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1.
Org Lett ; 26(17): 3557-3562, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38652078

RESUMO

A sequential dearomatization/rearrangement reaction between quinazoline-derived azomethine imines and crotonate sulfonium salts has been developed to provide a series of three-dimensional cage-like molecules. The reaction involves two dearomatizations, two cyclizations, and two C-C bond and three C-N bond formations in one step. The new transformation has a broad substrate scope, does not require any added reagents, and proceeds under room temperature in a short time. A mechanistic rationale for the sequential dearomatization/rearrangement is also presented. Furthermore, the synthetic compounds are evaluated for their glucose control effect. Compounds 3aa and 3aj were found to be hyperglycemic, which might be lead compounds for treating hypoglycemia.

2.
Lab Chip ; 23(8): 2068-2074, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-36928455

RESUMO

Open microfluidics has attracted increasing attention over the last decade because of its flexibility and simplicity with respect to cell culture and clinical diagnosis. However, traditional valves and pumps are difficult to integrate on open-channel microfluidic chips, in which a liquid is usually driven by capillary forces. Poor fluid control performance is a common drawback of open microfluidics. Herein, we proposed a method for controlling the liquid flow in open channels by controlling the continuous Laplace pressure induced by the deformation of the shape memory microstructures. The uniformly arranged cuboidal microcolumns in the open channels have magnetic/light dual responses, and the bending angle of the microcolumns can be controlled by adjusting Laplace pressure using near-infrared laser irradiation in a magnetic field. Laplace pressure and capillary force drove the liquid flow together, and the controllable fluid transport was realized by adjusting the hydrophilicity of the channel surface and the bending angle of the microcolumns. We demonstrated the controllability of the flow rate and the directional transport of water along a preset path. In addition, the start and stop of water transport were realized via local hydrophobic modification. The proposed strategy improves poor fluid control in traditional open systems and makes fluid flow highly controllable. We tried to extract and detect rhodamine B in tiny droplets on the open microfluidic chip, demonstrating the advantages of the proposed strategy in the separation and analysis of tiny samples.

3.
J Clin Invest ; 133(4)2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36626227

RESUMO

The role of tumor-associated macrophages (TAMs), along with the regulatory mechanisms underlying distinct macrophage activation states, remains poorly understood in prostate cancer (PCa). Herein, we report that PCa growth in mice with macrophage-specific Ubc9 deficiency is substantially suppressed compared with that in wild-type littermates, an effect partially ascribed to the augmented CD8+ T cell response. Biochemical and molecular analyses revealed that signal transducer and activator of transcription 4 (STAT4) is a crucial UBC9-mediated SUMOylation target, with lysine residue 350 (K350) as the major modification site. Site-directed mutation of STAT4 (K350R) enhanced its nuclear translocation and stability, thereby facilitating the proinflammatory activation of macrophages. Importantly, administration of the UBC9 inhibitor 2-D08 promoted the antitumor effect of TAMs and increased the expression of PD-1 on CD8+ T cells, supporting a synergistic antitumor efficacy once it combined with the immune checkpoint blockade therapy. Together, our results demonstrate that ablation of UBC9 could reverse the immunosuppressive phenotype of TAMs by promoting STAT4-mediated macrophage activation and macrophage-CD8+ T cell crosstalk, which provides valuable insights to halt the pathogenic process of tumorigenesis.


Assuntos
Ativação de Macrófagos , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Linfócitos T CD8-Positivos , Ativação de Macrófagos/genética , Neoplasias da Próstata/genética , Microambiente Tumoral
4.
J Virol ; 96(6): e0214121, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35044216

RESUMO

Due to the high mutation rate of influenza virus and the rapid increase of drug resistance, it is imperative to discover host-targeting antiviral agents with broad-spectrum antiviral activity. Considering the discrepancy between the urgent demand of antiviral drugs during an influenza pandemic and the long-term process of drug discovery and development, it is feasible to explore host-based antiviral agents and strategies from antiviral drugs on the market. In the current study, the antiviral mechanism of arbidol (ARB), a broad-spectrum antiviral drug with potent activity at early stages of viral replication, was investigated from the aspect of hemagglutinin (HA) receptors of host cells. N-glycans that act as the potential binding receptors of HA on 16-human bronchial epithelial (16-HBE) cells were comprehensively profiled for the first time by using an in-depth glycomic approach based on TiO2-PGC chip-Q-TOF MS. Their relative levels upon the treatment of ARB and virus were carefully examined by employing an ultra-high sensitive qualitative method based on Chip LC-QQQ MS, showing that ARB treatment led to significant and extensive decrease of sialic acid (SA)-linked N-glycans (SA receptors), and thereby impaired the virus utilization on SA receptors for rolling and entry. The SA-decreasing effect of ARB was demonstrated to result from its inhibitory effect on sialyltransferases (ST), ST3GAL4 and ST6GAL1 of 16-HBE cells. Silence of STs, natural ST inhibitors, as well as sialidase treatment of 16-HBE cells, resulted in similar potent antiviral activity, whereas ST-inducing agent led to the diminished antiviral effect of ARB. These observations collectively suggesting the involvement of ST inhibition in the antiviral effect of ARB. IMPORTANCE This study revealed, for the first time, that ST inhibition and the resulted destruction of SA receptors of host cells may be an underlying mechanism for the antiviral activity of ARB. ST inhibition has been proposed as a novel host-targeting antiviral approach recently and several compounds are currently under exploration. ARB is the first antiviral drug on the market that was found to possess ST inhibiting function. This will provide crucial evidence for the clinical usages of ARB, such as in combination with neuraminidase (NA) inhibitors to exert optimized antiviral effect, etc. More importantly, as an agent that can inhibit the expression of STs, ARB can serve as a novel lead compound for the discovery and development of host-targeting antiviral drugs.


Assuntos
Indóis , Sialiltransferases , Sulfetos , Antivirais/farmacologia , Antivirais/uso terapêutico , Linhagem Celular , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Células Epiteliais , Glicômica , Hemaglutininas , Humanos , Indóis/farmacologia , Indóis/uso terapêutico , Neuraminidase/farmacologia , Polissacarídeos/metabolismo , Sialiltransferases/antagonistas & inibidores , Sulfetos/farmacologia , Sulfetos/uso terapêutico
5.
Rare Metals ; 41(2): 559-569, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34177195

RESUMO

Copper (Cu)-bearing stainless steel has testified its effectiveness to reduce the risk of bacterial infections. However, its antibacterial mechanism is still controversial. Therefore, three 430 ferritic stainless steels with different Cu contents are selected to conduct deeper research by the way of bacterial inactivation from two aspects of material and biology. Hereinto, electrochemical and antibacterial results show that the increase in Cu content simultaneously improves the corrosion resistance and antibacterial property of 430 stainless steel. In addition, it is found that Escherichia coli (E. coli) on the surface 430 Cu-bearing stainless steel by the dry method of inoculation possesses a rapid inactivation ability. X-ray photoelectron spectroscopy (XPS) aids with ion chelation experiments prove that Cu (I) plays a more crucial role in the contact-killing efficiency than Cu (II), resulting from more production of reactive oxygen species (ROS).

6.
BMC Oral Health ; 21(1): 483, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34583665

RESUMO

BACKGROUND: Dental caries is one of the most preventable oral diseases among children in developing countries. This study aims to estimate the prevalence and severity of dental caries in the first permanent molar and analyze the related risk factors among sixth-grade students in São Tomé Island. METHODS: A cross-sectional study with a stratified cluster sampling method was conducted on 1855 sixth-grade school children, mainly aged 11 to 14 years old, from 10 schools in 6 regions of São Tomé Island, from April 17 to June 27, 2021. Dental caries examination was performed by using the CAST criteria (DMFT) index, and the self-administered questionnaires about family background, oral hygiene, and relevant behaviors were collected. Multivariable logistic regression was used to study risk factors related to dental caries of the first permanent molar, and all data analyses were done using SPSS version 25. RESULTS: The prevalence of dental caries in the first permanent molar was 68.79%, without significant difference between gender, age, residence, and whether only child or not. The mean Decayed, Missing, and Filled Teeth (DMFT) index and mean Decayed, Missing, and Filled Surface (DMFS) index were 1.751 ± 1.514 and 3.542 ± 3.941, respectively. The rate of filling teeth was 5.50%, and Pit and Fissure Sealant (PFS) rate was 2.21%. The overall prevalence and DMFT index of dental caries of permanent teeth was 76.01% and 2.753 ± 4.569, respectively. The results of logistic regression analysis indicated that the frequency of candy/chocolate consumption (OR = 1.095) and fair self-assessment of dental health (OR = 1.354) were significantly associated with dental caries (P < 0.05). CONCLUSIONS: The high prevalence of dental caries in the first permanent molar was a public health issue among sixth-grade school children in São Tomé Island. The prevalence of dental caries, mean DMFT and DMFS scores were higher, while the rate of filling and PFS teeth were lower than the average score of other African countries. Thus, oral health education, implement oral health preaching to school children and their parents is crucial to prevent dental caries.


Assuntos
Cárie Dentária , Adolescente , Criança , Estudos Transversais , Índice CPO , Cárie Dentária/epidemiologia , Humanos , Dente Molar , Prevalência , Fatores de Risco , Estudantes
7.
J Int Med Res ; 49(5): 3000605211013172, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33983064

RESUMO

The patient was a 62-year-old man diagnosed as having prostatic extra-gastrointestinal stromal tumor (EGIST) who was treated with imatinib. No recurrence or metastasis was found after a 6-month follow-up. We identified 14 cases of prostatic primary EGIST in PubMed and summarized these cases with our case. The patients' ages ranged from 31 to 78 years (average: 53.6 years), and most patients' prostate-specific antigen (PSA) concentrations were within normal limits (92.9%, 13/14). All patients underwent imaging examinations; prostatic masses measured 6 to 14.2 cm (mean: 9.43 cm), and imaging excluded secondary prostatic masses from the intestinal tract. By immunohistochemical staining, the tumors were positive for cluster of differentiation (CD)117 (71.4%, 10/14), DOG1 (100%, 7/7), and CD34 (100%, 14/14), and negative for smooth muscle actin (SMA) (71.4%, 10/14), desmin (100%, 11/11), and S100 (100%, 12/12). Treatment depended on the results of the gene mutation detection as well as the risk estimation according to tumor size and microscopic mitotic rates (>5 per 50 high-power fields: 60%, 6/10). Among the 12 patients with reported outcomes, nine achieved good results (no recurrence or metastasis), one achieved reduced mass volume, one experienced recurrence, and one died.


Assuntos
Tumores do Estroma Gastrointestinal , Adulto , Idoso , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Próstata/diagnóstico por imagem , Proteínas Proto-Oncogênicas c-kit/genética
8.
Lab Chip ; 21(6): 1131-1138, 2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33533387

RESUMO

In this work, we developed a digital microfluidic platform based on a shape memory micropillar array responsive to near-infrared light, and the droplets were programmatically manipulated through light-induced micropillar deformation. The micropillar array was constructed on the surface of a poly(ethylene-vinyl acetate) copolymer, a shape memory polymer sensitive to near-infrared light. Before droplet manipulation, the micropillar array was kept temporarily tilted by heating and pressing. Under the irradiation of a near-infrared laser, the micropillar array achieved the transition from the temporary shape to the original shape. Temperature gradient and micropillar deformation caused by near-infrared light irradiation produce the driving force for droplet movement. The movement of the laser mounted on an electronically controlled displacement platform was controlled by a computer to achieve the programmed control of the droplets. Moreover, we demonstrated light-manipulated droplet movement and fusion, and achieved ascorbic acid detection using this digital microfluidic platform. In particular, the micropillar array chip is able to manipulate droplets in a wide range of 0.1 µL to 10 µL. The proposed digital microfluidic platform will broaden the application of digital microfluidic technology in analytical chemistry and biomedicine.

9.
3 Biotech ; 10(4): 156, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32181118

RESUMO

To investigate the application of short elastin-like polypeptides (ELPs) in the purification of bioactive proteins, short hydrophobic ELP[I] n (n = 30, 40, 50) tags were constructed. Both the ELP[I] n tags and the ELP[I] n -Trx fusion proteins could be stably expressed in Escherichia coli and purified by inverse transition cycling, respectively. Total protein concentrations determined by BCA protein assay showed that the yield of the fusion proteins decreased with increasing ELP length. Measurements of the inverse transition temperature (T t) of the ELP[I] n -Trx under different salts or PEG8000 concentrations showed decreased T t upon elevated concentrations; while, all the T ts were suitable for generating proteins from 4 to 37.5 ºC. Furthermore, to identify a linker peptide for bioactive protein production without the need to remove the ELP[I] n tag, the activity of eGFP protein fused with ELP[I]30 tag by either a poly-N or a G4S linker was quantified using a fluorescence spectrophotometer. The results indicated that the ELP[I]30-eGFP fusion proteins with the poly-N linker showed higher fluorescence levels than those with the G4S linker. Our results demonstrated that short ELP[I] n tags with low T t were useful in protein expression and purification, and poly-N linker played the key role in producing bioactive proteins without the need to remove the ELPs.

11.
Mikrochim Acta ; 187(3): 194, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32124079

RESUMO

A controllable approach for preparing a portable colloidal photonic crystal (CPC) array chip is presented. The approach was inspired by the confinement effect of nanoparticle self-assembly on patterned surface. Hydrophobic polydimethylsiloxane substrate with reproducible micro-region array was fabricated by soft-lithography. The substrate was employed as the patterned template for self-assembly of monodisperse polystyrene nanoparticles. The CPC units can be prepared in several minutes, and exhibit consistent reflection wavelength. By adjusting the size of polystyrene nanoparticles and the shape of micro-regions, CPC units with multiple structure, colors and geometries were obtained. The CPC array chip features fluorescence enhancement owing to the optical modulation capability of the periodic nanostructure of the self-assembled CPC. With the reflection wavelength (523 nm) of green CPC units overlapping the emission wavelength (520 nm, with excitation wavelength of 490 nm) of 6-carboxyfluorescein-labeled DNA probe, the fluorescence intensity increased more than 10-fold. For signal-amplified assay of adenosine, the concentration range of linear response was 5.0 × 10-5 mol L-1 to 1.0 × 10-3 mol L-1, and the limit of detection was 1.3 × 10-6 mol L-1. Because of the enhancement effect of photonic crystal, the fluorescence images were more readable from the CPC array chip, compared with those from the planar substrate. The chip has potential applications in multiplex determination with high-throughput via encoding strategy based on the tunable structure, color or geometric shape. Graphical abstractSchematic diagram of signal-enhanced fluorescent detection of adenosine based on the colloidal photonic crystal array chip (PDMS, polydimethylsiloxane; PS NPs, polystyrene nanoparticles; CPC, colloidal photonic crystal; GO, graphene oxide; FAM, 6-carboxyfluorescein).


Assuntos
Adenosina/análise , Técnicas Biossensoriais/métodos , Fluoresceínas/química , Corantes Fluorescentes/química , Dispositivos Lab-On-A-Chip , Coloides , Cristalização , Sondas de DNA/química , Dimetilpolisiloxanos/química , Interações Hidrofóbicas e Hidrofílicas , Limite de Detecção , Fótons , Espectrometria de Fluorescência , Propriedades de Superfície
12.
J Proteome Res ; 19(4): 1470-1480, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32129075

RESUMO

Due to its relatively small size, homology to humans, and susceptibility to human viruses, the tree shrew becomes an ideal alternative animal model for the study of human viral infectious diseases. However, there is still no report for the comprehensive glycan profile of the respiratory tract tissues in tree shrews. In this study, we characterized the structural diversity of N-glycans in the respiratory tract of tree shrews using our well-established TiO2-PGC chip-Q-TOF-MS method. As a result, a total of 219 N-glycans were identified. Moreover, each identified N-glycan was quantitated by a high sensitivity and accurate MRM method, in which 13C-labeled internal standards were used to correct the inherent run-to-run variation in MS detection. Our results showed that the N-glycan composition in the turbinate and lung was significantly different from the soft palate, trachea, and bronchus. Meanwhile, 28 high-level N-glycans in turbinate were speculated to be correlated with the infection of H1N1 virus A/California/04/2009. This study is the first to reveal the comprehensive glycomic profile of the respiratory tract of tree shrews. Our results also help to better understand the role of glycan receptors in human influenza infection and pathogenesis.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Tupaiidae , Animais , Glicômica , Humanos , Espectrometria de Massas , Polissacarídeos , Titânio
13.
Anal Bioanal Chem ; 412(3): 647-655, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31836924

RESUMO

In this work, simple, rapid, and low-cost multiplexed detection of tumor-related micro-RNAs (miRNAs) was achieved based on multi-color fluorescence on a microfluidic droplet chip, which simplified the complexity of light path to a half. A four-T-junction structure was fabricated to form uniform nano-volume droplet arrays with customized contents. Multi-color quantum dots (QDs) used as the fluorescence labels were encapsulated into droplets to develop the multi-path fluorescence detection module. We designed an integrated multiplex fluorescence resonance energy transfer system assisted by multiple QDs (four colors) and one quencher to detect four tumor-related miRNAs (miRNA-20a, miRNA-21, miRNA-155, and miRNA-221). The qualitative analysis of miRNAs was realized by the color identification of QDs, while the quantitative detection of miRNAs was achieved based on the linear relationship between the quenching efficiency of QDs and the concentration of miRNAs. The practicability of the multiplex detection device was further confirmed by detecting four tumor-related miRNAs in real human serum samples. The detection limits of four miRNAs ranged from 35 to 39 pmol/L was achieved without any target amplification. And the linear range was from 0.1 nmol/L to 1 µmol/L using 10 nL detection volume (one droplet) under the detection speed of 320 droplets per minute. The multiple detection system for miRNAs is simple, fast, and low-cost and will be a powerful platform for clinical diagnostic analysis. Graphical abstract.


Assuntos
Colorimetria/métodos , MicroRNAs/metabolismo , Microfluídica , Fluorescência , Humanos , Limite de Detecção
14.
J Colloid Interface Sci ; 553: 631-638, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247502

RESUMO

This work demonstrated a microfluidic preparation process for novel Janus microparticles with individual drug release properties in each compartment. A flow-focusing microfluidic chip was designed to produce oil-in-water droplets from a mixed solution of poly(lactic-co-glycolic acid) and a triglyceride type lipid. Based on solvent evaporation-induced phase separation, droplets evolved and were solidified into Janus particles, each of which had a polymer compartment and a lipid compartment. The ratio of the two compartments in a particle can be discretionarily regulated, and the particle structure can also be flexibly altered to Janus-patchy, triple, quadruple or core-shell type. Phase transition of the chosen lipid from solid to liquid would occur under physiological temperature, which was applied for rapid release of the loaded drug. The polymer compartment would undergo a slow degradation process in physiological environment, facilitating sustained drug release. Paclitaxel was loaded into Janus particles during preparation, and staged release was achieved, leading to a combination of rapid and sustained release, which is highly desired in target drug delivery. This study would start the application of hybrid Janus particles of polymer-lipid type with novel release kinetics in drug delivery systems.


Assuntos
Sistemas de Liberação de Medicamentos , Lipídeos/química , Técnicas Analíticas Microfluídicas , Polímeros/síntese química , Técnicas Analíticas Microfluídicas/instrumentação , Tamanho da Partícula , Polímeros/química , Propriedades de Superfície
15.
Curr Med Sci ; 39(1): 99-110, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30868498

RESUMO

The aim of this review was to systematically compare the outcomes of enhanced recovery after surgery (ERAS) with standard care (SC) after radical cystectomy. We performed a systematic search of PubMed, Ovid, Web of Science, and the Cochrane Library to identify studies published until September 2017 which involved a comparison of ERAS and SC. A meta-analysis was performed to assess the outcomes of ERAS versus SC. Sixteen studies including 8 prospective and 8 retrospective trials met the eligibility criteria. A total of 2100 participants were assigned to ERAS (1258 cases) or SC (842 cases). The time to first flatus passage {WMD=-0.95 days, 95% CI (-1.50,-0.41), P=0.0006}, time until return to a regular diet {WMD=-2.15 days, 95% CI (-2.86,-1.45), P<0.00001} and the length of hospital stay {WMD=-3.75 days, 95% CI (-5.13,-2.36), P<0.00001} were significantly shorter, and the incidence of postoperative complications {OR=0.60, 95% CI (0.44, 0.83), P=0.002}, especially postoperative paralytic ileus {OR=0.43, 95% CI (0.30, 0.62), P<0.00001} and cardiovascular complications {OR=0.28, 95% CI (0.09, 0.90), P=0.03} was significantly lower in the ERAS group than those in the SC group. This meta-analysis demonstrated that ERAS was associated with a shorter time to first flatus passage, return of bowel function, and the length of hospital stay than SC in patients undergoing radical cystectomy, as well as a lower rate of postoperative complications, especially paralytic ileus and cardiovascular complications.


Assuntos
Cistectomia/métodos , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Bexiga Urinária/cirurgia , Humanos , Tempo de Internação , Estudos Prospectivos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Padrão de Cuidado , Neoplasias da Bexiga Urinária/reabilitação
16.
Emerg Microbes Infect ; 8(1): 232-241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30866776

RESUMO

Zika virus (ZIKV) is a mosquito-borne flavivirus that caused the public health emergency. Recently, we have proved a novel small animal tree shrew was susceptive to ZIKV infection and presented the most common rash symptoms as ZIKV patients. Here we further cultured the primary cells from different tissues of this animal to determine the tissue tropism of ZIKV infection in vitro. The results showed that the primary cells from tree shrew kidney, lung, liver, skin and aorta were permissive to ZIKV infection and could support viral replication by the detection of viral specific RNA intra- and extra-cells. In comparing, the skin fibroblast and vascular endothelial cells were highly permissive to ZIKV infection with high releasing of active virus particles in supernatants proved by its infectivity in established neonatal mouse model. The expressions of ZIKV envelop and nonstructural protein-1, and the effects and strong immune response of primary tree shrew cells were also detected followed by ZIKV infection. These findings provide powerful in vitro cell-level evidence to support tree shrew as animal model of ZIKV infection and may help to explain the rash manifestations in vivo.


Assuntos
Modelos Animais de Doenças , Tupaiidae/virologia , Infecção por Zika virus/virologia , Zika virus/patogenicidade , Animais , Aorta/citologia , Aorta/virologia , Células Cultivadas , Chlorocebus aethiops , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Rim/citologia , Rim/virologia , Fígado/citologia , Fígado/virologia , Pulmão/citologia , Pulmão/virologia , Pele/citologia , Pele/virologia , Células Vero , Replicação Viral
17.
Cancer Manag Res ; 10: 6581-6590, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555263

RESUMO

PURPOSE: The identification and discovery of prognostic markers for colorectal cancer (CRC) are of great clinical significance. CCBE1 is expressed in various tumors and its expression correlates with lymphangiogenesis and angiogenesis. However, the association between CCBE1 expression and CRC outcome has not been reported. The aim of this study was to investigate clinical significance of CCBE1 expression in CRC. PATIENTS AND METHODS: CCBE1 expression was examined in 30 pairs of fresh CRC tissues and compared with adjacent normal (AN) tissues using quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry (IHC) staining. Tissue microarray immunohistochemical staining was used to study the CCBE1 expression characteristics of 204 CRC patient samples collected from January 2002 to December 2007, and the relationship of CCBE1 with clinicopathological features and prognosis of CRC was analyzed. RESULTS: CCBE1 was highly expressed in CRC tissues compared with matched AN tissues (P=0.001). Moreover, high expression of CCBE1 was significantly associated with tumor differentiation, lymph node metastasis, vascular invasion, liver metastasis and TNM stage in CRC patients (P≤0.01). Kaplan-Meier survival analysis revealed that high CCBE1 expression, poor tumor differentiation, lymph node metastasis and vascular invasion were significantly associated (all P<0.001) with poor prognosis for patients. Furthermore, univariate and multivariate Cox analysis revealed that high CCBE1 expression, poor tumor differentiation, lymph node metastasis and vascular invasion were independent risk factors for both overall survival (OS) and disease-free survival (DFS) of CRC patients (all P<0.05). OS and DFS of 267 CRC patients from The Cancer Genome Atlas (TCGA) database showed the same trend (log-rank P=6e-04, HR [high] =2.4; log-rank P=0.0081, HR [high] =1.9). CONCLUSION: High levels of CCBE1 contribute to the aggressiveness and poor prognosis of CRC. CCBE1 can serve as a novel potential biomarker to predict CRC patients' prognosis.

18.
J Colloid Interface Sci ; 530: 465-472, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29990782

RESUMO

In this paper, a three-dimensional (3D) poly(lactic-co-glycolic acid) (PLGA)/silica colloidal crystal drug delivery system with sustained drug release and visualized release monitoring was developed. This system had employed silica colloidal crystal microparticles as template skeleton, PLGA as drug carrier and dexamethasone (DEX) as therapeutic agent. The fabrication of the microparticle-based system included droplet formation based-on microfluidics, silica nanoparticle self-assembly and layer-by-layer deposition of PLGA containing DEX. In 370 µm droplets, the silica colloidal nanoparticles could self-assemble orderly into microparticles with a diameter of 187 µm, featuring red structure color. During the deposition of PLGA with the drug into the voids of the template microparticles, the reflection peak red-shifted and weakened until the voids were completely filled. Owing to the gradual degradation of PLGA, the release of DEX was triggered and sustained for 4 weeks with a cumulative release of 94.9%, while the structure color of the microparticles recovered during the release process. The color change could be recognized by the naked eyes, which would benefit the non-invasive monitoring of the drug release. The in vitro cytotoxicity and long-term inhibiting proliferation were investigated on retinal pigment epithelial cells. The inhibition effect of DEX released from the microparticles showed concentration-dependence from 40 to 200 µg mL-1 and time-dependence within 7 days. As a sustained drug delivery system with self-reporting drug release, the particles have potential applications in treatment of intraocular diseases.


Assuntos
Coloides/química , Preparações de Ação Retardada/química , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Ácido Láctico/química , Ácido Poliglicólico/química , Dióxido de Silício/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/farmacocinética , Dexametasona/farmacologia , Liberação Controlada de Fármacos , Glucocorticoides/farmacocinética , Glucocorticoides/farmacologia , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/efeitos dos fármacos
19.
Biosens Bioelectron ; 92: 81-86, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28189069

RESUMO

A visualized sensing method for glucose and cholesterol was developed based on the hemispheres of the same Janus hydrogel microparticles. Single-phase and Janus hydrogel microparticles were both generated using a centrifugal microfluidic chip. For glucose sensing, concanavalin A and fluorescein labeled dextran used for competitive binding assay were encapsulated in alginate microparticles, and the fluorescence of the microparticles was positively correlated with glucose concentration. For cholesterol sensing, the microparticles embedded with γ-Fe2O3 nanoparticles were used as catalyst for the oxidation of 3,3',5,5'-Tetramethylbenzidine by H2O2, an enzymatic hydrolysis product of cholesterol. And the color transition was more sensitive in the microparticles than in solutions, indicating the microparticles are more applicable for visualized determination. Furthermore, Janus microparticles were employed for multitarget sensing in the two hemespheres, and glucose and cholesterol were detected within the same microparticles without obvious interference. Besides, the particles could be manipulated by an external magnetic field. The glucose and cholesterol levels were measured in human serum utilizing the microparticles, which confirmed the potential application of the microparticles in real sample detection.


Assuntos
Alginatos/química , Técnicas Biossensoriais/métodos , Glicemia/análise , Colesterol/sangue , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Dispositivos Lab-On-A-Chip , Nanopartículas/química , Benzidinas/química , Técnicas Biossensoriais/instrumentação , Concanavalina A/química , Dextranos/química , Compostos Férricos/química , Corantes Fluorescentes/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Peróxido de Hidrogênio/química , Limite de Detecção , Nanopartículas/ultraestrutura , Oxirredução
20.
J Colloid Interface Sci ; 466: 20-7, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26704472

RESUMO

A novel chip-based approach for the fabrication of oblate spheriodal calcium alginate particles was developed by combining the droplet template method and the centrifugal microfluidic strategy. Circular chips with multiple radial channels were designed. Sodium alginate solutions in radial channels were flung into CaCl2 solutions in the form of droplets under centrifugal force, and the droplets transformed into particles through cross-linking reaction. The size and morphology of particles could be controlled by regulating the centrifugal force, the channel geometry and the distance between the channel outlet and the CaCl2 solution. The throughput of particle production was evidently enhanced by increasing the number of radial channels to 48 and 64. The coefficients of variation of particle sizes were in the range of 5.2-5.6%, which indicated the monodisperse particles could be prepared by using the present method. With the chip configuration readily modified, the same platform could be used to produce Janus particles. The Janus particles showed clear interfaces owing to the high flight speed and the rapid gelling process of the droplets. This method would be capable of generating particles with complicated morphology and multifunction from diverse polymeric materials.

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