. The protein­protein interaction network was constructed using Cytoscape software to identify the molecular mechanisms of key signaling pathways and cellular activities in SCLC. The 1,402 miRNA­gene pairs encompassed 602 target genes of the DEMs using miRNAWalk, which is a bioinformatics platform that predicts DEM target genes and miRNA­gene pairs. There were 19 overlapping genes regulated by 32 miRNAs between target genes of the DEMs and DEGs. Bioinformatics analysis may help to better understand the role of DEGs, DEMs and miRNA­gene pairs in cell proliferation and signal transduction. The related hub genes may be used as biomarkers for the diagnosis and prognosis of SCLC, and as potential drug targets.

18.
J Org Chem ; 84(19): 12259-12267, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31315398

RESUMO

A general one-step synthesis of symmetrical or unsymmetrical 1,4-di(organo)fullerenes from organo(hydro)fullerenes (RC60H) is realized by direct oxidative arylation. The new combination of catalytic trifluoromethanesulfonic acid (TfOH) and stoichiometric o-chloranil is the first to be used to directly generate an R-C60+ intermediate from common RC60H. Unexpectedly, the in situ generated R-C60+ intermediate is shown to be quite stable in whole 13C NMR spectroscopy characterization in the absence of cation quenching reagents. Because the direct oxidation of common RC60H to form the corresponding R-C60+ has never been realized, the present combination of TfOH and o-chloranil solves the challenges associated with the formation of stable RC60+ cations from common RC60H without any coordination of an R group.

19.
Biomed Microdevices ; 21(3): 58, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227909

RESUMO

Traditional immunomagnetic assays for the isolation and recovery of circulating tumor cells (CTCs) usually require sophisticated device or intense magnetic field to simultaneously achieve high capture efficiency and high throughout. In this study, a simple microfluidic chip featured with nanoroughened channel substrate was developed for effectively capture and release of CTCs based on an immunomagnetic chip-based approach. The nanoroughened substrate aims to increase the cell-surface contact area, facilitate the immobilization of magnet particles (MPs) and accommodate cell attachment tendency. Hep3B tumor cells were firstly conjugated with MPs that were functionalized with anti-EpCAM. Comparing with the flat channel, MPs modified tumor cells can be more effectively captured on nanoroughened substrate at the presence of the magnetic field. Upon the removal of magnetic field, these captured cells can be released from the device and collected for further analysis. Under the optimum operating conditions, the capture efficiency of tumor cells was obtained as high as ~90% with a detection limit of 10 cell per mL. Additionally, recovery rates of trapped tumor cells at various densities all exceeded 90% and their biological potencies were well retained by investigating the cell attachment and proliferation. Therefore, the present approach may potentially be used in clinical CTC analysis for cancer diagnosis and prognosis as well as the fundamental understanding of tumor metastasis.

20.
J Cell Mol Med ; 23(8): 5380-5389, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31199046

RESUMO

Although several chemokines play key roles in the pathogenesis of acute lung injury (ALI), the roles of chemokine (C-X-C motif) ligand 16 (CXCL16) and its receptor C-X-C chemokine receptor type 6 (CXCR6) in ALI pathogenesis remain to be elucidated. The mRNA and protein expression of CXCL16 and CXCR6 was detected after lipopolysaccharide (LPS) stimulation with or without treatment with the nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC). Lung injury induced by LPS was evaluated in CXCR6 knockout mice. CXCL16 level was elevated in the serum of ALI patients (n = 20) compared with healthy controls (n = 30). CXCL16 treatment (50, 100, and 200 ng/mL) in 16HBE cells significantly decreased the epithelial barrier integrity and E-cadherin expression, and increased CXCR6 expression, reactive oxygen species (ROS) production, and p38 phosphorylation. Knockdown of CXCR6 or treatment with the p38 inhibitor SB203580 abolished the effects of CXCL16. Moreover, treatment of 16HBE cells with LPS (5, 10, 20 and 50 µg/mL) significantly increased CXCL16 release as well as the mRNA and protein levels of CXCL16 and CXCR6. The effects of LPS treatment (20 µg/mL) were abolished by treatment with PDTC. The results of the luciferase assay further demonstrated that PDTC treatment markedly inhibited the activity of the CXCL16 promoter. In conclusion, CXCL16, whose transcription was enhanced by LPS, may be involved in ROS production, epithelial barrier dysfunction and E-cadherin down-regulation via p38 signalling, thus contributing to the pathogenesis of ALI. Importantly, CXCR6 knockout or inhibition of p38 signalling may protect mice from LPS-induced lung injury by decreasing E-cadherin expression.

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