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1.
BMC Musculoskelet Disord ; 22(1): 189, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588810

RESUMO

BACKGROUND: To investigate the clinical, imaging and pathological features of dedifferentiated chondrosarcoma for better diagnosis. METHODS: Patients who had been confirmed to have dedifferentiated chondrosarcoma were enrolled in this study and analyzed in the clinical, imaging and pathological data. RESULTS: Twenty-five patients had pathologically confirmed dedifferentiated chondrosarcoma including 15 males and 10 females with an age range of 24-74 (median 58, interquartile range 49-65). Ten patients had the tumor at the femur, four at the ilium, two at the humerus, two at the tibia, two at cotyle, and one at each of the following locations: scapula, sacrum, rib, pubic branch, and calcaneus. Twenty-one patients had local pain and a soft tissue mass while the other four patients had only local pain without a soft tissue mass. Four patients had pathological fractures. Imaging showed extensive bone destruction with calcification inside the lesion and possible pathological fractures. On gross observation of the specimen, the chondrosarcoma components were usually located inside the bone, and the dedifferentiated sarcoma components were mainly located outside the bone. Microscopy showed the dedifferentiated tumor had two components: well-differentiated chondrosarcoma and poorly differentiated non-chondral sarcoma including malignant fibrous histiocytoma in eleven cases, osteosarcoma in ten cases, fibrosarcoma in two, liomyosarcoma in one, and lipoblastoma in the remaining one.. Followed up from 3 moths to 60 months (mean 15.6), eight patients died with a survival time of 10-23 months (mean 16), and the other 17 patients survived with the survival duration from three to 60 months (15). CONCLUSION: Dedifferentiated chondrosarcoma is a fatal disease with multiple components, and most of the cases have dual morphological and imaging features of chondrosarcoma and non-chondrosarcoma. The imaging presentations are primarily of common central chondrosarcoma, combined with cortical destruction, soft tissue mass, and pathological fractures.

2.
Water Sci Technol ; 83(3): 678-688, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33600371

RESUMO

Chitosan (CS) was modified with ferric chloride hexahydrate (FeCl3·6H2O) and sodium laurylsulfonate (SLS) to prepare the compound adsorbent CS-Fe-SLS. Taking Cr(VI) as the target pollutant, the influence of different factors (solution pH, adsorption time, initial adsorption concentration and coexisting ions) were investigated. The results showed that the optimal pH value was 3.0; the adsorption equilibrium was reached at 120 min, with both physical and chemical process being involved in the adsorption process; the maximum adsorption value was 131.91 mg/g, with the adsorption being both single-layer and multi-layer adsorption; Cl-, NO3- and SO42- had little effect on adsorption, CO32- reduced it and Cu(II) increased it. The characterization results of scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction showed that CS-Fe-SLS and chitosan had different morphological characteristics: in contrast with chitosan, CS-Fe-SLS had a larger volume and more flakes on the surface. CS-Fe-SLS was significantly lower in crystallinity than chitosan, and was more irregular and amorphous in shape, and the experimental results showed that CS-Fe-SLS had better adsorption capacity for Cr(VI). The adsorption Cr(VI) was related to -NH and -OH on the material. Some Cr(VI) was reduced to Cr(III) during the adsorption process.


Assuntos
Quitosana , Poluentes Químicos da Água , Adsorção , Cromo , Concentração de Íons de Hidrogênio , Cinética , Espectroscopia de Infravermelho com Transformada de Fourier
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 174-179, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33627214

RESUMO

OBJECTIVE: To evaluate the condition of subclinical cardiac damage in children with primary hypertension and the association between serum uric acid and subclinical cardiac damage. METHODS: A retrospective analysis was performed on the medical data of 55 children who were hospitalized and diagnosed with primary hypertension in the Department of Cardiology, Children's Hospital of Soochow University from January 2015 to June 2020. Forty-five healthy children, matched for age and sex, were enrolled as the control group. The two groups were compared in terms of clinical features, laboratory examination, and parameters for left ventricular structure, systolic function, and diastolic function. The correlation of serum uric acid with the parameters for left ventricular structure, systolic function, and diastolic function in children with primary hypertension was analyzed. RESULTS: Compared with the control group, the hypertension group had significantly higher left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT) (P < 0.05). Among the children with primary hypertension, 20 (36%) had left ventricular hypertrophy. The hypertension group had significantly larger left atrial diameter and aortic root diameter than the control group (P < 0.05). The hypertension group had a significantly higher ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity than the control group (P < 0.05). The correlation analysis showed that in children with primary hypertension, serum uric acid was positively correlated with LVM (r=0.534, P < 0.01), left atrial diameter (r=0.459, P < 0.01), and aortic root diameter (r=0.361, P=0.010). After adjustment for blood pressure, serum uric acid was still positively correlated with the above parameters (P < 0.05). CONCLUSIONS: Children with primary hypertension may have subclinical cardiac damage such as left ventricular hypertrophy, left ventricular diastolic dysfunction, left atrial enlargement, and proximal aortic dilation. Elevated serum uric acid is significantly associated with cardiac damage in children with primary hypertension.

4.
Analyst ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33624640

RESUMO

The presence of excessive ROS can cause much harm to the human body and can even cause diseases. Therefore, it is important to detect and remove ROS, but there is no ideal method available for this at present. In this research, using procyanidins, a type of plant extract with strong reducibility, as raw materials, fluorescent carbon dots (CDs) were prepared by a hydrothermal method. The proanthocyanidin-based carbon dots (PCDs) emit a light-green colored light under UV irradiation. The PCDs retain the strong reducibility of procyanidins and are highly water-soluble compared with procyanidins. The PCDs, in addition to having good biocompatibility, also have the superior properties of radical scavenging activity and cell imaging. In in vitro experiments, 1,1-diphenyl-2-picrylhydrazyl (DPPH; 100 µM) was reduced by 30% when PCDs were added up to a concentration of 87.5 µg mL-1. At the same time, the fluorescence quenching correlates with the concentration of hypochlorite and hydrogen peroxide and has a good linearity in the range of 250-2250 nM and 60-180 µM with a detection limit of 3.676 nM and 0.602 µM, respectively. Based on the previously described advantages, PCDs have potential as a biomedicine.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33556014

RESUMO

OBJECTIVE: The current state-of-the-art methods significantly improve the detection performance of the steady-state visual evoked potentials (SSVEPs) by using the individual calibration data. However, the time-consuming calibration sessions limit the number of training trials and may give rise to visual fatigue, which weakens the effectiveness of the individual training data. For addressing this issue, this study proposes a novel inter- and intra-subject maximal correlation (IISMC) method to enhance the robustness of SSVEP recognition via employing the inter- and intra-subject similarity and variability. Through efficient transfer learning, similar experience under the same task is shared across subjects. METHODS: IISMC extracts subject-specific information and similar task-related information from oneself and other subjects performing the same task by maximizing the inter- and intra-subject correlation. Multiple weak classifiers are built from several existing subjects and then integrated to construct the strong classifiers by the average weighting. Finally, a powerful fusion predictor is obtained for target recognition. RESULTS: The proposed framework is validated on a benchmark data set of 35 subjects, and the experimental results demonstrate that IISMC obtains better performance than the state of the art task-related component analysis (TRCA). SIGNIFICANCE: The proposed method has great potential for developing high-speed BCIs.

6.
Sci Adv ; 7(5)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33571110

RESUMO

Na+/K+-ATPase (NKA) plays important roles in maintaining cellular homeostasis. Conversely, reduced NKA activity has been reported in aging and neurodegenerative diseases. However, little is known about the function of NKA in the pathogenesis of Parkinson's disease (PD). Here, we report that reduction of NKA activity in NKAα1+/- mice aggravates α-synuclein-induced pathology, including a reduction in tyrosine hydroxylase (TH) and deficits in behavioral tests for memory, learning, and motor function. To reverse this effect, we generated an NKA-stabilizing monoclonal antibody, DR5-12D, against the DR region (897DVEDSYGQQWTYEQR911) of the NKAα1 subunit. We demonstrate that DR5-12D can ameliorate α-synuclein-induced TH loss and behavioral deficits by accelerating α-synuclein degradation in neurons. The underlying mechanism for the beneficial effects of DR5-12D involves activation of NKAα1-dependent autophagy via increased AMPK/mTOR/ULK1 pathway signaling. Cumulatively, this work demonstrates that NKA activity is neuroprotective and that pharmacological activation of this pathway represents a new therapeutic strategy for PD.

7.
Vaccine ; 39(8): 1241-1247, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33516600

RESUMO

Without approved vaccines and specific treatments, COVID-19 is spreading around the world with above 26 million cases and approximately 864 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 - Gly548 of spike protein of SARS-CoV-2 linked with Gln830 - Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5) were expressed and renatured. The antigenicity and immunogenicity of S1-4 were evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency was measured preliminarily by microneutralization assay (MN50). The soluble S1-4 and S1-5 protein was prepared to high homogeneity and purity. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity supplemented with Th1-type immunity. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralizing antibody titer 256. Recombinant SARS-CoV-2 RBD with a built in T helper epitope could stimulate both strong humoral immunity supplemented with cellular immunity in mice, demonstrating that it could be a promising subunit vaccine candidate.


Assuntos
Anticorpos Antivirais/imunologia , Epitopos de Linfócito T/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Formação de Anticorpos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Glicoproteína da Espícula de Coronavírus/genética
8.
Biosens Bioelectron ; 177: 112952, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33453463

RESUMO

Benefiting from emerging miniaturized and equipment-free nucleic acid testing (NAT) technologies, fully integrated NAT devices at point of care (POC) with the capability of "sample-in-answer-out" are proceeding at a break-neck speed to eliminate complex operations and reduce the risk of contamination. Like the development of polymerase chain reaction (PCR) technology (the standard technique for NAT), the detection signal of fully integrated NAT devices has evolved from qualitative to quantitative and recently to digital readout, aiming at expanding their extensive applications through gradually improving detection sensitivity and accuracy. This review firstly introduces the existing commercial products, and then illustrates recent fully integrated microfluidic devices for NAT at POC from the aspect of detection signals (i.e., qualitative, quantitative and digital). Importantly, the key issues of existing commercial products and the main challenges between scientific research and product development are discussed. On this basis, we envision that the MARCHED (miniaturized, automatic, reagent-preloaded, commercializable, high-throughput, environment-independent and disposable) NAT devices are expected to be realized in the near future.

9.
Clin Neurol Neurosurg ; 201: 106455, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33395618

RESUMO

OBJECTIVE: Bone invasive pituitary adenomas (BIPAs) show obvious malignant behaviour. The aim of this study was to analyse the clinical features, prognosis, recurrence risks and surgical strategies of BIPAs. PATIENTS AND METHODS: Clinical charts and radiological information were reviewed retrospectively in 107 consecutive cases of BIPAs. Transnasal endoscopic surgery was adopted with the goal of removing tumours. Scheduled follow-up was performed. RESULTS: Clinical variable analyses revealed a significant correlation between bone invasive range and sex, tumour volume and tumour regrowth. Gross total resection, subtotal resection and partial resection were achieved in 26 cases (24.3 %), 28 cases (26.2 %) and 53 cases (49.5 %), respectively. There was a significant correlation between nongross total resection and female sex, young age, large tumour volume, bone invasive range, tumour regrowth and functional pituitary adenomas in BIPAs. The tumour regrowth rates at 3 years, 5 years and 10 years were 45.3 %, 76.3 % and 97.5 %, respectively. Kaplan-Meier curve analysis showed that tumour volume, bone invasion range, age, recurrent tumours and tumour resection degree were associated with BIPA regrowth. Multivariate analysis showed that tumour resection degree, bone invasive range, and tumour diameter were independent risk factors for BIPA regrowth. CONCLUSION: BIPAs have the characteristics of high surgical risk, low GTR rate and high recurrence rate. There was a significant correlation between bone invasive range and sex, tumour volume and tumour regrowth in BIPAs. Bone invasive range is an independent risk factor for BIPA regrowth.

10.
J Nanobiotechnology ; 19(1): 20, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430889

RESUMO

BACKGROUND: Accumulating evidence shows that mesenchymal stem cell-derived extracellular vesicles (EVs) hold great promise to promote hair growth. However, large-scale production of EVs is still a challenge. Recently, exosome-mimetic nanovesicles (NV) prepared by extruding cells have emerged as an alternative strategy for clinical-scale production. Here, ReNcell VM (ReN) cells, a neural progenitor cell line was serially extruded to produce NV. RESULTS: ReN-NV were found to promote dermal papilla cell (DPC) proliferation. In addition, in a mouse model of depilation-induced hair regeneration, ReN-NV were injected subcutaneously, resulting in an acceleration of hair follicle (HF) cycling transition at the site. The underlying mechanism was indicated to be the activation of Wnt/ß-catenin signaling pathway. Furthermore, miR-100 was revealed to be abundant in ReN-NV and significantly up-regulated in DPCs receiving ReN-NV treatment. miR-100 inhibition verified its important role in ReN-NV-induced ß-catenin signaling activation. CONCLUSION: These results provide an alternative agent to EVs and suggest a strategy for hair growth therapy.

11.
BMC Musculoskelet Disord ; 22(1): 27, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407312

RESUMO

BACKGROUND: To investigate the imaging features of hemangiomas in long tabular bones for better diagnosis. METHODS: Twenty-four patients with long bone hemangiomas confirmed by pathology were enrolled. Nineteen patients had plain radiography, fourteen patients had computed tomography (CT) and eleven had magnetic resonance imaging (MRI). The hemangioma was divided into medullary [13], periosteal [6] and intracortical type [5]. RESULTS: Among 19 patients with plain radiography, eleven patients were medullary, three periosteal, and five intracortical. In the medullary type, the lesion was primarily osteolytic, including five cases with irregular and unclear rims and one lesion having osteosclerotic and unclear rims. In three patients with the periosteal type, the lesion had clear rims with involvement of the cortical bone in the form of bone defect, including two cases with local thickened bone periosteum and one case having expansile periosteum. Five intracortical hemangiomas had intracortical osteolytic lesions with clear margins. Among 14 patients with CT imaging, 8 cases were medullary, three periosteal, and three intracortical. Among 8 medullary hemangiomas, one had ground glass opacity, and seven had osteolytic, expansile lesions like soft tissue density with no calcification. In three periosteal cases, the lesion was osteolytic with thickened periosteum and narrowed medullary cavity. In three intracortical hemangiomas, the lesion was of even soft tissue density with no calcification. Among 11 patients with MRI imaging, seven were medullary, two periosteal, and two intracortical. Among 7 medullary lesions, six were of hypointense signal on T1WI and hyperintensesignal on T2 WI. In two periosteal cases, the periosteum was thickened, with one case being of equal signal, and the other having no signal. Two intracortical hemangiomas were both of slightly low signal on T1WI but hyperintense signal on T2WI. CONCLUSIONS: The long bone hemangiomas had characteristic cystic honeycomb-like presentations in plain radiograph. CT and MRI imagings are helpful for diagnosis of hemangiomas in long bone.

12.
J Nanosci Nanotechnol ; 21(2): 1266-1271, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33183471

RESUMO

Gold nanoparticles (GNPs) are widely used in life sciences and medicine due to their simple preparation, stable physical and chemical properties, controllable optical properties and no significant toxicity. However, in recent years, studies have found that there are still many uncertain factors in the application of gold nanoparticles in the field of biomedicine, and there are few studies on the main excretion organs and kidneys of the body, especially the toxicological effects under the disease state have not been reported. Obviously, carrying out relevant research is of great significance for accelerating the clinical application of GNPs. Chronic kidney disease (CKD) is a group of chronic progressive diseases that have high prevalence and high mortality and are serious threats to human life and health. Renal tubular injury and interstitial fibrosis are key factors in renal dysfunction in chronic kidney disease. Drug and toxic kidney damage mostly involve renal tubular epithelial cells; hypoxia is the most common pathological condition of cells. In renal lesions, renal tubular epithelial cells often have hypoxia. Based on this, we propose the hypothesis of this study: glomerular filtration membrane damage in kidney disease, GNPs increase in urine, followed by reabsorption of renal tubular epithelial cells, thereby causing damage to the latter; if accompanied by hypoxia, GNPs it will aggravate renal tubular epithelial cell damage and promote tubulointerstitial fibrosis. In order to verify the above hypothesis, this study used a mouse model of adriamycin nephropathy and tubular epithelial cells and macrophages in vitro, and observed the damage of GNPs on renal tubular epithelial cells by various means, and explored related mechanisms. The results show that under normal oxygen conditions, GNPs can induce autophagy after cell entry, which can damage damaged proteins and organelles to maintain cell survival. In the absence of oxygen, nanoparticles entering cells increase and induce excessive autophagy. In the absence of oxygen, GNPs also aggregate in macrophages, which can cause decreased cell proliferation activity and induce activation of macrophage inflammasome, which induces inflammatory response: GNPs-induced secretion of hypoxic macrophages can be promoted.

13.
Redox Biol ; 38: 101813, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33279869

RESUMO

Diabetic kidney disease is known as a major cause of chronic kidney disease and end stage renal disease. Polysulfides, a class of chemical agents with a chain of sulfur atoms, are found to confer renal protective effects in acute kidney injury. However, whether a polysulfide donor, sodium tetrasulfide (Na2S4), confers protective effects against diabetic nephropathy remains unclear. Our results showed that Na2S4 treatment ameliorated renal dysfunctional and histological damage in diabetic kidneys through inhibiting the overproduction of inflammation cytokine and reactive oxygen species (ROS), as well as attenuating renal fibrosis and renal cell apoptosis. Additionally, the upregulated phosphorylation and acetylation levels of p65 nuclear factor κB (p65 NF-κB) and signal transducer and activator of transcription 3 (STAT3) in diabetic nephropathy were abrogated by Na2S4 in a sirtuin-1 (SIRT1)-dependent manner. In renal tubular epithelial cells, Na2S4 directly sulfhydrated SIRT1 at two conserved CXXC domains (Cys371/374; Cys395/398), then induced dephosphorylation and deacetylation of its targeted proteins including p65 NF-κB and STAT3, thereby reducing high glucose (HG)-caused oxidative stress, cell apoptosis, inflammation response and epithelial-to-mesenchymal transition (EMT) progression. Most importantly, inactivation of SIRT1 by a specific inhibitor EX-527, small interfering RNA (siRNA), a de-sulfhydration reagent dithiothreitol (DTT), or mutation of Cys371/374 and Cys395/398 sites at SIRT1 abolished the protective effects of Na2S4 on diabetic kidney insulting. These results reveal that polysulfides may attenuate diabetic renal lesions via inactivation of p65 NF-κB and STAT3 phosphorylation/acetylation through sulfhydrating SIRT1.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 2079-2083, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283745

RESUMO

OBJECTIVE: To observe the clinical and laboratory characteristics of adult Langerhans cell histiocytosis(LCH) patients and to analyze the influencing factors of its prognosis. METHODS: The clinical and laboratory charac-teristics of 38 adult LCH patients treated in our hospital from January 2010 to August 2019 were retrospective analyzed, and the clinical prognosis of the patients was analyzed. RESULTS: The median age of 38 patients was 41 (21-65) years old, and the ratio of male and female was about 2∶1. Among 38 patients, 44.7% (17/38) were involved in multiple systems, and 31.6% (12/38) were involved in high-risk organs (including liver, lung, hematopoietic system or spleen). The bone involvement was the most common (21/38, 55.3%), and the most common clinical symptom was pain (19/38, 50.0%). The result of laboratory showed that anemia (4/38,10.5%), thrombocytopenia (1/38,2.6%), neutropenia (2/38,5.3%), lymphopenia (6/38,15.8%), monocytosis (11/38,28.9%), C-reactive protein increasing (6/21,28.6%), erythrocyte sedimentation rate increasing (10/18, 55.3%), and ferritin protein increasing (9/17, 55.3%). The median follow-up time was 53 months, and a total of 5 patients were died. The 10-year overall survival rate of patients with single-system involvement was 100%, which was significantly higher than that of patients with multiple-system involvement (70.1%) (P=0.0078). The prognosis of patients without risk-organ involvement was better than that of patients with risk-organ involvement (10-year overall survival rate: 100% vs 60.6%) (P=0.0007). Further analysis showed that in addition to multiple-system involvement and risk-organ involvement, the increase of peripheral blood monocyte cells and the increase of ferritin protein were also associated with poorer prognosis of the patients. CONCLUSION: The multiple system involve-ment and risk-organ involvement, the increasing of monocyte cells and the increasing of ferritin protein were the independent risk factors of adult LCH patients.

15.
Epigenomics ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33290106

RESUMO

Aims: Given the reversibility of methylation, biomarkers with discriminating ability are of great interest for targeted therapeutic sites. Materials & methods: Methylation array data of 461 lung adenocarcinoma (LUAD) patients comprising of 458 tumor and 32 LUAD paracancerous samples were compared using partial least squares discrimination analysis and receiver operating characteristics analysis. Results: A six-DNA methylation signature (corresponding to five genes) was found to significantly discriminate normal and LUAD samples. Kyoto Encyclopedia of Genes and Genomes analysis indicated enrichment of methylation sites in the Wnt pathway in LUAD compared with controls. Conclusion: This six-DNA methylation signature demonstrated potential as a novel biomarker for diagnosis and therapeutic targets. Further, inhibition of Wnt signaling pathway may be an important step in LUAD progression.

16.
Cell Res ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262452

RESUMO

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.

18.
Cancer Manag Res ; 12: 12001-12009, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262650

RESUMO

Purpose: Glioma is one of the most common malignant tumors affecting human health. Long non-coding RNA (lncRNA) TMPO-AS1 participates in the pathogenesis of various cancers. However, the role of lncRNA TMPO-AS1 in glioma remains largely unknown. This study aims to uncover the role of TMPO-AS1 and explore its potential mechanism in glioma. Methods: Expression levels of TMPO-AS1 and miR-383-5p in glioma cell lines were measured by real-time quantitative PCR (RT-qPCR). CCK-8, colony formation, wound-healing, and Transwell assays were conducted to determine cell proliferation, migration and invasion abilities, respectively. Western blotting was applied to detect the expression of corresponding proteins. Immunofluorescence assay was performed to measure the expression of Ki67. The binding condition between TMPO-AS1 and miR-383-5p was verified by dual-luciferase reporter assay. Results: We found that TMPO-AS1 was up-regulated while miR-383-5p was down-regulated in glioma cell lines, and knockdown of TMPO-AS1 significantly suppressed glioma cell proliferation, migration and invasion abilities. miR-383-5p was demonstrated to be a direct target of TMPO-AS1. Besides, inhibition of miR-383-5p abolished the effects of TMPO-AS1 knockdown on glioma cells. Conclusion: In summary, our study revealed that inhibition of lncRNA TMPO-AS1 could suppress glioma progression through targeting miR-383-5p. TMPO-AS1 might be used as a therapeutic target for glioma treatment.

19.
Xenobiotica ; : 1-32, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33269993

RESUMO

Gefitinib, the first approved inhibitor for oral epidermal growth factor receptor (EGFR), has been proved to be effective in non-small cell lung cancer with EGFR mutation. However, there are many metabolites of gefitinib that have not been identified in vivo. This study aims to identify the metabolites of gefitinib and its metabolic pathways in rats using ultra-high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) detector. Protein precipitation, solid-phase and ultrasonic extraction were used for the pretreatment of plasma, urine, bile and feces samples. In this study, a total of 28 compounds were identified in rat plasma, 29 in bile, 20 in urine and 16 in feces. 20 new compounds were firstly reported as metabolites of gefitinib. Reduction, hydroxylation, dealkylation and dehalogenation were the major metabolic pathways in phase I. For phase II, the main pathways were sulfate and glucuronide conjugation. The fragment ions of gefitinib and its metabolites were usually generated via the fracture of C1-O bond of propoxy on the C6 position of aniline quinazoline ring. The results may be valuable and important for understanding the metabolic process of gefitinib in clinical application and drug safety.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33299460

RESUMO

Background: In China, electroacupuncture based on meridians theory "treating flaccid paralysis by Yangming alone" has been widely used for stroke rehabilitation in clinical practice. The aim of this study was to explore the electroencephalography change of electroacupuncture intervention on strokes patients with flaccid paralysis. Methods: Twenty-three stroke patients with flaccid paralysis and six stroke patients with spasticity accepted electroacupuncture with the acupoints Hegu [LI4], Shousanli [LI10], and Quchi [LI11] for 20 minutes and their EEG data were recorded before, during, and after the electroacupuncture intervention. Results: Compared with the baseline EEG signals before electroacupuncture, the ipsilesional and contralesional beta-band average power of patients with flaccid paralysis and spasticity were significantly increased during the needles retention stage and decreased slightly after removing the needles. The significant decrease of the ipsilesional and contralesional delta band average power in patients with flaccid paralysis occurred during the electroacupuncture stimulation, and they increased after the removal of the needles. The ipsilesional delta band average power of patients with spasticity significantly decreased during the electroacupuncture stimulation. Conclusion: From this pilot electrophysiological study, we provided a possible electrophysiological mechanism of the curative effect of electroacupuncture for stroke rehabilitation.

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