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1.
Anal Chem ; 95(34): 12613-12622, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37583350

RESUMO

Trace analysis of lipophilic substances in complex environmental, food, or biological matrices has proven to be a challenge, on account of their high susceptibility to adsorption by particulate matter and liquid-solid interfaces. For this purpose, liquid-liquid extraction (LLE) is often employed as the separation method, which uses water-immiscible organic solvents. As an alternative, magnetic solid-phase extraction (MSPE) allows for adsorption, separation, and recovery of analytes from large volumes of aqueous samples with minimum usage of organic solvents. However, the poor selectivity hampers its performance in various scenarios, especially in sewage samples where complicated and unpredictable interference exists, resulting in block of the active adsorption sites of the sorbent. To this end, we propose receptor-affinity MSPE employing magnetic liposomes decorated with cell membranes expressing G-protein-coupled receptor as the sorbents. Application of the novel sorbent CM@Lip@Fe infused with CB1 cannabinoid receptors was demonstrated for the targeted extraction and enrichment of tetrahydrocannabinol from sewage matrix. Thanks to the high affinity and molecular selectivity of the ligand-receptor interactions, a limit of quantitation of 5.17 ng/L was achieved coupled with HPLC-MS/MS in unfiltered raw sewage, featuring minimum usage of organic solvents, fivefold enhanced sensitivity, low sorbent dosage (75 mg/L of sewage), and high efficiency as major advantages over conventional LLE. This work establishes a framework for efficient separation of specific molecules from complex media, thus promising to extend and refine standard LLE as the clean-up procedure for trace analysis.


Assuntos
Lipossomos , Esgotos , Espectrometria de Massas em Tandem/métodos , Solventes , Extração em Fase Sólida/métodos , Água , Membrana Celular , Fenômenos Magnéticos , Cromatografia Líquida de Alta Pressão/métodos
2.
Gynecol Oncol ; 170: 300-308, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36758420

RESUMO

OBJECTIVE: The primary purpose of this study was to determine if farletuzumab, an antifolate receptor-α monoclonal antibody, improved progression-free survival (PFS) versus placebo when added to standard chemotherapy regimens in patients with platinum-sensitive recurrent ovarian cancer (OC) in first relapse (platinum-free interval: 6-36 months) with low cancer antigen 125 (CA-125) levels. METHODS: Eligibility included CA-125 ≤ 3 x upper limit of normal (ULN, 105 U/mL), high-grade serous, platinum-sensitive recurrent OC, previous treatment with debulking surgery, and first-line platinum-based chemotherapy with 1st recurrence between 6 and 36 months since frontline platinum-based treatment. Patients received investigator's choice of either carboplatin (CARBO)/paclitaxel (PTX) every 3 weeks or CARBO/pegylated liposomal doxorubicin (PLD) every 4 weeks x6 cycles in combination with either farletuzumab [5 mg/kg weekly] or placebo randomized in a 2:1 ratio. Maintenance treatment with farletuzumab (5 mg/kg weekly) or placebo was given until disease progression or intolerance. RESULTS: 214 patients were randomly assigned to farletuzumab+chemotherapy (142 patients) versus placebo+chemotherapy (72 patients). The primary efficacy endpoint, PFS, was not significantly different between treatment groups (1-sided α = 0.10; p-value = 0.25; hazard ratio [HR] = 0.89, 80% confidence interval [CI]: 0.71, 1.11), a median of 11.7 months (95% CI: 10.2, 13.6) versus 10.8 months (95% CI: 9.5, 13.2) for farletuzumab+chemotherapy and placebo+chemotherapy, respectively. No new safety concerns were identified with the combination of farletuzumab+chemotherapy. CONCLUSIONS: Adding farletuzumab to standard chemotherapy does not improve PFS in patients with OC who were platinum-sensitive in first relapse with low CA-125 levels. Folate receptor-α expression was not measured in this study. (Clinical Trial Registry NCT02289950).


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Antígeno Ca-125 , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carboplatina , Paclitaxel , Doxorrubicina , Polietilenoglicóis , Recidiva , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico
3.
BMC Public Health ; 21(1): 1640, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496828

RESUMO

BACKGROUND: Hand-foot-mouth disease (HFMD) is a global public health issues, especially in China. It has threat the health of children under 5 years old. The early recognition of high-risk districts and understanding of epidemic characteristics can facilitate health sectors to prevent the occurrence of HFMD effectively. METHODS: Descriptive analysis was used to summarize epidemic characteristics, and the spatial autocorrelation analysis and space-time scan analysis were utilized to explore distribution pattern of HFMD and identify hot spots with statistical significance. The result was presented in ArcMap. RESULTS: A total of 52,095 HFMD cases were collected in Zibo city from 1 Jan 2010 to 31 Dec 2019. The annual average incidence was 129.72/100,000. The distribution of HFMD was a unimodal trend, with peak from April to September. The most susceptible age group was children under 5 years old (92.46%), and the male-to-female ratio is 1.60: 1. The main clusters were identified in Zhangdian District from 12 April 2010 to 18 September 2012. Spatial autocorrelation analysis showed that the global spatial correlation in Zibo were no statistical significance, except in 2012, 2014, 2015, 2016 and 2018. Cold spots were gathered in Boshan county and Linzi district, while hot spots only in Zhangdian District in 2018, but other years were no significance. CONCLUSION: Hot spots mainly concentrated in the central and surrounding city of Zibo city. We suggest that imminent public health planning and resource allocation should be focused within those areas.


Assuntos
Doença de Mão, Pé e Boca , Doenças da Boca , Criança , Pré-Escolar , China/epidemiologia , Cidades , Feminino , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Incidência , Lactente , Masculino , Análise Espaço-Temporal
4.
Clin Oral Investig ; 25(12): 6909-6918, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33991259

RESUMO

OBJECTIVES: To compare the treatment response and prognosis of oral cavity cancer between non-smoking and non-alcohol-drinking (NSND) patients and smoking and alcohol-drinking (SD) patients. METHODS: A total of 313 consecutively treated patients from 2000 to 2019 were included. Demographic, clinicopathologic, treatment, and prognosis information were obtained. Relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were compared between NSND and SD groups using Kaplan-Meier plots, log-rank test, and multivariate Cox regression analysis. RESULTS: Sample prevalence of NSND patients was 54.6%. These patients were predominantly females in their eighth decade with lower prevalence of floor of the mouth cancers compared to SD patients (1.8% vs 14.8%). No difference in the RFS and DSS between both groups was found following multivariable analysis; however, NSND patients had better OS (HR (95% CI) - 0.47 (0.29-0.75); p = 0.002). Extracapsular extension was associated with significantly poorer OS, DSS, and RFS in this oral cavity cancer cohort. CONCLUSION: Treatment response and disease-specific prognosis are comparable between NSND and SD patients with oral cavity cancer. However, NSND patients have better OS. CLINICAL RELEVANCE: This study shows that oral cavity cancer in NSND is not less or more aggressive compared to SD patients. Although better survival is expected for NSND than SD patients, this is likely due to the reduced incidence of other chronic diseases in the NSND group.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
5.
Acta Pharmacol Sin ; 41(7): 911-927, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32123302

RESUMO

Immunotherapy, as a powerful strategy for cancer treatment, has achieved tremendous efficacy in clinical trials. Despite these advancements, there is much to do in terms of enhancing therapeutic benefits and decreasing the side effects of cancer immunotherapy. Advanced nanobiomaterials, including liposomes, polymers, and silica, play a vital role in the codelivery of drugs and immunomodulators. These nanobiomaterial-based delivery systems could effectively promote antitumor immune responses and simultaneously reduce toxic adverse effects. Furthermore, nanobiomaterials may also combine with each other or with traditional drugs via different mechanisms, thus giving rise to more accurate and efficient tumor treatment. Here, an overview of the latest advancement in these nanobiomaterials used for cancer immunotherapy is given, describing outstanding systems, including lipid-based nanoparticles, polymer-based scaffolds or micelles, inorganic nanosystems, and others.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Imunoterapia , Neoplasias/terapia , Materiais Biocompatíveis/química , Humanos , Nanopartículas/química , Neoplasias/imunologia
6.
Br J Cancer ; 120(4): 379-386, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30679780

RESUMO

BACKGROUND: This phase 1 study examined the safety, tolerability, pharmacokinetics and preliminary efficacy of eribulin-liposomal formulation (eribulin-LF) in patients with advanced solid tumours. METHODS: Eligible patients with ECOG PS 0-1 were treated with eribulin-LF either on day 1 every 21 days (Schedule 1), or on days 1 and 15 every 28 days (Schedule 2). Doses ranged from 1.0 to 3.5 mg/m2, with dose escalation in a 3 + 3 design. The dose-expansion phase evaluated eribulin-LF in select tumour types. PRIMARY OBJECTIVES: maximum tolerated dose (MTD) and the recommended dose/schedule of eribulin-LF. RESULTS: Totally, 58 patients were enroled (median age = 62 years). The MTD was 1.4 mg/m2 (Schedule 1) or 1.5 mg/m2 (Schedule 2), the latter dose selected for the dose-expansion phase. Dose-limiting toxicity (DLTs) in Schedule 1: hypophosphatemia and increased transaminase levels. DLTs in Schedule 2: stomatitis, increased alanine aminotransferase, neutropenia and febrile neutropenia. The pharmacokinetic profile of eribulin-LF showed a similar half-life to that of eribulin (~30 h), but with a 5-fold greater maximum serum concentration and a 40-fold greater area-under-the-curve. Eribulin-LF demonstrated clinical activity with approximately 10% of patients in both schedules achieving partial responses. CONCLUSIONS: Eribulin-LF was well tolerated with a favourable pharmacokinetic profile. Preliminary evidence of clinical activity in solid tumours was observed.


Assuntos
Furanos/administração & dosagem , Cetonas/administração & dosagem , Neoplasias/tratamento farmacológico , Adulto , Idoso , Composição de Medicamentos , Feminino , Furanos/efeitos adversos , Furanos/farmacocinética , Humanos , Cetonas/efeitos adversos , Cetonas/farmacocinética , Lipossomos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/metabolismo
7.
Virol J ; 15(1): 161, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30340611

RESUMO

BACKGROUND: Rotaviruses (RVs) are a major cause of acute children gastroenteritis. The rotavirus P [10] belongs to P[I] genogroup of group A rotaviruses that mainly infect animals, while the rotavirus P [10] was mainly identified from human infection. The rotavirus P [10] is an unusual genotype and the recognition pattern of cellular receptors remains unclear. METHODS: We expressed and purified the RV P [10] VP8* protein and investigated the saliva and oligosaccharide binding profiles of the protein. A homology model of the P [10] VP8* core protein was built and the superimposition structural analysis of P [10] VP8* protein on P [19] VP8* in complex with mucin core 2 was performed to explore the possible docking structural basis of P [10] VP8* and mucin cores. RESULTS: Our data showed that rotavirus P [10] VP8* protein bound to all ABO secretor and non-secretor saliva. The rotavirus P [10] could bind strongly to mucin core 2 and weakly to mucin core 4. The homology modeling indicated that RV P [10] VP8* binds to mucin core 2 using a potential glycan binding site that is the same to P [19] VP8* belonging to P[II] genogroup. CONCLUSION: Our results suggested an interaction of rotavirus P [10] VP8* protein with mucin core 2 and mucin core 4. These findings offer potential for elucidating the mechanism of RV A host specificity, evolution and epidemiology.


Assuntos
Polissacarídeos/química , Proteínas de Ligação a RNA/química , Infecções por Rotavirus/virologia , Rotavirus/genética , Proteínas não Estruturais Virais/química , Sítios de Ligação , Escherichia coli/genética , Gastroenterite/virologia , Humanos , Simulação de Acoplamento Molecular , Mucinas/química , Mucinas/metabolismo , Polissacarídeos/metabolismo , Ligação Proteica , Proteínas de Ligação a RNA/metabolismo , Saliva/química , Saliva/virologia , Análise de Sequência de Proteína , Proteínas não Estruturais Virais/metabolismo
8.
J Am Chem Soc ; 139(33): 11616-11621, 2017 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-28782946

RESUMO

Early detection of ovarian cancer, the most lethal type of gynecologic cancer, can dramatically improve the efficacy of available treatment strategies. However, few screening tools exist for rapidly and effectively diagnosing ovarian cancer in early stages. Here, we present a facile "lock-key" strategy, based on rapid, specific detection of plasma lysophosphatidic acid (LPA, an early stage biomarker) with polydiacetylenes (PDAs)-based probe, for the early diagnosis of ovarian cancer. This strategy relies on specifically inserting LPA "key" into the PDAs "lock" through the synergistic electrostatic and hydrophobic interactions between them, leading to conformation transition of the PDA backbone with a concomitant blue-to-red color change. The detailed mechanism underlying the high selectivity of PDAs toward LPA is revealed by comprehensive theoretical calculation and experiments. Moreover, the level of LPA can be quantified in plasma samples from both mouse xenograft tumor models and patients with ovarian cancer. Impressively, this approach can be introduced into a portable point-of-care device to successfully distinguish the blood samples of patients with ovarian cancer from those of healthy people, with 100% accuracy. This work provides a valuable portable tool for early diagnosis of ovarian cancer and thus holds a great promise to dramatically improve the overall survival.


Assuntos
Detecção Precoce de Câncer/métodos , Lisofosfolipídeos/sangue , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Fitas Reagentes/análise , Animais , Detecção Precoce de Câncer/instrumentação , Desenho de Equipamento , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lisofosfolipídeos/análise , Camundongos , Camundongos Endogâmicos C57BL , Ovário/patologia , Polímero Poliacetilênico , Polímeros/química , Poli-Inos/química , Fitas Reagentes/economia , Eletricidade Estática
9.
Nanotechnology ; 27(8): 085106, 2016 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-26820630

RESUMO

Suppression of the reticuloendothelial system (RES) uptake is one of the most challenging tasks in nanomedicine. Coating stratagems using polymers, such as poly(ethylene glycol) (PEG), have led to great success in this respect. Nevertheless, recent observations of immunological response toward these synthetic polymers have triggered a search for better alternatives. In this work, natural red blood cell (RBC) membranes are camouflaged on the surface of Fe3O4 nanoparticles for reducing the RES uptake. In vitro macrophage uptake, in vivo biodistribution and pharmacokinetic studies demonstrate that the RBC membrane is a superior alternative to the current gold standard PEG for nanoparticle 'stealth'. Furthermore, we systematically investigate the in vivo potential toxicity of RBC membrane-coated nanoparticles by blood biochemistry, whole blood panel examination and histology analysis based on animal models. The combination of synthetic nanoparticles and natural cell membranes embodies a novel and biomimetic nanomaterial design strategy and presents a compelling property of functional materials for a broad range of biomedical applications.


Assuntos
Materiais Biomiméticos/farmacocinética , Portadores de Fármacos/farmacocinética , Membrana Eritrocítica/química , Óxido Ferroso-Férrico/farmacocinética , Nanopartículas Metálicas/química , Animais , Transporte Biológico , Materiais Biomiméticos/síntese química , Linhagem Celular , Portadores de Fármacos/síntese química , Ferro/análise , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Nanopartículas Metálicas/administração & dosagem , Camundongos , Camundongos Endogâmicos ICR , Sistema Fagocitário Mononuclear/fisiologia , Polietilenoglicóis/química , Espectrofotometria Atômica
10.
World J Stem Cells ; 16(5): 575-590, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38817328

RESUMO

BACKGROUND: Atherosclerosis (AS), a chronic inflammatory disease of blood vessels, is a major contributor to cardiovascular disease. Dental pulp stem cells (DPSCs) are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflammation-related diseases. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases. AIM: To modify DPSCs with HGF (DPSC-HGF) and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout (ApoE-/-) mouse model and an in vitro cellular model. METHODS: ApoE-/- mice were fed with a high-fat diet (HFD) for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs (DPSC-Null) through tail vein at weeks 4, 7, and 11, respectively, and the therapeutic efficacy and mechanisms were analyzed by histopathology, flow cytometry, lipid and glucose measurements, real-time reverse transcription polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay at the different time points of the experiment. An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells (HAOECs), and indirect co-cultured with supernatant of DPSC-Null (DPSC-Null-CM) or DPSC-HGF-CM, and the effect and mechanisms were analyzed by flow cytometry, RT-PCR and western blot. Nuclear factor-κB (NF-κB) activators and inhibitors were also used to validate the related signaling pathways. RESULTS: DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors, and the percentage of macrophages in the aorta, and DPSC-HGF treatment had more pronounced effects. DPSCs treatment had no effect on serum lipoprotein levels. The FACS results showed that DPSCs treatment reduced the percentages of monocytes, neutrophils, and M1 macrophages in the peripheral blood and spleen. DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-α stimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway. CONCLUSION: This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/- mice on a HFD, and could be of greater value in stem cell-based treatments for AS.

11.
Zhonghua Gan Zang Bing Za Zhi ; 21(1): 23-6, 2013 Jan.
Artigo em Zh | MEDLINE | ID: mdl-23663758

RESUMO

OBJECTIVE: To investigate the outcomes of chronic hepatitis C (CHC) patients treated with antiviral regimens of interferon (IFN) plus ribavirin (RBV) using individualized doses and durations. METHODS: This study was designed as an open-label, prospective clinical trial to analyze the virological responses of 169 CHC patients who received individualized dosages of IFNa-2b or pegylated (Peg)IFNa-2a combined with RBV based on their weight ( less than 60 kg or more than or equal to 60 kg), age (less than 65 years or 65-75 years), morbid state (liver cirrhosis or not), and complications (such as heart disease, diabetes, thyroid disorder). Treatment duration was calculated using the time required to induce HCV RNA negativity. The rates of virological response and adverse effects among the different groups were compared. RESULTS: The IFNa-2b treatment was given to 116 patients, and PegIFNa-2a was given to 53 patients. Compared to the IFNa-2b group, the PegIFNa-2a group showed significantly higher rates of complete early virological response (cEVR; 76.7% vs. 92.5%, P less than 0.05) and sustained virological response (SVR; 53.6% vs. 92.3%, P less than 0.05) among the patients who had completed their course of treatment; the rapid virological response (RVR) rate was also higher for the PegIFNa-2a group but the difference did not reach statistical significance (48.7% vs. 60.4%, P more than 0.05). Seventy-eight patients received the routine dose, and 91 patients received the low dose; there were no significant differences between these two groups for RVR (53.8% vs. 58.9%, P more than 0.05), cEVR (78.0% vs. 80.8%, P more than 0.05), or SVR (65.5% vs. 58.3%, P more than 0.05). CONCLUSION: Use of an individualized antiviral treatment strategy designed according to the patient's baseline condition, early viral kinetics, and tolerability to adverse reactions can achieve a high rate of SVR, as well as improve the safety, prognosis, and cost-effectiveness associated with treating CHC patients.


Assuntos
Hepatite C Crônica , Polietilenoglicóis , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Estudos Prospectivos , Ribavirina/uso terapêutico , Resultado do Tratamento
12.
Environ Sci Pollut Res Int ; 29(29): 44573-44581, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35133585

RESUMO

Hand, foot, and mouth disease (HFMD) poses a great disease burden in China. However, there are few studies on the relationship between temperature variability (TV) and HFMD. Moreover, whether air pollutions have modified effects on this relationship is still unknown. Therefore, this study aims to explore the modified effects of air pollutants on TV-HFMD association in Zibo City, China. Daily data of HFMD cases, meteorological factors, and air pollutants from 2015 to 2019 were collected for Zibo City. TV was estimated by calculating standard deviation of minimum and maximum temperatures over the exposure days. We used generalized additive model to estimate the association between TV and HFMD. The modified effects of air pollutants were assessed by comparing the estimated TV-HFMD associations between different air stratums. We found that TV increased the risk of HFMD. The effect was strongest at TV03 (4 days of exposure), when the incidence of HFMD increased by 3.6% [95% CI: 1.3-5.9%] for every 1℃ increases in TV. Males, children aged 0-4 years, were more sensitive to TV. We found that sulfur dioxide (SO2) enhanced TV's effects on all considered exposure days, while ozone (O3) reduced TV's effects on some exposure days in whole concerned population. However, we did not detect significant effect modification by particulate matter less than 10 microns in aerodynamic diameter (PM10). These findings are of significance in developing policies and public health practices to reduce the risks of HFMD by integrating changes in temperatures and air pollutants.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doença de Mão, Pé e Boca , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Criança , China/epidemiologia , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Incidência , Masculino , Temperatura
13.
Head Neck ; 43(11): 3662-3680, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34313348

RESUMO

Oral cavity cancer is often described as a lifestyle-related malignancy due to its strong associations with habitual factors, including tobacco use, heavy alcohol consumption, and betel nut chewing. However, patients with no genetically predisposing conditions who do not indulge in these risk habits are still being encountered, albeit less commonly. The aim of this review is to summarize contemporaneous reports on these nonsmoking, nonalcohol drinking (NSND) patients. We performed database searching to identify relevant studies from January 1, 2000 to March 31, 2021. Twenty-six articles from 20 studies were included in this study. We found that these individuals were mostly females in their eighth decade with tumors involving the tongue and gingivobuccal mucosa. This review also observed that these patients were likely diagnosed with early stage tumors with overexpression of programmed death-ligand 1 (PD-L1) and increased intensity of tumor infiltrating lymphocytes. Treatment response and disease-specific prognosis were largely comparable between NSND and smoking/drinking patients.


Assuntos
Neoplasias Bucais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Areca/efeitos adversos , Humanos , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/terapia , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia
14.
Chemistry ; 16(43): 12935-40, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20878798

RESUMO

A new family of artificial transcription factor (ATF)-based conjugates have been designed and synthesized as potent chemical nucleases. Polyamides as the important and efficient ATFs were used to modify and activate several anchor compounds. The results demonstrate that the resulting conjugates remarkably promote the rate accelerations and non-random double-strand DNA cleavage activity. Interestingly, the cleavage activity of both the hydrolytic and oxidative agents was promoted efficiently through the modification of the ATFs.


Assuntos
Clivagem do DNA , DNA/química , Nylons/química , Fatores de Transcrição/síntese química , Fatores de Transcrição/metabolismo , Desenho de Fármacos , Modelos Moleculares , Estrutura Molecular , Conformação de Ácido Nucleico , Oxirredução , Fatores de Transcrição/química
15.
Int J Pharm ; 578: 119127, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32036009

RESUMO

The purpose of this review is to introduce the functionalities of hyaluronic acid (HA) and its potential application as an effective carrier for topical/transdermal delivery. Specifically, several delivery mechanisms of HA were summarized here in order to explain its potential permeation-enhancing roles for the skin, which includes receptor-based delivery pathway, skin hydration, hydrophobic interaction with stratum corneum, bioadhesive properties, and viscoelastic properties. To achieve the optimum delivery efficacy for bioactive compounds at different target layers of the skin, HA with various molecular weights and chemical modifications were applied to design different delivery systems, including hydrogel, nanoemulsion, microemulsion, prodrug, microneedle, liposome/hyalurosome. Delivery efficacy has been evaluated using in vitro Franz Cell Diffusion method and/or in vivo animal models. Throughout this review, it was confirmed that HA could be an effective carrier for both topical and transdermal deliveries due to its unique viscoelasticity, biocompatibility, biodegradability, non-immunogenicity, and biomedical benefits for the skin.


Assuntos
Ácido Hialurônico/química , Pele/efeitos dos fármacos , Animais , Sistemas de Liberação de Medicamentos/métodos , Emulsões/administração & dosagem , Emulsões/química , Humanos , Hidrogéis/administração & dosagem , Hidrogéis/química , Lipossomos/química , Agulhas , Permeabilidade/efeitos dos fármacos
16.
BMC Biotechnol ; 9: 52, 2009 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-19480716

RESUMO

BACKGROUND: Transfection in mammalian cells based on liposome presents great challenge for biological professionals. To protect themselves from exogenous insults, mammalian cells tend to manifest poor transfection efficiency. In order to gain high efficiency, we have to optimize several conditions of transfection, such as amount of liposome, amount of plasmid, and cell density at transfection. However, this process may be time-consuming and energy-consuming. Fortunately, several mathematical methods, developed in the past decades, may facilitate the resolution of this issue. This study investigates the possibility of optimizing transfection efficiency by using a method referred to as least-squares support vector machine, which requires only a few experiments and maintains fairly high accuracy. RESULTS: A protocol consists of 15 experiments was performed according to the principle of uniform design. In this protocol, amount of liposome, amount of plasmid, and the number of seeded cells 24 h before transfection were set as independent variables and transfection efficiency was set as dependent variable. A model was deduced from independent variables and their respective dependent variable. Another protocol made up by 10 experiments was performed to test the accuracy of the model. The model manifested a high accuracy. Compared to traditional method, the integrated application of uniform design and least-squares support vector machine greatly reduced the number of required experiments. What's more, higher transfection efficiency was achieved. CONCLUSION: The integrated application of uniform design and least-squares support vector machine is a simple technique for obtaining high transfection efficiency. Using this novel method, the number of required experiments would be greatly cut down while higher efficiency would be gained. Least-squares support vector machine may be applicable to many other problems that need to be optimized.


Assuntos
Lipossomos , Software , Transfecção/métodos , Algoritmos , Linhagem Celular Transformada , Vetores Genéticos , Humanos , Análise dos Mínimos Quadrados , Modelos Biológicos
17.
Int J Pharm ; 557: 74-85, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30557680

RESUMO

Drug resistance and recurrence are the main clinical challenges in chemotherapy of lymphoma. Methotrexate (MTX), especially high dose MTX (HD MTX), is extensively used to treat some aggressive subtypes of lymphoma, such as Burkitt's lymphoma, in order to overcome drug resistance. But poor solubility of the free drug and severe side effects of HD MTX limit its clinical application. Polymeric micelle, as an ideal nano delivery system, provides effective solutions to these problems. In this work, monomethyl poly (ethylene glycol)-poly (ε-caprolactone) (MPEG-PCL) was employed to load MTX through a one-step solid dispersion method. MTX loaded micelles had a small particle size of 25.64 ±â€¯0.99 nm and polydisperse index (PDI) of 0.176 ±â€¯0.05. Drug loading and encapsulation efficiency of MTX loaded micelles were 5.57 ±â€¯0.14% and 92.46 ±â€¯2.38%. Compared with free MTX, MTX loaded micelles demonstrated a much slower and sustained release behavior in vitro. MTT assay and cell apoptosis study suggested that MTX loaded micelles were more effective in inhibiting proliferation and inducing apoptosis on Raji lymphoma cells than MTX injection, which was especially distinct in high dose groups. Cellular uptake study indicated that MPEG-PCL micelle had a 1.5 times higher uptake rate in Raji cells. As for in vivo studies, MTX loaded micelles were more competent to suppress tumor growth and prolong survival time than MTX injection in the subcutaneous Raji lymphoma model. Notably, the high dose group of micelle formulation exhibited the strongest anti-tumor effect without additional toxicity. Furthermore, immunofluorescent and immunohistochemical studies showed that tumors of MPEG-PCL-MTX treated mice had more apoptotic cells and fewer proliferative cells. In conclusion, MPEG-PCL-MTX micelle is an excellent intravenously injectable formulation of MTX with both good solubility and enhanced anti-tumor activity, which perfectly meets clinical demands, especially for administration of HD MTX.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Linfoma/tratamento farmacológico , Micelas , Poliésteres/administração & dosagem , Polietilenoglicóis/administração & dosagem , Animais , Antineoplásicos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Injeções Intravenosas , Linfoma/patologia , Camundongos SCID , Poliésteres/química , Polietilenoglicóis/química , Carga Tumoral/efeitos dos fármacos
18.
Zhonghua Yan Ke Za Zhi ; 44(11): 998-1001, 2008 Nov.
Artigo em Zh | MEDLINE | ID: mdl-19176095

RESUMO

OBJECTIVE: To study the clinical features of silicone oil dependent eyes. METHOD: Retrospective observational case series. Twenty four silicone oil dependent eyes collected from the Peking Union Medical College from Jan.2000 to Dec.2006 were studied. The pathogeny, surgical process and prognosis were analyzed. RESULTS: There were 5.9% silicone oil dependent eyes in eyes underwent vitrectomy and silicone oil tamponade. Silicone oil tamponade was performed again in 17 eyes because of severe proliferative vitreoretinopathy (PVR) or repeated vitreous hemorrhage after silicone oil removal and C3F8 tamponade. Silicone oil replacement was performed in 3 eyes because of severe PVR. Continually low intraocular pressure occurred after silicone oil removal in 4 eyes with 360 degree peripheral retinotomy. Thirteen of 24 patients had visual acuities of finger counting to 0.1, 9 had hand movement, one had light perception and one had no light perception. CONCLUSIONS: The incidence of silicone oil dependent eye is approximately 5.9%. This is often seen in the patients with severe or repeated PVR, or 360 degree peripheral retinotomy. The visual prognosis is poor in most cases.


Assuntos
Complicações Pós-Operatórias , Óleos de Silicone/efeitos adversos , Vitreorretinopatia Proliferativa/diagnóstico , Vitreorretinopatia Proliferativa/etiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Vitrectomia/efeitos adversos , Adulto Jovem
19.
Mater Sci Eng C Mater Biol Appl ; 71: 186-194, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27987697

RESUMO

Carbon nanotubes (CNTs) possess large potential as extraction absorbents in solid phase extraction. They have been widely applied in biomedicine research, while very rare application in natural product chemistry has been reported. In this work, methoxypolyethylene glycol amine (mPEG-NH2) is covalently coupled to CNTs-magnetic nanoparticles (CNTs-MNP) to prepare a novel magnetic nanocomposite (PEG-CNTs-MNP) for use as dispersive solid-phase extraction (DSPE) absorbent. The average particle size was 86nm, and the saturation magnetization was 52.30emu/g. This nanocomposite exhibits excellent dispersibility in aqueous systems, high selectivity and fast binding kinetics when used for extraction of Z-ligustilide, the characteristic bioactive compound from two popular Asian herbal plants, R. chuanxiong and R. ligusticum. HPLC quantification of Z-ligustilide extracted from the standard sample solution showed a high recovery of 98.9%, and the extraction rate from the extracts of the above two herbs are both around 70.0%. To our knowledge, this is the first report on using PEG-CNTs-MNP as DSPE nanosorbents for selective extraction of natural products. This nano-material has promising application in isolation and enrichment of targeted components from complex matrices.


Assuntos
4-Butirolactona/análogos & derivados , Campos Magnéticos , Nanocompostos/química , Nanotubos de Carbono/química , Pinellia/química , Polietilenoglicóis/química , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação
20.
Colloids Surf B Biointerfaces ; 149: 379-387, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27855357

RESUMO

Endothelialization has proved to be critical for maintaining long-term success of implantable vascular devices. The formation of monolayer of endothelial cells (ECs) on the implant surfaces is one of the most important factors for the endothelialization. However, endothelial function of regenerated EC monolayer, which plays a much more important role in preventing the complications of post-implantation, has not received enough attention. Here, a vascular endothelial growth factor (VEGF)-incorporated poly(l-lysine)/hyaluronan (PLL/HA) polyelectrolyte multilayer film was fabricated. Through varying the crosslinking degree, stiffness of the film was manipulated, offering either soft or stiff film. We demonstrated that ECs were able to adhere and proliferate on both soft and stiff films, subsequently forming an integrated EC monolayer. Furthermore, endothelial functions were evaluated by characterizing EC monolayer integrity, expression of genes correlated with the endothelial functions, and nitric oxide production. It demonstrated that EC monolayer on the soft film displayed higher endothelial function compared to that on the stiff film. Our study highlights the influence of substrate stiffness on endothelial function, which offers a new criterion for surface design of vascular implants.


Assuntos
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Ácido Hialurônico/farmacologia , Polieletrólitos/farmacologia , Polilisina/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Antígenos CD/genética , Antígenos CD/metabolismo , Biglicano/genética , Biglicano/metabolismo , Caderinas/genética , Caderinas/metabolismo , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo IV/genética , Colágeno Tipo IV/metabolismo , Módulo de Elasticidade , Fibronectinas/genética , Fibronectinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Dureza , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Ácido Hialurônico/química , Membranas Artificiais , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Polieletrólitos/química , Polilisina/química , Propriedades de Superfície , Fator A de Crescimento do Endotélio Vascular/metabolismo
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