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1.
Artigo em Inglês | MEDLINE | ID: mdl-33001017

RESUMO

BACKGROUND: G protein-coupled receptor 4 (GPR4) has been reported to play an essential role in regulating the proliferation, migration and angiogenesis of vascular endothelial cells. GPR4 is also suggested play roles in the growth and angiogenesis of ovarian cancer. OBJECTIVE: To explore the function of GPR4 and transcription factor 7 (TCF7) in ovarian cancer. METHODS: The expression levels of genes involved in Wnt signaling were validated by quantitative real-time-PCR (q-RT-PCR). The effects of GPR4 and TCF7 on ovarian cancer cell invasion and apoptosis were determined using soft agar, Transwell assay and flow cytometric assay. Protein levels of beta-catenin, MMP-2 and MMP-9 were evaluated by Western blotting. RESULTS: In this study, we found that GPR4 and TCF7 had the capacity to control cell division by altering cell cycle distribution, anchorage-independent growth, and directional cell motility of ovarian cancer cell, A2780. Also, we showed that knockdown of GPR4 and TCF7 in ovarian cancer cells A2780 induced significantly decreased cell growth and decreased invasion, as well as increased apoptosis. Down-regulation of TCF7 resulted in the decreased MMP-2 and MMP-9 level. CONCLUSION: The results implicate that GPR4 behaves like an oncogene and may function through WNT pathway molecule, TCF7. Downregulation of GPR4 and TCF7 essentially inhibited cell growth and invasion and enhanced apoptosis of ovarian cancer cells, which may lay the foundation of ovarian cancer treatment.

2.
Sci Rep ; 10(1): 13659, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32788609

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most representative subtype of renal cancer. CircRNA acts as a kind of ceRNA to play a role in regulating microRNA (miRNA) in many cancers. However, the potential pathogenesis role of the regulatory network among circRNA/miRNA/mRNA is not clear and has not been fully explored. CircRNA expression profile data were obtained from GEO datasets, and the differentially expressed circRNAs (DECs) were identified through utilizing R package (Limma) firstly. Secondly, miRNAs that were regulated by these circRNAs were predicted by using Cancer-specific circRNA database and Circular RNA Interactome. Thirdly, some related genes were identified by intersecting targeted genes, which was predicted by a web tool (miRWalk) and differentially expressed genes, which was obtained from TCGA datasets. Function enrichment was analyzed, and a PPI network was constructed by Cytoscape software and DAVID web set. Subsequently, ten hub-genes were screened from the network, and the overall survival time in patients of ccRCC with abnormal expression of these hub-genes were completed by GEPIA web set. In the last, a circRNA/miRNA/mRNA regulatory network was constructed, and potential compounds and drug which may have the function of anti ccRCC were forecasted by taking advantage of CMap and PharmGKB datasets. Six DECs (hsa_circ_0029340, hsa_circ_0039238, hsa_circ_0031594, hsa_circ_0084927, hsa_circ_0035442, hsa_circ_0025135) were obtained and six miRNAs (miR-1205, miR-657, miR-587, miR-637, miR-1278, miR-548p) which are regulated by three circRNAs (hsa_circ_0084927, hsa_circ_0035442, hsa_circ_0025135) were also predicted. Then 497 overlapped genes regulated by these six miRNAs above had been predicted, and function enrichment analysis revealed these genes are mainly linked with some regulation functions of cancers. Ten hub-genes (PTGER3, ADCY2, APLN, CXCL5, GRM4, MCHR1, NPY5R, CXCR4, ACKR3, MTNR1B) have been screened from a PPI network. PTGER3, ADCY2, CXCL5, GRM4 and APLN were identified to have a significant effect on the overall survival time of patients with ccRCC. Furthermore, one compound (josamycin) and four kinds of drugs (capecitabine, hmg-coa reductase inhibitors, ace Inhibitors and bevacizumab) were confirmed as potential therapeutic options for ccRCC by CMap analysis and pharmacogenomics analysis. This study implies the potential pathogenesis of the regulatory network among circRNA/miRNA/mRNA and provides some potential therapeutic options for ccRCC.

3.
Drug Des Devel Ther ; 14: 2263-2274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606596

RESUMO

Purpose: Lung cancer remains the leading cancer-associated deaths worldwide. Cisplatin (CDDP) was used in combination with curcumin (CUR) for the treatment of non-small cell lung cancer. The aim of this study was to prepare and characterize CDDP prodrug and CUR co-encapsulated layer-by-layer nanoparticles (CDDP-PLGA/CUR LBL NPs) to induce cooperative response, maximize the therapeutic effect, overcome drug resistance, and reduce adverse side effects. Methods: CDDP prodrug (CDDP-PLGA) was synthesized. CDDP-PLGA/CUR LBL NPs were constructed and their physicochemical properties were investigated by particle-size analysis, zeta potential measurement, drug loading, drug entrapment efficiency, and in vitro drug release behavior. In vitro cytotoxicity against human lung adenocarcinoma cell line (A549 cells) was investigated, and in vivo anti-tumor efficiency of CDDP-PLGA/CUR LBL NPs was evaluated on mice bearing A549 cell xenografts. Results: CDDP-PLGA/CUR LBL NPs have a size of 179.6 ± 6.7 nm, a zeta potential value of -29.9 ± 3.2 mV, high drug entrapment efficiency of 85.6 ± 3.9% (CDDP) and 82.1 ± 2.8% (CUR). The drug release of LBL NPs exhibited a sustained behavior, which made it an ideal vehicle for drug delivery. Furthermore, CDDP-PLGA/CUR LBL NPs could significantly enhance in vitro cytotoxicity and in vivo antitumor effect against A549 cells and lung cancer animal model compared to the single drug-loaded LBL NPs and free drug groups. Conclusion: CDDP-PLGA/CUR LBL NPs were reported for the first time in the combination therapy of lung cancer. The results demonstrated that the CDDP-PLGA/CUR LBL NPs might be a novel promising system for the synergetic treatment of lung carcinoma.

4.
J Cell Mol Med ; 24(13): 7479-7489, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32420685

RESUMO

Long non-coding RNAs (lncRNAs) are key regulators or a range of diseases and chronic conditions such as cancers, but how they function in the context of ovarian cancer (OC) is poorly understood. The Coding-Potential Assessment Tool was used to assess the likely protein-coding potential of SNHG7. SNHG7 expression was elevated in ovarian tumour tissues measured by qRT-PCR. The online database JASPAR was used to predict the transcription factors binding to SNHG7. Twenty-four-well Transwell plates were used for invasion assays. RNA immunoprecipitation was performed to determine RNA-protein associations. EdU assay was introduced to detect cell proliferation. Chromatin immunoprecipitation was performed to confirm the directly interaction between DNA and protein. We discovered that in the context of OC there is a significant up-regulation of the lncRNA SNHG7. Knocking down this lncRNA disrupted both OC cell invasion and proliferation, while its overexpression had the opposite effect. SP1 binding sites were present in the SNHG7 promoter, and chromatin immunoprecipitation (ChIP) confirmed direct SP1 binding to this region, activating SNHG7 transcription. We found that at a mechanistic level in OC cells, KLF2 is a probable SNHG7 target, as we found that SHNCCC16 directly interacts with EZH2 and thus represses KLF2 expression. In summary, this research demonstrates that lncRNA SNHG7 is an SP1-activated molecule that contributes to OC progression by providing a scaffold whereby EZH2 can repress KLF2 expression.

5.
Sheng Li Xue Bao ; 72(2): 181-189, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32328612

RESUMO

Long-term exposure to high altitude affects spatial working memory. Previous studies have focused on the analysis of electroencephalogram (EEG) components in time domain rather than in frequency domain. To explore the influence of long-term high altitude exposure on time dynamic characteristics and neural oscillation process of the spatial working memory, n-back task combined with the technology of event related potential recording was performed on 20 young migrants who grew at low altitude before the age of 18 and moved to high altitude more than three years ago, and 21 young people who had never been to the high altitude. EEG data were recorded, and the time domain and frequency domain analyses were performed. The results showed that the response time was longer and the accuracy rate was lower under the 2-back condition in the high altitude group compared with those in low altitude group. The late positive potential (LPP) amplitude was more negative, P2 amplitude was more positive in the 2-back condition, and the power value of early delta frequency band (1-4 Hz, 160-300 ms) was larger, while the power values of late delta frequency band (1-4 Hz, 450-650 ms) and theta frequency band (4-8 Hz, 450-650 ms) were smaller in the high altitude group compared with those in low altitude group. The results suggested that long-term exposure to high altitude affected the spatial working memory ability of the migrants, which was reflected in the lack of attention resources in the later matching stage, decreased response inhibition ability and information maintenance ability, and thus resulted in impaired spatial working memory.


Assuntos
Altitude , Encéfalo/fisiopatologia , Memória de Curto Prazo , Memória Espacial , Migrantes , Eletroencefalografia , Humanos , Tempo de Reação
6.
Oncol Lett ; 19(4): 2609-2620, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32218811

RESUMO

G-protein coupled receptor 4 (GPR4) acts as a proton-sensing receptor and plays a role in regulating angiogenesis. Endoglin/CD105 is a marker of cell proliferation in vascular endothelial cells, particularly in tumor vasculature cells. Although there have been several studies investigating angiogenesis in hepatocellular carcinoma (HCC), none have investigated the association between GPR4 and microvessel density (MVD)-CD105 in this type of cancer. In the present study, CD105 and GPR4 were found to be expressed in benign and malignant liver tissues by immunofluorescence staining and laser confocal microscopy. Compared with levels in benign tissues, CD105 and GPR4 were highly expressed in neoplastic tissues. Furthermore, the average fluorescence intensity of GPR4 and MVD-CD105 was positively correlated. GPR4 and CD105 were found to be co-localized in the vascular endothelium in tumor tissues. Furthermore, the expression of GPR4 was higher in the marginal region of tumor tissues compared with the central region. These findings suggest that the expression of GPR4 in tumor microvessels in HCC may be implicated in tumor angiogenesis and development. Furthermore, the association between the expression of GPR4 and the clinicopathological features of patients with HCC further suggests a role for GPR4 in tumor angiogenesis and growth. Overall, these results suggest the potential of GPR4 as a prognostic factor and as an antiangiogenic target in patients with HCC.

7.
Int J Radiat Oncol Biol Phys ; 107(3): 499-511, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32179132

RESUMO

PURPOSE: To evaluate the effect of hyperthermia combined with concurrent radiochemotherapy (RCT) and treatment-related toxicity in patients with cervical cancer (CC) stage IB-IV. METHODS AND MATERIALS: This study was conducted between 2009 and 2013 in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IV CC. The patients were randomly assigned into 2 treatment groups: RCT and RCT plus hyperthermia (RCHT). Five-year survival, treatment-related toxicity, and other prognostic factors were evaluated. RESULTS: Three hundred seventy-three patients completed treatment and were analyzed by per-protocol (PP) analysis. The 5-year overall survival (OS) in the RCHT group (81.9%) was better than that in RCT group (72.3%), and the log-rank test showed a statistically significant difference between the 2 groups (P = .040). Univariate and multivariate Cox regression analysis for 5-year OS showed a statistically significant difference (P = .043, P = .045, respectively). The 5-year local relapse-free survival in RCHT (86.8%) was also better than that in RCT (82.7%), but the difference was not significant. Acute or late toxicity was not significantly different between the 2 groups. Advanced clinical stage (FIGO) and larger tumor size showed higher risk of death and a relatively poor prognosis in univariate and multivariate analysis. CONCLUSIONS: The study confirmed that hyperthermia combined with RCT yielded a better 5-year OS in CC. Acute and late toxicity was similar between the RCT and RCHT groups. Clinical stage (FIGO) and tumor size were independent prognostic factors in CC.

8.
3 Biotech ; 9(12): 452, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31832299

RESUMO

Xylanase is widely used in pulp and paper bleaching. In this study, the effects of rare earth ions (La3+, Ce3+, Er3+ and Gd3+) on the activity of xylanase produced by Penicillium are investigated and the application of a xylanase solution containing La3+ in paper bleaching is presented. Our results indicate that the bleaching effect of the enzyme solution containing La3+ was markedly better when the concentration of La3+ was 10-8 g/L after 4 days of incubation. The mechanism of lanthanum on the improvement of xylanase activity was revealed through electrical conductivity, atomic absorption spectrometer, infrared spectroscopy and fluorescence microscopy analyses. The PCR result clearly demonstrates that a low concentration of La3+ led to the transversions of three base pair of gene sequences. Our experiment also reveals that the La3+ may have been involved in the cellular metabolic processes of Penicillium and intervened in the base pairing and DNA replication. This research may provide new insights into the improvement of enzymatic activity by lanthanum (III) and its application in paper pulp bleaching.

9.
Sheng Li Xue Bao ; 71(6): 833-838, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31879738

RESUMO

Exposure to a high altitude hypoxia environment has significant negative effects on human central nervous system. Many previous studies have explored the influence of the high altitude environment on human color perception in a simulated high altitude environment or in an environment acutely exposed to high altitude, but little has been done in migrators and natives exposed to high altitude and low oxygen for a long period of time. In this study, the minimal-change method was used to examine whether the color perception of red, green, blue and yellow was affected by the high altitude in 30 plain residents, 30 Han migrators who have lived in the high altitude for 2 years, and 28 high-altitude-adapted Tibetan natives. The results showed that long-term high altitude exposure had the most significant effect on the blue and red color perception in the natives and the migrators, with the effect on the blue color being significantly greater than that on the red color. However, the effects on green color processing only happened to the natives. The results suggest that there is an internal correlation between blood supply and selectivity changes of visual color processing caused by exposure to the plateau environment.


Assuntos
Altitude , Percepção de Cores , China , Percepção de Cores/fisiologia , Humanos , Hipóxia , Oxigênio/metabolismo
10.
PLoS One ; 14(12): e0226624, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851704

RESUMO

The issue of how to alleviate the negative effects imposed by water stress is an interesting problem. Plant growth-promoting rhizobacteria (PGPR) colonize the rhizosphere of plants and are known to promote the growth of crops. However, there are few studies characterizing the physiological response of plants to drought stress after PGPR inoculation. The aim of this study was to investigate the effectiveness of different PGPRs in arid environments and then investigated the effects of PGPR inoculation under drought stress on the physiological characteristics and growth of North China red elder (Sambucus williamsii) nursery container seedlings. The viable count of different PGPRs under drought stress varies widely, and the drought tolerance of Acinetobacter calcoaceticus X128 was significantly higher than that of other PGPRs. In comparison with non-inoculation, inoculation with X128 in an arid environment significantly increased stomatal conductance and mitigated the inhibition of net photosynthetic rate caused by drought stress; this mitigating effect of inoculation is enhanced as the level of drought stress increases. Relative to non-inoculated seedlings, cytokinin levels in the leaves increased by 91.17% under severe drought stress conditions in inoculated seedlings. However, X128 inoculation decreased this deficit to only 44.54%. Compared with non-inoculated seedlings, the relative water content of inoculated seedlings under severe drought stress increased by 15.06%, however the relative conductivity decreased by 12.48%. Consequently, X128 could increase dry matter accumulation of S. williamsii regardless of watering status, indicative of the greater benefits of PGPR on shoot growth than root. Therefore, inoculation of A. calcoaceticus X128 under drought conditions play a significant role for alleviating the negative effects imposed by water stress and promoting plant growth.


Assuntos
Secas , Rizosfera , Sambucus/microbiologia , Plântula/microbiologia , Estresse Fisiológico , Citocininas/metabolismo , Fotossíntese , Desenvolvimento Vegetal , Sambucus/crescimento & desenvolvimento
11.
AMB Express ; 9(1): 169, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673866

RESUMO

Plant growth-promoting rhizobacteria (PGPR) are beneficial bacteria that survive within the range of plant rhizosphere and can promote plant growth. The effects of PGPR in promoting plant growth, activating soil nutrients, reducing fertilizer application, and improving the resistance of plant inducible system have been widely investigated. However, few studies have investigated PGPR as elicitors of tolerance to abiotic stresses, especially drought stress. In this study, the effects of Acinetobacter calcoaceticus X128 on the photosynthetic rate (Pn), stomatal conductance (Gs), intracellular CO2 concentration (Ci), and total chlorophyll content [Chl(a+b)] of Sambucus williamsii Hance seedling leaves under moderate drought stress and drought-rewatering conditions were determined. Compared with those of uninoculated seedlings, the average Pn values during the entire drought stress of inoculated seedlings increased by 12.99%. As the drought duration was lengthened, Ci of uninoculated leaves continued to increase after rapidly declining, whereas Gs continuously decreased. Furthermore, their photosynthetic properties were simultaneously restricted by stomatal and non-stomatal factors. After X128 inoculation, Ci and Gs of S. williamsii Hance leaves continued to decrease, and their photosynthetic properties were mainly restricted by stomatal factors. At the end of the drought stress, water stress reduced [Chl(a + b)] of S. williamsii Hance leaves by 13.49%. However, X128 inoculation decreased this deficit to only 7.39%. After water supply was recovered, Pn, Gs, and [Chl(a+b)] in uninoculated leaves were reduced by 14.23%, 12.02%, and 5.86%, respectively, relative to those under well-watered conditions. However, Ci increased by 6.48%. Compared with those of uninoculated seedlings, Pn, Gs, and [Chl(a+b)] in X128-inoculated seedlings were increased by 9.83%, 9.30%, and 6.85%, respectively. Therefore, the inoculation of X128 under arid environments can mitigate the reduction of chlorophyll, delay the restriction caused by non-stomatal factors to Pn in plant leaves under water stress, and can be more conducive to the recovery of photosynthetic functions of leaves after water supply is recovered.

12.
AMB Express ; 9(1): 145, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515637

RESUMO

In this study, a pot experiment was carried out in greenhouse to investigate the potentials of Xerocomus badius and Serendipita indica to penetrate and colonize roots of ryegrass (Lolium multiflorum Lam.) and to induce beneficial effects on seed germination and seedling growth. The results showed that X. badius and S. indica successfully colonized in the root system of L. multiflorum seedlings and the root colonization rate was 72.65% and 88.42%, respectively. By microscopy, the hyphae, chlamydospores and spores produced by S. indica were observed in roots cortex of L. multiflorum seedlings. In comparison with the non-inoculated seedlings, seedlings inoculated with X. badius and S. indica showed significant increase in growth parameters with plant height, basal diameter, biomass accumulation, relative growth rate, leaf relative water content and chlorophyll content. Also, we found that seedlings inoculated with S. indica exhibited a greater growth-promotion as compared with X. badius-inoculated seedlings. No significant influence of the two fungus application has been observed with respect to seed germination. It suggested that well establishments of mutualistic symbiosis between L. multiflorum and X. badius or S. indica were not so essential to seed germination but contributed highly to the survival and growth of the seedlings.

13.
Oncol Lett ; 18(2): 1824-1830, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423250

RESUMO

The aim of the present study was to establish a prediction index (PI) model for the 5-year survival rate of patients with hepatitis B-related hepatocellular carcinoma (HCC) after radical resection, and to evaluate the effect of prophylactic transcatheter arterial chemoembolization (TACE). A total of 201 patients with hepatitis B-related HCC who had undergone radical hepatic resection at The First Affiliated Hospital of Xinjiang Medical University (Xinjiang, China) were enrolled, and the clinical, pathological and complete follow-up data were collected. Univariate and multivariate Cox regression analyses were performed to identify which clinicopathological factors were considered significant risk factors and the PI model was established based on these factors. The receiver operating characteristic curve was generated, and the area under the curve (0.841) and the cut-off value for PI were calculated. A Kaplan-Meier plot was used for survival analysis and the log-rank test was used to determine differences in survival. Cox regression analysis demonstrated that there were seven independent factors that may have affected the 5-year survival of HCC patients: Neutrophil-to-lymphocyte ratio (NLR), maximum size of tumor (MTS), tumor histological grade (HG), positive resection margin (PRM), microvascular invasion (MVI), the amount of tumor (AT), and antivirus therapy (AVT). A PI model on 5-year survival was established based on these factors, which was PI=0.32 × NLR + 0.39 × HG (high=1, medium=2, low=3) + 0.92 × PRM (yes=1, no=0) + 0.87 × MVI (yes=1, no=0) + 0.73 × AT (single=0, many=1) + 0.53 × MTS (≥5 cm=1, <5 cm=0)-0.87 × AVT (yes=1, no=0). PI was an independent predictor for survival, with a cut-off value of 2.75. For low-risk patients (PI <2.75), there was no significant difference in cumulative survival between TACE and non-TACE. For high-risk patients (PI >2.75), the cumulative survival rates showed significant differences among patients who had received ≥3 TACE procedues, patients who had received <3 TACE procedures, and patients who had not undergone TACE. The PI model predicts the 5-year survival rate of patients with hepatitis B-related HCC. For high-risk patients with a PI >2.75, if they had received ≥3 prophylactic TACE procedures, they demonstrated a more favorable outcome. For low-risk patients (PI <2.75) with 1 or 2 risk factors, TACE is recommended 1-2 times after surgery. TACE treatment is not required for low-risk patients without any risk fctors. These results may contribute to the decision-making process for whether prophylactic intervention is recommended after radical resection of HCC.

14.
PeerJ ; 7: e7269, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31328037

RESUMO

Background: The existence of a particular threshold of hypoxia severity, beyond which neuropsychological functioning is compromised, is unclear. We investigated the neurocognitive profile related to conflict control in healthy young Tibetans born and living at three different altitudes (2,700 m, 3,700 m, and 4,500 m) in Tibet to investigate the existence of this threshold. Methods: Using event-related potentials (ERPs), the conflict control functions of individuals in the three altitude groups were investigated by means of a flanker task, using congruent and incongruent stimuli. The data were analyzed using mixed-model analyses of variance. Results: Although effect of altitude was not significant at a behavioral level (p > 0.05), the ERPs showed cognitive conflict modulation. The N2 difference wave (for incongruent minus congruent conditions) was smaller in the 4,500-m group than in the groups living below 4,000 m (p < 0.05). The study's findings suggest that the influence of high altitude in the conflict monitoring stage becomes significant above 4,000 m. Thus, the altitude threshold for impairment of cognition may be 4,000 m.

15.
Brain Behav ; 9(4): e01256, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30891949

RESUMO

INTRODUCTION: This study aimed to determine the neurocognitive basis underlying the effects of long-term high-altitude (HA) exposure on working memory (WM). METHODS: Using event-related potentials (ERPs), we compared the performance of an HA group (individuals who had lived at HA for 3 years but were born and raised at low altitude [LA]) to that of an LA group (individuals who had only lived at LA) on verbal and spatial n-back tasks (i.e., 1- and 2-back memory load). RESULTS: Response accuracy of the HA group was significantly decreased in comparison to the LA group in both the verbal and spatial 2-back tasks. The P2 amplitude was larger in the HA than in the LA group in the spatial, but not the verbal 2-back task. A smaller late-positive potential (LPP) amplitude was found in the HA group in both the verbal and spatial 2-back tasks. CONCLUSIONS: These results suggest that HA impairs the matching (P2) process in spatial WM tasks and the maintenance (LPP) process in both verbal and spatial WM tasks, indicating that HA had a different effect on verbal and spatial 2-back task performance.


Assuntos
Altitude , Encéfalo/fisiologia , Potenciais Evocados/fisiologia , Memória de Curto Prazo/fisiologia , Memória Espacial/fisiologia , Eletroencefalografia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Adulto Jovem
16.
Pathol Oncol Res ; 25(2): 791-799, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30761450

RESUMO

Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have different clinicopathological characteristics compared with EGFR wild type NSCLC. A growing number of studies focused on the relevance between EGFR mutation status and brain metastases (BM) in NSCLC, but it remains controversial. Therefore, this study performed a comprehensive meta-analysis to untangle this issue. Several electronic databases including Pubmed, Embase, Web of science and Cochrane database were thoroughly searched. The odds ratio (OR) with 95% confidence interval (95%CI) was pooled to evaluate the relevance. Meta-regression analysis and subgroup analysis were conducted according to the heterogeneity. A total of 26 studies were identified finally in this meta-analysis. The overall OR was 1.58 (95%CI: 1.36-1.84), which indicated that EGFR mutation had a positive association with BM of NSCLC. The subgroup analysis resulted from eleven studies with lung adenocarcinoma revealed a higher possibility of BM in NSCLC with EGFR mutation compared with EGFR wild (p < 0.05). There was no significant difference in the risk of BM between NSCLC EGFR exon 19 mutation and exon 21 point mutation (p = 0.23). This meta-analysis suggests that EGFR mutation can be a risk factor for BM in NSCLC.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Mutação
17.
Biomed Pharmacother ; 112: 108614, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30798129

RESUMO

Lung cancer is the leading cause of cancer death worldwide. To overcome the toxic side effects and multidrug resistance (MDR) during doxorubicin (DOX) chemotherapy, a urokinase plasminogen activator receptor (uPAR) targeting U11 peptide decorated, pH-sensitive, dual drugs co-encapsulated nanoparticles (NPs) system is employed in this study. A U11 peptide conjugated, pH-sensitive DOX prodrug (U11-DOX) was synthesized and used as materials to produce NPs. A curcumin (CUR) and U11-DOX co-encapsulated NPs system (U11-DOX/CUR NPs) was constructed to treat lung cancer. After the characterization of biophysical properties of this NPs system, synergistic chemotherapeutic efficacy was evaluated in both cultured cancer cells and tumor-bearing animal model. U11-DOX/CUR NPs had a uniformly spherical shape with a core-shell structure. The mean particle size and zeta potential of the U11-DOX/CUR NPs was 121.3 nm and -33.5 mV, with a DOX and CUR EE of 81.7 and 90.5%, respectively. The DOX release from U11-DOX/CUR NPs was 83.5, 55.2, and 32.8% correspondence to the pH of 5.0, 6.0 and 7.4. Cellular uptake efficiency of U11-DOX/CUR NPs was significantly higher than non U11 peptide decorated DOX/CUR NPs. U11-DOX/CUR NPs displayed a pronounced synergy effects in vitro and an obvious tumor tissue accumulation efficiency in vivo. In vivo antitumor experiment showed that U11-DOX/CUR NPs could inhibit the tumor growth to a level of 85%.In vitro and in vivo studies demonstrated that U11-DOX/CUR NPs is a sustained released, pH responsive, synergistic antitumor system. This study suggests that the U11-DOX/CUR NPs have promising potential for combination treatment of lung cancer.


Assuntos
Curcumina/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Pulmonares/tratamento farmacológico , Nanomedicina/métodos , Pró-Fármacos/administração & dosagem , Células A549 , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Curcumina/síntese química , Doxorrubicina/síntese química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Células Endoteliais da Veia Umbilical Humana , Humanos , Concentração de Íons de Hidrogênio , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/administração & dosagem , Nanopartículas/química , Pró-Fármacos/síntese química , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
18.
Sci Rep ; 8(1): 17417, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30479363

RESUMO

High altitude (HA) exposure reduces the behavioral response to visual attention and the neural basis is still largely unclear. The present study explored the stimulus-driven and goal-directed factors that are hidden within this attentional behavior impairment via a visual search paradigm in young immigrants in Tibet by recording event-related potential (ERPs). We found that HA explosure significantly slowed the stimulus-driven behaviors instead of the goal-directed behaviors. Furthermore, the P1, N1, and P3 amplitudes collectively indicated the poor efficiency of entire attention behaviors, in which the P3 magnitude of resources allocation was negatively correlated with the attentional behavior response. And the P3 scalp distribution suggested a compensation for insufficient resources of sensory processing only in the goal-directed behaviors. Together, the present study made the point on how stimulus-driven and goal-directed attentional behaviors changed as a result of chronic HA environment exposure, which is similar to aging.


Assuntos
Adaptação Fisiológica , Envelhecimento/fisiologia , Altitude , Atenção , Potenciais Evocados , Adolescente , Adulto , Feminino , Objetivos , Humanos , Masculino , Recompensa , Tibet , Percepção Visual
19.
Front Plant Sci ; 9: 974, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30065732

RESUMO

Large-scale application of the doubled haploid (DH) technology by in vivo haploid induction has greatly improved the efficiency of maize breeding. While the haploid induction rate and the efficiency of identifying haploid plants have greatly improved in recent years, the low efficiency of doubling of haploid plants has remained and currently presents the main limitation to maize DH line production. In this study, we aimed to assess the available genetic variation for haploid male fertility (HMF), i.e., the production of fertile pollen on haploid plants, and to investigate the underlying genetic architecture. To this end, a diversity panel of 481 maize inbred lines was crossed with "Mo17" and "Zheng58," the F1 hybrids subjected to haploid induction, and resulting haploid plants assessed for male fertility in two environments. Across both genetic backgrounds, we observed a large variation of HMF ranging from zero to ~60%, with a mean of 18%, and a heritability of 0.65. HMF was higher in the "Mo17" than in the "Zheng58" background and the correlation between both genetic backgrounds was 0.68. Genome-wide association mapping identified only few putative QTL that jointly explained 22.5% of the phenotypic variance. With the exception of one association explaining 11.77% of the phenotypic variance, all other putative QTL were of minor importance. A genome-wide prediction approach further corroborated the quantitative nature of HMF in maize. Analysis of the 14 significantly associated SNPs revealed several candidate genes. Collectively, our results illustrate the large variation of HMF that can be exploited for maize DH breeding. Owing to the apparent genetic complexity of this trait, this might best be achieved by rapid recurrent phenotypic selection coupled with marker-assisted selection for individual QTL.

20.
Neuroscience ; 386: 339-350, 2018 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-30049664

RESUMO

Human spatial manipulation ability is sensitive to high-altitude (HA) environment. The present study aimed to investigate the electrophysiological basis of spatial manipulation ability on adult immigrants with long-term HA exposure using the mental rotation (MR) task and the ERP approach. Toward this end, we explored the MR effect in individuals who immigrated to HA areas for three years compared with individuals who lived in low altitude areas. We found that the reaction time related to the MR effect was significantly slower in the HA group than that of the low-altitude group. The ERP component analysis further indicated that the rotation-related negativity (RRN) amplitude was highly corresponding to the MR effect in each group, the RRN amplitude was significantly larger in the HA group than the low-altitude group related to each rotation angle condition. The brain topographical map further showed that only the right hemisphere regions instead of the bilateral hemisphere regions involved into the MR effect in the HA group, which was different to the low-altitude group. Together, these findings might collectively suggest that the mental resource was insufficient as a result of HA exposure which can be reflected on the RRN amplitude, which may help understanding the neural basis of spatial ability change from the long-term HA exposure.


Assuntos
Altitude , Emigrantes e Imigrantes/psicologia , Processos Mentais/fisiologia , Estimulação Luminosa/métodos , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Tibet/epidemiologia , Fatores de Tempo , Adulto Jovem
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