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1.
BMC Pregnancy Childbirth ; 23(1): 863, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102587

RESUMO

BACKGROUND: To investigate the predictive value of ultrasound indicators in early pregnancy for the outcome of caesarean scar pregnancy (CSP) after pregnancy termination. METHODS: This study retrospectively analysed the ultrasound images of 98 CSP patients who underwent transabdominal ultrasound-guided hysteroscopic curettage during early pregnancy at Changsha Hospital for Maternal and Child Health Care between January 2017 and October 2021. Patients were equally divided into a case group and a control group. The case group included 49 CSP patients with postoperative complications, such as intraoperative blood loss ≥ 200 ml or retained products of conception (RPOC). The remaining 49 CSP patients, with similar age and gestational age and with good postoperative outcomes, such as intraoperative blood loss ≤ 50 ml and no RPOC, were included in the control group. CSP was classified into three types according to the location of the gestational sac (GS) relative to the uterine cavity line (UCL) and serosal contour. Differences in ultrasound indicators between the case and control group were compared. RESULTS: There were significant differences between the case and control groups in the mean gestational sac diameter (MGSD), residual myometrium thickness (RMT) between the GS and the bladder, blood flow around the GS at the site of the previous caesarean incision, and types of CSP (P < 0.05). The rs of each ultrasound indicator were as follows: 0.258, -0.485, 0.369, 0.350. The optimal threshold for predicting good postoperative outcomes, such as intraoperative blood loss ≤ 50 ml and no RPOC, by receiver operating characteristic (ROC) curve analysis of the RMT was 2.3 mm. CONCLUSION: Our findings show that the RMT, blood flow around the GS at the site of the previous caesarean incision, and types of CSP have a low correlation with postoperative complications, such as intraoperative blood loss ≥ 200 ml or RPOC, of early pregnancy termination in patients with CSP. To some extent, this study may be helpful for clinical prognostic prediction of patients with CSP and formulation of treatment strategies. Given the low correlation between these three indicators and postoperative complications, further studies are needed to identify indicators that can better reflect the postoperative outcomes of CSP patients.


Assuntos
Aborto Induzido , Complicações na Gravidez , Gravidez Ectópica , Gravidez , Feminino , Criança , Humanos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Cicatriz/etiologia , Cicatriz/complicações , Ultrassom , Cesárea/efeitos adversos , Gravidez Ectópica/diagnóstico por imagem , Gravidez Ectópica/etiologia , Gravidez Ectópica/cirurgia , Aborto Induzido/efeitos adversos , Complicações na Gravidez/etiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
2.
Acc Chem Res ; 54(7): 1779-1790, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33751886

RESUMO

Atom-transfer radical polymerization (ATRP) is a well-known technique for the controlled polymerization of vinyl monomers under mild conditions. However, as with any other radical polymerization, ATRP typically requires rigorous oxygen exclusion, making it time-consuming and challenging to use by nonexperts. In this Account, we discuss various approaches to achieving oxygen tolerance in ATRP, presenting the overall progress in the field.Copper-mediated ATRP, which we first discovered in the late 1990s, uses a CuI/L activator that reversibly reacts with the dormant C(sp3)-X polymer chain end, forming a X-CuII/L deactivator and a propagating radical. Oxygen interferes with activation and chain propagation by quenching the radicals and oxidizing the activator. At ATRP equilibrium, the activator is present at a much higher concentration than the propagating radicals. Thus, oxidation of the activator is the dominant inhibition pathway. In conventional ATRP, this reaction is irreversible, so oxygen must be strictly excluded to achieve good results.Over the last two decades, our group has developed several ATRP techniques based on the concept of regenerating the activator. When the oxidized activator is continuously converted back to its active reduced form, then the catalytic system itself can act as an oxygen scavenger. Regeneration can be accomplished by reducing agents and photo-, electro-, and mechanochemical stimuli. This family of methods offers a degree of oxygen tolerance, but most of them can tolerate only a limited amount of oxygen and do not allow polymerization in an open vessel.More recently, we discovered that enzymes can be used in auxiliary catalytic systems that directly deoxygenate the reaction medium and protect the polymerization process. We developed a method that uses glucose oxidase (GOx), glucose, and sodium pyruvate to very effectively scavenge oxygen and enable open-vessel ATRP. By adding a second enzyme, horseradish peroxidase (HPR), we managed to extend the role of the auxiliary enzymatic system to generating carbon-based radicals and changed ATRP from an oxygen-sensitive to an oxygen-fueled reaction.While performing control experiments for the enzymatic methods, we noticed that using sodium pyruvate under UV irradiation triggers polymerization without the presence of GOx. This serendipitous discovery allowed us to develop the first oxygen-proof, small-molecule-based, photoinduced ATRP system. It has oxygen tolerance similar to that of the enzymatic methods, exhibits superior compatibility with both aqueous media and organic solvents, and avoids problems associated with purifying polymers from enzymes. The system was able to rapidly polymerize N-isopropylacrylamide, a challenging monomer, with a high degree of control.These contributions have substantially simplified the use of ATRP, making it more practical and accessible to everyone.


Assuntos
Oxigênio/metabolismo , Radicais Livres/química , Radicais Livres/metabolismo , Glucose/química , Glucose/metabolismo , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Oxirredução , Oxigênio/química , Polimerização , Ácido Pirúvico/química , Ácido Pirúvico/metabolismo
3.
Indoor Air ; 32(1): e12952, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34747064

RESUMO

This study aims to develop a fast-response sulfur hexafluoride (SF6 ) measuring system, and evaluate its performance in tracer gas measurements for studying transient airborne contaminant transport. The new system is based on a quartz-enhanced photoacoustic spectroscopy (QEPAS) sensor using a quantum cascade laser. Transient SF6 tracer gas measurements were carried out in an environmental chamber with an instantaneous source using both the QEPAS system and a traditional commercial instrument. Real-time SF6 concentrations, peak SF6 concentrations and average SF6 concentrations for one room time constant under two air change rates obtained by the two instruments were compared. The results show that the QEPAS system, which features a 0.4 s data acquisition interval, can provide detailed real-time SF6 concentrations even when the concentration is changing rapidly. The QEPAS system successfully captured the peak SF6 concentrations for all the studies cases, while commercial instrument failed in most studied cases. In most of the cases, the two instruments obtained similar average SF6 concentrations for one room time constant. However, when the concentration was in rapid change, the two systems would report significantly different results. The QEPAS system can be potentially applied in transient tracer gas measurements under complex scenarios.


Assuntos
Poluição do Ar em Ambientes Fechados , Quartzo , Poluição do Ar em Ambientes Fechados/análise , Análise Espectral/métodos , Hexafluoreto de Enxofre/análise , Hexafluoreto de Enxofre/química
4.
J Obstet Gynaecol Res ; 48(7): 1683-1690, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35384174

RESUMO

AIM: This study aimed to ascertain whether the lower anterior myometrial thickness (MT) between the bladder and the gestational sac in early pregnancy can be used to predict clinical outcomes in women with cesarean scar pregnancy (CSP) after expectant management. METHODS: We retrospectively analyzed the clinical data and early pregnancy ultrasound images of 21 patients who received expectant management for CSP. Among them, 11 patients with serious complications during pregnancy, such as intraoperative blood loss ≥1000 mL or with severe forms of morbidly adherent placenta (MAP; placenta increta or placenta percreta), were assigned to group A. The remaining 10 patients without serious complications during pregnancy were assigned to group B. The difference in MT between groups A and B was analyzed using nonparametric Mann-Whitney U test. RESULTS: There was a statistically significant difference in MT between the groups (U = 20.000, p = 0.013). The area under the receiver operating characteristics (ROC) curve was 0.818, and the optimal cut-off value for MT was 3.3 mm. CONCLUSION: Lower anterior MT around the gestational sac was correlated with severe complications, such as massive intraoperative bleeding or severe forms of MAP in patients with CSP.


Assuntos
Placenta Acreta , Gravidez Ectópica , Cesárea/efeitos adversos , Cicatriz/complicações , Feminino , Humanos , Placenta Acreta/etiologia , Gravidez , Gravidez Ectópica/cirurgia , Estudos Retrospectivos , Conduta Expectante
5.
Environ Sci Technol ; 55(15): 10758-10768, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34283571

RESUMO

Determination of how the properties of nanocarriers of agrochemicals affect their uptake and translocation in plants would enable more efficient agent delivery. Here, we synthesized star polymer nanocarriers poly(acrylic acid)-block-poly(2-(methylsulfinyl)ethyl acrylate) (PAA-b-PMSEA) and poly(acrylic acid)-block-poly((2-(methylsulfinyl)ethyl acrylate)-co-(2-(methylthio)ethyl acrylate)) (PAA-b-P(MSEA-co-MTEA)) with well-controlled sizes (from 6 to 35 nm), negative charge content (from 17% to 83% PAA), and hydrophobicity and quantified their leaf uptake, phloem loading, and distribution in tomato (Solanum lycopersicum) plants 3 days after foliar application of 20 µL of a 1g L-1 star polymer solution. In spite of their property differences, ∼30% of the applied star polymers translocated to other plant organs, higher than uptake of conventional foliar applied agrochemicals (<5%). The property differences affected their distribution in the plant. The ∼6 nm star polymers exhibited 3 times higher transport to younger leaves than larger ones, while the ∼35 nm star polymer had over 2 times higher transport to roots than smaller ones, suggesting small star polymers favor symplastic unloading in young leaves, while larger polymers favor apoplastic unloading in roots. For the same sized star polymer, a smaller negative charge content (yielding ζ ∼ -12 mV) enhanced translocation to young leaves and roots, whereas a larger negative charge (ζ < -26 mV) had lower mobility. Hydrophobicity only affected leaf uptake pathways, but not translocation. This study can help design agrochemical nanocarriers for efficient foliar uptake and targeting to desired plant organs, which may decrease agrochemical use and environmental impacts of agriculture.


Assuntos
Folhas de Planta , Polímeros , Transporte Biológico , Interações Hidrofóbicas e Hidrofílicas , Raízes de Plantas
6.
Exp Mol Pathol ; 117: 104522, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32866521

RESUMO

OBJECTIVE: This study aimed to investigate whether the protection of miR-302a-3p in myocardial ischemia-reperfusion injury (MIRI) is mediated through the suppression of mitophagy. METHODS: We constructed a mouse I/R model in vivo by the ligation of left anterior descending coronary artery for 45 min followed by 2 h reperfusion, and an in vitro model by treating mouse cardiomyocytes with hypoxia-reoxygenation (H/R). Knockdown experiments were then performed in vivo and in vitro to determine the effects of miR-302a-3p knockdown on the mitophagy, mitochondrial dysfunction and oxidative stress and apoptosis. The potential targets of miR-302a-3p were further studied by bioinformatics analysis, luciferase assays, quantitative real-time PCR and western blotting. RESULTS: MiR-302a-3p expression was significantly upregulated in mice subjected to MIRI and in H/R-treated mouse cardiomyocytes. Functional analyses demonstrated that inhibition of miR-302a-3p protected cardiac tissues against I/R-induced apoptosis and mitophagy, mitochondrial damage and mitochondrial oxidative stress. Furthermore, FOXO3 was identified as the direct target of miR-302a-3p. Mechanistically, knockdown of FOXO3 partially reversed the cardioprotective effects of miR-302a-3p inhibitor. CONCLUSION: Our study suggested that inhibition of miR-302a-3p promoted mitochondrial autophagy and inhibited oxidative stress by targeting FOXO3 to suppress myocardial apoptosis, representing a potential target for MIRI treatment.


Assuntos
Proteína Forkhead Box O3/genética , MicroRNAs/genética , Isquemia Miocárdica/genética , Traumatismo por Reperfusão/genética , Animais , Apoptose/genética , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Ligadura , Camundongos , Mitofagia/genética , Isquemia Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo/genética , Traumatismo por Reperfusão/patologia
7.
Macromol Rapid Commun ; 41(1): e1900424, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31631429

RESUMO

Small molecule biomimetics inspired by the active site of the [FeFe]-hydrogenase enzymes have shown promising electrocatalytic activity for hydrogen (H2 ) generation. However, most of the active-site mimics based on [2Fe-2S] clusters are not water-soluble which limits the use of these electrocatalysts to organic media. Polymer-supported [2Fe-2S] systems, in particular, single-site metallopolymer catalysts, have shown drastic improvements for electrocatalytic H2 generation in aqueous milieu. [2Fe-2S] complexes functionalized within well-defined macromolecular supports via covalent bonding have demonstrated water solubility, enhanced site-isolation, and improved chemical stability during catalysis. In this report, the synthesis of a new propanedithiolate (pdt)-[2Fe-2S] complex bearing a single α-bromoester moiety for use in atom transfer radical polymerization (ATRP) is demonstrated as a novel metalloinitiator to prepare water-soluble poly(2-dimethylaminoethyl methacrylate) grafted (PDMAEMA-g-[2Fe-2S]) metallopolymers. Using this approach, metallopolymers with controllable molecular weights (Mn = 5-40 kg mol-1 ) and low dispersity (D, Mw /Mn = 1.09-1.36) are prepared, which allows for the first time observation of the effect of the metallopolymers' chain length on the electrocatalytic activity. The ability to control the composition and molecular weight of these metallopolymers enables macromolecular engineering via ATRP of these materials to determine optimal structural features of metallopolymer catalysts for H2 production.


Assuntos
Hidrogênio/metabolismo , Ferro/química , Polímeros/química , Enxofre/química , Catálise , Domínio Catalítico , Complexos de Coordenação/química , Técnicas Eletroquímicas , Hidrogênio/química , Hidrogenase/química , Conformação Molecular , Peso Molecular , Polimerização , Polímeros/síntese química
8.
Macromol Rapid Commun ; 40(10): e1800877, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30650236

RESUMO

Good control of tacticity, molecular weight, and architecture is attained via atom transfer radical polymerization (ATRP) of N-hydroxyethyl acrylamide (HEAA), in a one-pot process in the presence of Y(OTf)3 . The effect of temperature, ratio of [Y(OTf)3 ]/[HEAA], and ATRP procedure on the tacticity and degree of control over the polymerization is investigated in detail. Under optimal conditions, using photo ATRP and 15% Y(OTf)3, the content of meso dyads (m) can be increased from 42% to 80% in a homopolymer with a dispersity D = 1.22. Well-defined stereoblock copolymers, atactic- b -isotactic poly(HEAA), with D = 1.27, are obtained by adding Y(OTf)3 at a specific conversion, initially started without Y(OTf)3 .


Assuntos
Acrilamidas/síntese química , Ácidos de Lewis/química , Polimerização , Polímeros/síntese química , Acrilamidas/química , Ácidos de Lewis/síntese química , Peso Molecular , Polímeros/química , Temperatura
9.
Molecules ; 24(21)2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31684005

RESUMO

Copper is the most common metal catalyst used in atom transfer radical polymerization (ATRP), but iron is an excellent alternative due to its natural abundance and low toxicity compared to copper. In this work, two new iron-porphyrin-based catalysts inspired by naturally occurring proteins, such as horseradish peroxidase, hemoglobin, and cytochrome P450, were synthesized and tested for ATRP. Natural protein structures were mimicked by attaching imidazole or thioether groups to the porphyrin, leading to increased rates of polymerization, as well as providing polymers with low dispersity, even in the presence of ppm amounts of catalysts.


Assuntos
Biomimética , Ferro/química , Polimerização , Porfirinas/química , Catálise , Cobre/química , Sistema Enzimático do Citocromo P-450/química , Hemoglobinas/química , Peroxidase do Rábano Silvestre/química , Imidazóis/química , Estrutura Molecular , Oxirredução , Polímeros/química , Sulfetos/química
10.
J Cell Biochem ; 119(10): 8611-8622, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29923216

RESUMO

Betulinic acid (BA), a natural product with a broad range of biological properties, is a lupane-type pentacyclic triterpene isolated from various plants. Evidence is accumulating that BA is cytotoxic against multiple types of human cancer cells; however, its effects on renal carcinoma cells remain obscure. This study aimed to evaluate the anticancer activity of BA in human renal cancer cells in vitro and in vivo. In the current study, we found that BA inhibited renal cancer cell proliferation in a time-dependent and dose-dependent manner in vitro. Moreover, flow cytometry analysis revealed that BA affected the survival of renal cancer cells via the induction of apoptosis. Western blot analysis showed that the occurrence of apoptosis was associated with upregulation of Bcl2-associated X protein and cleaved caspase-3 and downregulation of B-cell lymphoma 2 in renal cancer cells. Additionally, BA treatment augmented the production of reactive oxygen species and induced a significant loss of mitochondrial membrane potential in renal cancer cells, suggesting that BA may trigger apoptosis via the mitochondria-mediated apoptotic pathway. Furthermore, the migrative and invasive capabilities of renal cancer cells were markedly repressed by BA treatment, which was related to upregulation of matrix metalloproteinase (MMP)2, MMP9, and vimentin, and downregulation of tissue inhibitor of metalloproteinase 2 and E-cadherin. Notably, administration of BA retarded tumor growth in 786-O-bearing mice in vivo. Taken together, our results demonstrated the anticancer potential of BA in human renal cancer cells by triggering apoptosis and suppressing migration and invasion.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Triterpenos/uso terapêutico , Análise de Variância , Animais , Carcinoma de Células Renais/secundário , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Neoplasias Renais/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Triterpenos Pentacíclicos , Espécies Reativas de Oxigênio/metabolismo , Resultado do Tratamento , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/metabolismo , Ácido Betulínico
11.
Angew Chem Int Ed Engl ; 57(4): 933-936, 2018 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-29240973

RESUMO

The first well-controlled aqueous atom-transfer radical polymerization (ATRP) conducted in the open air is reported. This air-tolerant ATRP was enabled by the continuous conversion of oxygen to carbon dioxide catalyzed by glucose oxidase (GOx), in the presence of glucose and sodium pyruvate as sequential sacrificial substrates. Controlled polymerization using initiators for continuous activator regeneration (ICAR) ATRP of oligo(ethylene oxide) methyl ether methacrylate (OEOMA, Mn =500) yielded polymers with low dispersity (1.09≤D≤1.29) and molecular weights (MWs) close to theoretical values in the presence of pyruvate. Without added pyruvates, lower MWs were observed due to generation of new chains by H2 O2 formed by reaction of O2 with GOx. Successful chain extension of POEOMA500 macroinitiator with OEOMA300 (D≤1.3) and Bovine Serum Albumin bioconjugates (D≤1.22) confirmed a well-controlled polymerization. The reactions in the open air in larger scale (25 mL) were also successful.


Assuntos
Radicais Livres/química , Oxigênio/química , Polímeros/química , Biocatálise , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Metacrilatos/química , Polimerização , Ácido Pirúvico/química
12.
Angew Chem Int Ed Engl ; 57(49): 16157-16161, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30329207

RESUMO

Atom transfer radical polymerization (ATRP) can be carried out in a flask completely open to air using a biocatalytic system composed of glucose oxidase (GOx) and horseradish peroxidase (HRP) with an active copper catalyst complex. Nanomolar concentrations of the enzymes and ppm amounts of Cu provided excellent control over the polymerization of oligo(ethylene oxide) methyl ether methacrylate (OEOMA500 ), generating polymers with high molecular weight (Mn >70 000) and low dispersities (1.13≤D≤1.27) in less than an hour. The continuous oxygen supply was necessary for the generation of radicals and polymer chain growth as demonstrated by temporal control and by inducing hypoxic conditions. In addition, the enzymatic cascade polymerization triggered by oxygen was used for a protein and DNA functionalized with initiators to form protein-b-POEOMA and DNA-b-POEOMA bioconjugates, respectively.

13.
Angew Chem Int Ed Engl ; 57(37): 11898-11902, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30053346

RESUMO

Electrocatalytic [FeFe]-hydrogenase mimics for the hydrogen evolution reaction (HER) generally suffer from low activity, high overpotential, aggregation, oxygen sensitivity, and low solubility in water. By using atom-transfer radical polymerization (ATRP), a new class of [FeFe]-metallopolymers with precise molar mass, defined composition, and low polydispersity, has been prepared. The synthetic methodology introduced here allows facile variation of polymer composition to optimize the [FeFe] solubility, activity, and long-term chemical and aerobic stability. Water soluble functional metallopolymers facilitate electrocatalytic hydrogen production in neutral water with loadings as low as 2 ppm and operate at rates an order of magnitude faster than hydrogenases (2.5×105  s-1 ), and with low overpotential requirement. Furthermore, unlike the hydrogenases, these systems are insensitive to oxygen during catalysis, with turnover numbers on the order of 40 000 under both anaerobic and aerobic conditions.


Assuntos
Materiais Biomiméticos/química , Complexos de Coordenação/química , Hidrogênio/química , Água/química , Materiais Biomiméticos/metabolismo , Catálise , Domínio Catalítico , Complexos de Coordenação/metabolismo , Técnicas Eletroquímicas , Eletrodos , Hidrogênio/metabolismo , Hidrogenase/química , Hidrogenase/metabolismo , Proteínas Ferro-Enxofre/química , Proteínas Ferro-Enxofre/metabolismo
14.
Biomacromolecules ; 18(2): 475-482, 2017 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-28055185

RESUMO

The synthesis of a sulfoxide-based water-soluble polymer, poly(2-(methylsulfinyl)ethyl acrylate) (polyMSEA), a polymeric analogue of DMSO, by atom transfer radical polymerization (ATRP) is reported. Well-defined linear polymers were synthesized using relatively low amounts of copper catalyst (1000 or 100 ppm). Two types of star polymers were synthesized by either an "arm-first" approach or a "core-first" approach using a biodegradable ß-cyclodextrin core. The glass transition temperatures of both the linear polymer (16 °C) and star polymer (32 °C) were determined by differential scanning calorimetry (DSC). The lower critical solution temperature (LCST) of poly(MSEA) was estimated to be ca. 140 °C by extrapolating the LCST of a series of copolymers with NIPAM. Cytotoxicity tests revealed that both the linear and star polymers have low toxicity, even at concentrations up to 3 mg/mL.


Assuntos
Materiais Biocompatíveis/administração & dosagem , Dimetil Sulfóxido/química , Polímeros/administração & dosagem , Materiais Biocompatíveis/química , Varredura Diferencial de Calorimetria , Catálise , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Humanos , Polimerização , Polímeros/química , Temperatura de Transição , Água/química
15.
Cell Physiol Biochem ; 39(5): 2088-2098, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27825169

RESUMO

BACKGROUND/AIMS: Rapamycin is a potential anti-cancer agent, which modulates the activity of mTOR, a key regulator of cell growth and proliferation. However, several types of cancer cells are resistant to the anti-proliferative effects of rapamycin. In this study, we report a MDM2/p53-mediated rapamycin resistance in human renal cancer cells. METHODS: Trypan blue exclusion tests were used to determine the cell viability. Changes in mRNA and protein expression were measured using real-time PCR and western blot, respectively. Xenograft models were established to evaluate the in vivo effects of rapamycin combined with a MDM2 inhibitor. RESULTS: Rapamycin treatment suppresses the expression of MDM2 and exogenous overexpression of MDM2 in A498 cells contributes to rapamycin resistance. By establishing a rapamycin resistant cell line, we observed that MDM2 was significantly upregulated in rapamycin resistant cells than that in rapamycin sensitive cells. Importantly, the rapamycin resistant cells demonstrated attenuated accumulation of p53 in the nucleus in response to rapamycin treatment. Moreover, the inhibition of MDM2 by siMDM2 sensitizes A498 cells to rapamycin through the activation of p53. In both in vitro and in vivo models, the combination of rapamycin with the MDM2 inhibitor, MI-319, demonstrated a synergistic inhibitory effect on rapamycin resistant cells. CONCLUSION: Our study reports a novel mechanism for rapamycin resistance in human renal cancer and provides a new perspective for the development of anti-cancer drugs.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Indóis/farmacologia , Neoplasias Renais/tratamento farmacológico , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Sirolimo/farmacologia , Compostos de Espiro/farmacologia , Proteína Supressora de Tumor p53/agonistas , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Combinação de Medicamentos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica , Humanos , Injeções Subcutâneas , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Biochem Biophys Res Commun ; 453(1): 106-11, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25261726

RESUMO

Renal cell carcinoma (RCC) is common renal malignancy within poor prognosis. TGF-ß-activated kinase 1 (TAK1) plays vital roles in cell survival, apoptosis-resistance and carcinogenesis through regulating nuclear factor-κB (NF-κB) and other cancer-related pathways. Here we found that TAK1 inhibitors (LYTAK1, 5Z-7-oxozeanol (5Z) and NG-25) suppressed NF-κB activation and RCC cell (786-O and A489 lines) survival. TAK1 inhibitors induced apoptotic cytotoxicity against RCC cells, which was largely inhibited by the broad or specific caspase inhibitors. Further, shRNA-mediated partial depletion of TAK1 reduced 786-O cell viability whiling activating apoptosis. Significantly, TAK1 was over-expressed in human RCC tissues, and its level was correlated with phosphorylated NF-κB. Finally, kinase inhibition or genetic depletion of TAK1 enhanced the activity of vinblastine sulfate (VLB) in RCC cells. Together, these results suggest that TAK1 may be an important oncogene or an effective target for RCC intervention.


Assuntos
Carcinoma de Células Renais/enzimologia , Neoplasias Renais/enzimologia , MAP Quinase Quinase Quinases/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Renais/genética , Neoplasias Renais/terapia , Lactonas/farmacologia , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Oncogenes , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , RNA Interferente Pequeno/genética , Resorcinóis/farmacologia , Ensaio Tumoral de Célula-Tronco , Regulação para Cima , Vimblastina/farmacologia
17.
Tumour Biol ; 35(1): 103-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23943369

RESUMO

Tumor necrosis factor alpha (TNF-α) has been suggested to play an important role in the development and liver cancer. TNF-α 238 G/A polymorphism was hypothesized to increase the risk of liver cancer, but findings from previous studies were controversial. To explore a more precise estimation of the relationship between TNF-α 238 G/A polymorphism and liver cancer, we performed a meta-analysis. PubMed, Embase, and China Biology Medicine databases were searched for all publications on this association through March 12, 2013. Odds ratios (ORs) with its 95% confidence intervals (CIs) were used to assess the strength of this association. Eleven studies with 1,406 liver cancer cases and 2,386 noncancer controls were included into this meta-analysis. Overall, there was a significant association between TNF-α 238 G/A polymorphism and increased risk of liver cancer under all three genetic models (A vs. G, OR 1.51, 95% CI 1.20-1.89, P < 0.001, I(2) = 37.7%; AG vs. GG, OR 1.49, 95% CI 1.01-2.21, P = 0.045, I(2) = 53.2%; AA/AG vs. GG, OR 1.76, 95% CI 1.35-2.30, P < 0.001, I(2) = 36.5%). The sensitivity analysis further strengthened the validity of the positive association. Subgroup analysis of nine studies from Asian countries showed that there was a significant association between TNF-α 238 G/A polymorphism and increased risk of liver cancer in Asians (A vs. G, OR 1.35, 95% CI 1.03-1.76, P = 0.027, I(2) = 40.2%; AA/AG vs. GG, OR 1.56, 95% CI 1.14-2.15, P = 0.006, I(2) = 41.9%). In conclusion, TNF-α 238 G/A polymorphism is significantly associated with increased risk of liver cancer, especially in Asians.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Alelos , Estudos de Associação Genética , Genótipo , Humanos , Razão de Chances , Viés de Publicação
18.
Tumour Biol ; 35(6): 6065-72, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24609903

RESUMO

Vitamin D receptor (VDR) gene polymorphisms have previously been associated with susceptibility to renal cell carcinoma, although the findings are inconsistent. This study therefore evaluated the association of three single nucleotide polymorphisms (SNPs) in VDR (FokI, BsmI, and TaqI) with the risk of renal cell carcinoma in five previous studies of a total of 1,510 cases and 2,101 controls identified from PubMed, Web of Science, Embase, and Wanfang databases. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were calculated, and stratified analysis by ethnicity was conducted for further estimation. All statistical analyses were conducted using STATA software. Obvious heterogeneity was noted among the five studies. The VDR BsmI polymorphism was not found to be associated with renal cell carcinoma risk, although subgroup analysis revealed a significant association with renal cell carcinoma risk in Asians (b vs B OR=1.479, 95 % CI=1.171-1.869, P OR=0.001 and bb vs BB OR=2.608, 95 % CI=1.529-4.449, P OR=0.001). No significant association was found between renal cell carcinoma risk and either FokI or TaqI polymorphisms in different models and populations. Further large-scale studies are required to confirm these conclusions.


Assuntos
Carcinoma de Células Renais/genética , Predisposição Genética para Doença , Neoplasias Renais/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Carcinoma de Células Renais/etiologia , Humanos , Neoplasias Renais/etiologia , Viés de Publicação , Risco
19.
ACS Macro Lett ; 13(4): 415-422, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38526986

RESUMO

Linear polyisoprene (PI) and SiO2-g-PI particle brushes were synthesized by both conventional and activators regenerated by electron transfer (ARGET) atom transfer radical polymerization (ATRP). The morphology and solution state study on the particle brushes by transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed the successful grafting of PI ligands on the silica surface. The presence of nanoparticle clusters suggests low grafting density (associated with the limited initiation efficiency of ARGET for PI). Nevertheless, particle brushes with very high molecular weights, Mn > 300,000, were prepared, which significantly improved the dispersion of silica nanoparticles and also contributed to excellent mechanical performance. The reinforcing effects of SiO2 nanofillers and very high molecular weight PI ligands were investigated by dynamic mechanical analysis (DMA) as well as computational simulation for the cured linear PI homopolymer/SiO2-g-PI particle brush bulk films.

20.
Tumour Biol ; 34(5): 2589-97, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23749486

RESUMO

X-ray repair cross-complementing group 3 (XRCC3) plays a vital role in maintaining the stability of genome by homologous recombination repair for DNA double-strand breaks. The genetic polymorphism of XRCC3 C241T has been implicated in lung cancer risk, but the findings across published studies in Asians are inconsistent and inconclusive. To estimate the precise association of XRCC3 C241T polymorphism with lung cancer risk, a meta-analysis of all currently available studies in Asians was performed. A comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases was conducted for eligible studies based on the inclusion criteria. The pooled odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to assess the association. Besides, subgroup analysis and sensitivity analysis were also performed for further estimation. Seven available studies with a total of 7,398 subjects were finally included into this meta-analysis. The overall ORs indicated that the XRCC3 C241T polymorphism was not associated with a lung cancer risk among Asians in all genetic contrast modes (ORT allele vs. C allele = 1.08, 95 % CI 0.95-1.24, P OR = 0.252; ORTT vs. CC = 1.30, 95 % CI 0.69-2.45, P OR = 0.426; ORCT vs. CC = 1.07, 95 % CI 0.93-1.24, P OR = 0.363; ORTT + CT vs. CC = 1.08, 95 % CI 0.94-1.24, P OR = 0.300; ORTT vs. CC + CT = 1.29, 95 % CI 0.68-2.43, P OR = 0.439). We failed to identify significant association between the XRCC3 C241T polymorphism and risk of lung cancer in Chinese and population-based studies. Interestingly, the pooled ORs in hospital-based studies indicated that the XRCC3 C241T variant carriers were more susceptible to lung cancer (ORT allele vs. C allele = 1.27, 95 % CI 1.04-1.56, P OR = 0.019; ORCT vs. CC = 1.26, 95 % CI 1.01-1.57, P OR = 0.045; ORTT + CT vs. CC = 1.28, 95 % CI 1.03-1.59, P OR = 0.027). Sensitivity analysis confirmed the stability and liability of all results. This meta-analysis suggests that the XRCC3 C241T polymorphism may not exert a risk effect on the lung cancer risk in Asians, although a statistically significant association was observed among the hospital-based studies. Thus, the precise relationship between the XRCC3 C241T variant and lung cancer risk needs further confirmation in future studies with large available data.


Assuntos
Proteínas de Ligação a DNA/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Povo Asiático , Estudos de Casos e Controles , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Razão de Chances , Fatores de Risco
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