Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.329
Filtrar
1.
J Nanosci Nanotechnol ; 20(3): 1440-1446, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492305

RESUMO

The effects of six metal oxide nanoparticles (MO-NPs) on the activity and biosynthesis of an enzyme (ß-galactosidase) were examined using a mutant strain of E. coli. Different sensitivities were observed according to the type of NP and metabolic process. The toxic effects on enzyme activity were significantly greater than on biosynthesis (p < 0.011), except in the presence of NiO. In both cases, ZnO NP caused the greatest inhibition among the tested NPs, followed by CuO. The EC50s for ZnO were 0.19 and 3.68 mg/L for enzyme activity and biosynthesis, respectively. Similar orders of toxicity were observed as follows: ZnO > CuO > NiO > Co3O4 > TiO2, Al2O3 for enzyme activity; and ZnO > CuO > NiO ≫ Al2O3, TiO2, Co3O4 for the biosynthetic process. More systematic research, including in-depth studies like investigation of the molecular mechanisms, is necessary to elucidate the detailed mechanisms of inhibition involved in both metabolic processes.

2.
J Phys Chem Lett ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597421

RESUMO

Cobalt-nitrogen functionalized materials have been recognized as promising catalysts for CO2RR due to their superior activity. In order to further improve their activity, we proposed an optimization method through coordination engineering in cobalt-nitrogen functionalized porphyrin and graphene. By considering a series of derived structures with coordinating nitrogen atoms substituted by carbon or oxygen atoms, a clear activity trend is obtained by constructing a volcano-type plot for activity against adsorption energies of *CO. Detailed electronic structure analysis shows that the enhanced catalytic activity is due to the lacking of π bonding in Co-O bonds compared to Co-C or Co-N bonds in cobalt centered motifs. This difference allow us to predict the catalytic activity by using vacancy formation energy of cobalt atom. Our work provides a general guideline for a rational design of efficient catalysts, which may stimulate further study of coordination engineering for other key energy conversion processes.

3.
Chin Med J (Engl) ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31592908

RESUMO

BACKGROUND: Plant homeodomain finger protein 23 (PHF23) is a novel autophagy inhibitor gene that has been few studied with respect to orthopedics. This study was to investigate the expression of PHF23 in articular cartilage and synovial tissue, and analyze the relationship between PHF23 and chondrocyte autophagy in osteoarthritis (OA). METHODS: Immunohistochemical staining and western blot were applied to show the expression of PHF23 in cartilage of different outbridge grades and synovial tissue of patient with OA and healthy control. The normal human chondrocyte pre-treated with rapamycin or 3-methyladenine, treated with interleukin-1ß (IL-1ß). IL-1ß induced expression level of PHF23 and autophagy-related proteins light chain 3B-I (LC3B-I), LC3B-II, and P62, were examined by Western blot. A PHF23 gene knock-down model was constructed with small interfering RNA. Western blot was performed to detect the efficiency of PHF23 and the impact of PHF23 knockout on IL-1ß-induced expression of autophagy-related and apoptotic-related proteins in chondrocyte. RESULTS: The expression of PHF23 was significantly increased in the high-grade cartilage and synovial tissue of patients with OA. The IL-1ß-induced expression of PHF23 was gradually enhanced with time. The level of LC3B-II, P62 changed with time. After knockdown of PHF23, the level of autophagy-related proteins increased and apoptotic-related proteins decreased in IL-1ß-induced OA-like chondrocytes. CONCLUSIONS: The expression of PHF23 increased in human OA cartilage and synovium, and was induced by IL-1ß through inflammatory stress. PHF23 can suppress autophagy of chondrocytes, and accelerate apoptosis.

4.
Cancer Med ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566899

RESUMO

BACKGROUND: Portal vein tumor thrombus (PVTT) is a common complication in hepatocellular carcinoma (HCC), signaling dismal outcomes. This study was conducted to evaluate the survival benefit of postoperative portal vein perfusion chemotherapy (PVC) in patients with HCC and PVTT. METHODS: A retrospective review was conducted in 401 consecutive patients with HCC and PVTT who underwent hepatic resection between January 2009 and December 2015 and 67 patients received adjuvant postoperative PVC. A propensity score matching (PSM) was used to match patients with and without PVC at a ratio of 1:1. RESULTS: After PSM, the median time to recurrence (TTR) and overall survival (OS) were significantly longer in PVC group compared with control group (12.3 vs 5.8 months, P = .001; 19.0 vs 13.4 months, P = .037; respectively). At 1, 2, 3, and 5 years, the cumulative recurrence rates in PVC group were 48.1%, 86.5%, 92.3% ,96.2%, respectively, with OS rates of 63.8%, 37.9%, 24.4%, 18.3%, respectively; whereas cumulative recurrence rates of 76.6%, 91.5%, 94.3%, and 97.2%, respectively and OS rates of 55.4%, 23.0%, 12.4%, and 12.4%, respectively were recorded for the control group. In multivariate analysis, postoperative PVC emerged as a significant predictor for TTR (hazard ratio [HR], 0.523; P = .001) and OS (HR, 0.591; P = .010). PVC could reduce early recurrence (≤1 year) rate after surgical resection (40.3% vs 64.2%, P = .006) and clinical outcomes were further enhanced by adding sorafenib to postoperative PVC. CONCLUSIONS: Compared with surgical resection alone, postoperative adjuvant PVC treatment boosts survival and reduces early tumor recurrences in patients surgically treated for HCC and PVTT.

5.
Oncologist ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578274

RESUMO

BACKGROUND: Primary vaginal melanomas are uncommon and aggressive tumors with poor prognosis, and the development of new targeted therapies is essential. This study aimed to identify the molecular markers occurring in these patients and potentially improve treatment strategies. MATERIALS AND METHODS: The clinicopathological characteristics of 36 patients with primary vaginal melanomas were reviewed. Oncogenic mutations in BRAF, KIT, NRAS, GNAQ and GNA11 and the promoter region of telomerase reverse transcriptase (TERT) were investigated using the Sanger sequencing. The expression and copy number of programmed death-ligand 1 (PD-L1) were also assessed. RESULTS: Mutations in NRAS, KIT, and TERT promoter were identified in 13.9% (5/36), 2.9% (1/34), and 5.6% (2/36) of the primary vaginal melanomas, respectively. PD-L1 expression and amplification were observed in 27.8% (10/36) and 5.6% (2/36) of cases, respectively. PD-L1 positive expression and/or amplification was associated with older patients (p = .008). Patients who had NRAS mutations had a poorer overall survival compared with those with a wild-type NRAS (33.5 vs. 14.0 months; hazard ratio [HR], 3.09; 95% CI, 1.08-8.83). Strikingly, two patients with/without PD-L1 expression receiving immune checkpoint inhibitors had a satisfying outcome. Multivariate analysis demonstrated that >10 mitoses per mm2 (HR, 2.96; 95% CI, 1.03-8.51) was an independent prognostic factor. CONCLUSIONS: NRAS mutations and PD-L1 expression were most prevalent in our cohort of primary vaginal melanomas and can be potentially considered as therapeutic targets. IMPLICATIONS FOR PRACTICE: This study used the Sanger sequencing, immunohistochemistry, and fluorescence in situ hybridization methods to detect common genetic mutations and PD-L1 expression and copy number in 36 primary vaginal melanomas. NRAS mutations and PD-L1 expression were the most prevalent, but KIT and TERT mutations occurred at a lower occurrence in this rare malignancy. Two patients receiving immune checkpoint inhibitors had a satisfying outcome, signifying that the PD-L1 expression and amplification can be a possible predictive marker of clinical response. This study highlights the possible prospects of biomarkers that can be used for patient selection in clinical trials involving treatments with novel targeted therapies based on these molecular aberrations.

7.
Fish Shellfish Immunol ; 94: 761-768, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585240

RESUMO

This study was designed to evaluate the effects of zinc on inflammation and tight junction (TJ) in different intestinal regions of common carp under sub-chronic arsenic insult. Fish were exposed to zinc (0, 1 mg/L) and arsenic trioxide (0, 2.83 mg/L) in individual or combination for a month. Inflammatory infiltration and TJ structure changes were displayed by H&E staining and transmission electron microscope. To further explore these changes, biochemical indicator (SOD), gene or protein expressions of inflammatory responses (NF-κB, IL-1ß, IL-6 and IL-8) and TJ proteins (Occludin, Claudins and ZOs) were determined. In the anterior intestine, arsenic decreased activity of SOD, mRNA levels of Occludin, Claudins and ZOs, increased mRNA levels of ILs. However, unlike the anterior intestine, arsenic has an upregulation effects of Occludin and Claudin-4 in the mid intestine. These anomalies induced by arsenic, except IL-8, were completely or partially recovered by zinc co-administration. Furthermore, transcription factor (NF-κB) nuclear translocation paralleled with its downstream genes in both intestinal regions. In conclusion, our results unambiguously suggested that under arsenic stress, zinc can partly relieve intestinal inflammation and disruption of tight junction segment-dependently.

8.
Int J Mol Sci ; 20(20)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600879

RESUMO

The whitefly (Bemisia tabaci), an important invasive pest that causes severe damage to crops worldwide, has developed resistance to a variety of insecticides. Carboxylesterases (COEs) are important multifunctional enzymes involved in the growth, development, and xenobiotic metabolism of insects. However, systematic studies on the COEs of B. tabaci are scarce. Here, 42 putative COEs in different functional categories were identified in the Mediterranean species of B. tabaci (B. tabaci MED) based on a genome database and neighbor-joining phylogeny. The expression patterns of the COEs were affected by the development of B. tabaci. The expression levels of six COEs were positively correlated with the concentration of imidacloprid to which B. tabaci adults were exposed. The mortality of B. tabaci MED adults fed dsBTbe5 (67.5%) and dsBTjhe2 (58.4%) was significantly higher than the adults fed dsEGFP (41.1%) when treated with imidacloprid. Our results provide a basis for functional research on COEs in B. tabaci and provide new insight into the imidacloprid resistance of B. tabaci.

9.
J Am Heart Assoc ; 8(20): e012052, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31595836

RESUMO

Background The impact of estimated glomerular filtration rate (eGFR) on clinical short-term outcomes after stroke thrombolysis with tissue plasminogen activator remains controversial. Methods and Results We analyzed 18 320 ischemic stroke patients who received intravenous tissue plasminogen activator at participating hospitals in the Chinese Stroke Center Alliance between June 2015 and November 2017. Multivariate logistic regression models were used to evaluate associations between eGFR (<45, 45-59, 60-89, and ≥90 mL/min per 1.73 m2) and in-hospital mortality and symptomatic intracerebral hemorrhage, adjusting for patient and hospital characteristics and the hospital clustering effect. Of the 18 320 patients receiving tissue plasminogen activator, 601 (3.3%) had an eGFR <45, 625 (3.4%) had an eGFR 45 to 59, 3679 (20.1%) had an eGFR 60 to 89, and 13 415 (73.2%) had an eGFR ≥90. As compared with eGFR ≥90, eGFR values <45 (6.7% versus 0.9%, adjusted odds ratio, 3.59; 95% CI, 2.18-5.91), 45 to 59 (4.0% versus 0.9%, adjusted odds ratio, 2.00; 95% CI, 1.18-3.38), and 60 to 89 (2.5% versus 0.9%, adjusted odds ratio, 1.67; 95% CI, 1.20-2.34) were independently associated with increased odds of in-hospital mortality. However, there was no statistically significant association between eGFR and symptomatic intracerebral hemorrhage. Conclusions eGFR was associated with an increased risk of in-hospital mortality in acute ischemic stroke patients after treatment with tissue plasminogen activator. eGFR is an important predictor of poststroke short-term death but not of symptomatic intracerebral hemorrhage.

10.
Biomed Chromatogr ; : e4701, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596954

RESUMO

Patrinia villosa (Thunb.) Juss. (PVJ) is described as pungent, bitter and slightly cold in Chinese medicine, and is associated with the large intestine, stomach and liver meridians. The preliminary experiments of our research team proved that PVJ total flavonoids have excellent inhibitory effects on liver cancer cells. And, the present experiment use the UPLC-Q-TOF-MS technology and serum pharmacochemistry methods to analyze the chemical components in vitro and in vivo of PVJ anti-liver tumors. The results show that a total of 14 chemical components are identified in the total flavonoids extract of PVJ, and it is mainly composed of flavonoids, flavonones, flavonols and phenolic acids. At the same time, 7 prototypical components and 7 metabolic components are detected in the drug-containing plasma. Hydrocaffeate and scutellarein are the phase I metabolites of caffeic acid and scutellarin, respectively. Sulfated apigenin, sulfated luteolin, sulfated kaempferol, and methylated kaempferol are the II phase metabolites of apigenin, luteolin, kaempferol, respectively. The experiment provides a reference for the research and development of anti-tumor drug candidates, and provides a basis for revealing the bioactive components of PVJ and anti-tumor mechanism.

11.
Yi Chuan ; 41(9): 827-835, 2019 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-31549681

RESUMO

Crop improvement by domestication and traditional breeding often results in fitness penalties and loss of genetic diversity, which greatly threatens crop production and food security under the challenging global climate. De novo domestication has been proposed as a novel strategy for crop breeding. By combining multi-omics, genome editing and synthetic biology approaches, domestication of wild or semi-wild plant species can be accelerated by rapidly introducing desirable traits without causing an associated drag on their inherent traits. In this review, we summarize the history of crop domestication, emphasize the urgency for breeding strategy innovation, and discuss recent progress of de novo crop domestication.


Assuntos
Produtos Agrícolas , Domesticação , Melhoramento Vegetal , Edição de Genes
12.
J Geriatr Psychiatry Neurol ; 32(6): 291-297, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31480980

RESUMO

This study was performed to compare the treatment status between older (≥65 years) and younger adults (18-64 years) with severe mental illness (SMI) and explore factors associated with treatment status in rural China. Persons with SMI were identified in one mental health survey in 2015 in 6 townships of Xinjin County, Chengdu, China. Logistic regressions were conducted to explore factors associated with treatment status. Older adults with SMI, especially major depressive disorder, reported significantly lower rates of treatment than younger group. Older age, longer duration of illness, and poor mental status were risk factors for never-treated status in these patients. Never-treated status (46.3%) and poor treatment status in these older patients are serious issues. Different treatment statuses in these patients had various influencing factors. It is crucial to develop culture-specific, community-based mental health services to improve early identification, diagnosis, treatment, and recovery of older adults with SMI in rural China.

13.
Int J Clin Oncol ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31473884

RESUMO

PURPOSE: To determine whether patients can avoid systematic prostate biopsy (PBx) if their Prostate Imaging Reporting and Data System version 2 (PI-RADs v2) score is ≤ 3 and how we clinicians make decisions that can maximize benefit. MATERIALS AND METHODS: We reviewed our prospectively maintained database of consecutive men who received transrectal ultrasound-guided 24-core biopsy as well as pre-biopsy multi-parametric magnetic resonance imaging (mp-MRI). Of the 1276 men who were performed PBx in our institution from 2012 to July 2018, 491 patients conformed to the criteria. Negative predictive value (NPV) of negative mp-MRI (defined as PI-RADs < 3) combined prostate-specific antigen density (PSAD) were calculated. Models based on PI-RADs v2 were developed to predict the absence of clinically significant prostate cancer (CSPCa) and prostate cancer (PCa). Nomograms as well as receiver operating curves (ROC) were established to estimate the discrimination. Calibration curves were used to assess the concordance between predictive value and true risk. Decision curves were made to measure the overall net benefit. RESULTS: Prostate cancer and CSPCa detection rates were 21.6%, 7.3% and 36.7%, 23.4% in PIRADs v2 < 3 cohort and PIRADs v2 = 3 cohort, respectively. Men with biopsy-proved CSPCa had higher prostate-specific antigen (PSA), lower prostate volume (PV) and higher PSAD (all p < 0.05 in the two cohorts) than patients with clinically insignificant prostate cancer (CIPCa) or negative results. NPV of negative mp-MRI for detection of PCa was much higher when the PSAD was less than 0.15 (p < 0.001) and 0.2 for CSPCa (p = 0.007). According to multivariate analysis, we developed the model comprising Age, PSAD and PI-RADs v2 to predict the absence of CSPCa and PCa. The area under the curve (AUC) of the model for non-CSPCa was 0.75 (95% CI 0.68-0.80, PSAD cutoff 0.20), better than 0.71 (95% CI 0.65-0.80, PSAD cutoff 0.15). As for model for non-PCa, the AUC was 0.76 (95% CI 0.70-0.80, PSAD cutoff 0.15), higher than 0.71(95% CI 0.67-0.78, PSAD cutoff 0.20). Internally validated calibration curves showed that the model might overestimated the risk of the absence of CSPCa when the threshold was between 53 and 72%, and if the threshold was between 72 and 87%, it might underestimate the risk. As for the absence of PCa, the model might overestimate the risk between 52 and 76%. Decision curves showed that a better clinical net benefit was met when the threshold was 55% for non-PCa and 70% for non-CSPCa. CONCLUSIONS: NPV of negative mp-MRI for detection of CSPCa and PCa was improved with decreasing PSAD. The nomograms based on PI-RADs v2, age and PSAD showed internally validated high discrimination and calibration for the absence of PCa and CSPCa. When the predictive value was greater than 70% for the absence of CSPCa and 55% for the absence of PCa, we could avoid unnecessary PBx to maximize net benefit.

14.
Biol Trace Elem Res ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31473897

RESUMO

Arsenic and copper, two toxic pollutants, are powerful inducers of oxidative stress. Exposure to copper and arsenic can cause intestinal injury in cockerel. This study was carried out to investigate the effects of these two pollutants on the gastrointestinal tract of cockerels. Experimental results showed that the activity of antioxidant enzymes (catalase and glutathione peroxidase) was inhibited and the ionic balance was destroyed after exposure to copper sulfate (300 mg/kg) and/or arsenic trioxide (30 mg/kg). However, the expression of pro-inflammatory cytokines (nuclear factor kappa-B, cyclooxygenase-2, tumor necrosis factor-α, and prostaglandin E2 synthases) increased markedly. Damages to the biofilm structure and inflammatory cell infiltration were simultaneously observed during histological examination. Heat-shock proteins were also expressed in large quantities after exposure to the poisons. Collectively, exposure to arsenite and/or Cu2+ can cause rectal damage in cockerels, inducing inflammation and an imbalance in immune system responses. Sometimes, exposure to both pollutants can produce even more toxic effects. Heat-shock proteins can protect the tissue from the exotoxins but the specific mechanisms require exploration. After oral ingestion of toxins, the rectum can still be damaged, necessitating attention to the safety of poultry breeding, human food safety, and environmental protection.

15.
Chemosphere ; 238: 124658, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31548174

RESUMO

Adsorption is a common process used to remove pharmaceuticals, personal care products and endocrine disrupting chemicals (PPCPs/EDCs) from water. However, as PPCPs/EDCs cover a wide range of molecules and chemical structures, prediction of the adsorption capacity is very challenging. In this study, a novel model was developed to predict adsorption isotherms of PPCPs/EDCs onto various types of adsorbents using a combination of Polanyi potential theory, molecular connectivity indices (MCIs) and molecular characteristics. Polanyi theory provided the basic mathematical form for the correlation. MCIs, hydrophobicity and H-bond count were used to normalize the Polanyi equation based on the molecular structure and interactions among the chemicals, the adsorbents, and the solution. In total, adsorption data were collected from 158 reports for 55 PPCPs/EDCs onto 306 different adsorbent materials. The correlation was first trained with 46 PPCPs/EDCs adsorbed onto 162 carbonaceous adsorbents (CAs), with 44.8% SDEV. Then the model was employed to predict 46 PPCPs/EDCs onto 118 other CAs and 9 new PPCPs/EDCs onto 23 CAs in ultrapure water, with error from 42 to 48% SDEV. When applying to non-carbonaceous adsorbents, the models can still predict the adsorption of PPCPs/EDCs with 90.09% SDEV. For the first time, a model, the PD - MCI - hydrophobic - H bond model, was developed to predict adsorption of a wide group of complicated PPCPs/EDCs onto a big variety of carbonaceous and non-carbonaceous adsorbents. The proposed model approach may provide a simple means for predicting adsorption capacities of PPCPs/EDCs onto various adsorbents.

17.
J Neurochem ; 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31563141

RESUMO

Peripheral nerve injury elicits spinal microgliosis, contributing to neuropathic pain. The aurora kinases A (AURKA), B (AURKB), and C (AURKC) are potential therapeutic targets in proliferating cells. However, their role has not been clarified in microglia. The aim of this study was to examine the regulation of aurora kinases and their roles and druggability in spinal microgliosis and neuropathic pain. Sprague-Dawley rats received chronic constriction injury (CCI). Gene expression of aurora kinases A-C was evaluated by quantitative RT-PCR and western blot, respectively, in spinal cords at 1, 3, 7, and 14 d after CCI. AURKB gene and protein expression was up-regulated concomitantly with the development of spinal microgliosis and neuropathic pain. Using lentiviral overexpression and adeno-associated viral knockdown approaches, the function of AURKB was further investigated by western blot, immunohistochemistry, RNA sequencing and pain behavior tests. We found that AURKB overexpression in naive rats caused spinal microgliosis and pain hypersensitivity, whereas AURKB knockdown reduced microgliosis and alleviated CCI-induced neuropathic pain. Accordingly, RNA sequencing data revealed down-regulation of genes critically involved in signaling pathways associated with spinal microgliosis and neuropathic pain after AURKB knockdown in CCI rats. To examine its therapeutic potential for treatment of neuropathic pain, animals were treated intrathecally with the pharmacological AURKB inhibitor AZD1152-HQPA resulting in the alleviation of CCI-induced pain. Taken together, our findings indicated that AURKB plays a critical role in spinal microgliosis and neuropathic pain. Targeting AURKB may be an efficient method for treatment of neuropathic pain subsequent to peripheral nerve injury.

18.
Appl Opt ; 58(18): 4892-4897, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31503805

RESUMO

An axial-resolution-enhanced two-photon laser scanning microscopy system is presented in this paper. In the proposed method, we use a spatial light modulator (SLM) for the phase modulation of the excitation light. The axially split point spread function (PSF) is generated by loading a 0-π pattern on the SLM. The final quality-enhanced images are acquired by subtracting the two consecutive images acquired by the original PSF and the split PSF. Because of the fluorescence differential processing, the axial elongation of the particles images is suppressed, and the axial resolution is enhanced accordingly. With the axial resolution enhanced, the overlap between layer images is also reduced, which decreases the background noise of the images and enhances the contrast and image quality of the acquired fluorescence images. The capability of axial resolution and contrast enhancement is successfully demonstrated by both theoretical calculation and experimental results.

19.
Cereb Cortex ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31504279

RESUMO

Integrated neural inputs from different dendrites converge at the soma for action potential generation. However, it is unclear how the convergent dendritic inputs interact at the soma and whether they can be further modified there. We report here an entirely new plasticity rule in hippocampal neurons in which repetitive pairing of subthreshold excitatory inputs from proximal apical and basal dendrites at a precise interval induces persistent bidirectional modifications of the two dendritic inputs. Strikingly, the modification of the dendritic inputs specially occurs at soma in the absence of somatic action potential and requires activation of somatic N-methyl-D-aspartate receptors (NMDARs). Once induced, the somatic modification can also be observed in other unpaired dendritic inputs upon their arrival at the soma. We further reveal that the soma can employ an active mechanism to potentiate the dendritic inputs by promoting sustained activation of somatic NMDARs and subsequent down-regulating of the fast inactivating A-type potassium current (IA) at the soma. Thus, the input-timing-dependent somatic plasticity we uncovered here is in sharp contrast to conventional forms of synaptic plasticity that occur at the dendrites and is important to somatic action potential generation.

20.
Cell Cycle ; 18(21): 2939-2953, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31522588

RESUMO

Background: Hepatocellular carcinoma (HCC) afflicts more than half a million people each year worldwide. It was reported that circ_0015756 was up-regulated in HCC, but the mechanism did not extensively studied. Methods: we collected 24 paired cancerous and noncancerous liver tissues surgically resected from HCC patients. HCC cell proliferation, invasion, migration and apoptosis in vitro were evaluated using MTT assay, Transwell assay, scratch test and Annexin-V/PI staining respectively. Interactions between circ_0015756 and miR-7, miR-7 and FAK were further validated by the luciferase reporter assay. Tumor xenografts of HCC cells with circ_0015756 knockdown were established in nude mice. Results: The expression level of circ_0015756 was increased and the expression level of miR-7 was diminished in cancerous liver tissues relative to noncancerous liver tissues. Circ_0015756 knockdown was shown to increase the expression of miR-7, reduce the proliferation, invasion, migration and resistance to apoptosis, and down-regulate the expression of FAK in HCC. We found miR-7 impaired expression of FAK to inhibit HCC cells, suggesting that miR-7 is responsible for the dysfunction of FAK. Importantly, we showed circ_0015756 could up-regulate FAK via targeting miR-7. These in vitro findings were reproduced in vivo that circ_0015756 knockdown decreased HCC xenograft growth. Conclusion: Our present study reveals a model of HCC development that is composed of circ_0015756, miR-7 and FAK. Modulation of their levels exhibits a promise in the treatment of HCC. Abbreviations: HCC: hepatocellular carcinoma; circRNAs: circular RNAs; miRNA/miR: microRNA; miR-7: microRNA-7; FAK: focal adhesion kinase; KLF-4: kruppel like factor 4; DKK1: dickkopf WNT signaling pathway inhibitor 1; ccRCC: clear cell renal cell carcinoma; PI3K: phosphoinositide 3-kinase; Ct: comparative threshold cycle; RPMI: Roswell Park Memorial Institute; FBS: fetal bovine serum; RT: reverse transcription; qPCR: quantitative polymerase chain reaction; RIPA: radioimmunoprecipitation assay; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; PVDF: polyvinylidene difluoride; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; DMSO: dimethyl sulfoxide; DMEM: Dulbecco's modified Eagle's medium; PI: propidium iodide; SPF: specific pathogen-free; SD: standard deviation; p-Akt: phosphorylated-Akt; shRNAs: small hairpin RNAs; 3'UTR: 3'-untranslated regions.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA