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1.
Analyst ; 148(18): 4339-4345, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37580992

RESUMO

Meloxicam (Mel), as a powerful and effective anti-inflammatory drug, is commonly employed for the treatment of various inflammatory diseases; however, the use of Mel at high doses or for extended periods could cause severe side effects in human visceral organs. Therefore, a simple, rapid, and reliable method is urgently needed to monitor Mel in biological samples. Herein, novel water-soluble luminescent nano-carbon dots (nano-Cdots) with outstanding physicochemical properties were prepared by a one-pot high-temperature hydrothermal process of ellagic acid and guanidine. The nano-Cdots were further used as an optical probe for the sensitive detection of Mel in serum samples through the cooperative mechanisms of the inner filter effect and photoelectron transfer. By employing this sensor, an excellent linear correlation was achieved between the relative luminescent intensity [(PL0 - PL)/PL0] and the concentration of Mel in the range of 0.1 to 200 µM, with a limit of detection of 34.68 nM (3σ/k). This sensor was effectively employed for the analysis of Mel in real serum samples, implying its potential development prospects for the advancement of drug analysis with carbon-based probes.


Assuntos
Pontos Quânticos , Água , Humanos , Meloxicam/uso terapêutico , Fluorometria , Água/química , Espectrometria de Fluorescência/métodos , Carbono/química , Pontos Quânticos/química , Corantes Fluorescentes
2.
J Asian Nat Prod Res ; 25(9): 880-889, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36573490

RESUMO

Echinacoside (ECH) is the main compound of Cistanche deserticola, which possesses antioxidant, antitumor, antifatigue, and anti-inflammatory properties. The present study investigated the protective effects of echinacoside on type 2 diabetes mellitus (T2DM)-induced injury in T2DM injury db/db mice model and insulin-resistant LO2 cell model. The results demonstrated that ECH probably alleviated T2DM-induced injury by mediating the AKT pathway, which provided a new direction for the treatment of T2DM-induced injury.


Assuntos
Diabetes Mellitus Tipo 2 , Proteínas Proto-Oncogênicas c-akt , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glicosídeos/farmacologia , Antioxidantes
3.
J Trop Pediatr ; 66(6): 648-654, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32388558

RESUMO

We reported a Chinese boy with X-linked hyper IgM (XHIGM) syndrome, manifesting as recurrent and severe pneumonia caused by Pneumocystis jirovecii. His parents were healthy and unrelated. In August 2018, the 5-month-old boy manifested as cough and dyspnea, and then in July 2019, he was admitted because of the same symptoms. Immunological results of the two admissions both showed low IgG, low IgA, normal IgM and high levels of 1,3-ß-D-glucan (BDG). Using next-generation sequencing (NGS), great reading counts of P. jirovecii were identified from the deep sputum in both admissions. Caspofungin combined with trimethoprim-sulfamethoxazole were used to anti-infection, and he recovered quickly. Whole-exome sequencing was performed for this family because of immune suppression, the disease-causing gene (exon 10-22 of CD40L) deletion for XHIGM syndrome was identified. NGS is beneficial for etiology diagnosis. Pneumocystis jirovecii pneumonia as an opportunistic infection could be recurrent in patients with XHIGM syndrome.


Assuntos
Caspofungina/uso terapêutico , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Tosse/etiologia , Dispneia/etiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/tratamento farmacológico , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Lactente , Masculino , Pneumocystis carinii/genética , Resultado do Tratamento
4.
Syst Appl Microbiol ; 47(4): 126515, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38776610

RESUMO

A novel anaerobic, thermophilic bacterium of the class Atribacteria, strain M15T, was isolated from a high-temperature gas reservoir, Japan. Cells of strain M15T were gram-negative, short oval-shaped, and lacked flagella. Growth occurred at 45-75 °C (optimum 70-75 °C) and pH 6.5-8.5 (optimum pH 7.5-8.0) and was fast under optimal conditions (doubling time 11.4 h). Yeast extract was required for growth. Fermentative growth with glucose, arabinose, xylose, and cellobiose was observed. The major fermentative end products of glucose were acetate and hydrogen. The major cellular fatty acids were C16:0, iso-C15:0, and C18:0. The genomic G + C content was 46.0 mol%. Fluorescence and electron microscopy observations revealed the intracellular localization of genomic DNA surrounded by a membrane in the cells of strain M15T as reported in a sole validly described species of the class Atribacteria in the phylum Atribacterota, Atribacter laminatus strain RT761T, suggesting that the unique morphological traits are widely shared in this class. Phylogenetic analyses indicated that strain M15T belongs to a distinct family-level lineage in the class Atribacteria and shows low similarities to Atribacter laminatus strain RT761T (16S rRNA gene sequence identity of 90.1 %, average nucleotide identity [ANI] of 66.1 %, average amino acid identity [AAI] of 55.8 %). Phenotypic traits of strain M15T (thermophilic, fast-growing, relatively high G + C content, etc.) were clearly distinct from A. laminatus. Based on these phenotypic and genomic properties, we propose a novel genus and species, Atrimonas thermophila gen. nov., sp. nov. for strain M15T (=JCM39389T, =KCTC25731T) representing a novel family Atrimonadaceae fam., nov. in the class Atribacteria.


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , RNA Ribossômico 16S/genética , Ácidos Graxos/análise , DNA Bacteriano/genética , Japão , Temperatura Alta , Fermentação , Campos de Petróleo e Gás/microbiologia
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 322: 124805, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39003827

RESUMO

A novel fluorimetric ratiometric probe of green and eco-friendily nitrogen-enriched, oxygen-doped carbon nanodots (Cnanodots) was prepared for the quantitative analysis of mercury(II) (HgII) and nitrofurantoin (Nit) in the environmental sewage. The Cnanodots exhibits dual-emission peaks respectively at 345 and 445 nm under 285 nm excitation, with excitation-independent properties. Unexpectedly, this Cnanodots displays two obvious ratiometric responses to HgII and Nit through decreasing the signal at 345 nm and remaining invariable at 445 nm. Experimental results confirm that the highly sensitive analysis of HgII and Nit are achieved respectively based on matching energy-level electron transfer and inner filter effect mechanisms. The fluorescence (FL) ratiometric intensity of [FL345nm/FL445nm] expresses a good linear relationship with the concentration of HgII in the scope of 0.01-20 µM, while the logarithm of [Log(FL0345nm-FL345nm)] on the quenching degree of the probe by Nit also shows a good linear correlation within the range of 0.01-100 µM. The detection limits were calculated to be 4.14 nM for HgII, and 7.84 nM for Nit. Moreover, recovery experiments of Cnanodots for HgII and Nit sensing in real sewage samples obtained satisfactory results, comfirming the feasibility of practical application.

6.
Zhonghua Zhong Liu Za Zhi ; 35(1): 38-42, 2013 Jan.
Artigo em Zh | MEDLINE | ID: mdl-23648298

RESUMO

OBJECTIVE: To analyze the factors affecting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: A retrospective cohort study was carried out to analyze the clinical data of 141 breast cancer patients treated with neoadjuvant chemotherapy. The factors affecting pCR and the changes of tumor receptor status before and after treatment were analyzed. RESULTS: Among all the 141 patients, 21 patients (14.9%) achieved pCR. The rate of pCR achieved by regimens of anthracycline combined with taxane was higher (16.8%, 19/113) than that by anthracycline-containing regimens (7.1%, 1/14). The dose intensity of anthracycline had a significant correlation with pCR rate (P < 0.05). The pCR rate in the relative dose intensity of taxane ≥ 0.85 arm was higher than that of < 0.85 arm (P = 0.02). Eighty patients (56.7%) had completed more than 4 cycles of chemotherapy and the median time to achieve pCR was 6 (3 to 10) cycles. The pCR rate had a significant difference between patients < 6 and ≥ 6 cycles (7.1% vs. 22.5%,P = 0.01). Multivariate analysis showed that tumor size measured by palpation ≤ 5 cm and ≥ 6 chemotherapy cycles were significantly related with pCR rate (P < 0.05). In all the 21 pCR patients, the pre-treatment ER(-), PR(-), HER-2(-) statuses were in 14, 14 and 17 patients, respectively. The status of ER, PR, HER-2 of most patients (74.2%, 69.7% and 87.7%, respectively) was not changed after treatment. Among the patients with changes in receptor status, ER changed from negative to positive was in the majority (37.1%, 13/35 vs. 12.9%, 4/31, P < 0.05), and the percentage of changes in PR and HER-2 status had no significant differences. CONCLUSIONS: The regimens of anthracycline combined with taxane can achieve a higher pCR rate. The lymph node and receptor status before therapy have no significant correlation with pCR. Patients who have primary tumor size ≤ 5 cm, ≥ 6 chemotherapy cycles and enough dose intensity are easier to achieve pCR. The receptor status before and after therapy should be determined, and according to any positive results, physicians can chose HER-2 targeted therapy and/or endocrine therapy after surgery to benefit the patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Terapia Neoadjuvante/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/metabolismo , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Quimioterapia Adjuvante , Relação Dose-Resposta a Droga , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Indução de Remissão , Estudos Retrospectivos , Taxoides/administração & dosagem , Carga Tumoral
7.
Zhonghua Yi Xue Za Zhi ; 93(2): 96-8, 2013 Jan 08.
Artigo em Zh | MEDLINE | ID: mdl-23648343

RESUMO

OBJECTIVE: To observe the preliminary efficacies and adverse events of sunitinib in the treatment of metastatic breast cancer ulcer. METHODS: From December 2008 to May 2010, patients with advanced breast cancer ulcer took a single sunitinib. The dosage was adjusted on the basis of adverse events. And clinical response was evaluated. RESULTS: Nine patients with advanced breast cancer ulcer finished the treatment. The objective response and the clinical benefit time to progression of sunitinib were 3 and 7 patients with metastatic breast cancer ulcer, and the median time to progression (TTP) was 2.0 months. The most common adverse events included fatigue, hand-foot syndrome, neutropenia, thrombocytopenia and hypertension. CONCLUSION: Single-agent sunitinib treatment of refractory advanced breast cancer ulcer has marked efficacies. However, neutropenia, thrombocytopenia and hypertension are the major dose-limited toxicities.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Indóis/uso terapêutico , Pirróis/uso terapêutico , Úlcera/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Sunitinibe , Resultado do Tratamento
8.
Zhonghua Zhong Liu Za Zhi ; 34(10): 764-9, 2012 Oct.
Artigo em Zh | MEDLINE | ID: mdl-23291071

RESUMO

OBJECTIVE: To evaluate the correlation of clinical effects and reasonable doses of docetaxel salvage therapy for patients with metastatic breast cancer. METHODS: We reviewed retrospectively the clinical records of patients with metastatic breast cancer treated with docetaxel and statistically analyzed the correlation between clinical effects and reasonable doses of docetaxel. RESULTS: The objective response rate and clinical benefit rate of docetaxol in patients with metastatic breast cancer were 27.0% and 35.0%, respectively, and the median progression free survival (PFS) was 5.0 (3.8 - 6.3) months. In the analysis at a single dose level, the clinical benefit rate and PFS of the ≥ 90.0 mg/m(2) docetaxel group were superior to that of the < 90.0 mg/m(2) group (P = 0.008, P = 0.045). Multi-dose level group stratified analysis showed that the docetaxel < 75.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) PFS group (P = 0.018), and the ≥ 95.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) group (P = 0.048). In patients who received >third line treatment or previously received paclitaxel adjuvant therapy, the PFS of the ≥ 94.9 mg/m(2) docetaxel group was 6.0 months, better than the 3.0 months of the 75.0 ∼ 84.9 mg/m(2) group (P = 0.031; P = 0.021). CONCLUSION: There is a clear correlation between clinical effects and reasonable doses of docetaxel salvage therapy in patients with metastatic breast cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama/tratamento farmacológico , Terapia de Salvação , Taxoides , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Docetaxel , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Taxoides/administração & dosagem , Taxoides/uso terapêutico , Adulto Jovem
9.
Zhonghua Yi Xue Za Zhi ; 92(42): 3001-3, 2012 Nov 13.
Artigo em Zh | MEDLINE | ID: mdl-23328295

RESUMO

OBJECTIVE: To explore the chemotherapeutic efficacies and prognostic factors of metastatic triple-negative breast cancer. METHODS: The clinicopathologic data of 151 patients with metastatic triple-negative breast cancer were collected from September 1994 to November 2011 and their clinicopathologic characteristics, recurrence and survival were analyzed. RESULTS: Platinum plus taxol or vinorelbine was significantly higher than others for these patients (42.1% vs 23.1%, P = 0.022). The median overall survivals of those on first-line chemotherapy with partial remission, stable disease and progressive disease were 29.6, 24.7 and 13.1 months respectively. The differences were statistically significant (P = 0.045). Two or three-line chemotherapy showed no obvious statistical relationship with total overall survival. Simple factor analysis showed that the number of metastasis, visceral metastases and the efficacies of first-line chemotherapy were correlated with overall survival (all P < 0.05). Multivariate Cox regression showed that disease-free survival and the efficacies of first-line chemotherapy were the independent prognostic factors of metastatic triple-negative breast cancer. CONCLUSION: The combined chemotherapy of platinum may achieve better efficacies in the treatment of metastatic triple-negative breast cancer. And the efficacies of first-line chemotherapy are closely correlated with survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/uso terapêutico , Compostos de Platina/uso terapêutico , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/análogos & derivados , Vimblastina/uso terapêutico , Vinorelbina , Adulto Jovem
10.
Electrophoresis ; 32(23): 3331-40, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22134977

RESUMO

In this paper, a novel, simple, economical and environmentally friendly method based on in situ chemically induced synthesis strategy was designed and developed for the modification of a poly(dimethylsiloxane) (PDMS) microchip channel with polydopamine/gold nanoparticles (PDA/Au NPs) to create a hydrophilic and biofouling resistant surface. Dopamine as a reductant and a monomer, and HAuCl(4) as an oxidant to trigger dopamine polymerization and the source of metallic nanoparticles, were filled into the PDMS microchannel to yield in situ a well-distributed and robust PDA/Au NP coating. Au NPs were highly and uniformly dispersed in/on the PDA matrix with a narrow size distribution, as verified by scanning electron microscopy and UV-vis spectra. Compared with the native PDMS microchannel, the modified surfaces exhibited much better wettability, high stability and suppressed electroosmotic mobility, and less nonspecific adsorption towards biomolecules. The water contact angle and EOF of PDA/Au NP-coated PDMS microchip were measured to be 13° and 4.17×10(-4) cm(2)/V s, compared to those of 111° and 5.33×10(-4) cm(2)/V s from the native one, respectively. Fast and efficient separations of five amino acids such as arginine, proline, histidine, valine and threonine suggested greatly improved electrophoretic performance of the PDA/Au NP-functionalized PDMS microchips. This one-step procedure offers an effective approach for a biomimetic surface design on microfluidic chips, which is promising in high-throughput and complex biological analysis.


Assuntos
Aminoácidos/isolamento & purificação , Dimetilpolisiloxanos/química , Eletroforese em Microchip/instrumentação , Ouro/química , Nanopartículas Metálicas/química , Eletro-Osmose , Eletroforese em Microchip/métodos , Concentração de Íons de Hidrogênio , Indóis , Cinética , Microscopia Eletrônica de Varredura , Polímeros , Reprodutibilidade dos Testes , Difração de Raios X
11.
Am J Transl Res ; 13(5): 5659-5664, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150173

RESUMO

PURPOSE: To explore the correlation of changes in homocysteine (HCY) l, blood lipids and blood glucose levels in patients with cerebral infarction. METHODS: 120 patients with cerebral infarction admitted to our hospital from February 2018 to February 2020 were selected as the experimental group, and 120 healthy volunteers in the same period were selected as the control group. The blood pressure and the homocysteine, blood lipids, blood glucose levels were compared; the experimental group was subdivided into single cerebral infarction group, combined diabetes group and combined hypertension group, and their blood lipid levels were compared with the control group; Spearman method was used to analyze the relationship between HCY, blood lipid, blood sugar levels and cerebral infarction. RESULTS: ① The diastolic and systolic blood pressure levels of the experimental group were higher, whereas the control group were lower (P<0.05). ② The levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and TC/[high density lipoprotein cholesterol (HDL-C)] of the experimental group were higher, but the level of HDL-C was lower than that of the control group (all P<0.05). ③ The fasting blood glucose (FBG) and glycosylated hemoglobin (GHb) levels of the experimental group were higher than those of the control group (all P<0.05). ④ The HCY level in the experimental group was higher than that in the control group (P<0.05). ⑤ The levels of TC, TG, LDL-C and TC/HDL-C in single cerebral infarction group, combined diabetes group and combined hypertension group were higher, and HDL-C level was lower than that in control group (all P<0.05). ⑥ Spearman analysis revealed that HCY was positively correlated with TC, TG, LDL-C and FBG (all P<0.05). CONCLUSION: The level of HCY is positively correlated with the levels of TC, TG, LDL-C and FBG in patients with cerebral infarction.

12.
J Cell Biochem ; 111(1): 75-81, 2010 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-20506264

RESUMO

Previous studies demonstrated that the expression of testes-specific protease 50 (TSP50) was increased in breast cancer cells and that overexpression of TSP50 can promote tumorigenesis. Thus, it is important to identify the regulatory mechanisms of TSP50 for tumor therapy. In this study, we elucidated the mechanism underlying TSP50 downregulation by basic fibroblast growth factor (bFGF). We used MDA-MB-231 and HEK293T cell lines to address this issue. RT-PCR and promoter activity assays indicated that bFGF downregulates TSP50 expression via transcriptional activation. We next investigated the signaling pathway that mediated the effect of bFGF on TSP50 transcription, and identified that bFGF induced the phosphorylation of ERK and Sp1. An ERK inhibitor suppressed Sp1 phosphorylation and bFGF-reduced TSP50 expression at the mRNA level. In addition, the dominant negative (DN) mutants of ERK and Sp1 both suppressed the reduction of TSP50 by bFGF. Deletion and mutation analyses indicated that the Sp1 site, located within the +237/+239 region of the human TSP50 promoter, is the major responsive element for bFGF. Taken together, our results strongly suggest that bFGF mediates TSP50 downregulation by ERK activation, leading to the phosphorylation of Sp1 in this process.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Serina Endopeptidases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição Sp1/metabolismo , Linhagem Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Ativação Enzimática , Inibidores Enzimáticos/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/genética , Humanos , Regiões Promotoras Genéticas , Serina Endopeptidases/genética , Fator de Transcrição Sp1/genética , Ativação Transcricional
13.
J Investig Med ; 68(1): 75-81, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31300469

RESUMO

The clinical findings and CT images are investigated in order to fulfill an early preoperative diagnosis and increase awareness of low-grade appendiceal mucinous neoplasm (LAMN) confined to the appendix. 17 cases with histologically proven LAMNs confined to the appendix were included in this study. All patients had received multiphase CT examinations before the surgery. The imaging criteria included shape, size, margin, attenuation, secondary degeneration and internal mass enhancement pattern. In CT images, all cases appeared as oval or tubular cystic masses (average attenuation 20.4±3.6 Hounsfield units), with the longest dimensions ranging from approximately 38 to 106 mm (mean 66.3 mm), and the ratio of length against width was 1.83 in average. The cystic wall was unevenly thickened, with a mean maximal wall thickness of 5.7 mm (>10 mm in 3 cases). The inner capsule wall was rough, and calcification was observed in 3 cases. A few amounts of periappendiceal fat stranding were noted in 2 cases. Mild ring mural enhancement of the cystic wall was seen during the arterial phase, with progressive enhancement during the portal venous phase. In addition, mini enhancing mural nodules was observed in 5 cases. Although preoperative diagnosis of LAMNs confined to the appendix remains challenging, it should be considered when a focal well-defined cystic mass with slightly higher than water attenuation, thickened cystic wall with ring mural enhancement and a characteristic progressive contrast enhancement in CT imaging, especially in older females with non-specific symptoms similar to appendicitis.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico por imagem , Neoplasias do Apêndice/diagnóstico por imagem , Apêndice/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Apêndice/patologia , Apendicite/diagnóstico por imagem , Apêndice/patologia , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Cuidados Pré-Operatórios , Prognóstico
14.
ACS Biomater Sci Eng ; 6(1): 664-672, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33463219

RESUMO

Local resection or ablation remains an important approach to treat drug-resistant central neurological disease. Conventional surgical approaches are designed to resect the diseased tissues. The emergence of photothermal therapy (PTT) offers a minimally invasive alternative. However, their poor penetration and potential off-target effect limit their clinical application. Here, polydopamine nanoparticles (PDA-NPs) were prepared and characterized. Studies were performed to evaluate whether PDA-NPs combined with near-infrared (NIR) light can be used to ablate deep brain structures in vitro and in vivo. PDA-NPs were prepared with a mean diameter of ∼150 nm. The particles show excellent photothermal conversion efficiency. PDA-NPs did not show remarkable cytotoxicity against neuronal-like SH-SY5Y cell lines. However, it can cause significant cell death when combined with NIR irradiation. Transcranial NIR irradiation after PDA-NPs administration induced enhanced local hyperthermia as compared with NIR alone. Local temperature exceeded 60 °C after 6 min of irradiation plus PDA while it can only reach 48 °C with NIR alone. PTT with PDA (10 mg/mL, 3 µL) and NIR (1.5 W/cm2) can ablate deep brain structures precisely with an ablation volume of ∼6.5 mm3. Histological analysis confirmed necrosis and apoptosis in the targeted area. These results demonstrate the potential of NP-assisted PTT for the treatment against nontumorous central neurological diseases.


Assuntos
Nanopartículas , Fototerapia , Encéfalo/cirurgia , Indóis , Polímeros
15.
Cytokine ; 46(2): 251-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19349195

RESUMO

Activin, a member of the TGF-beta superfamily, inhibits the proliferation of breast cancer cells. Activin interacts with its type I and type II receptors to induce phosphorylation of intracellular signaling molecules known as Smads. Previous studies showed that mouse ARIP2 can reduce activin signaling by interacting with activin type II receptors (ActRIIs); however, the activity of ARIP2 in breast cancer is still unclear. In this study, we used RT-PCR to obtain a human homologue of mouse ARIP2, human activin receptor-interacting protein 2 (hARIP2). Like murine ARIP2, hARIP2 has a PDZ domain in its NH2-terminal region and can interact specifically with ActRIIs. Overexpression of hARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formation in human breast adenocarcinoma MCF-7 cells and MDA-MB-231 cells. However, down-regulation of hARIP2 expression by RNAi enhanced activin-induced transcriptional activity and reduced cell proliferation and colony formation. Immunohistochemistry revealed that hARIP2 was expressed more frequently and much more intensely in malignant breast tissues such as simple carcinoma, invasive ductal carcinoma and mucinous adenocarcinoma than in benign hyperplasia or fibroadenoma cases. These results suggest that hARIP2 is a putative growth-promoting factor involved in breast tumorigenesis and tumor development.


Assuntos
Receptores de Activinas Tipo II/metabolismo , Neoplasias da Mama/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Receptores de Activinas Tipo II/genética , Ativinas/genética , Ativinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/patologia , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Proteínas de Membrana/genética , Camundongos , Dados de Sequência Molecular , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transcrição Gênica , Técnicas do Sistema de Duplo-Híbrido
16.
Biomed Res Int ; 2019: 2761241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016187

RESUMO

The aim of the present study was to investigate the effects of phosphorylatable nucleus localization signal linked nucleic kinase substrate short peptide (pNNS)-conjugated chitosan (pNNS-CS) mediated miR-140 and IGF-1 in both rabbit chondrocytes and cartilage defects model. pNNS-CS was combined with pBudCE4.1-IGF-1, pBudCE4.1-miR-140, and negative control pBudCE4.1 to form pDNA/pNNS-CS complexes. Then these complexes were transfected into chondrocytes or injected intra-articularly into the knee joints. High levels of IGF-1 and miR-140 expression were detected both in vitro and in vivo. Compared with pBudCE4.1 group, in vitro, the transgenic groups significantly promoted chondrocyte proliferation, increased glycosaminoglycan (GAG) synthesis, and ACAN, COL2A1, and TIMP-1 levels, and reduced the levels of nitric oxide (NO), MMP-13, and ADAMTS-5. In vivo, the exogenous genes enhanced COL2A1, ACAN, and TIMP-1 expression in cartilage and reduced cartilage Mankin score and the contents of NO, IL-1ß, TNF-α, and GAG contents in synovial fluid of rabbits, MMP-13, ADAMTS-5, COL1A2, and COL10A1 levels in cartilage. Double gene combination showed better results than single gene. This study indicate that pNNS-CS is a better gene delivery vehicle in gene therapy for cartilage defects and that miR-140 combination IGF-1 transfection has better biologic effects on cartilage defects.


Assuntos
Doenças das Cartilagens/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Quitosana/farmacologia , Condrócitos/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , MicroRNAs/metabolismo , Peptídeos/farmacologia , Animais , Doenças das Cartilagens/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Técnicas de Transferência de Genes , Humanos , Articulação do Joelho/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Óxido Nítrico/metabolismo , Coelhos , Líquido Sinovial/efeitos dos fármacos , Líquido Sinovial/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Transfecção/métodos
17.
Mol Med Rep ; 14(4): 3293-300, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27573470

RESUMO

Angiopoietin-like protein 4 (Angptl4) is a secreted protein predominantly expressed in liver and adipose tissues, and has been identified as an adipokine. Angptl4 is the target gene of peroxisome proliferator­activated receptors, which are widely used as lipid­lowering and anti­diabetic drugs, and previous studies have demonstrated that Angptl4 is able to directly stimulate adipocyte lipolysis. The current study focused on how Angptl4 was involved in regulating lipid and glucose metabolism in high­fat­diet (HFD) C57 mice. In the present study, mice were divided into three groups, with standard chow mice as a normal control, adenovirus (adv)­injected HFD mice as a model control and adv­Angptl4­injected HFD mice as the Angptl4+ group. Firstly, compared with the normal control group, mice in the model control group gained more body weight with severe liver steatosis and increased serum levels of triglyceride, total cholesterol, free fatty acids, alanine aminotransferase and aspartate aminotransferase. In the Angptl4+ group, Angptl4 reduced the weight growth rate, aggravated hepatic steatosis and further increased all the aforementioned serum indexes. Secondly, compared with the normal control, the model control group had a reduced glucose tolerance and developed insulin resistance. Angptl4 expression and the phosphorylation levels of several insulin signaling pathway­associated genes, insulin receptor substrate 1, protein kinase B, janus kinase 2, signal transducer and activator of transcription 3 were downregulated in the liver samples. Adv­Angptl4 injection was observed to improve glucose tolerance and insulin resistance. The genes measured were identified to be upregulated close to normal levels. All the results suggested that Angptl4 served an important role in lipid and glucose metabolism in HFD­induced obese mice, and this may have a great significance for treatment of hyperlipidemia, diabetes, metabolic syndrome and other diseases.


Assuntos
Angiopoietinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Resistência à Insulina , Fígado/metabolismo , Alanina Transaminase/sangue , Proteína 4 Semelhante a Angiopoietina , Angiopoietinas/genética , Animais , Aspartato Aminotransferases/sangue , Colesterol/sangue , Ácidos Graxos/sangue , Fígado Gorduroso/sangue , Fígado Gorduroso/patologia , Glucose/metabolismo , Insulina/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Triglicerídeos/sangue , Regulação para Cima
18.
Int J Clin Exp Med ; 8(11): 21311-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26885071

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the extent to which hypertension (HT) interacts with diabetes mellitus (DM) to affect diastolic heart failure (DHF) in a high-risk population. METHODS: We conducted a hospital-based case-control study to investigate the relationship between HT or DM and DHF in 251 patients (case: 133 patients with DHF; control: 118 patients without DHF). Echocardiography was used to assess left ventricular (LV) diastolic function. The association between HT or DM and DHF was assessed by multivariate logistic regression (MLR) analysis controlling for confounders. The effect of the interaction between HT and DM on DHF was assessed in MLR models. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). RESULTS: The MLR analyses showed that HT and DM were independent predictors of DHF after adjustment for potential confounders (OR = 2.35-3.14, P<0.05 for all models). DHF was affected by the interaction between HT and DM (ORInt = 3.11-4.31, P Int<0.1, RETI = 2.13-2.69, AP = 0.38-0.49 and S = 4.11-6.80). CONCLUSION: The findings provide evidence that HT and DM are independent predictors of DHF and that both risk factors act synergistically to influence DHF in a Chinese high-risk population.

19.
J Chromatogr A ; 1323: 135-42, 2014 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-24331371

RESUMO

A novel chip-based enantioselective open-tubular capillary electrochromatography (OT-CEC) was developed employing bovine serum albumin (BSA) conjugated polydopamine-graphene oxide (PDA/GO) nanocomposites (PDA/GO/BSA) as stationary phase. After the poly(dimethylsiloxane) (PDMS) microfluidic chip was filled with a freshly prepared solution containing dopamine and graphene oxide, PDA/GO nanocomposites were formed and deposited on the inner wall of microchannel as permanent coating via the oxidation of dopamine by the oxygen dissolved in the solution. The PDA/GO-coated PDMS microchips not only have the adhesion of PDA that make them easily immobilized in the microchannel, but also have the larger surface and excellent biocompatibility of graphene which can incorporate much more biomolecules and well maintain their biological activity. In addition, incorporation of GO in PDA film can make surface morphology more rough, which is beneficial for enhancing the loading capacity of proteins in the microchannels and increasing sample capacity of OT-CEC columns. BSA was stably immobilized in the PDMS microchannel to fabricate a protein-stationary phase. Compared with the native PDMS microchannels, the modified surfaces exhibited much better wettability, more stable electroosmotic mobility, and less nonspecific adsorption. The efficient separation of chiral amino acids (tryptophan and threonine) and chiral dipeptide demonstrate that the constructed OT-CEC columns own ideal enantioselectivity. The presented strategy using PDA/GO coating as a versatile platform for facile conjugation of proteins may offer new processing strategies to prepare a functional surface designed on microfluidic chips.


Assuntos
Eletrocromatografia Capilar/métodos , Grafite/química , Indóis/química , Óxidos/química , Polímeros/química , Proteínas/química , Proteínas/isolamento & purificação , Adesividade , Adsorção , Dimetilpolisiloxanos/química , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Eletro-Osmose , Técnicas Analíticas Microfluídicas , Nanocompostos/química , Soroalbumina Bovina/química , Treonina/química , Treonina/isolamento & purificação , Triptofano/química , Triptofano/isolamento & purificação
20.
J Chromatogr A ; 1362: 301-8, 2014 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-25182855

RESUMO

A facile approach for preparation of molecularly imprinted polymers was developed and successfully used as chiral stationary phase for rapid enantioseparation by open tubular capillary electrochromatography (OT-CEC). In this work, molecularly imprinted polymers were one-step prepared employing Fe3O4 nanoparticles (NPs) as the supporting substrate and dopamine as the functional monomer. By simply mixing Fe3O4 NPs with template molecules in a weak alkaline solution of dopamine, a thin adherent polydopamine (PDA) film imprinted with template molecules was formed by the self-polymerization of dopamine on the surface of Fe3O4 NPs. After extracting the embedded template molecules, the produced imprinted Fe3O4@PDA NPs are of three dimensional shape of template molecules favoring high binding capacity and magnetism property for easy manipulation. The imprinted Fe3O4@PDA NPs prepared with l-tryptophan, l-tyrosine, Gly-l-Phe or s-ofloxacin as template molecules were packed in the PDMS microchannel via magnetic field as novel stationary phase for the successful enantioseparation of corresponding target analysts. In addition, the imprinted Fe3O4@PDA NPs-based OT-CEC system exhibited excellent reproducibility, stability and repeatability, which provides a powerful protocol for separation enantiomers within a short analytical time and opens up a promising avenue for high-throughput screening of chiral compounds.


Assuntos
Eletrocromatografia Capilar/métodos , Compostos Férricos/química , Indóis/química , Impressão Molecular/métodos , Nanopartículas/química , Polímeros/química , Fenômenos Magnéticos , Nanopartículas/ultraestrutura , Reprodutibilidade dos Testes , Estereoisomerismo
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