Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 135
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Theranostics ; 10(7): 3206-3222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194863

RESUMO

With the rapid development of nanotechnology, inorganic nanomaterials (NMs) have been widely applied in modern society. As human exposure to inorganic NMs is inevitable, comprehensive assessment of the safety of inorganic NMs is required. It is well known that autophagy plays dual roles in cell survival and cell death. Moreover, inorganic NMs have been proven to induce autophagy perturbation in cells. Therefore, an in-depth understanding of inorganic NMs-modulated autophagy is required for the safety assessment of inorganic NMs. This review presents an overview of a set of inorganic NMs, consisting of iron oxide NMs, silver NMs, gold NMs, carbon-based NMs, silica NMs, quantum dots, rare earth oxide NMs, zinc oxide NMs, alumina NMs, and titanium dioxide NMs, as well as how each modulates autophagy. This review emphasizes the potential mechanisms underlying NMs-induced autophagy perturbation, as well as the role of autophagy perturbation in cell fate determination. Furthermore, we also briefly review the potential roles of inorganic NMs-modulated autophagy in diagnosis and treatment of disease.

2.
J Nanosci Nanotechnol ; 20(4): 2138-2143, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492222

RESUMO

With the higher and higher application level of medical technology, more and more genetic diseases have been diagnosed. Nucleic acid, as an important genetic material, has been found to have important functions in the storage and transmission of the genetic information in the replication and synthesis of proteins. As the first step in nucleic acid detection experiments, nucleic acid extraction performance is associated with the purity of target nucleic acid samples, which is very important for the downstream steps. In this paper, we employed the magnetic bead for extracting nucleic acids based on the platform of large liquid handling workstation and designed a matching magnetic separation module. It was shown that the temperature control block designed in this paper has reliable stability, high accuracy by using the incremental PID algorithm, with the control accuracy up to ±0.5 °C, and the control stabilization time is about 90 s, which can satisfy the experimental requirements. Besides, the average magnetic bead transfer rate of this module was further verified by mimicking the manual magnetic bead nucleic acid extraction process. The results proved that the module has an excellent performance with the average magnetic bead transfer rate greater than 95% and the magnetic bead transfer rate in each well greater than 90%, which could be consistent with the experimental indictors of nucleic acid extraction.

3.
J Nanosci Nanotechnol ; 20(4): 2165-2170, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492225

RESUMO

The high-throughput nucleic acid detection system provides a good solution for detecting nucleic acids more safely, rapidly and accurately, which greatly improves the detection efficiency. Highthroughput nucleic acid detection mainly includes three steps: signal acquisition, signal amplification and signal processing. Therefore, obtaining the purified nucleic acid is the primary task of the nucleic acid detection, and the quality of the nucleic acid has a significant impact on results. In this paper, we employed the magnetic nanoparticle technology for extracting nucleic acids based on the platform of large liquid handling workstation and designed a matching vibrating module. The involved steps of core method, magnetic bead nucleic acid extraction technology, are mainly concerned with the cell lysis, nucleic acid binding, nucleic acid purification and magnetic particles elution. During the extraction process, specific temperature is required for the lysis and elution. It was shown that the temperature control part designed in this paper has the reliable stability, high accuracy by using the incremental proportion-integration-differentiation (PID) algorithm, with the control accuracy up to ±0.5 °C. The temperature regulating time is about 90 s, which can meet the experimental requirements. Besides, the vibrating uniformity of this module was further verified by protein concentration test, which proved that the module has the excellent performance and can be consistent with the experimental indictors of the nucleic acid extraction.

4.
J Nanosci Nanotechnol ; 20(3): 1470-1477, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492309

RESUMO

Entomopathogenic nematodes (EPNs) have been cited as a safe and effective method for pest management. Their virulence against lepidopterans and other foliar pest has been demonstrated in the laboratory, but achieving field efficacy is challenged with environmental conditions such as desiccation and ultraviolet radiations. Nanoparticles (NPs) as UV-blocking agents have been reported to provide an alternative approach to enhance the EPNs efficacy. We screened the effect of ZnO, TiO2 and Fe3O4 NPs on survival and pathogenicity of EPNs, and determined whether the nanoparticles could provide protection to the EPNs at low concentrations when applied in direct sunlight. All nanoparticles had less influence on the survival of infective juveniles and did not deprive their pathogenic properties following prolonged exposure. The survival rate of nematodes decreased with increased concentrations, with no measurable difference between NPs. Moreover, the survival rate of nematodes exposed to UV radiation in different formulation decreased significantly with the increase in exposure time (p < 0.001). On the other side when EPNs in nanoparticles formulations were exposed to sunlight, their efficacy significantly improved by protecting nematodes from ultraviolet radiation when compared to the water-based formulation. Pathogenic efficacy after exposure to sunlight was in the order of ZnO > TiO2 > Fe3O4 > H2O, indicating the compatibility of nematodes and NPs, and the benefit of different NPs in EPNs formulations. General nanoparticles are novel ingredients that provide suitable protection of EPNs for management of foliar pests. However, the EPNs nanoparticles formulation under a specific agricultural system and climatic condition need to be established.

5.
J Ethnopharmacol ; 246: 112128, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31386888

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine provides a unique curative treatment of complex chronic diseases, including chronic kidney disease (CKD), which is not effectively treated with the current therapies. The pharmacological mechanisms of Shenkang (SK), a herbal medicine containing rhubarb (Rheum palmatum L. or R. tanguticum Maxim. ex Balf.), red sage (Salvia miltiorrhiza Bunge), safflower (Carthamus tinctorius L.), and astragalus (Astragalus mongholicus Bunge), widely used to treat CKD in China, are still unclear. AIM OF THE STUDY: In this study, the comprehensive approach used for elucidating the pharmacological mechanisms of SK included the identification of the effective constituents, target prediction and network analysis, by investigating the interacting pathways between these molecules in the context of CKD. These results were validated by performing an in vivo study and by comparison with literature reviews. MATERIALS AND METHODS: This approach involved the following main steps: first, we constructed a molecular database for SK and screened for active molecules by conducting drug-likeness and drug half-life evaluations; second, we used a weighted ensemble similarity drug-targeting model to accurately identify the direct drug targets of the bioactive constituents; third, we constructed compound-target, target-pathway, and target-disease networks using the Cytoscape 3.2 software and determined the distribution of the targets in tissues and organs according to the BioGPS database. Finally, the resulting drug-target mechanisms were compared with those proposed by previous research on SK and validated in a mouse model of CKD. RESULTS: By using Network analysis, 88 potential bioactive compounds in the four component herbs of SK and 85 CKD-related targets were identified, including pathways that involve the nuclear factor-κB, mitogen-activated protein kinase, transient receptor potential, and vascular endothelial growth factor, which were categorized as inflammation, proliferation, migration, and permeability modules. The results also included different tissues (kidneys, liver, lungs, and heart) and different disease types (urogenital, metabolic, endocrine, cardiovascular, and immune diseases as well as pathological processes) closely related to CKD. These findings agreed with those reported in the literature. However, our findings with the network pharmacology prediction did not account for all the effects reported for SK found in the literature, such as regulation of the hemodynamics, inhibition of oxidative stress and apoptosis, and the involvement of the transforming growth factor-ß/SMAD3, sirtuin/forkhead box protein O (SIRT/FOXO) and B-cell lymphoma-2-associated X protein pathways. The in vivo validation experiment revealed that SK ameliorated CKD through antifibrosis and anti-inflammatory effects, by downregulating the levels of vascular cell adhesion protein 1, vitamin D receptor, cyclooxygenase-2, and matrix metalloproteinase 9 proteins in the unilateral ureteral obstruction mouse model. This was consistent with the predicted target and pathway networks. CONCLUSIONS: SK exerted a curative effect on CKD and CKD-related diseases by targeting different organs, regulating inflammation and proliferation processes, and inhibiting abnormal extracellular matrix accumulation. Thus, pharmacological network analysis with in vivo validation explained the potential effects and mechanisms of SK in the treatment of CKD. However, these findings need to be further confirmed with clinical studies.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Modelos Biológicos , Insuficiência Renal Crônica/metabolismo , Animais , Medicamentos de Ervas Chinesas/uso terapêutico , Ontologia Genética , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos Endogâmicos C57BL , Farmacologia/métodos , Mapeamento de Interação de Proteínas , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia , Reprodutibilidade dos Testes
6.
Neuroreport ; 30(16): 1121-1128, 2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31568208

RESUMO

Baicalin, an ingredient drawn from Scutellaria amoena Georgi, plays a brain-protective role through anti-inflammatory, antioxidant, and other pathways. The aim of this study was to investigate the possible protective mechanism of baicalin on middle cerebral artery occlusion rats. Rats were divided into 4 groups: sham, middle cerebral artery occlusion, middle cerebral artery occlusion + baicalin, middle cerebral artery occlusion + baicalin treated + inhibitor (bromocriptine, which inhibit progesterone induction). After 7 days treatment, neurological deficits and infarct volume were determined, morphological change of penumbra was examined by (hematoxylin-eosin) staining. The expressions of neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), and progesterone receptor were also assessed by immunofluorescent staining or immunohistochemistry, progesterone, and adrenocorticotropic hormone in serum were also determinated by ELISA. We found that baicalin could reduce the neurological deficits, infarct volume caused by middle cerebral artery occlusion, increase the expression of NeuN, GFAP, and progesterone receptor in ischemic penumbra and increase the expression of progesterone and adrenocorticotropic hormone level in serum. Those indicated that baicalin plays a protective role in cerebral ischemia rats by improvement of progesterone.

7.
Biomolecules ; 9(10)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600936

RESUMO

Hedyotis diffusa Willd (HDW) is one of the most well-known herbs used in the treatment of prostate cancer. However, the potential mechanisms of its anti-tumor effects have not been fully explored. Here, we applied a network pharmacology approach to explore the potential mechanisms of HDW against prostate cancer (PCa). We obtained 14 active compounds from HDW and 295 potential PCa related targets in total to construct a network, which indicated that quercetin and ursolic acid served as the main ingredients in HDW. Mitogen-activated Protein Kinase 8 (MAPK8), Interleukin 6 (IL6), Vascular Endothelial Growth Factor A (VEGFA), Signal Transducer and Activator of Transcription 3 (STAT3), Jun Proto-Oncogene (JUN), C-X-C Motif Chemokine Ligand 8 (CXCL8), Interleukin-1 Beta (IL1B), Matrix Metalloproteinase-9 (MMP9), C-C Motif Chemokine Ligand 2 (CCL2), RELA Proto-Oncogene (RELA), and CAMP Responsive Element Binding Protein 1 (CREB1) were identified as key targets of HDW in the treatment of PCa. The protein-protein interaction (PPI) cluster demonstrated that CREB1 was the seed in this cluster, indicating that CREB1 plays an important role in connecting other nodes in the PPI network. This enrichment demonstrated that HDW was highly related to translesion synthesis, unfolded protein binding, regulation of mitotic recombination, phosphatidylinositol and its kinase-mediated signaling, nucleotide excision repair, regulation of DNA recombination, and DNA topological change. The enrichment results also showed that the underlying mechanism of HDW against PCa may be due to its coordinated regulation of several cancer-related pathways, such as angiogenesis, cell differentiation, migration, apoptosis, invasion, and proliferation.

8.
Nanoscale ; 11(33): 15589-15595, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31403149

RESUMO

Exosomes have been recognized as promising sources of biomarkers for early cancer diagnosis due to their important role in the occurrence and metastasis of cancer, and so the development of a sensitive low-cost detection method for exosomes is highly desirable. In this paper, we report a fluorescence method for the competitive detection of exosomes based on an aptamer specific to CD63 (an exosome transmembrane protein). Aptamer-modified magnetic beads were hybridized with a Cy3-labeled short sequence complementary to a region of the aptamer. In the presence of exosomes, the CD63 on the exosomes bound to the aptamer, resulting in the shedding of the short sequence into the supernatant. The quantity of the exosomes could be estimated by detecting the fluorescence intensity in the supernatant. This method could detect exosomes at a concentration as low as 1.0 × 105 particles per µL under optimal conditions, and the feasibility of the method for exosome detection in complex clinical samples was also proved using simulated serum samples. The detection cost and difficulty are significantly reduced compared to conventional methods, while ensuring sensitivity, and so this method provides a basis for subsequent exosome detection in specific cancer cells.


Assuntos
Aptâmeros de Nucleotídeos/química , Exossomos/química , Corantes Fluorescentes/química , Imagem Óptica/métodos , Células A549 , Humanos , Nanopartículas de Magnetita/química , Temperatura Ambiente
9.
J Cancer ; 10(16): 3860-3870, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333803

RESUMO

The nucleoprotein AHNAK (AHNAK) is a large scaffold protein that is involved in several biological processes. Previous studies have suggested a possible relation between AHNAK and the epithelial-mesenchymal transition (EMT). However, the role of AHNAK in pancreatic ductal adenocarcinoma (PDAC) has not been unveiled. The present study focuses on identifying the potential value of the biological effects of AHNAK in PDAC, which is one of the most lethal malignancies. Bioinformatic analysis was carried for driver gene prediction, and we proved that AHNAK was a driver gene of pancreatic adenocarcinoma and a predictor of poor outcomes of PDAC by clinical characteristics analysis and in vitro experiments. High AHNAK expression was associated with short disease-free survival and poor overall survival. In vitro assays showed that AHNAK was associated with cell proliferation and migration, and a positive relation was observed between AHNAK and the EMT. In conclusion, AHNAK is a crucial biomarker that may promote cellular proliferation and migration and thus impact PDAC outcomes via the EMT, which suggests that AHANK might be a potential target for PDAC.

10.
Cancer Lett ; 462: 51-60, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31352078

RESUMO

Pancreatic stellate cells (PSCs) are activated in pancreatic ductal adenocarcinoma (PDAC) and are responsible for dense desmoplastic stroma. Yes-associated protein 1 (YAP1) can induce cancer-associated fibroblast activation in liver and breast tumors, but its effect on PSCs is unknown. In the present study, we determined that YAP1 was highly expressed in the nuclei of PDAC-derived activated PSCs. RNAi-mediated or pharmacological inhibition of YAP1 led to PSC deactivation. In addition, YAP1 stimulated the expression of secreted protein acidic and cysteine rich (SPARC) in PSCs, which was inhibited by RUNX1. SPARC secreted from PSCs inhibited pancreatic cancer cell (PCC) proliferation. High expression of nuclear YAP1 in tumor stroma was significantly correlated with SPARC expression and fibrosis degree in human PDAC tissues. Our study revealed a critical role for YAP1 in the regulation of PSC activation and paracrine signaling. Our findings provide insights into a novel rationale for targeting YAP1 to reprogram the PDAC microenvironment.

11.
FEBS Open Bio ; 9(5): 1008-1019, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30945455

RESUMO

Panax notoginseng saponins (PNS) are a commonly used traditional medicine to treat diabetes in China. Recent studies have confirmed their anti-diabetic effects, but the underlying mechanisms have remained unclear. The present study was designed to explore whether PNS decrease hyperglycemia by improving insulin sensitivity in skeletal muscle and to elucidate the molecular mechanisms. The anti-diabetic effects of PNS were analyzed in a skeletal myoblast cell line, C2C12, and in high fat diet-induced diabetic KKAy mice. C2C12 cells were treated with PNS (50, 100, and 200 µg·L-1 ) and examined for glucose uptake, cell viability and expression of components of the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. KKAy mice were intraperitoneally injected with PNS (200 mg·kg-1 ) for 6 weeks. Body weight, blood glucose, serum insulin, serum lipid, glucose and insulin tolerance were measured to evaluate the anti-diabetic effects of PNS. Pathological changes, apoptosis and the PI3K-AKT signaling pathway were analyzed in KKAy skeletal muscle. PNS significantly increased insulin-induced glucose uptake, but did not affect the cell viability of C2C12 cells. In addition, PNS reduced blood glucose and serum insulin levels and improved glucose tolerance and insulin tolerance of KKAy mice. Pathological changes and apoptosis of skeletal muscle were relieved by PNS treatment. Moreover, PNS treatment enhanced expression of mRNA encoding IRS1 and GLUT4, as well as the protein expression of phosphorylated (p) -insulin receptor substrate 1 (IRS1), p-PI3K, p-AKT and glucose transporter type 4 (GLUT4) in C2C12 and KKAy mouse muscle. Collectively, these data indicate that PNS reduces hyperglycemia and insulin resistance through up-regulating GLUT4 expression and the IRS1-PI3K-AKT signaling pathway. Furthermore, PNS alleviated diabetes skeletal muscle pathological damage. Thus, our data suggest that PNS may be promising anti-diabetic compounds.


Assuntos
Transportador de Glucose Tipo 4/genética , Resistência à Insulina/fisiologia , Panax notoginseng/química , Saponinas/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular , Diabetes Mellitus Experimental/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Distribuição Aleatória , Saponinas/química , Transdução de Sinais/fisiologia
12.
J Biomed Nanotechnol ; 15(4): 647-661, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30841960

RESUMO

Although zinc oxide nanoparticles are known as an effective antimicrobial agent, the mechanism for its antifungal activity has been assessed by only few studies. In this study, antifungal activity mechanism for ZnO via the change of physiology was explored. It was showed that the activities of SOD and CAT and the MDA content were increased significantly. The possible mechanisms were obtained that zinc oxide directly acts on the mycelium of penicillium to produce oxidative stress and destroy intracellular physiological balance. RNA-seq was then used to verify the conclusion obtained before, and obtained results suggested that the antifungal mechanism is attributed to oxidative stress and changes in membrane function.


Assuntos
Nanopartículas , Antifúngicos , Antioxidantes , Fungos , Estresse Oxidativo , Óxido de Zinco
13.
J Tradit Chin Med ; 39(4): 451-458, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32186091

RESUMO

OBJECTIVE: To investigate the effect of Shenkang injection (SKI) on chronic kidney disease (CKD). METHODS: Seven databases including Cochrane Central Register of Controlled Trials, PubMed, EMBASE, MEDLINE, China National Knowledge Infrastructure, Wanfang Database, and CQVIP from their inception to March 2018 were searched. Only randomized controlled trials that evaluated conventional treatment and conventional treatment with SKI in CKD patients were investigated. Outcomes such as fibrinogen (FIB), D-dimer, prothrombin time (PT), activated partial thromboplastin time (APTT), and the side effects of SKI were analyzed using Revman 5.3 software. The quality of the studies was assessed using the Cochrane Collaboration's Risk of Bias tool and the quality of evidence was assessed using GRADEpro. RESULTS: Four randomized controlled trials were investigated in our analysis, and these studies were of moderate quality. For FIB and D-dimer, SKI had a superior effect compared with the control group [mean difference (MD)= -1.23, 95% confidence interval (CI): -1.46, -1.99, P < 0.01; MD = -1.36, 95% CI: -1.51, -1.21, P < 0.01, respectively]. SKI increased APTT and PT compared with the control (MD = 7.34, 95% CI: 3.05, 11.62, P < 0.01; MD = 3.40, 95% CI: 2.2, 4.61, P < 0.01, respectively). In the four studies, there were no side effects that were related to SKI. CONCLUSION: SKI may be effective in improving coagulation in patients with CKD without obvious adverse reactions. However, more well-designed studies are required to confirm the findings.

14.
J Vis Exp ; (138)2018 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-30199013

RESUMO

Alternative splicing (AS) occurs in more than 90% of human genes. The expression pattern of an alternatively spliced exon is often regulated in a cell type-specific fashion. AS expression patterns are typically analyzed by RT-PCR and RNA-seq using RNA samples isolated from a population of cells. In situ examination of AS expression patterns for a particular biological structure can be carried out by RNA in situ hybridization (ISH) using exon-specific probes. However, this particular use of ISH has been limited because alternative exons are generally too short to design exon-specific probes. In this report, the use of BaseScope, a recently developed technology that employs short antisense oligonucleotides in RNA ISH, is described to analyze AS expression patterns in mouse brain sections. Exon 23a of neurofibromatosis type 1 (Nf1) is used as an example to illustrate that short exon-exon junction probes exhibit robust hybridization signals with high specificity in RNA ISH analysis on mouse brain sections. More importantly, signals detected with exon inclusion- and skipping-specific probes can be used to reliably calculate the percent spliced in values of Nf1 exon 23a expression in different anatomical areas of a mouse brain. The experimental protocol and calculation method for AS analysis are presented. The results indicate that BaseScope provides a powerful new tool to assess AS expression patterns in situ.


Assuntos
Processamento Alternativo , Encéfalo/metabolismo , Hibridização In Situ/métodos , Precursores de RNA/genética , Animais , Encéfalo/citologia , Éxons/genética , Camundongos , Neurofibromatose 1/genética , RNA Mensageiro/genética
15.
Med Sci Monit ; 24: 4572, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29966139

RESUMO

This paper was retracted on the authors' request due to duplicate publication. This experiment was entrusted to a third party called Nanjing Changcong Biology Company, and we found that some of the data reported in the Results figures were duplicated in another published paper. The pdf file of the above-mentioned paper is available from the Editorial Office on request.

16.
Oncotarget ; 9(34): 23845, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29809193

RESUMO

[This retracts the article DOI: 10.18632/oncotarget.20552.].

17.
Diagn Pathol ; 13(1): 5, 2018 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-29378617

RESUMO

BACKGROUND: Programmed death ligand 1 (PD-L1) has shown potential as a therapeutic target in numerous solid tumors. Its prognostic significance has also been established in pancreatic ductal adenocarcinoma (PDAC). The present study aimed to explore PD-L1 expression in PDAC cases in a large Chinese cohort using an in vitro diagnostic (IVD) assay to provide further insight into the potential value of programmed cell death protein 1 (PD-1) as a therapeutic target. METHODS: Three hundred seventy-three PDAC patients were retrospectively recruited in this study. Tissue microarray (TMA) blocks were made from available formalin-fixed and paraffin-embedded (FFPE) tumor and matched adjacent tissue specimens. We evaluated PD-L1 protein expression via immunohistochemistry (IHC) using a U.S. Food and Drug Administration (FDA)-approved IVD assay. The relationships between PD-L1 positivity and both clinicopathological characteristics and patient prognosis were analyzed. PD-1 expression and clinicopathological significance were also evaluated. RESULTS: PD-L1 and PD-1 positivity were observed in 3.2% and 7.5% of cases, respectively. PD-L1 showed a predominantly membranous pattern in tumor cells, while no positive PD-L1 staining was observed in normal regions. Statistical analyses revealed that PD-L1 expression was associated with lymph node metastasis. PD-L1 positivity was a prognostic indicator of progression-free survival (PFS) and overall survival (OS) in univariate analyses, but only PFS remained statistically significant in multivariate analysis. PD-1 expression was detected in lymphocytes and was not associated with any clinicopathological feature except a history of pancreatitis. CONCLUSIONS: The PD-L1 positivity rate is low in PDAC when evaluated using a companion diagnostic assay. It remains an independent prognostic factor for poor PFS.


Assuntos
Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Antígeno B7-H1/análise , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
18.
Exp Ther Med ; 14(6): 6052-6058, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29285156

RESUMO

Renal tubular cell apoptosis and tubular dysfunction is an important process underlying diabetic nephropathy (DN). Understanding the mechanisms underlying renal tubular epithelial cell survival is important for the prevention of kidney damage associated with glucotoxicity. Curcumin has been demonstrated to possess potent anti-apoptotic properties. However, the roles of curcumin in renal epithelial cells are yet to be defined. The present study investigated advanced glycation or glycoxidation end-product (AGE)-induced toxicity in renal tubular epithelial cells via several complementary assays, including cell viability, cell apoptosis and cell autophagy in the NRK-52E rat kidney tubular epithelial cell line. The extent of apoptosis was significantly increased in the NRK-52E cells following treatment with AGEs. The results also indicated that curcumin reversed this effect by promoting autophagy through the phosphoinositide 3-kinase/AKT serine/threonine kinase signaling pathway. These conclusions suggested that curcumin exerts a renoprotective effect in the presence of AGEs, at least in part by activating autophagy in NRK-52E cells. Collectively, these findings indicate that curcumin not only exerts renoprotective effects, however may also act as a novel therapeutic strategy for the treatment of diabetic nephropathy.

19.
Oncotarget ; 8(42): 72893-72909, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-29069834

RESUMO

Phosphorylation is a recently established cause of phosphatase and tensin homolog (PTEN) gene inactivation, which leads to defect tumour-suppressor function. In pancreatic cancer, this phenomenon has not been reported. Based on database and clinical sample analyses, we found that PTEN phosphorylation occurs in pancreatic ductal adenocarcinoma patient tissues and cell lines, and we aimed to find a method for dephosphorylation. PDZ-containing 1 (PDZK1), a tumour-associated protein that shares its PDZ-binding sequence with the carboxyl-terminal domain of PTEN, was significantly down-regulated in pancreatic cancer as compared to adjacent non-tumour tissues. In vitro, PDZK1 overexpression reversed the proliferation and migration abilities of pancreatic cancer cells and led to significantly decreased PTEN phosphorylation and AKT phosphorylation by interacting with wild-type PTEN. In addition, a transcription factor-activation assay supported that PDZK1 overexpression enhanced the anti-oncogene function of PTEN by regulating the activities of its downstream transcription factors, including p53, NF-κB, and FOXO1. In vivo, nude mice stably over-expressing PDZK1 had lower tumour weights and volumes and showed significantly down-regulated PTEN phosphorylation in xenograft tumour tissues as compared to the control group. Moreover, low PDZK1 expression strongly correlated with advanced stage and poor prognosis of patients with pancreatic ductal adenocarcinoma. In conclusion, our study elucidated the tumour-suppressor role of PDZK1 in pancreatic cancer through down-regulating PTEN phosphorylation, and established PDZK1 as a potential novel prognostic marker for pancreatic cancer.

20.
PLoS One ; 12(8): e0183988, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28859155

RESUMO

Diabetes is caused by the lack of release or action of insulin. Some foods and supplements can compensate for this deficiency; thus, they can aid in the prevention or treatment of diabetes. The aim of this study was to investigate the effects of Cyclocarya paliurus extract (CPE) on insulin signaling and its capacity to correct hyperglycemia in the absence of insulin. To investigate the hypoglycemic effects of CPE, C2C12 cells were exposed to CPE (50 and 100 µg/mL). CPE promoted 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2NBDG) uptake into the cells via translocation of glucose transporter 4 (Glut4) to the plasma membrane. In addition, CPE enhanced tyrosine phosphorylation of insulin receptor substrate and activated phosphatidylinositol 3-kinase and protein kinase B (Akt) via sirtuin1 in C2C12 cells. Moreover, we found that oral administration of CPE (1 g/kg) to streptozotocin-induced hyperglycemic mice produced a progressive decrease in plasma glucose levels at 1 h after single dosing. At that point, CPE significantly increased the expression of skeletal muscle membrane Glut4 and enhanced the phosphorylation of Akt. These results suggest that CPE exerts antidiabetic effects similar to those of insulin, and may be an oral therapeutic alternative for the management of diabetes.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Fagaceae/química , Hipoglicemiantes/farmacologia , Insulina/agonistas , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/genética , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Linhagem Celular , Desoxiglucose/análogos & derivados , Desoxiglucose/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Regulação da Expressão Gênica , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hipoglicemiantes/isolamento & purificação , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Fosfatidilinositol 3-Quinase/genética , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação/efeitos dos fármacos , Transporte Proteico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirtuína 1/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA