Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 111
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Anal Chem ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382097

RESUMO

Lysosomes are multifunctional organelles vital for cellular homeostasis with distinct subpopulations characterized by varying levels of Cl-, Ca2+, and H+. In situ visualization of these parameters is crucial for lysosomal research, yet developing probes that can simultaneously detect multiple ions remains challenging. Herein, we developed a lysosome-targeting ternary recognition ratiometric fluorescent probe based on tetrahedral DNA nanostructures (TDNs) to analyze lysosome subpopulations by Cl-, Ca2+, and pH. The TDN probe is assembled from four single-stranded DNAs, each end-modified with responsive fluorophores (Pr-Cl for Cl-, Pr-Ca for Ca2+, and Pr-pH for pH) or a reference fluorophore (Cy5). The fluorophores are integrated at the vertices of the rigid TDN to minimize mutual interference, and their fixed stoichiometry establishes a robust ternary recognition ratiometric fluorescence sensor for in situ resolution of lysosome subpopulations in living cells. Accordingly, a rise in lysosome subpopulations 2/6 characterized by low [Cl-], medium/high [Ca2+], and high pH was observed in the Niemann-Pick disease model cells but seldom observed in the control group. Conversely, there was a marked decline in the fraction of subpopulations 1/4/5 characterized by high [Cl-], medium to low [Ca2+], and pH. These changes were substantially reversed upon treatment. The probe holds great promise for studying lysosome subpopulations and the diagnosis and treatment of related diseases.

2.
Drug Resist Updat ; 66: 100907, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36527888

RESUMO

The binding of programmed death-1 (PD-1) on the surface of T cells and PD-1 ligand 1 (PD-L1) on tumor cells can prevent the immune-killing effect of T cells on tumor cells and promote the immune escape of tumor cells. Therefore, immune checkpoint blockade targeting PD-1/PD-L1 is a reliable tumor therapy with remarkable efficacy. However, the main challenges of this therapy are low response rate and acquired resistance, so that the outcomes of this therapy are usually unsatisfactory. This review begins with the description of biological structure of the PD-1/PD-L1 immune checkpoint and its role in a variety of cells. Subsequently, the therapeutic effects of immune checkpoint blockers (PD-1 / PD-L1 inhibitors) in various tumors were introduced and analyzed, and the reasons affecting the function of PD-1/PD-L1 were systematically analyzed. Then, we focused on analyzing, sorting out and introducing the possible underlying mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade including abnormal expression of PD-1/PD-L1 and some factors, immune-related pathways, tumor immune microenvironment, and T cell dysfunction and others. Finally, promising therapeutic strategies to sensitize the resistant patients with PD-1/PD-L1 blockade treatment were described. This review is aimed at providing guidance for the treatment of various tumors, and highlighting the drug resistance mechanisms to offer directions for future tumor treatment and improvement of patient prognosis.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias , Receptor de Morte Celular Programada 1 , Humanos , Antígeno B7-H1 , Resistência a Medicamentos , Imunoterapia , Microambiente Tumoral
3.
Anal Chem ; 95(11): 5087-5094, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36892999

RESUMO

In situ visualization of lipid composition diversity in lipid droplets (LDs) is essential for decoding lipid metabolism and function. However, effective probes for simultaneously localizing and reflecting the lipid composition of LDs are currently lacking. Here, we synthesized full-color bifunctional carbon dots (CDs) that can target LDs as well as respond to the nuance in internal lipid compositions with highly sensitive fluorescence signals, due to lipophilicity and surface state luminescence. Combined with microscopic imaging, uniform manifold approximation and projection, and sensor array concept, the capacity of cells to produce and maintain LD subgroups with varying lipid composition was clarified. Moreover, in oxidative stress cells, LDs with characteristic lipid compositions were deployed around mitochondria, and the proportion of LD subgroups changed, which gradually disappeared when treated with oxidative stress therapeutics. The CDs demonstrate great potential for in situ investigation of the LD subgroups and metabolic regulations.


Assuntos
Gotículas Lipídicas , Mitocôndrias , Gotículas Lipídicas/metabolismo , Mitocôndrias/metabolismo , Metabolismo dos Lipídeos , Lipídeos
4.
Small ; 19(40): e2301934, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37271893

RESUMO

Supramolecular hydrogels involved macrocycles have been explored widely in recent years, but it remains challenging to develop hydrogel based on solitary macrocycle with super gelation capability. Here, the construction of lantern[33 ]arene-based hydrogel with low critical gelation concentration (0.05 wt%), which can be used for efficient oil-water separation, is reported. The lantern[33 ]arenes self-assemble into hydrogen-bonded organic nanoribbons, which intertwine into entangled fibers to form hydrogel. This hydrogel which exhibits reversible pH-responsiveness characteristics can be coated on stainless-steel mesh by in situ sol-gel transformation. The resultant mesh exhibits excellent oil-water separation efficiency (>99%) and flux (>6 × 104 L m-2 h-1 ). This lantern[33 ]arene-based hydrogel not only sheds additional light on the gelation mechanisms for supramolecular hydrogels, but also extends the application of macrocycle-based hydrogels as functional interfacial materials.

5.
Mol Cancer ; 21(1): 37, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130920

RESUMO

PURPOSE: The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. EXPERIMENTAL DESIGN: The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity. RESULTS: Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1). CONCLUSIONS: Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.


Assuntos
Antineoplásicos , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Carcinoma de Células de Transição/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo U , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
6.
Biochem Biophys Res Commun ; 630: 167-174, 2022 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-36155063

RESUMO

BACKGROUND AND AIMS: Patients with liver fibrosis who have pain in the liver region may have changed nerve factors. The expression of neurokines and hepatic nerves in liver fibrosis, however, was little understood. In order to better understand how liver fibrosis develops, we plan to look into the hepatic nerve and neurokine changes and how they relate to hepatic stellate cells (HSCs). METHODS: The expression of neurokines in liver samples from 55 chronic hepatitis B patients and the carbon tetrachloride (CCl4) animal model were studied. The co-staining of Nissl and α-SMA allowed us to investigate the neurons and their interaction with α-SMA in fibrotic livers, as well as the expression of the glial cell marker glial fibrillary acidic protein (GFAP) and its relationship with α-SMA, a marker of HSCs. SH-SY5Y cells were treated with a fibrotic serum to imitate the hepatic microenvironment on neuronal cells. We also used brain-derived neurotrophic factor (BDNF) to stimulate mouse primary HSCs and LX2. RESULTS: The levels of mRNA for neurokines such as BDNF, GFAP, and growth-associated protein (GAP43) are significantly increased in both human and animal liver fibrosis. As liver fibrosis advances, we found that Nissl bodies and α-SMA may co-localize, suggesting a connection between hepatic nerves and HSCs. Human fibrotic serum may increase neurkines, notably BDNF, in SH-SY5Y cells. We also found that BDNF increased pro-inflammatory cytokines and fibrogenic markers in hHSCs. CONCLUSIONS: Patients with hepatic fibrosis had significantly higher levels of BDNF, GFAP, GAP43, and nerve fibers. HSC and nerve fibers interact, and nerves also create neurogenic substances that promote liver fibrosis and HSC activation.


Assuntos
Células Estreladas do Fígado , Neuroblastoma , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Tetracloreto de Carbono/toxicidade , Citocinas/metabolismo , Fibrose , Proteína Glial Fibrilar Ácida/metabolismo , Células Estreladas do Fígado/metabolismo , Humanos , Fígado/metabolismo , Cirrose Hepática/patologia , Camundongos , Neuroblastoma/patologia , RNA Mensageiro/metabolismo , Microambiente Tumoral
7.
J Cardiovasc Pharmacol ; 80(1): 48-55, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35170494

RESUMO

ABSTRACT: Angioplasty often fails due to the abnormal proliferation of vascular smooth muscle cells (VSMCs). Success rates of angioplasty may increase following the administration of an agent that effectively ameliorates aberrant vascular remodeling. Icariside II (ICS-II) is a natural flavonol glycoside extract from the Chinese herbal medicine Epimedii that possesses several medicinal qualities that are beneficial in humans. Nevertheless, the role of ICS-II in addressing aberrant vascular remodeling have yet to be clarified. The current investigation studies the molecular effects of ICS-Ⅱ on balloon-inflicted neointimal hyperplasia in rats in vivo and on platelet-derived growth factor-induced vascular proliferation in primary rat aortic smooth muscle cells (VSMCs) in vitro. ICS-II was found to be as effective as rapamycin, the positive control used in this study. ICS-II inhibited neointimal formation in injured rat carotid arteries and notably reduced the expression of Wnt7b. ICS-Ⅱ significantly counteracted platelet-derived growth factor-induced VSMCs proliferation. Cell cycle analysis showed that ICS-II triggered cell cycle arrest during the G1/S transition. Western blot analysis further indicated that this cell cycle arrest was likely through Wnt7b suppression that led to CCND1 inhibition. In conclusion, our findings demonstrate that ICS-II possesses significant antiproliferative qualities that counteracts aberrant vascular neointimal hyperplasia. This phenomenon most likely occurs due to the suppression of the Wnt7b/CCND1 axis.


Assuntos
Lesões das Artérias Carótidas , Remodelação Vascular , Animais , Lesões das Artérias Carótidas/tratamento farmacológico , Lesões das Artérias Carótidas/metabolismo , Movimento Celular , Proliferação de Células , Flavonoides , Hiperplasia/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Neointima/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fator de Crescimento Derivado de Plaquetas/farmacologia , Ratos , Ratos Sprague-Dawley
8.
Curr Microbiol ; 79(12): 382, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329315

RESUMO

BJC16-A38T, a Gram-negative, aerobic and non-motile rod-shaped strain was isolated from a permafrost wetland soil sample. BJC16-A38T was oxidase- and catalase-positive, and produced pale yellow colonies on modified R2A agar plates. The 16S rRNA gene sequence of BJC16-A38T shared the highest sequence similarity with those of Mucilaginibacter xinganensis BJC16-A31T (97.44%), Mucilaginibacter gotjawali SA3-7T (96.79%) and Mucilaginibacter frigoritolerans FT22T (96.14%). Phylogenetic analysis revealed that BJC16-A38T formed a separate lineage together with strain M. xinganensis BJC16-A31T in the genus Mucilaginibacter. BJC16-A38T contained menaquinone-7 (MK-7) as the predominant isoprenoid quinine. Major fatty acids in cells were iso-C15:0, summed feature 3 (16:1ω7c/16:1ω6c) and iso-C17:03-OH. BJC16-A38T contained phosphatidylethanolamine, two unknown polar lipids, six unidentified phospholipids and an unidentified aminolipid. The Genome of BJC16-A38T was sequenced using the Genome Analyzer IIx sequence platform and 38 contigs were produced in total with an average G + C percentage of 44.00%. The average nucleotide identity (ANI) of BJC16-A38T with respect to those of M. xinganensis BJC16-A31T, M. gotjawali SA3-7T and M. frigoritolerans FT22T were 79.60%, 77.24% and 77.58%, respectively. Digital DNA-DNA hybridization (DDH) values between BJC16-A38T and the tree reference strains were 21.30%, 19.60% and 19.70%, respectively. BJC16-A38T exhibited phenanthrene biodegradation activity that can degrade 88.02% phenanthrene in the MM medium after 7 days cultivation. Phenotypic, chemotaxonomic, phylogenetic and genomic characteristics concluded that strain BJC16-A38T represents a novel species of the genus Mucilaginibacter. Hence, the name Mucilaginibacter phenanthrenivorans sp. nov. is proposed. The type strain is BJC16-A38T (= CGMCC 1.12693T = NBRC 110383T).


Assuntos
Fenantrenos , Solo , RNA Ribossômico 16S/genética , Filogenia , Áreas Alagadas , Microbiologia do Solo , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , Análise de Sequência de DNA , Ácidos Graxos/metabolismo , Vitamina K 2
9.
Sheng Li Xue Bao ; 73(3): 369-388, 2021 Jun 25.
Artigo em Zh | MEDLINE | ID: mdl-34230941

RESUMO

Spinal cord magnetic resonance imaging (MRI) is an advanced imaging technique (mainly in the cervical cord) and has been gradually used in basic scientific research such as human sensation and motor function, and clinical applications such as spinal cord injury, myelitis, and chronic pain, etc. The development of spinal cord MRI is still at the early stage compared with brain MRI and limited by the current MRI technology and data analysis methods. This review focuses on the methods and applications of spinal cord MRI technology in the basic research fields of cognitive neuroscience and clinical application. Firstly, we will introduce the imaging principle, methods, measurement standards, and applications of most commonly used multimodal spinal cord MRI techniques, including quantitative spinal cord MRI (such as structural, diffusion, spectroscopy, myelin water, magnetization transfer, and chemical exchange saturation transfer imaging, etc.) and spinal functional MRI (fMRI). Secondly, we will discuss the technical challenges and possible solutions of spinal cord MRI data processing from the three dimensions of denoising, data processing pipeline optimization, and repeatability and reliability. Finally, we will discuss the application status and development prospects of spinal cord MRI.


Assuntos
Traumatismos da Medula Espinal , Medula Espinal , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Reprodutibilidade dos Testes , Medula Espinal/diagnóstico por imagem
10.
Bioorg Med Chem Lett ; 29(2): 189-193, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30527868

RESUMO

Previously we have reported that 25-OCH3-PPD could suppress the reproduction of cancer cells and cause apoptosis without obvious toxicity. Herein, we aimed to enhance its bioactivity by introducing aromatic groups to its dammarane-type skeleton. These synthesized derivatives were tested for their inhibitory activities against five cancer cell lines. Of them, compounds 3a, 14a and 18a had the strongest antiproliferative activities against tumor cells (IC50 < 15 µM, 5-fold to 10-fold increases than 25-OCH3-PPD). Especially compound 14a displayed the most potent activity against DU145, MCF-7 and HepG2 cells (IC50 = 6.7 ±â€¯0.8, 4.3 ±â€¯0.8 and 5.8 ±â€¯0.6 µM, respectively). Structure-activity relationships demonstrated that having aromatic ester at the C3 position could improve the bioactivity. The data provided new insights into exploring novel antiproliferative lead compounds.


Assuntos
Antineoplásicos/farmacologia , Ginsenosídeos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ginsenosídeos/síntese química , Ginsenosídeos/química , Células Hep G2 , Humanos , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade
11.
Regul Toxicol Pharmacol ; 103: 229-236, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30703409

RESUMO

Perilla seeds are used as food and traditional medicine in China. This study aimed to investigate the toxicity profile of Perilla seed oil (PSO), which is the main constituent of Perilla seeds in rodents and Beagle dogs. No significant treatment-associated toxicity or mortality was observed at PSO dosages of up to 50 g/kg and 20 g/kg in KM mice and Wistar rats, respectively, suggesting that PSO was well tolerated by the experimental rodents. Sub-chronic oral toxicity of PSO was studied in dogs at doses of 3, 6 and 12 g/kg/d for 90 days followed by a 30 day recovery period. The results indicated that the body weight increased in all-dose groups more than control group, typical of animals on diets rich in fatty acids. Treatment-related side effects, including changes in hematology and serum biochemistry parameters, histopathology of liver and lymph glands, were observed in the high and moderate-dose dogs. However, these changes disappeared after the doses were withdrawn during the recovery period, except for alteration of liver in the high-dose group. In conclusion, the "no observed adverse effect level" (NOAEL) of oral administration of PSO for 90 days in Beagle dogs was considered to be 3 g/kg/d.


Assuntos
Fígado/efeitos dos fármacos , Linfonodos/efeitos dos fármacos , Ácido alfa-Linolênico/administração & dosagem , Ácido alfa-Linolênico/toxicidade , Administração Oral , Animais , Cães , Relação Dose-Resposta a Droga , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Óleos de Plantas/administração & dosagem , Óleos de Plantas/toxicidade , Ratos , Ratos Wistar , Testes de Toxicidade Subcrônica
12.
J Ultrasound Med ; 38(12): 3283-3289, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31218729

RESUMO

OBJECTIVES: The purpose of this study was to reveal the correlation between superior mesenteric artery (SMA) blood flow in the first 12 hours of life and the risk of necrotizing enterocolitis (NEC) in preterm neonates. METHODS: We conducted a prospective study. There were 104 preterm neonates included in our study. The SMA blood flow of each neonate was measured during the first 12 hours of life if the hemodynamic situation was stable. The results of Doppler ultrasound were confidential to the neonatologists and nurses. All of the demographics, comorbidities, and outcomes were recorded and analyzed. RESULTS: Among all of the demographics and comorbidities, the gestational age was related to the measurements of SMA blood flow. We conducted a single-factor analysis of the occurrence of NEC, including the peak systolic velocity (PSV), end-diastolic velocity, time-averaged mean velocity, differential velocity (DV), resistive index, and pulsatility index. A higher PSV (median [interquartile range], 54.165 [42.423-68.463] versus 42.195 [34.278-48.553] cm/s; P = .027) and DV (median [interquartile range], 47.445 [35.010-60.043] versus 32.565 [27.545-39.073] cm/s; P = .020) were significantly related to the risk of NEC. In the logistic analysis including gestational age, PSV, and DV, NEC was significantly associated with gestational age (odds ratio [95% confidence interval], 0.644 [0.456-0.908]; P = .012) and DV (odds ratio [95% confidence interval], 1.144 [1.058-1.237]; P < .01). The area under the receiver operating characteristic curve for the DV was 0.768, with sensitivity 0.875 and specificity 0.604. The cutoff value of the DV was 34.835 cm/s. CONCLUSIONS: From this single-center study, we can see the promising value of Doppler ultrasound for the prediction of NEC, but further research is needed.


Assuntos
Enterocolite Necrosante/diagnóstico por imagem , Artéria Mesentérica Superior/diagnóstico por imagem , Ultrassonografia Doppler , Correlação de Dados , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Tempo
13.
J Cell Mol Med ; 22(8): 3825-3836, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29726618

RESUMO

Beneficial effects of metformin on cancer risk and mortality have been proved by epidemiological and clinical studies, thus attracting research interest in elucidating the underlying mechanisms. Recently, tumour-associated macrophages (TAMs) appeared to be implicated in metformin-induced antitumour activities. However, how metformin inhibits TAMs-induced tumour progression remains ill-defined. Here, we report that metformin-induced antitumour and anti-angiogenic activities were not or only partially contributed by its direct inhibition of functions of tumour and endothelial cells. By skewing TAM polarization from M2- to M1-like phenotype, metformin inhibited both tumour growth and angiogenesis. Depletion of TAMs by clodronate liposomes eliminated M2-TAMs-induced angiogenic promotion, while also abrogating M1-TAMs-mediated anti-angiogenesis, thus promoting angiogenesis in tumours from metformin treatment mice. Further in vitro experiments using TAMs-conditioned medium and a coculture system were performed, which demonstrated an inhibitory effect of metformin on endothelial sprouting and tumour cell proliferation promoted by M2-polarized RAW264.7 macrophages. Based on these results, metformin-induced inhibition of tumour growth and angiogenesis is greatly contributed by skewing of TAMs polarization in microenvironment, thus offering therapeutic opportunities for metformin in cancer treatment.

14.
Cancer Sci ; 109(5): 1627-1637, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29532562

RESUMO

Substantial data from preclinical studies have revealed the biphasic effects of statins on cardiovascular angiogenesis. Although some have reported the anti-angiogenic potential of statins in malignant tumors, the underlying mechanism remains poorly understood. The aim of this study is to elucidate the mechanism by which simvastatin, a member of the statin family, inhibits tumor angiogenesis. Simvastatin significantly suppressed tumor cell-conditioned medium-induced angiogenic promotion in vitro, and resulted in dose-dependent anti-angiogenesis in vivo. Further genetic silencing of hypoxia-inducible factor-1α (HIF-1α) reduced vascular endothelial growth factor and fibroblast growth factor-2 expressions in 4T1 cells and correspondingly ameliorated HUVEC proliferation facilitated by tumor cell-conditioned medium. Additionally, simvastatin induced angiogenic inhibition through a mechanism of post-transcriptional downregulation of HIF-1α by increasing the phosphorylation level of AMP kinase. These results were further validated by the fact that 5-aminoimidazole-4-carboxamide ribonucleotide reduced HIF-1α protein levels and ameliorated the angiogenic ability of endothelial cells in vitro and in vivo. Critically, inhibition of AMPK phosphorylation by compound C almost completely abrogated simvastatin-induced anti-angiogenesis, which was accompanied by the reduction of protein levels of HIF-1α and its downstream pro-angiogenic factors. These findings reveal the mechanism by which simvastatin induces tumor anti-angiogenesis, and therefore identifies the target that explains the beneficial effects of statins on malignant tumors.


Assuntos
Proteínas Quinases Ativadas por AMP/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Neovascularização Patológica/prevenção & controle , Sinvastatina/farmacologia , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Proliferação de Células , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Feminino , Fator 2 de Crescimento de Fibroblastos/análise , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos BALB C , Fator A de Crescimento do Endotélio Vascular/análise
15.
J Vasc Interv Radiol ; 29(6): 781-789, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29705225

RESUMO

PURPOSE: To compare outcomes of patients who received simultaneous tributary endovenous laser ablation (EVLA) or foam sclerotherapy (FS) with EVLA of the great saphenous vein (GSV) trunk. METHODS AND MATERIALS: This study recruited 418 patients (542 legs) with diagnosed varicose veins. Patients in the EVLA/FS group (255 patients, 327 legs) received concomitant FS for the tributaries with truncal lasering. For the EVLA-alone group (163 patients, 215 legs), tributaries (8W) were ablated with EVLA in addition to the GSV trunk (14W). Complications, Aberdeen Varicose Vein Questionnaire (AVVQ), EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D), numerical rating scale (NRS) scores, and condition of residual varicosities were assessed at 3 days, 4 weeks, and 6 months after procedure. All residual varicosities were identified and treated with a staged FS at 6 months. RESULTS: Except for ecchymosis, incidence of other complications was not significantly different between both groups at 6 months. Pain NRS scores of the EVLA/FS group were remarkably elevated at 4 weeks and then, at 6 months, declined to a level similar to the EVLA-alone group. The EVLA/FS group exhibited more significant improvement in both AVVQ and EQ-5D scales than the EVLA group at 6 months, while exhibiting poor improvement at 4 weeks. The EVLA/FS group had a significantly lower rate of residual varicosities than the EVLA group, thus reducing the need for the staged FS. CONCLUSIONS: These results confirm the feasibility and safety of simultaneous tributary EVLA and FS. In addition, they indicate better early quality-of-life improvement and a reduced reoperation rate of simultaneously combined truncal EVLA and tributary FS.


Assuntos
Terapia a Laser/métodos , Perna (Membro)/irrigação sanguínea , Veia Safena , Escleroterapia/métodos , Varizes/terapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento , Ultrassonografia de Intervenção
16.
J Asian Nat Prod Res ; 20(9): 875-882, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29171292

RESUMO

As a part of our continuing research for bioactive constituents from Cynanchum limprichtii Schltr., two new C21 steroidal glycosides limproside A (1) and limproside B (2) were isolated from the roots of Cynanchum limprichtii. Their structures were elucidated on the basis of 1D- and 2D-NMR spectroscopic data as well as HR-ESI-MS analysis. The cytotoxicity of two compounds against two selected human cancer cell lines was assayed.


Assuntos
Cynanchum/química , Fitosteróis/isolamento & purificação , Saponinas/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Espectroscopia de Ressonância Magnética , Fitosteróis/química , Fitosteróis/farmacologia , Raízes de Plantas/química , Saponinas/química , Saponinas/farmacologia
17.
Am J Ther ; 23(6): e1320-e1328, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25938902

RESUMO

To determinate the optimal treatment for distal radius fractures (DRF) by comparing the pin-track infection (PTI) rates in patients treated with 7 surgical techniques [bridging external fixation (EF), nonbridging EF, K-wire fixation, plaster fixation, dorsal plating, dorsal and volar plating, and volar plating]. After an exhaustive search of electronic databases for relevant published studies, high-quality randomized controlled trails were selected for the present network meta-analysis based on predefined selection criteria. Statistical analyses of the extracted data were conducted using Stata 12.0 software. After careful selection, 19 randomized controlled trails were included in our network meta-analysis and contained a combined total of 1805 subjects who underwent various surgical procedures. The network meta-analysis results showed that compared with bridging EF for treating DRF, the nonbridging EF, plaster fixation, volar plating, and dorsal and volar plating showed statistically significant differences in PTI rates. Importantly, the surface under the cumulative ranking curve values of the surgical interventions revealed that the PTI rates of plaster fixation and of dorsal and volar plating were the lowest, suggesting that these 2 surgical techniques are optimal for DRFs treatment, compared with the other methods. Our results suggest that plaster fixation and dorsal and volar plating are the best surgical treatments for DRFs compared with 5 other most common techniques. Thus, plaster fixation and dorsal and volar plating emerge as the most effective and credible treatments in consideration of PTI rates.


Assuntos
Fixação Interna de Fraturas/métodos , Infecções Relacionadas à Prótese/epidemiologia , Fraturas do Rádio/cirurgia , Pinos Ortopédicos , Placas Ósseas , Moldes Cirúrgicos , Fixação de Fratura/efeitos adversos , Fixação de Fratura/instrumentação , Fixação de Fratura/métodos , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/instrumentação , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
18.
BMC Musculoskelet Disord ; 16: 254, 2015 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-26370895

RESUMO

BACKGROUND: Osteomyelitis is a challenge for orthopaedic surgeons. There is a lack of scientific evidence to guide treatment. The purpose of this study was to report the clinical outcome of unplanned retention of antibiotic-impregnated cement spacer (ACS) in the management of osteomyelitis. METHODS: Eight patients (7 with tibial infections and 1 with a calcaneal infection) with osteomyelitis received radical debridement and insertion of an ACS into the bone defect as the definitive management. The mean follow-up period was 2 years (6 months to 4 years). All of these patients had a cement spacer in place. RESULTS: No patient exhibited radiographic evidence of excessive bone loss. The patients reported no or occasional mild pain and exhibited complete weight-bearing abilities, with the exception of one patient who required a crutch because of a spinal cord injury. Signs of recurrence of the osteomyelitis were not noted in any of the patients, and no fractures occurred at last follow-up. CONCLUSION: Our study suggests that a proportion of patients with unplanned retention of ACS appear to function well without necessarily requiring further surgical intervention.


Assuntos
Antibacterianos/administração & dosagem , Cimentos Ósseos/uso terapêutico , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Tíbia/microbiologia , Adulto , Idoso , Calcâneo/efeitos dos fármacos , Calcâneo/cirurgia , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/cirurgia , Tíbia/efeitos dos fármacos , Tíbia/cirurgia
19.
Bioprocess Biosyst Eng ; 38(4): 661-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25341364

RESUMO

To determine whether the U(VI) in groundwater under anoxic conditions at a decommissioned in situ leaching (ISL) uranium mine could be bioreduced, groundwater samples containing suspended sediments were taken from the mine, experimental setup was fabricated, and the jar containing the groundwater in the setup was amended with ethanol and incubated under anoxic conditions. The variations of pH, chemical oxygen demand, nitrate, sulfate, U(VI), and dissolved oxygen (DO) concentrations were monitored during the incubation. U(VI) concentration dropped to 0.043 mg/L when the stimulated microorganisms were active, and it then increased to 0.835 mg/L within 10 days after the metabolism of the stimulated microorganisms was inhibited. The DO variation was observed in the amended jar during the incubation, and the metabolism of the stimulated microorganisms was found to affect the DO concentration. Firmicutes were found to be dominant in the sediments in the amended jar through the 16S rRNA pyrosequencing. The results indicate that it is possible to bioreduce U(VI) in the groundwater under anoxic conditions at the decommissioned ISL uranium mine by adding carbon source into it without removing the oxygen from it.


Assuntos
Água Subterrânea/química , Mineração , Oxigênio/química , Urânio/química , Anaerobiose , Biodegradação Ambiental , Análise da Demanda Biológica de Oxigênio , Carbono/química , Firmicutes , Sedimentos Geológicos , Concentração de Íons de Hidrogênio , Nitratos/química , RNA Ribossômico 16S/química , Análise de Sequência de RNA , Sulfatos/química
20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 35(1): 71-5, 2015 Jan.
Artigo em Zh | MEDLINE | ID: mdl-25790678

RESUMO

OBJECTIVE: To observe the relation between Pi deficiency syndrome (PDS) and the configuration and functions of extensor digitorum longus (EDL)and soleus (SOL). METHODS: Totally 36 ICR mice were randomly divided into 3 groups according to weight matching principle, the control group, the exhausted group, and the rhubarb group, 12 in each group. Two PDS models were established by either purgation with rhubarb diarrhea (as Group A) or exhausted swimming plus sleep deprivation (as Group B).The cross sectional area (CSA) of type I and II fibers of extensor digitorum longus (EDL) and soleus (SOL), relative proportions of type I and II fibers were measured by m-ATPase histochemical method. The isotonic contraction and the maximum tetanus contraction of EDL and SOL were detected by PowerLab system. RESULTS: Compared with the control group, the body weight, body temperature, and the general health condition of PDS model rats obviously decreased; the spleen index and the thymus index were also lower; the maximal isotonic contraction and the maximum tetanus contraction obviously decreased; the cross section areas of EDL and SOL were reduced with loosely arranged cells. In EDL, the proportion of type I fibers was added and the proportion of type II fibers was lowered. In SOL, there was no change in the proportion of type I and type II fibers. CONCLUSIONS: EDL and SOL were obviously atrophied in the two PDS model mice. The type I fibers of SOL was more significantly atrophied in Group B.


Assuntos
Modelos Animais de Doenças , Medicina Tradicional Chinesa , Músculo Esquelético/fisiopatologia , Animais , Camundongos , Camundongos Endogâmicos ICR , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA