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1.
Cytokine ; 129: 155004, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32058275

RESUMO

Hepatocarcinogenesis is a complicated process that is affected by a variety of microenvironmental factors, such as secretory chemokines and cell-extracellular matrix (ECM). Retinoic acid receptor-related orphan receptor (ROR)-α has been shown to attenuate tumor invasiveness by inducing suppressive cell microenvironment, and its low expression was associated with a worse prognosis in HCC patients. In the present study, we attempted to investigate the role and mechanism of the dominant transcript of ROR-α, ROR-α-1, in HCC development and progression. Among the four transcripts (ROR-α-1/-2/-3/-4), overexpression of ROR-α-1 dramatically suppressed the capacity of MHCC97H cells to proliferate, migrate and invade. We analyzed the differentially expressed genes in ROR-α-1-overexpressed and non-overexpressed MHCC97H cells, performed Gene Ontology (GO) enrichment analysis on these differentially-expressed genes, and found out that factors involved in the tumor microenvironment and ECM are related to the anti-tumor effects of ROR-α-1. Among these factors, chemokine CXCL5 was significantly downregulated by ROR-α-1 overexpression. Overexpression of ROR-α-1 remarkably inhibited the capacity of HCC cells to proliferate, migrate, invade, and downregulated the protein levels of ß-catenin, c-Myc, Cyclin D1, and N-cadherin, suggesting the tumor-suppressive role of ROR-α-1 in MHCC97H cells. Moreover, overexpression of CXCL5 dramatically attenuated the suppressive effects of cell proliferation, migration and invasion induced by ROR-α-1 overexpression in MHCC97H, suggesting that ROR-α-1 exerts its anti-tumor effects via downregulating CXCL5. In conclusion, we demonstrate the tumor-suppressive role of ROR-α-1 in MHCC97H cells and that ROR-α-1 might play a tumor-suppressive role via regulation of chemokine CXCL5.

2.
Cancer Lett ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32061951

RESUMO

Hepatic stellate cells (HSCs) play vital roles in tumorigenesis and progression of hepatocellular carcinoma (HCC). However, there remains a lack of high-throughput studies on gene expression alterations in HCC cells in response to direct interactions with HSCs. In this study, we established a direct co-culture model of HSCs and HCC cells. We found that the expression of a set of miRNAs, most notably miR-1246, was triggered by HSCs. RORα was confirmed as the target gene of miR-1246. Either overexpression of miR-1246 or knockdown of RORα enhanced the proliferation, invasiveness, and metastatic capability of HCC both in vitro and in vivo, through Wnt/ß-catenin pathway activation and promotion of epithelial-mesenchymal transition (EMT). Moreover, upregulation of miR-1246 and repression of RORα were prominent features of aggressive clinical HCC. The miR-1246-RORα-Wnt/ß-catenin axis is a novel pathway through which HSCs accelerate HCC progression.

3.
BMC Cancer ; 20(1): 32, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931758

RESUMO

BACKGROUND: Vasculogenic mimicry (VM), defined as a capability of aggressive tumor Cells to mimic embryonic vasculogenic networks, caused poor prognosis in hepatocellular carcinoma (HCC). Rho kinases (ROCK), p21-activated kinase (PAK), hypoxia or epithelial-mesenchymal transition (EMT) contributed to the VM potential. However, the details underlying these biological behaviors have not been completely elucidated. METHODS: Kaplan-Meier analysis was conducted to predict relationship with hypoxia Inducible factor (HIF-1α), EMT related markers: Vimentin and patient prognosis. CD34/periodic acid-Schiff (PAS) double staining was examined to differentiate VM-positive (VM+) and VM-negative (VM-) samples. Cells were cultured under controlled hypoxic environments (1% O2) or normoxic conditions. The effect of hypoxia on RhoA/ROCK, Rac1/PAK and EMT were evaluated by real time-qPCR and western blot. HIF-1α small interfering RNA (siRNA), overexpressed or short hairpin RNA (shRNA) of ROCK and kinase inhibitors were used to explore the effect of HIF-1α, RhoA/ROCK, Rac1/PAK and Vimentin on VM. RESULTS: HIF-1α or Vimentin was upregulated in VM+ HCC tissues, compared to non-cancerous tissues (P < 0.01), and patients with high expression of HIF-1α or Vimentin had worse prognosis (P < 0.001). We showed hypoxia induced RhoA/ROCK and Rac1/PAK signaling transduction, and EMT could be repressed by HIF-1α siRNA. Notably, RhoA/ROCK or Rac1/PAK stabilized HIF-1α in hypoxia, whereas HIF-1α did not significantly altered RhoA/ROCK or Rac1/PAK signaling in hypoxia. Moreover, we found distinct roles of ROCK1, ROCK2 and PAK in regulating Vimentin phosphorylation. CONCLUSIONS: RhoA/ROCK and Rac/PAK signaling played crucial roles in hypoxia-induced VM via Ser72 and Ser56 Vimentin phosphorylation in HCC.

4.
Prog Neurobiol ; 184: 101721, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31704315

RESUMO

Although exogenous nerve growth factor (NGF) demonstrated great potential for post-traumatic stress disorder (PTSD) treatment, its therapeutic effect and underlying cytological mechanism were not fully elucidated so far. We employed a controlled, prospectively designed modified single prolonged stress mice model to investigate the role of exogenous NGF on the modified single prolonged stress induced PTSD-like symptoms and hippocampal cytoarchitecture impairment, as well as the potential neuronal signaling modulation. We discovered that the modified single prolonged stress-exposure induced significant PTSD-like symptoms as well as mildly impaired hippocampal Cornu Ammonis 1 (CA1) subregion cytoarchitecture, but not dentate gyrus neurogenesis, together with a gradual inhibition of TrkA-CREB-ERK signalings in hippocampal CA1 subregion. NGF treatment dose-dependently ameliorated the modified single prolonged stress induced PTSD-like symptoms. NGF increased the cytoplasm/nucleus ratio and improved the neuronal plasticity, mainly via the TrkA-ERK-CREB pathway. Our study offered the translational evidence for the potential application of exogenous NGF for treating or early preventing PTSD after stress exposure.

5.
Eur J Vasc Endovasc Surg ; 59(1): 98-107, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31744785

RESUMO

OBJECTIVE: This study aimed to investigate the effect of long non-coding RNA (lncRNA) DLGAP1 antisense RNA 1 (DLGAP1-AS1) on vascular endothelial cell (VEC) injury via the phosphoinositide 3-kinase (PI3K)/Akt pathway in rat models of acute lower limb ischaemia-reperfusion (I/R). METHODS: Differentially expressed lncRNAs related to I/R were screened using the gene expression omnibus database. Acute lower limb I/R models were induced in male Wistar rats, in which the regulatory mechanisms of DLGAP1-AS1 silencing were analysed after the treatment of small interfering RNA (siRNA) against DLGAP1-AS1 or an inhibitor of the PI3K/Akt pathway. The relationship between DLGAP1-AS1 and the PI3K/Akt pathway was analysed. The levels of tumour necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1), as well as malondialdehyde (MDA) concentration and creatine kinase (CK) activity, were measured. The number of circulating endothelial cells (CECs) and apoptosis of VECs were identified. RESULTS: Microarray based analysis indicated that DLGAP1-AS1 was highly expressed in I/R, which was further confirmed by detection of expression in rat models of acute lower limb I/R. Notably, the treatment of siRNA against DLGAP1-AS1 led to the activation of the PI3K/Akt pathway. In response to siRNA against DLGAP1-AS1, the levels of TNF-α and VCAM-1 were decreased, and MDA concentration and CK activity was downregulated. Reduced CEC numbers and suppressed VEC apoptosis were also observed. CONCLUSION: DLGAP1-AS1 silencing could further suppress the oxidative stress, exert an anti-apoptosis effect, and reduce inflammatory reaction, whereby VEC injury is alleviated by activation of the PI3K/Akt pathway in rats with acute lower limb I/R.

7.
J Cell Physiol ; 235(2): 1624-1636, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31309563

RESUMO

While hundreds of consistently altered metabolic genes had been identified in hepatocellular carcinoma (HCC), the prognostic role of them remains to be further elucidated. Messenger RNA expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma and GSE14520 data set from the Gene Expression Omnibus database. Univariate Cox regression analysis and lasso Cox regression model established a novel four-gene metabolic signature (including acetyl-CoA acetyltransferase 1, glutamic-oxaloacetic transaminase 2, phosphatidylserine synthase 2, and uridine-cytidine kinase 2) for HCC prognosis prediction. Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group. The signature was significantly correlated with other negative prognostic factors such as higher α-fetoprotein. The signature was found to be an independent prognostic factor for HCC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction. Furthermore, gene set enrichment analyses revealed several significantly enriched pathways, which might help explain the underlying mechanisms. Our study identified a novel robust four-gene metabolic signature for HCC prognosis prediction. The signature might reflect the dysregulated metabolic microenvironment and provided potential biomarkers for metabolic therapy and treatment response prediction in HCC.

8.
ACS Omega ; 4(22): 20024-20035, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31788637

RESUMO

The electron-transport layer in planar perovskite solar cells plays an important role in improving photoelectric conversion efficiency. At present, the main electronic transmission materials in perovskite solar cells include TiO2, ZnO, WO3, ZrO2, SnO2, ZnO2, etc. This work mainly studies the electron-transport characteristics of six different electron-transport layers in perovskite solar cells. Based on the density functional theory, the electron-transport model of a solar cell doped with formamidinium iodide lead compound perovskite under six different electron-transport materials was constructed, and their effective electron mass and the mobility of carriers were obtained by optimizing the structure and theoretical calculation. The results show that the mobility of electrons in TiO2 crystal is slightly higher than that of FA0.75Cs0.25Sn0.5Pb0.5I3 carriers. Because of their high matching degree, it can be reasonably explained that titanium dioxide has been widely used in perovskite solar cells and achieved higher photoelectric conversion efficiency. In addition, the mobility of carriers in WO3 and SnO2 crystals is also high, so they also have great advantages in carrier transport. Due to its abundant, nontoxic, and low-pollution content, TiO2 has become the most widely used electronic transmission layer material for solar cells. Furthermore, we have explored eight new semiconductor materials that have not yet been used in perovskite solar cells as the electron-transport layer. The calculation results show that Ta2O5 and Bi2O3 are promising materials for the electron-transport layer. This study provides a theoretical basis for seeking better electronic transmission materials for solar cells in the future.

9.
Aging (Albany NY) ; 11(23): 11111-11123, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829979

RESUMO

BACKGROUND: Mixed evidence challenges preoperative alpha-fetoprotein (AFP) as an independent prognostic factor for patients with hepatocellular carcinoma (HCC) after hepatectomy. RESULTS: Daily post-operative decrease of AFP by 9% as compared to the preoperative level (A09) were selected as the Cut-off. The Kaplan-Meier curve showed that A09 was significantly different for OS (P=0.043) and RFS (P=0.03). A decrease in risk by 54% was observed for OS and 32% for RFS in the at-risk population (A09>9%). A better concordance was observed after adding A09 into TNM and BCLC staging systems. Moreover, a consistent concordance was observed in the internal (FDZS5:0.63; FDZS3:0.608) and external (FDZS5:0.85; FDZS3:0.762) validation cohorts, suggesting its prognostic value in HCC population with elevated AFP. CONCLUSIONS: Decrease in perioperative serum AFP rather than preoperative AFP is an independent prognostic factor for HCC patients after hepatectomy. Cut-off A09 significantly discriminates overall and recurrence-free survival and could be interpret into TNM and BCLC staging systems to improve the stratification power for HCC patients with elevated AFP. METHODS: Kaplan-Meier curve depicted the differences of overall survival (OS) and recurrence-free survival (RFS). Nomogram and concordance were employed to evaluate the superiority of the current staging system.

10.
Pathol Res Pract ; 215(11): 152510, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31591054

RESUMO

Accumulating evidence indicates a strong correlation between type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC), but the underlying pathophysiology is still elusive. We aimed to identify unrecognized but important genes and pathways related to T2DM and HCC by bioinformatic analysis. The GSE64998 and GSE15653 datasets (for T2DM), the GSE121248 dataset and the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset (for HCC) were downloaded. Differential expression analysis, functional and pathway enrichment analysis, protein-protein interaction (PPI) network construction, survival analysis, transcription factor (TF) prediction, and correlation of gene expression with methylation and tumour-infiltrating immune cells were conducted. Nine genes, namely, CDNF, CRELD2, DNAJB11, DTL, GINS2, MANF, PDIA4, PDIA6, and VCP, were recognized as hub genes. Enrichment analysis revealed several enriched terms and pathways. Transcription factors such as Kruppel-like factor 6, abnormal methylation and immune dysregulation might help explain the dysregulation of hub genes. Our study identified nine hub genes that might play a critical role in both T2DM and HCC. However, more studies are warranted to clarify the mechanisms of these genes.

11.
Materials (Basel) ; 12(21)2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31661824

RESUMO

To study the effect of redispersible polymer emulsion powder on the mechanical properties of carbon fiber-reinforced polymer concrete (CFRPC), the compressive, flexural, and splitting tests of CFRPC specimens with different polymer-cement ratios (polymer-cement mass ratios) were performed in this study. The modification effect of emulsion powder on CFRPC was analyzed from the perspectives of the strength and deformation properties of the specimens. The results show that the static properties of CFRPC increased first and then decreased with the increase of the polymer-cement ratio, in which the splitting tensile strength had the most significant increase; the flexural strength took second place and the compressive strength had a slight increase. When the polymer-cement ratio was 8%, the flexural and splitting tensile strength of the CFRPC specimens increased significantly by 36% and 61%, respectively. According to electron microscopy images, adding emulsion powder can effectively improve the structure of fiber-matrix transition zones and enhance the bond property between fibers and the matrix.

12.
Int J Ophthalmol ; 12(9): 1386-1394, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31544031

RESUMO

AIM: To investigate the effects of blockade of insulin receptor substrate-1 (IRS-1) on the bio-function of tube formation of human choroidal endothelial cells (HCECs). METHODS: Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were performed to determine the expression level of IRS-1 and phospho-IRS-1 in HCECs. Tube formation of HCECs was analyzed using three dimensional in vitro Matrigel assay with or without IRS-1 blockage via IRS-1 inhibitor (GS-101) and vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor. In addition, cell counting kit (CCK)-8 and Transwell migration assay were exerted to analyze the effects of blockade of IRS-1 on the bio-function of proliferation and migration of HCECs, respectively. The apoptosis of HCECs was examined using flow cytometry (FCM). RESULTS: RT-PCR and Western blot revealed that IRS-1 phospho-IRS-1 were expressed in HCECs and the expression level was enhanced by stimulation of VEGF-A. The number of tube formation was decreased significantly in GS-101 treated groups compared to phosphate buffered saline (PBS) treated control groups. Furthermore, both cell proliferation and migration of HCECs were decreased in the presence of GS-101. FCM analysis showed that the apoptosis of HCECs was enhanced when the cells were treated with GS-101. Western blot also showed that the expression level of cleaved-caspase 3 in GS-101 treated group was higher than that in control group. CONCLUSION: Blockade of IRS-1 can inhibit tube formation of HCECs through reducing cell proliferation and migration and promoting cell apoptosis.

13.
Biomed Pharmacother ; 118: 109270, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401394

RESUMO

The landscape of cellular plasticity and sources with relevant niche signals in hepatocellular carcinoma is still obscure. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel, is involved in a variety of malignancies and overexpressed in hepatocellular carcinoma (HCC). We have investigated the role of TRPV1 in HCC from different angles by various experimental techniques, such as in vivo and in vitro experiments, and by bioinformatics analysis of data from genetic models induced by diethylnitrosamine (DEN), mice samples and human HCC samples. We find that TRPV1 knockout promotes to hepatocarcinogenesis and deconstructs the portal triad adjacent to tumor border that is contributed by originations of tumor initiating cells and biliary cells. Epithelial to mesenchymal transition (EMT) is involved and transcription factors Ovol2 and Zeb1 coordinated with Sox 10 drive gene expression in the event which is also confirmed by the expression of these proteins in human HCC samples. Treatment with TRPV1 agonist Capsaicin inhibits the growth of HCC cells in xenograft models. Our findings demonstrate that TRPV1 is a potential therapeutic target in human HCC and exerts effects on cellular plasticity with modulation of Ovol2, Zeb1 and Sox10.

14.
ACS Appl Mater Interfaces ; 11(37): 33987-33999, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31448888

RESUMO

Lithium sulfur (Li-S) batteries can offer great opportunities for the next-generation energy storage systems with tremendous energy density. However, challenges still exist in practical Li-S batteries including low sulfur utilization, and poor cycling stability and rate capability. Herein, we propose a novel hybrid catalyst structure by in situ implanting nanocrystal CoS2 in three-dimensional honeycomb-like hierarchical porous graphitic carbon (HPGC) for high-performance Li-S batteries. A unique synergistic absorption-catalysis-functional effect is demonstrated by comprehensive experimental and theoretical analysis: strong physical and chemical co-absorption effects are originated from the large quantity of microporous HPGC and the polar surface of metallic CoS2; the introduced nanocrystal CoS2 with a large specific area can impose an exceptional catalytic effect on the liquid-liquid, solid-liquid, and solid-solid phase redox reactions in Li-S batteries; the reaction dynamics are further guaranteed by the multifunctional properties of the HPGC backbone, including the capabilities in polysulfide sustention, reaction product transportation, electrolyte compensation, and efficiency in assisting diverse electrochemical reaction dynamics. In this way, our results not only develop a novel CoS2@HPGC structure, but also provide fundamental understanding on the catalytic dynamics during each reaction process. Moreover, we further propose the necessity and philosophy of the rational design of catalysts' special structure, which can fulfill the functional dynamics requirements of Li-S batteries, and can be promoted to other Li-S-related cathode design and composite catalytic structure design.

15.
Biosens Bioelectron ; 143: 111613, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31450095

RESUMO

Incorporating elements of triple-helix aptamer probes (TAP), catalyzed hairpin assembly (CHA) signal amplification and host-guest recognition, a novel "signal-on" sensing strategy for sensitive electrochemical quantification of tetracycline (TC) was reported unprecedentedly. TAP was formed involving an aptamer loop, two-segment stems and a triplex oligonucleotide serving as trigger probe. Then, the trigger probe would be released from TAP once the target presented due to the conformational variation of TAP induced by aptamer binding event, sparking off the upcoming CHA amplification reaction, in which two coexisting DNA hairpins (H1 and H2 both modified with the electroactive molecules) would hybridize into plentiful H1-H2 double helices. Afterwards, the Exonuclease III was added, demolishing double helices and simultaneously releasing plentiful electroactive molecules which were capable of diffusing onto the electrode surface under the assistance of ß-cyclodextrin due to host-guest recognition, where appreciable signals were enriched and generated. As thus, considerably slight amounts of targets though, emitted trigger probes, yet efficiently engining spectacular CHA cycles of reactions through which amplified signals were yielded, and in turn progressively enabling the sensitive target detection done. Under optimal conditions, the growing signal stayed a linear relation along with the logarithm of the target concentrations ranging from 0.2 nM to 100 nM, the detection limit reaching as low as 0.13 nM. This approach was desirable regarding to sensitivity, detection limit and range, prospectively rendering a service for diverse targets detection by easily replacing the matched aptamer loop of TAP.


Assuntos
Antibacterianos/isolamento & purificação , Técnicas Biossensoriais , Técnicas Eletroquímicas , Tetraciclina/isolamento & purificação , Antibacterianos/química , Aptâmeros de Nucleotídeos/química , DNA/química , Eletrodos , Exodesoxirribonucleases/química , Técnicas de Amplificação de Ácido Nucleico , Tetraciclina/química
16.
Materials (Basel) ; 12(15)2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31366052

RESUMO

The trap-assisted charge injection in polyfluorene-poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) model systems with an Al or Al/LiF cathode is investigated. We find that inserting 1.3 nm LiF increases electron and hole injections simultaneously and the increase of holes is greater than electrons. The evolution of internal interfaces within polymer light-emitting diodes is observed by transmission electron microscopy, which reveals that the introduction of LiF improves the interface stability at both the cathode (cathode/polymer) and the anode (indium tin oxide (ITO)/PEDOT:PSS). Above-mentioned experimental results have been compared to the numerical simulations with a revised Davids model and potential physical mechanisms for the trap-assisted charge injection are discussed.

17.
Int J Ophthalmol ; 12(7): 1061-1066, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341793

RESUMO

AIM: To clarify the effect of autophagy on human lens epithelial cells (HLECs) under high glucose conditions. METHODS: HLECs were cultured with different concentrations of glucose and 3-methyladenine (3-MA); the expression of autophagy-related protein LC3B was detected by Western blotting and immunofluorescence histochemistry. The migration of HLECs was quantified by scratch wound assay and the expression of transforming growth factor-ß (TGF-ß) was measured by real-time polymerase chain reaction. RESULTS: Compared with 5 mmol/L normal glucose treatment, 40 mmol/L glucose treatment can significantly increase the generation of autophagosome in HLECs, which could be inhibited by 0.375 mmol/L 3-MA treatment. The migration of HLECs and the expression of TGF-ß in HLECs induced by high glucose were significantly suppressed by 0.375 mmol/L 3-MA treatment. CONCLUSION: Autophagy promotes HLECs cell migration and increases the expression of TGF-ß after exposed to high glucose, which may relate to the development of diabetic cataract.

18.
Int J Biol Macromol ; 138: 556-564, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31336116

RESUMO

Native and acetylated broken-rice starches (nanocrystals) with different degrees of substitution (DS) and their corresponding films were individually prepared, and the drug release profiles, weight loss, solubility and dispersion and surface morphology were comparatively studied. Bovine serum albumin (BSA) was used as a model drug. Acetylated native starch (ANS) DS 2.58, acetylated starch nanocrystals (ASN) DS 0.98, ASN DS 1.86, and ASN DS 2.72 were observed to be very soluble in chloroform. BSA was released rapidly from the native rice starch (NS) and ANS DS 2.58 films. ASN with high DS significantly slowed down the release of BSA from films, the percentages of BSA released from film ASN DS 2.72 only reached to 13% after 3.5 weeks release, and the release data followed Korsmeyer-Peppas equation. Further studies reveal that the particle size of ASN DS 2.72 was smallest, and the weight loss of ASN DS 2.72 film was lowest. The results demonstrate that acetylation and nanometer particle form of rice starch film can effectively retard protein drug release, and the prepared films based on ASN with high DS from broken rice may be suitable for the controlled protein delivery.


Assuntos
Membranas Artificiais , Nanopartículas/química , Oryza/química , Proteínas/química , Amido/química , Acetilação , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/ultraestrutura , Tamanho da Partícula , Proteínas/administração & dosagem , Solubilidade , Análise Espectral , Água/química
19.
Onco Targets Ther ; 12: 5269-5279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308697

RESUMO

Background: Helicobacter pylori infection is recognized as a major risk factor for gastric cancer (GC) progression; however, the underlying molecular mechanisms have remained to be fully elucidated. Methods: qPCR and Western blot were used to detect mRNA level and relative protein expression. Wound healing assay and transwell were used to determine migration and invasion of cells. Calcium imaging was used to determine calcium signaling in cells. Luciferase reporter assay and immunohistochemistry were performed. Results: In the present study, it was demonstrated that H. pylori infection in GC is closely associated with the depth of tumor invasion, lymph node metastasis, tumor-nodes-metastasis stage, and distant metastasis. Migration and invasion assays indicated that H. pylori infection enhanced the migration and invasion of GC cells in a Ca2+-dependent manner. Calcium imaging was applied to detect intracellular Ca2+ and revealed that H. pylori induced an increase of intracellular Ca2+ in GC cells through release from Ca2+ stores and extracellular Ca2+ influx. Further study indicated that H. pylori infection led to an upregulation of the expression of transient receptor potential cation channel subfamily C member 6 (TRPC6) and induced an increase of Ca2+ through the TRPC6 channel. Furthermore, H. pylori increased TRPC6 transcription through the Wnt/ß-catenin pathway, and Wnt/ß-catenin/TRPC6 signaling was identified to be at least in part responsible for H. pylori-induced GC migration and invasion. Finally, it was observed that TRPC6 expression was significantly associated with the H. pylori infection status in GC tissues, and H. pylori infection was associated with metastasis and poor prognosis for GC patients. Conclusion: The present results indicate that H. pylori causes an upregulation of TRPC6 expression through the Wnt/ß-catenin pathway to promote GC progression, and this interaction may serve as a promising target for GC therapy.

20.
Biomed Environ Sci ; 32(6): 438-445, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262389

RESUMO

OBJECTIVE: This study was conducted to investigate the viral and bacterial etiology and epidemiology of patients with acute febrile respiratory syndrome (AFRS) in Qinghai using a commercial routine multiplex-ligation-nucleic acid amplification test (NAT)-based assay. METHODS: A total of 445 nasopharyngeal swabs specimens from patients with AFRS were analyzed using the RespiFinderSmart22kit (PathoFinder BV, Netherlands) and the LightCycler 480 real-time PCR system. RESULTS: Among the 225 (225/445, 51%) positive specimens, 329 positive pathogens were detected, including 298 (90.58%) viruses and 31 (9%) bacteria. The most commonly detected pathogens were influenza virus (IFV; 37.39%; 123/329), adenovirus (AdV; 17.02%; 56/329), human coronaviruses (HCoVs; 10.94%; 36/329), rhinovirus/enterovirus (RV/EV; 10.03%; 33/329), parainfluenza viruses (PIVs; 8.51%; 28/329), and Mycoplasma pneumoniae (M. pneu; 8.51%; 28/329), respectively. Among the co-infected cases (17.53%; 78/445), IFV/AdV and IFV/M. pneu were the most common co-infections. Most of the respiratory viruses were detected in summer and fall. CONCLUSION: In our study, IFV-A was the most common respiratory pathogen among 22 detected pathogens, followed by AdV, HCoV, RV/EV, PIV, and M. pneu. Bacteria appeared less frequently than viruses, and co-infection was the most common phenomenon among viral pathogens. Pathogens were distributed among different age groups and respiratory viruses were generally active in July, September, and November. Enhanced surveillance and early detection can be useful in the diagnosis, treatment, and prevention of AFRS, as well as for guiding the development of appropriate public health strategies.


Assuntos
Síndrome Respiratória Aguda Grave/virologia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Estações do Ano , Vigilância de Evento Sentinela , Síndrome Respiratória Aguda Grave/epidemiologia , Adulto Jovem
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