Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 79
Filtrar
1.
Front Cell Dev Biol ; 9: 633035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540820

RESUMO

Genistein is a natural isoflavone with pharmacological or potentially anti-tumor properties. However, the resistance of cancer cells to genistein remains a major obstacle. This study focused on the mechanism implicated in the resistance of pancreatic cancer (PC) cells to genistein and the mechanism of action. First, key molecules and signaling pathways related to genistein resistance in PC cells were explored using bioinformatics tools. DEP domain containing MTOR interacting protein (DEPTOR), a typical inhibitor of the mammalian target of rapamycin (mTOR) signaling, was predicted to be poorly expressed in the genistein-resistant PC cells. Thereafter, genistein-resistant PC cells (Panc-1 and PaCa) were constructed. Altered expression of DEPTOR was introduced in cells, and everolimus (ELM), an mTOR-specific antagonist, was administrated in cells as well to examine their roles in genistein resistance. The cell apoptosis was examined in vitro and in vivo in mouse xenograft tumors. The upstream regulator of DEPTOR was predicted via bioinformatic tools. The bioinformatic analyses showed that the PI3K/AKT/mTOR signaling pathway was activated in the setting of DEPTOR downregulation in genistein-resistant PC cells. DEPTOR overexpression reduced the 50% inhibiting concentration (IC50) of genistein in PC cells and suppressed mTOR phosphorylation, and it increased caspase-3 activity, LDH release and apoptosis in PC cells. ELM treatment enhanced the sensitivity of PC cells to genistein in vitro and it strengthened the tumor-eliminating role of genistein in mice. ETS transcription factor ELK1 (ELK1), a transcription factor that negatively regulated DEPTOR transcription, was suppressed by genistein. Upregulation of ELK1 suppressed DEPTOR transcription and reduced the genistein sensitivity of cells, and it also blocked the genistein-sensitizing roles of ELM in PC cells. In conclusion, this study demonstrated that ELK1 reduces DEPTOR transcription, leading to mTOR phosphorylation and the drug resistance of PC cells.

2.
Mol Ther Nucleic Acids ; 26: 280-294, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34513310

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of most lethal cancers and is projected to be the second leading cause of cancer deaths in the United States by 2030. The lack of effective treatment and increased incidence in PDAC encourage a deeper knowledge of PDAC progression. By analyzing a long noncoding RNA (lncRNA) dataset, we found that increased LINC00941 expression led to poor outcomes in PDAC patients. Furthermore, in vitro and in vivo experiments revealed that LINC00941 promoted PDAC cancer cell growth by enhancing aerobic glycolysis. Mechanistically, LINC00941 was found to interact with mammalian STE20-like protein kinase 1 (MST1), which facilitated the protein phosphatase 2A (PP2A)-mediated dephosphorylation of MST1, resulting in Hippo pathway activation and consequently, enhanced glycolysis in PDAC. These results suggest that LINC00941 plays a key role in regulating PDAC tumorigenesis, potentially highlighting novel avenues for PDAC therapy.

3.
ACS Appl Mater Interfaces ; 13(36): 43641-43647, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34473930

RESUMO

Multiferroic tunnel junctions (MFTJs), normally consisting of a four-state resistance, have been studied extensively as a potential candidate for nonvolatile memory devices. More interestingly, the MFTJs whose resistance can be tuned continuously with applied voltage were also reported recently. Since the performance of MFTJs is closely related to their interfacial structures, it is necessary to investigate MFTJs at the atomic scale. In this work, atomic-resolution HAADF, ABF, and EELS of the La0.7Sr0.3MnO3/BaTiO3/La0.7Sr0.3MnO3 MFTJ memristor have been obtained with aberration-corrected scanning transmission electron microscopy (STEM). These results demonstrate varied degree of interfacial cation intermixing at the bottom BTO/LSMO interface, which has a direct influence on the polarization of the ferroelectric barrier BTO and the electronic structure of Mn near the interfaces. We also took advantage of a simplified model to explain the relation between the interfacial behavior and polarization states, which could be a contributing factor to the transport properties of this MFTJ.

4.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361016

RESUMO

Although small water clusters (SWCs) are important in many research fields, efficient methods of preparing SWCs are still rarely reported, which is mainly due to the lack of related materials and understanding of the molecular interaction mechanisms. In this study, a series of functional molecules were added in water to obtain small water cluster systems. The decreasing rate of the half-peak width in a sodium dodecyl sulfate (SDS)-water system reaches ≈20% at 0.05 mM from 17O nuclear magnetic resonance (NMR) results. Based on density functional theory (DFT) and molecular dynamics (MD) simulation calculation, it can be concluded that functional molecules with stronger negative electrostatic potential (ESP) and higher hydrophilicity have a stronger ability to destroy big water clusters. Notably, the concentrations of our selected molecule systems are one to two magnitudes lower than that of previous reports. This study provides a promising way to optimize aqueous systems in various fields such as oilfield development, protein stability, and metal anti-corrosion.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Dodecilsulfato de Sódio/química , Espectroscopia de Ressonância Magnética , Eletricidade Estática , Água/química
5.
Biomater Sci ; 9(18): 6153-6168, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34346410

RESUMO

Foam cells with the pro-inflammatory macrophage phenotype (M1) play an essential role in atherosclerosis progression. Either cellular cholesterol removal or drug intervention was reported to polarize M1 into the anti-inflammatory phenotype (M2) for atherosclerosis regression. These might be realized simultaneously by drug-loaded discoidal reconstituted high-density lipoproteins (d-rHDLs) with the functions of cellular cholesterol efflux and targeted drug delivery on macrophages. However, cholesterol reception can drive the remodelling of d-rHDLs, which serves to release drugs specifically in the atherosclerotic plaque but might incur premature drug leakage in blood circulation. Given that, the proposed strategy is to inhibit the remodelling behaviour of the carrier in blood circulation and responsively accelerate it under the atherosclerotic microenvironmental stimulus. Herein, atorvastatin calcium-loaded d-rHDL was modified by a PEGylated ferrocene/ß-cyclodextrin supramolecular copolymer (PF/TC) to construct ROS-responsive PF/TC-AT-d-rHDL, which is expected to possess plasma stability and biosafety as well as triggered drug release by cholesterol efflux promotion. As a result, PF/TC-AT-d-rHDL could responsively dissemble into ß-cyclodextrin modified AT-d-rHDL under the ROS-triggered dissociation of PF/TC, therefore exhibiting increased cholesterol efflux from the cholesterol donor and drug release through the remodelling behaviour of the carrier in vitro. Moreover, PF/TC-AT-d-rHDL enhanced cellular cholesterol removal in foam cells after response to ROS, inhibiting intracellular lipid deposition compared with other d-rHDL carriers. Interestingly, cellular drug uptake was significantly promoted upon cellular cholesterol removal by restoring the permeability and fluidity of foam cell membranes as indicated by flow cytometry and fluorescence polarization analysis, respectively. Importantly, compared with untreated foam cells, PF/TC-AT-d-rHDL obviously increased the ratio of M2/M1 by 6.3-fold, which was even higher than the effect of PF/TC-d-rHDL (3.4-fold) and free drugs (1.9-fold), revealing that PF/TC-AT-d-rHDL synergistically promoted the M2 polarization of macrophages. Accordingly, PF/TC-AT-d-rHDL boosted the secretion of anti-inflammatory cytokines and inhibited that of inflammatory cytokines. Collectively, PF/TC-AT-d-rHDL exerted synergistic M2 polarization effects on foam cells for atherosclerotic immunomodulatory therapy via responsively mediating cholesterol efflux and delivering drugs.


Assuntos
Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Anti-Inflamatórios , Aterosclerose/tratamento farmacológico , Colesterol , Humanos , Macrófagos
6.
Oncol Rep ; 46(4)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34396437

RESUMO

Exosomal pyruvate kinase isoenzyme type M2 (PKM2) has been found to play a key role in the progression of human hepatocarcinoma. However, exosomal PKM2 (especially plasma­derived exosomal PKM2), in patients with oesophageal squamous cell carcinoma (ESCC) has not been well defined. In the present study, plasma­derived exosomes were isolated from healthy controls and patients with ESCC, and identified by transmission electronic microscopy, western blotting, nano­flow cytometry, nanoparticle tracking and phagocytosis analysis; exosomal PKM2 was detected by western blotting and ELISA. In addition, changes in cellular proliferation and motility in recipient cells (Eca109) were assessed using Cell Counting Kit­8, colony formation, wound­healing and Transwell assays. The PKM2 content was higher in exosomes from patients with ESCC than in those from healthy donors. Furthermore, exosomes from patients with ESCC enhanced the proliferation and motility of ESCC cells in vitro. Notably, PKM2 was found to be transferred by exosomes, and was able to act by activating STAT3. To verify the association between PKM2 and STAT3, immunohistochemistry was employed to analyse the protein levels of PKM2 and pSTAT3Tyr705. These data revealed that PKM2 and pSTAT3Tyr705 were upregulated and associated with overall survival in patients with ESCC. Therefore, the present study highlights that exosomes from patients with ESCC enhance the migration and invasiveness of ESCC cells by transferring PKM2.

7.
J Exp Bot ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34397079

RESUMO

In soybean, heterosis achieved through the three-line system has been gradually applied in breeding to increase yield, but the underlying molecular mechanism remains unknown. We conducted a genetic analysis using the pollen fertility of offspring of the cross NJCMS1A×NJCMS1C. All F1 plants' pollen was semi-sterile; in F2, the ratio of pollen-fertile plants to pollen semi-sterile plants was 208:189. This result indicates NJCMS1A is gametophyte sterile, and the fertility restoration of NJCMS1C to NJCMS1A is a quality trait controlled by a single gene locus. Using bulked segregant analysis, the fertility restorer gene Rf in NJCMS1C was located on chromosome 16 between the markers BARCSOYSSR_16_1067 and BARCSOYSSR_16_1078. Sequence analysis of genes in that region showed that GmPPR576 was non-functional in rf cultivars. GmPPR576 has one functional allele in Rf cultivars but three non-functional alleles in rf cultivars. Phylogenetic analysis showed that the GmPPR576 locus evolved rapidly with the presence of male-sterile cytoplasm. GmPPR576 belongs to the RFL fertility restorer gene family and is mitochondrial-targeted. GmPPR576 was knocked out in soybean N8855 using CRISPR/Cas9. The T1 plants showed sterile pollen, and T2 plants produced few pods at maturity. The results indicate that GmPPR576 is the fertility restorer gene of NJCMS1A.

8.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208767

RESUMO

Promoting fluid transportation in porous media has important applications in energy, pedology, bioscience, etc. For this purpose, one effective way is to prevent swelling through surface modification; however, it is far from enough in real cases, such as ultra-low permeability reservoirs and tight oils. In this study, we considered the comprehensive effects of inhibiting clay swelling, flocculation performance, reducing water clusters and interfacial tension and developed a series of imidazole-based tetrafluoroborate ionic liquids (ILs) with different lengths of alkyl chains. Through measurements of anti-swelling rates, XRD, SEM, 17O NMR, molecular dynamics simulation, zeta potential, flocculation evaluation, interfacial tension and a core flooding experiment based on ultra-low permeability reservoirs, the relationships between the molecular structure and physicochemical properties of ILs have been revealed. Interestingly, one of the selected ILs, imidazole-based tetrafluoroborate ILs (C8-OMImBF4), shows excellent performance, which is helpful to design an effective strategy in promoting fluid transportation in narrow spaces.


Assuntos
Argila/química , Imidazóis/química , Líquidos Iônicos/química , Água/química , Algoritmos , Fenômenos Químicos , Modelos Moleculares , Modelos Teóricos , Conformação Molecular , Estrutura Molecular , Difração de Raios X
9.
J Cancer ; 12(16): 4830-4840, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234853

RESUMO

Background: Shikonin, a small molecule inhibitor of pyruvate kinase 2 (PKM2), has been demonstrated to play the antitumor effect in various cancers. However, the specific effects and related regulatory mechanism of Shikonin in esophageal squamous cell carcinoma (ESCC) have not been clearly declared. Materials and methods: Cell viability was valued through 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Glucose consumption, lactate production, glycolytic intermediates and pyruvate kinase enzymatic activity were measured using corresponding assay kits. Patient-derived xenograft (PDX) models were constructed to observe the anti-ESCC effect of Shikonin in vivo. PKM2, p-PKM2, signal transducer and activator of transcription 3 (STAT3), p-STAT3, glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) in ESCC tissues were assessed by western blot. The expression of PKM2, p-PKM2, p-STAT3, GLUT1 and HK2 was assessed by immunohistochemistry (IHC) in ESCC tissue based on PDXs. Results: Shikonin effectively inhibited cell proliferation in dose-dependent and time-dependent manner compared with the control group. The detection of glycolysis showed that Shikonin suppressed the glucose consumption, lactate production, glycolytic intermediates and pyruvate kinase enzymatic activity. Furthermore, Shikonin not only inhibited the growth of ESCC, but also decreased the expression of p-PKM2 and p-STAT3 in vivo. Finally, Shikonin suppressed the expression of GLUT1 and HK2 proteins which are related to glycolysis. Conclusion: Shikonin has a significant antitumor effect in the ESCC by suppressing PKM2 mediated aerobic glycolysis and regulating PKM2/STAT3 signal pathway.

10.
Front Genet ; 12: 654869, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122509

RESUMO

Objective: The present study was designed to investigate whether the extracellular signal-regulated kinase (ERK) signaling pathway, a downstream component of dopamine signaling, is involved in myopia among Chinese children. Methods: During a 3.5-year follow-up, 488 primary school students were enrolled in this study. Non-cycloplegic spherical equivalent refraction (SE) and other ocular parameters were assessed. Four variants of four genes in the ERK signaling pathway were selected: RASGRF1 rs6495367, PTPN5 rs1550870, PTPRR rs11178469, and PDGFRA rs6554163. SNPscan was used to genotype single-nucleotide polymorphisms (SNPs). PLINK software was used to assess the associations of the genetic variants with the occurrence or development of myopia, SE, and other ocular parameters. We created a protein-protein interaction (PPI) network and microRNA (miRNA)-gene network using String and Cytoscape and conducted enrichment analyses on the genes in these networks. Results: In total, 426 children (baseline age: 7.28 ± 0.26 years; 236 (55.4%) boys and 190 girls) wereenrolled. After adjusting for confounding factors with 10,000 permutations, children with the CT or TT genotype of PTPN5 rs1550870 were more susceptible to myopia than those with the CC genotype (adjusted p = 0.011). Additionally, PTPN5 rs1550870 was correlated with significant myopic shift and increasing axial length (AL) and lens thickness (LT) but had a negative effect on central corneal thickness (CCT). RASGRF1 rs6495367 was negatively associated with myopic shift (additive: adjusted p = 0.034; dominant: adjusted p = 0.020), myopic SE and AL. PDGFRA rs6554163 TA or AA was negatively associated with increasing LT (adjusted p = 0.033). Evaluation of the effects of SNP-SNP combinations on incident myopia revealed a statistically significant one-locus model: PTPN5 rs1550870 [cross-validation consistency (CVC) = 10/10, adjusted p = 0.0107]. The genes in the PPI and miRNA-gene interaction networks were subjected to enrichment analyses, which suggested that these genes are involved mainly in eye development and dopaminergic synapse-related processes. Conclusion: We identified genetic variants of crucial ERK signaling pathway genes that were significantly correlated with myopia and ocular parameter alterations in Chinese children. A combination of gene and miRNA functional analyses with enrichment analyses highlights the regulatory effects associated with ocular development and dopamine biological functions. This study offers novel clues to understand the role of dopamine in the molecular mechanisms of myopia.

11.
Small ; 17(29): e2101128, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34137169

RESUMO

Electrochemical CO2 reduction to formate offers a mild and feasible pathway for the utilization of CO2 , and bismuth is a promising metal for its unique hydrogen evolution reaction inhibition. Reported works of Bi-based electrodes generally exhibit high selectivity while suffering from relatively narrow working potential range. From the perspective of electronic modification engineering, B-doped Bi is prepared by a facile chemical reduction method in this work. With B dopant, above 90% Faradaic efficiency for formate over a broad window of working potential of -0.6 to -1.2 V (vs. reversible hydrogen electrode) is achieved. In situ Raman spectroscopy, X-ray adsorption spectroscopy, and computational analysis demonstrate that the B dopant induces the formation of electron-rich bismuth, which is in favor of the formation of formate by fine-tuning the adsorption energy of *OCHO. Moreover, full-cell electrolysis system coupled with photovoltaic device is constructed and achieves the solar-to-formate conversion efficiency as high as 11.8%.

12.
World J Surg Oncol ; 19(1): 112, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845841

RESUMO

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a nonimmunogenic tumor, and very little is known about the relationship between the host immune response and patient survival. We aimed to develop an immune prognostic model (IPM) and analyze its relevance to the tumor immune profiles of patients with PAAD. METHODS: We investigated differentially expressed genes between tumor and normal tissues in the TCGA PAAD cohort. Immune-related genes were screened from highly variably expressed genes with weighted gene correlation network analysis (WGCNA) to construct an IPM. Then, the influence of IPM on the PAAD immune profile was comprehensively analyzed. RESULTS: A total of 4902 genes highly variably expressed among primary tumors were used to construct a weighted gene coexpression network. One hundred seventy-five hub genes in the immune-related module were used for machine learning. Then, we established an IPM with four core genes (FCGR2B, IL10RA, and HLA-DRA) to evaluate the prognosis. The risk score predicted by IPM was an independent prognostic factor and had a high predictive value for the prognosis of patients with PAAD. Moreover, we found that the patients in the low-risk group had higher cytolytic activity and lower innate anti-PD-1 resistance (IPRES) signatures than patients in the high-risk group. CONCLUSIONS: Unlike the traditional methods that use immune-related genes listed in public databases to screen prognostic genes, we constructed an IPM through WGCNA to predict the prognosis of PAAD patients. In addition, an IPM prediction of low risk indicated enhanced immune activity and a decreased anti-PD-1 therapeutic response.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pancreáticas/genética , Prognóstico , Transcriptoma
13.
Biomed Res Int ; 2021: 6682758, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33834072

RESUMO

It was initially found that neural-restrictive silencer factor/repressor 1-silencing transcription factor (REST) is a transcriptional repressor of neuronal genes in nonneuronal cells. However, it is reported to be abundantly expressed in various types of aggressive cancer cells. In this study, we evaluated the expression patterns of REST in renal cell carcinoma and found that its expression is lower in tumor tissues compared to normal tissues. The chi-square test showed that the low REST expression was closely related to patients' clinicopathologic parameters, including the pathologic stage and survival status. ROC curve showed that REST had excellent clinical diagnostic prospect. In addition, patients with low REST expression had poor over survival (OS) and relapse-free survival (RFS). Univariate and multivariate Cox regression analysis confirmed that the low REST expression was an independent predictor of poor prognosis in renal cell carcinoma. Gene set enrichment analysis identified P53 pathway, reactive oxygen species pathway, glycolysis, DNA repair, cholesterol homeostasis, and MYC targets V2 enriched with low REST expression phenotype. These results suggested that REST may be a novel biomarker for the diagnosis and prognosis of renal cell carcinoma in clinical applications.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/diagnóstico , Neoplasias Renais/metabolismo , Proteínas Repressoras/metabolismo , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/genética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Prognóstico , Curva ROC , Proteínas Repressoras/genética , Transdução de Sinais
14.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33671046

RESUMO

MicroRNAs (miRNAs), a class of noncoding small RNAs (sRNAs), are widely involved in the response to high temperature (HT) stress at both the seedling and flowering stages. To dissect the roles of miRNAs in regulating male fertility in soybean cytoplasmic male sterility (CMS)-based F1 under HT, sRNA sequencing was performed using flower buds from HT-tolerant and HT-sensitive CMS-based F1 combinations (NF1 and YF1, respectively). A total of 554 known miRNAs, 59 new members of known miRNAs, 712 novel miRNAs, and 1145 target genes of 580 differentially expressed miRNAs (DEMs) were identified under normal temperature and HT conditions. Further integrated analysis of sRNA and transcriptome sequencing found that 21 DEMs and 15 differentially expressed target genes, such as gma-miR397a/Laccase 2, gma-miR399a/Inorganic phosphate transporter 1-4, and gma-miR4413a/PPR proteins, mitochondrial-like, were negatively regulated under HT stress. Furthermore, all members of the gma-miR156 family were suppressed by HT stress in both NF1 and YF1, but were highly expressed in YF1 under HT condition. The negative correlation between gma-miR156b and its target gene squamosa promoter-binding protein-like 2b was confirmed by expression analysis, and overexpression of gma-miR156b in Arabidopsis led to male sterility under HT stress. With these results, we proposed that miRNAs play an important role in the regulation of male fertility stability in soybean CMS-based F1 under HT stress.


Assuntos
Citoplasma/metabolismo , Regulação da Expressão Gênica de Plantas , Temperatura Alta , MicroRNAs/genética , Infertilidade das Plantas/genética , Proteínas de Soja/metabolismo , Soja/fisiologia , Perfilação da Expressão Gênica , Proteínas de Soja/genética , Estresse Fisiológico , Transcriptoma
15.
Technol Cancer Res Treat ; 20: 1533033820971610, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33752525

RESUMO

OBJECTIVE: Dysregulation of long noncoding RNA is associated with a variety of cancers and LncRNA has anticancer or carcinogenic activities. PVT1, as a long noncoding RNA, plays an important role in the development of cancer. METHODS: We use R to download and analyze the data in TCGA database. ROC curve is generated to evaluate the significance of PVT1 expression for the diagnosis of prostate cancer. Chi-square test is used to test correlation between PVT1 expression and clinical pathological features. Survival curve and univariate and multivariate cox regression analysis is performed to compare differences in the effect on the survival rate between PVT1 high expression and low expression. RESULTS: The expression of PTV1 in tumor tissues was significantly higher than that in normal tissues(P<2.2e-16). The difference of PTV1 expression was observed according to vital status (P = 0.0051) and Gleason score (P = 0.0012). The expression of PTV1 is significantly associated with T classification (P < 0.0001), N classification (P = 0.0499), PSA (P = 0.0001), Gleason Score (P < 0.0001), targeted molecular therapy (P = 0.0264) and vital status(P = 0.0036). The area under the ROC curve (AUC) was 0.860, which revealed PTV1 expression has excellent diagnostic value in prostate cancer. Patients with high PVT1 expression had a worse prognosis. CONCLUSIONS: PVT1 expression may be a biomarker for the diagnosis and prognosis of prostate cancer.

16.
Cancer Cell Int ; 21(1): 121, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602237

RESUMO

BACKGROUND: Calmodulin1 (CALM1) has been identified as one of the overexpression genes in a variety of cancers and EGFR inhibitor have been widely used in clinical treatment but it is unknown whether CALM1 and epidermal growth factor receptor (EGFR) have a synergistic effect in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to explore the synergistic effects of knock-out CALM1 combined with EGFR inhibitor (Afatinib) and to elucidate the role of CALM1 in sensitizing the resistance to Afatinib in ESCC. METHOD: Immunohistochemistry (IHC) and qRT-PCR were used to examine the expression of CALM1 and EGFR in ESCC tissues. Kaplan-Meier survival analysis was used to analyze the clinical and prognostic significance of CALM1 and EGFR expression in ESCC. Furthermore, to evaluate the biological function of CALM1 in ESCC, the latest gene editing technique CRISPR/Cas9(Clustered regularly interspaced short palindromic repeats)was applied to knockout CALM1 in ESCC cell lines KYSE150, Eca109 and TE-1. MTT, flow cytometry, Transwell migration, scratch wound-healing and colony formation assays were performed to assay the combined effect of knock-out CALM1 and EGFR inhibitor on ESCC cell proliferation and migration. In addition, nude mice xenograft model was used to observe the synergistic inhibition of knock-out CALM1 and Afatinib. RESULTS: Both CALM1 and EGFR were found to be significantly over-expressed in ESCC compared with paired normal control. Over-expressed CALM1 and EGFR were significantly associated with clinical stage, T classification and poor overall prognosis, respectively. In vitro, the combined effect of knock-out CALM1 mediated by the lentivirus and EGFR inhibitor was shown to be capable of inhibiting the proliferation, inducing cell cycle arrest at G1/S stage and increasing apoptosis of KYSE-150 and Eca109 cells; invasion and migration were also suppressed. In vivo, the results of tumor weight and total fluorescence were markedly reduced compared with the sgCtrl-infected group and sgCAML1 group. CONCLUSION: Our data demonstrated that knock-out of CALM1 could sensitize ESCC cells to EGFR inhibitor, and it may exert oncogenic role via promotion of EMT. Taken together, CALM1 may be a tempting target to overcome Afatinib resistance.

17.
Angew Chem Int Ed Engl ; 60(19): 10820-10827, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33538391

RESUMO

Covalent Organic Frameworks (COFs) have recently emerged as light-harvesting devices, as well as elegant heterogeneous catalysts. The combination of these two properties into a dual catalyst has not yet been explored. We report a new photosensitive triazine-based COF, decorated with single Ni sites to form a dual catalyst. This crystalline and highly porous catalyst shows excellent catalytic performance in the visible-light-driven catalytic sulfur-carbon cross-coupling reaction. Incorporation of single transition metal sites in a photosensitive COF scaffold with two-component synergistic catalyst in organic transformation is demonstrated for the first time.

18.
Immunol Lett ; 229: 1-7, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33186634

RESUMO

Thymocyte selection-associated high mobility group box protein (TOX), a member of the high-motility group box (HMG) protein superfamily, is an evolutionarily conserved DNA-binding protein. It functions as a transcription factor that modulates transcriptional programs by binding to DNA in a structure-dependent manner. It has been well established that TOX is required for the development of CD4+ T cells, natural killer (NK) cells and innate lymphoid cells (ILCs), as well as the autoimmunity mediated by CD8+ T cells. Recently, emerging evidence supports an essential role for TOX in the induction of T cell exhaustion in the setting of tumor or chronic viral infection by mediating transcriptional and epigenetic changes, which are cardinal hallmarks of exhausted T cells. Moreover, TOX plays a key role in the persistence of antigen-specific T cells and in the mitigation of tissue damage caused by immunopathology over the course of tumorigenesis and chronic infection. Additionally, TOX contributes to the high level of programmed cell death protein 1 (PD-1) on the cell surface by participating in the process of endocytic recycling of PD-1. In this review, we summarize the most recent information about the role of TOX in the process of T cell exhaustion, which enriches our understanding of the molecular mechanisms of CD8+ T cell exhaustion upon chronic antigen stimulation and reveals promising therapeutic targets for persisting infection and cancer.

19.
Nanomedicine ; 32: 102323, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33186693

RESUMO

Reconstituted high-density lipoproteins (rHDLs) hold promise as nanocarriers for atherosclerosis-targeted delivery, with biofunctions typified by mediating cholesterol efflux. The paradox is how rHDL offloads the delivered drugs into atherosclerotic foam cells, while simultaneously transferring cholesterol out of cells. Herein, simvastatin-loaded discoidal rHDL (ST-d-rHDL), constructed based on established paradigms, was employed to investigate its basic trafficking mechanism in foam cells. As proved, ST-d-rHDL was resecreted via lysosomal and Golgi apparatus-recycling endosome-mediated pathways following clathrin-mediated endocytosis. And the resecretion ratio reached 60% within 6-h chase with excessive ST-d-rHDLs. During the rHDL resecretion, 39% of cellular cholesterol efflux was detected, accompanied by 85% of the encapsulated cargo released intracellularly. Furthermore, the recycling rate was demonstrated to be promoted by smaller rHDL size and higher cellular lipid contents. Collectively, endocytic recycling confers the synergism in ST-d-rHDL to coordinate cholesterol efflux and intracellular drug release, providing new insights into design of biofunctional rHDL.

20.
J Cell Physiol ; 236(7): 5373-5386, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33368292

RESUMO

CXCL6, contraction of C-X-C motif chemokine ligand 6, whose biological roles have been rarely described in esophageal squamous cell carcinoma (ESCC). To understand the clinicopathological and biological roles played by CXCL6 in the growth and metastasis of ESCC, immunohistochemistry was used to detect the expression of CXCL6 in ESCC tissues, totaling 105 cases; and the correlation was statistically analyzed between CXCL6 expression and clinicopathological parameters. The role mediated in migration and invasion was evaluated using wound-healing and Transwell assays. MTT and flow cytometry were used to assay the proliferative variation. In vivo, tail vein injection model was established in nude mice xenografted with human ESCC cell lines whose CXCL6 were artificially manipulated. It was found that relative to normal control, CXCL6 was profoundly higher in ESCC; upregulated CXCL6 only significantly correlated with differentiation degree. In vitro, CXCL6 was found to promote the proliferation, migration, and invasion of ESCC cells; which was fully corroborated by nude mice experiment that CXCL6 can promote the growth and metastases of ESCC cells in vivo. Mechanistically, CXCL6 was discovered to be capable of promoting epithelial-mesenchymal transition and upregulating PD-L1 expression through activation of the STAT3 pathway. Collectively, all the data we showed here demonstrate that CXCL6 can enhance the growth and metastases of ESCC cells both in vivo and in vitro.


Assuntos
Antígeno B7-H1/metabolismo , Quimiocina CXCL6/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Fator de Transcrição STAT3/metabolismo , Animais , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica/patologia , Transdução de Sinais/fisiologia , Regulação para Cima
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...