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1.
Org Lett ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710501

RESUMO

A direct and convenient approach for the coupling of propargylic substrates with diphenylphosphine oxide in the presence of Tf2O and 2,6-lutidine has been developed. The method provides a general approach for the construction of attractive allenylphosphoryl skeletons with high atom and step economy under metal free conditions.

2.
J Crohns Colitis ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31710674

RESUMO

BACKGROUND AND AIMS: Epigenetic information delivered by intestinal exosomes can be useful for diagnosing intestinal diseases, such as ulcerative colitis, but the therapeutic effects of intestinal exosomes have not been fully exploited. We herein developed an autologous exosome therapy that could treat intestinal disease without any risk of inducing a systemic immunological reaction. METHODS: Intestinal exosomes were isolated and purified from feces by our newly developed multi-step sucrose gradient ultracentrifugation method. Lipopolysaccharide (LPS)-activated macrophages were employed to test the in vitro anti-inflammatory ability of intestinal exosomes. To evaluate the in vivo anti-inflammatory activity of our system, we gavaged DSS-induced colitic mice with their own healing-phase intestinal exosomes. RESULTS: Mouse intestinal exosomes are round extracellular vesicles with a hydrodynamic diameter of ~ 140 (±20) nm and a surface charge of ~ -12 (±3) mV. Among the exosomes obtained at four different stages of DSS-induced ulcerative colitis (1, before treatment; 2, DSS-treated; 3, healing-phase; and 4, back to normal), the healing-phase exosomes showed the best in vitro anti-inflammatory effects and promotion of wound healing. Moreover, oral co-administration of autologous healing-phase exosomes with DSS was found to significantly reduce the risk of a second round of DSS-induced ulcerative colitis in mice. CONCLUSIONS: Intestinal exosomes obtained during the healing phase that follows induced intestinal inflammation could strongly promote wound-healing in the host. Oral administration of autologous exosomes from the healing phase could be a safe and effective approach for treating the ulcerative colitis of a given patient in the context of personalized medicine.

3.
Org Lett ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713429

RESUMO

A catalyst-free method for the highly regioselective chloroboration of allenylsilanes is described. In the presence of BCl3 and 2,6-lutidine, chloroboration of allenylsilanes proceeds smoothly without any catalyst, and the product could be treated with pinacol to afford the corresponding pinacol borates in one-pot reaction. This reaction provides a direct approach to construct valuable 2-silylallylboronate frameworks with operational simplicity and high atom-economy.

5.
Discov Med ; 27(150): 235-243, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31421692

RESUMO

In recent years, with the westernization of lifestyle, reduced physical activity and increased prostate-specific antigen (PSA) testing, the incidence of prostate cancer (PCa) has risen significantly in developing countries. Currently, PSA is the only PCa biomarker applied clinically, but it does not perform well in the early diagnosis and distinguishing between benign prostatic hyperplasia and prostate cancer. With the advances in deep sequencing technology, a series of new PCa biomarkers have been recently proposed to improve the diagnostic value of PSA, such as prostate cancer antigen 3 (PCA3), TMPRSS2-ETS fusion gene, microRNA, and other regulatory non-coding RNAs. In addition, the prostate health index (PHI) has been approved by the U.S. Food and Drug Administration (FDA) for clinical use in the detection of PCa. The prostate-specific membrane antigen (PSMA) has been confirmed to be specifically expressed on the surface of PCa cells. In this review, we provide an updated summary of the value and features of these novel biomarkers in the diagnosis and treatment of PCa.

6.
ISA Trans ; 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31324340

RESUMO

Deep learning networks have been recently utilized for fault detection and diagnosis (FDD) due to its effectiveness in handling industrial process data, which are often with high nonlinearities and strong correlations. However, the valuable information in the raw data may be filtered with the layer-wise feature compression in traditional deep networks. This cannot benefit for the subsequent fine-tuning phase of fault classification. To alleviate this problem, an extended deep belief network (EDBN) is proposed to fully exploit useful information in the raw data, in which raw data is combined with the hidden features as inputs to each extended restricted Boltzmann machine (ERBM) during the pre-training phase. Then, a dynamic EDBN-based fault classifier is constructed to take the dynamic characteristics of process data into consideration. Finally, to test the performance of the proposed method, it is applied to the Tennessee Eastman (TE) process for fault classification. By comparing EDBN and DBN under different network structures, the results show that EDBN has better feature extraction and fault classification performance than traditional DBN.

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 223: 117370, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31301648

RESUMO

In the zinc sulfate solution, the concentration ratio of zinc to metal ion impurities can be up to 105, which causes impurity ion signals to be severely masked by the zinc signal. In particular, nickel exhibits a strong nonlinearity. Conventional spectroscopic methods are commonly used to detect multi-component analytes with similar concentrations and require the detection component to be linear to satisfy Beer-Lambert law. In order to solve high concentration ratio and nonlinear problems, a spectrophotometric method combining the extended Kalman filter and derivative methods is proposed to simultaneously determine copper, cobalt and nickel in the zinc sulfate solution by ultraviolet-visible spectroscopy. The derivative method developed by using continuous wavelet transform with a Haar wavelet function was applied to detect copper and cobalt in regions with wavelengths greater than 500nm, in which the absorbance of zinc and nickel changed to a fixed value, where linear regression graphs for copper and cobalt were established at zero-crossing wavelengths. Extended Kalman filter spectrophotometry is a filtering algorithm for nonlinear systems, so it was proposed to iteratively detect nickel concentration. The detection range was found to be 0.5-5mg/L for copper, 0.3-3mg/L for cobalt, and 0.6-6mg/L. The predicted root mean square error was 0.097 for copper, 0.049 for cobalt, and 0.206 for nickel. The average relative deviations of copper, cobalt, and nickel in 10 sets of mixed solutions were 3.19%, 2.23%, and 4.56%, respectively. The spectrophotometric method studied is suitable for real-time detection and control of trace amounts of copper, cobalt, and nickel in purification process of zinc hydrometallurgy, and can be applied to more fields.

8.
J Crohns Colitis ; 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31168612

RESUMO

BACKGROUND AND AIMS: Heat shock protein 90 (Hsp90)-targeted therapy has been proposed as a promising strategy for the treatment of ulcerative colitis (UC) and colitis-associated cancer (CAC). The systemic administration of the Hsp90 inhibitor, 17-AAG, was found to be profoundly protective in preclinical mouse models of inflammatory bowel disease (IBD). However, the therapeutic potential of 17-AAG is limited by potential side effects associated with its systemic exposure and the modest bioavailability afforded by its oral administration. METHODS: In an effort to address these issues, we herein used a versatile single-step surface-functionalizing technique to prepare a 17-AAG oral delivery system using PLGA/PLA-PEG-FA nanoparticles (NP-PEG-FA/17-AAG). RESULTS: NP-PEG-FA could be efficiently taken up by mouse Colon-26 cells and activated Raw 264.7 cells in vitro and by inflamed mouse colitis tissues in vivo. The therapeutic efficacy of orally administrated NP-PEG-FA/17-AAG was evaluated in in vivo models using dextran sulfate sodium (DSS)-induced UC and azoxymethane (AOM)/DSS-induced CAC, and results indicated that NP-PEG-FA/17-AAG significantly alleviated the symptoms of UC and CAC. More importantly, our inflamed colitis-targeted 17-AAG nano-formulation reduced systemic exposure and provided a degree of therapeutic response similar to that obtained by systemic administration (intraperitoneal, IP) of 17-AAG, but at a 10-fold lower dose. CONCLUSIONS: We therefore describe a convenient, orally administrated 17-AAG delivery system that exhibits enhanced efficacy in UC and CAC therapy while reducing systemic exposure. This system may represent a promising therapeutic approach for treating UC and CAC.

9.
Appl Opt ; 58(14): 3913-3920, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31158209

RESUMO

The spectrum acquired on the optical instrument usually contains the pure spectrum and undesirable components such as baseline and random noise. However, the intensity of the baseline, which seriously submerges the spectrum, is the primary limitation of spectral applications. Thus, baseline correction has become one of the most significant challenges for spectral applications. In this paper, we propose a doubly reweighted penalized least squares method to estimate the baseline. This method utilizes the first-order derivative of the original spectrum and established spectrum as a constraint of similarity. Meanwhile, the doubly reweighted strategy achieves a better effort. Considering the drawbacks of the weighting rules for the adaptive iteratively reweighted penalized least squares method, we adapt a boosted weighting rule based on the softsign function, which performs well when the spectrum contains high noise. The simulated results confirm that the proposed method yields better outcomes. The proposed method can be applied to Raman and near-infrared spectra as well, and the result shows that it can estimate various kinds of baselines effectively.

10.
Chaos ; 29(4): 043101, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31042950

RESUMO

The evolution of a cooperative strategy on multilayer networks is arousing increasing concern. Most of the previous studies assumed that agents can only choose cooperation or defection when interacting with their partners, whereas the actual provisions in real world scenarios might not be discrete, but rather continuous. Furthermore, in evolutionary game, agents often make use of their memory which keeps the most successful strategy in the past, as well as the best current strategy gained by their directed neighbors, to find the best available strategies. Inspired by these observations, we study the impact of the particle swarm optimization (PSO) algorithm on the evolution of cooperation on interdependent networks in the continuous version of spatial prisoner's dilemma games. Following extensive simulations of this setup, we can observe that the introduction of the PSO mechanism on the interdependent networks can promote cooperation strongly, regardless of the network coupling strength. In addition, we find that the increment of coupling strength is more suitable for the propagation of cooperation. More interestingly, we find that when the coupling strength is relatively large, a spontaneous symmetry breaking phenomenon of cooperation occurs between the interdependent networks. To interpret the symmetry breaking phenomenon, we investigate the asynchronous expansion of heterogeneous strategy couples between different networks. Since this work takes cooperation from a more elaborate perspective, we believe that it may provide a deep understanding of the evolution of cooperation in social networks.

11.
J Hum Genet ; 64(6): 535-543, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30944401

RESUMO

Insertion and deletion markers (InDels) have gained considerable attentions in population genetics and forensic research. In this study, we investigated genetic distributions of 30 InDels in Gansu Yugur and Guizhou Miao groups and evaluated their forensic application values. Genetic relationship analyses between Gansu Yugur, Guizhou Miao groups and other published populations were conducted based on these 30 InDels. Power of discrimination and power of exclusion in trio and duo cases of 30 InDels ranged from 0.3528 to 0.6247, 0.0937 to 0.1873, and 0.0219 to 0.1247 in Gansu Yugur group; and they ranged from 0.2579 to 0.6247, 0.0671 to 0.1874, and 0.0105 to 0.1247 in Guizhou Miao group. Obtained cumulative power of discrimination values indicated these InDels could be used for forensic individual identifications in both ethnic groups. Principal component analysis and phylogenetic reconstruction revealed that Gansu Yugur and Guizhou Miao groups had close affinities with their neighboring populations. Genetic structure analyses among these populations also indicated that studied Gansu Yugur and Guizhou Miao groups showed similar genetic structure with their neighboring populations. Further analyses of Y-STR, mtDNA, and ancestry informative markers should be conducted to better understand genetic backgrounds of Gansu Yugur and Guizhou Miao groups in the future.


Assuntos
Cromossomos Humanos Y/genética , DNA Mitocondrial/genética , Genética Populacional , Mutação INDEL/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , China , Grupos Étnicos/genética , Feminino , Ciências Forenses , Testes Genéticos , Variação Genética/genética , Genótipo , Haplótipos/genética , Humanos , Masculino
12.
Eur J Pharmacol ; 858: 172338, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31029709

RESUMO

Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) has been validated as a potent protective agent of Atherosclerosis (AS). Here, we explored the molecular mechanism of MALAT1 exerting protective function in oxidized low-density lipoprotein (ox-LDL)-stimulated human umbilical vein endothelial cells (HUVECs). qRT-PCR assay was used to assess the expression of MALAT1 and miR-216a-5p. Western blot analysis was performed to detect LC3-I, LC3-II, Beclin-1 and p62 levels. The autophagosome formation was analyzed by immunofluorescence analysis. Cell apoptosis was measured by flow cytemotry and caspase 3 activity. Dual-luciferase reporter assay or RNA immunorecipitation assay was performed to verify the targeted interrelation between MALAT1 and miR-216a-5p, or miR-216a-5p and Beclin-1. Our data revealed that MALAT1 was upregulated and miR-216a-5p was downregulated in serum of AS patients and ox-LDL-treated HUVECs. ox-LDL treatment induced HUNECs autophagy. Moreover, MALAT1 enhanced autophagy and survival in ox-LDL-treated HUVECs. MALAT1 directly binded to miR-216a-5p and MALAT1 enhanced Beclin-1 expression by sponging miR-216a-5p. Also, miR-216-5p-mediated repressive effect on autophagy and survival was abrogated by MALAT1. Additionally, Beclin-1 knockdown inhibited autophagy and survival in ox-LDL-treated HUVECs. In all, our data suggested that MALAT1 might play a protective role at least partly by sponging miR-216a-5p and regulating Beclin-1, highlighting that MALAT1 might be a potential therapeutic target of AS.

13.
Clin Rheumatol ; 38(7): 1873-1880, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30806857

RESUMO

OBJECTIVES: To distinguish brucellosis patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for spondyloarthritis (SpA) from SpA patients. METHODS: Brucellosis patients diagnosed from September 2012 to December 2017 who met the ASAS classification criteria for SpA were analyzed with clinical characteristics and laboratory and imaging examinations. Axial or peripheral SpA patients were respectively included into the comparative analysis with a 4:1 ratio. RESULTS: Twenty-two brucellosis (10 axial and 12 peripheral) patients (male, 16 cases; 72.72%; mean (S.D.) age, 40.23 (16.49) years) and 88 SpA patients were included. All brucellosis patients had been misdiagnosed or considered as SpA before admission to our center. The brucellosis patients had shorter disease duration (axial, P = 0.001; peripheral, P = 0.108). More than half (59.09%) of the patients had contact history with livestock. The low back pain (LBP) of brucellosis patients was generally less improved with exercise (axial, P = 0.001; peripheral, P = 0.008). More brucellosis patients had myalgia (axial, P < 0.001; peripheral, P = 0.071) or fever (axial, P < 0.001; peripheral, P = 0.107). None of them had positive HLA-B27. Blood culture tests were performed in all brucellosis patients and only 4 (18.18%) were positive. Twenty (90.91%) brucellosis patients were gold-immunochromatographic assay (GICA) positive. Bone marrow edema and bone erosion in sacroiliac joints were respectively detected in 100% (10/10) and 90% (9/10) axial brucellosis patients by MRI. Adjacent muscle involvement was found in 80% (8/10) of the patients. CONCLUSIONS: Indicators including disease duration, contact history of livestock, features of LBP, myalgia, fever, and HLA-B27 can help the differential diagnosis of brucellosis and SpA. GICA test and sacroiliac joints MRI can furtherly confirm the diagnosis of brucellosis.

14.
Mol Ther ; 27(3): 493-506, 2019 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-30713087

RESUMO

Nanoparticles (NPs) have been utilized to deliver drugs to the intestinal epithelium in vivo. Moreover, NPs derived from edible plants are less toxic than synthetic NPs. Here, we utilized ginger NP-derived lipid vectors (GDLVs) in a proof-of-concept investigation to test the hypothesis that inhibiting expression of divalent metal-ion transporter 1 (Dmt1) would attenuate iron loading in a mouse model of hereditary hemochromatosis (HH). Initial experiments using duodenal epithelial organ cultures from intestine-specific Dmt1 knockout (KO) (Dmt1int/int) mice in the Ussing chamber established that Dmt1 is the only active iron importer during iron-deficiency anemia. Further, when Dmt1int/int mice were crossed with mice lacking the iron-regulatory hormone, hepcidin (Hepc-/-), iron loading was abolished. Hence, intestinal Dmt1 is required for the excessive iron absorption that typifies HH. Additional experiments established a protocol to produce GDLVs carrying functional Dmt1 small interfering RNAs (siRNAs) and to target these gene delivery vehicles to the duodenal epithelium in vivo (by incorporating folic acid [FA]). When FA-GDLVs carrying Dmt1 siRNA were administered to weanling Hepc-/- mice for 16 days, intestinal Dmt1 mRNA expression was attenuated and tissue iron accumulation was blunted. Oral delivery of functional siRNAs by FA-GDLVs is a suitable therapeutic approach to mitigate iron loading in murine HH.

15.
Carbohydr Res ; 473: 123-128, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30684847

RESUMO

Lipopolysaccharide (LPS) is a well-known pathogen-associated molecular pattern (PAMP) produced by gram-negative bacteria. Previous studies showed that a key metabolic intermediate in LPS biosynthesis, d-glycero-ß-d-manno-heptose 1,7-bisphosphate (HBP), could activate the NF-κB pathway and trigger the innate immune responses. However, it was unclear whether HBP could be a novel PAMP and its pattern recognition receptor (PRR) is not fully understood. Very recently, the Shao group reported that another key metabolic intermediate in LPS biosynthesis, ADP-heptose, could be transported into mammalian cells and bind with ALPK1 (alpha-kinase 1), which leads to a series of strong immune responses. These findings broaden our understanding on bacterial metabolites as a new type of PAMP and these small molecules hold great potential to be applied in the development of novel immune modulators. This minireview focuses on the roles of ADP-heptose related metabolites in innate immunity.


Assuntos
Heptoses/metabolismo , Imunidade Inata , Imunomodulação , Animais , Heptoses/biossíntese , Heptoses/química , Humanos
16.
EMBO J ; 38(2)2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30530478

RESUMO

Centrosome amplification is a hallmark of human cancers that can trigger cancer cell invasion. To survive, cancer cells cluster amplified extra centrosomes and achieve pseudobipolar division. Here, we set out to prevent clustering of extra centrosomes. Tubulin, by interacting with the centrosomal protein CPAP, negatively regulates CPAP-dependent peri-centriolar material recruitment, and concurrently microtubule nucleation. Screening for compounds that perturb CPAP-tubulin interaction led to the identification of CCB02, which selectively binds at the CPAP binding site of tubulin. Genetic and chemical perturbation of CPAP-tubulin interaction activates extra centrosomes to nucleate enhanced numbers of microtubules prior to mitosis. This causes cells to undergo centrosome de-clustering, prolonged multipolar mitosis, and cell death. 3D-organotypic invasion assays reveal that CCB02 has broad anti-invasive activity in various cancer models, including tyrosine kinase inhibitor (TKI)-resistant EGFR-mutant non-small-cell lung cancers. Thus, we have identified a vulnerability of cancer cells to activation of extra centrosomes, which may serve as a global approach to target various tumors, including drug-resistant cancers exhibiting high incidence of centrosome amplification.

17.
ISA Trans ; 87: 264-271, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30538041

RESUMO

Due to the complex and harsh operation conditions, like corrosion, aging cable and static electricity, of electrical traction drive system, ground fault will generate large short circuit current to harm the key components. Effective fault diagnosis is important, but also challenging. The conventional method used for ground fault detection only takes advantage of voltage measurements of DC-link. Other measurements onboard are also available, which are correlated with the voltage measurements. Taking the correlation into account will improve the detection performance. To this end, this paper presents a data-driven solution, which makes full use of the correlation between the voltage measurements with other measurements onboard. The proposed method consists of two components: (1) a canonical correlation analysis-based fault detection method, which takes into account the correlation within measurements; (2) a fault isolation method by means of the fault direction, which can be obtained with the available faulty data stored in the long-term operation. The developed method is applied to a traction drive system. It is shown that the proposed approach is able to improve the fault detection and isolation performance significantly with respect to three performance indicators, namely fault detection rate, detection delay and correct isolation rate, in comparison with the conventional method, which only uses the voltage measurements of DC-link.

18.
J Cancer ; 9(23): 4391-4397, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519344

RESUMO

PURPOSE: Oncolytic adenoviruses emerge as new agents for cancer therapy. This study aimed to investigate the synergistic anti-tumor activity of oncolytic adenovirus armed with IL-24 (ZD55-IL-24) and docetaxel (DTX) on advanced prostate cancer in vitro and in vivo. METHODS: DU145 prostate cancer cells or nude mice xenografted with DU145 prostate cancer cells were treated by ZD55-IL-24 and DTX alone or in combination. RESULTS: DTX did not affect ZD55-IL-24 replication and IL-24 expression in DU145 cells. In vitro, the combination of ZD55-IL-24 and DTX showed synergistic inhibitory effects on prostate cancer cell viability and invasion. In vivo, ZD55-IL-24 and DTX synergistically inhibited the growth and activated the apoptosis of DU145 xenografts, accompanied by significantly decreased PARP-1 levels and increased caspase-3 and caspase-8 levels as well as decreased CD31 expression. CONCLUSION: We reported the synergistic anti-tumor efficacy of ZD55-IL-24 and DTX on prostate cancer. Our results suggest that chemotherapy combined with oncolytic adenovirus mediated gene therapy is a promising strategy for the treatment of advanced prostate cancer.

19.
J Exp Clin Cancer Res ; 37(1): 317, 2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30547803

RESUMO

BACKGROUND: Gastric cancer is one of the most common malignant tumors. Cyclin G2 has been shown to be associated with the development of multiple types of tumors, but its underlying mechanisms in gastric tumors is not well-understood. The aim of this study is to investigate the role and the underlying mechanisms of cyclin G2 on Wnt/ß-catenin signaling in gastric cancer. METHODS: Real-time PCR, immunohistochemistry and in silico assay were used to determine the expression of cyclin G2 in gastric cancer. TCGA datasets were used to evaluate the association between cyclin G2 expression and the prognostic landscape of gastric cancers. The effects of ectopic and endogenous cyclin G2 on the proliferation and migration of gastric cancer cells were assessed using the MTS assay, colony formation assay, cell cycle assay, wound healing assay and transwell assay. Moreover, a xenograft model and a metastasis model of nude mice was used to determine the influence of cyclin G2 on gastric tumor growth and migration in vivo. The effects of cyclin G2 expression on Wnt/ß-catenin signaling were explored using a TOPFlash luciferase reporter assay, and the molecular mechanisms involved were investigated using immunoblots assay, yeast two-hybrid screening, immunoprecipitation and Duolink in situ PLA. Ccng2-/- mice were generated to further confirm the inhibitory effect of cyclin G2 on Wnt/ß-catenin signaling in vivo. Furthermore, GSK-3ß inhibitors were utilized to explore the role of Wnt/ß-catenin signaling in the suppression effect of cyclin G2 on gastric cancer cell proliferation and migration. RESULTS: We found that cyclin G2 levels were decreased in gastric cancer tissues and were associated with tumor size, migration and poor differentiation status. Moreover, overexpression of cyclin G2 attenuated tumor growth and metastasis both in vitro and in vivo. Dpr1 was identified as a cyclin G2-interacting protein which was required for the cyclin G2-mediated inhibition of ß-catenin expression. Mechanically, cyclin G2 impacted the activity of CKI to phosphorylate Dpr1, which has been proved to be a protein that acts as a suppressor of Wnt/ß-catenin signaling when unphosphorylated. Furthermore, GSK-3ß inhibitors abolished the cyclin G2-induced suppression of cell proliferation and migration. CONCLUSIONS: This study demonstrates that cyclin G2 suppresses Wnt/ß-catenin signaling and inhibits gastric cancer cell growth and migration through Dapper1.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Ciclina G2/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/metabolismo , beta Catenina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Células COS , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Cercopithecus aethiops , Ciclina G2/biossíntese , Ciclina G2/genética , Feminino , Genes Supressores de Tumor , Células HT29 , Células HeLa , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Transfecção , Via de Sinalização Wnt
20.
Sci Rep ; 8(1): 16220, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30385787

RESUMO

CD98 has been implicated in the experimental model of inflammatory bowel disease. We have previously shown that IEC-specific overexpression of CD98 mediates intestinal inflammation and intestinal epithelial barrier dysfunction. Mice overexpressing CD98 exhibited severe colitis and a greater susceptibility to CAC. Here we demonstrated CD98 overexpression to dysregulate homeostatic gradient profile of miRNA and protein expression along the ileal villus-crypt axis. Using miRNA-target gene prediction module, we observed differentially expressed miRNAs to target proteins of villus and crypt profoundly affected by CD98 overexpression. We have utilized online bioinformatics as methods to further scrutinize the biological meanings of miRNA-target data. We identified significant interactions among the differentially regulated proteins targeted by altered miRNAs in Tg mice. The biological processes affected by the predicted targets of miRNAs deviate from the homeostatic functions of the miRNA-gene-protein axis of the wildtype mice. Our results emphasize a dynamic perturbation of miRNA and protein expression in villus-crypt axis contributing to potential biological consequences of altering CD98 expression. Our findings also suggest the need for a consideration of arrays of interacting biological entities (i.e. miRNAs-mRNAs, protein-protein interaction) or a combination comparison for a better understanding of the disease pathology which is necessary for an effective therapeutic target development.

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