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1.
HIV Med ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38533603

RESUMO

INTRODUCTION: In China, young men who have sex with men (YMSM) are one of the groups most at risk of HIV/AIDS. The uptake of pre-exposure prophylaxis (PrEP) among YMSM has not been well documented. A cascade analysis of awareness, willingness, use and adherence with regard to PrEP was conducted separately among YMSM students and non-students. METHODS: From 20 October to 30 December 2021, all adolescents aged 16-24 years were selected for the study from among MSM recruited from 31 provincial administrative regions in mainland China. Participants were included in a cross-sectional study of awareness, willingness, use and adherence with regard to PrEP among YMSM. Logistic regression modelling was used to identify factors associated with the four outcomes. RESULTS: Among 1014 student and 866 non-student YMSMs, respectively, 88.07% and 81.64% had heard of PrEP; 58.16% and 50.35% were willing to use PrEP; 7.59% and 7.62% had used PrEP; and 3.16% and 3.58% had adhered to PrEP. Among students, those living in high-risk areas and pilot cities and those who had engaged in commercial sex and group sex had a positive effect on PrEP use, and the same trends were found among non-students living in high-risk areas and pilot cities and those who had engaged in group sex. 'Daily oral' and 'flexible' PrEP use positively influenced adherence among both groups. CONCLUSIONS: A differentiation strategy of PrEP promotion should be implemented among YMSM. Material support for students, such as financial resources, should increase, while non-students should increase their level of perception of HIV risk.

2.
Sensors (Basel) ; 22(5)2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35271082

RESUMO

Precise stochastic approaches to quantitatively calculate the source uncertainties offers the opportunity to eliminate the influence of anisotropy on moment tensor inversion. The effects of ignoring anisotropy were tested by using homogeneous Green's functions. Results indicate the influence of anisotropy and noise on fault plane rotation is very small for a pure shear source whether it is restricted to double couple solution or full moment tensor solution. Green's functions with different prior rough anisotropy information were tested, indicating that the complex source is more sensitive to velocity models than the pure shear source and the fault plane rotation caused by full moment tensor solution is larger than the pure double couple solution. Collaborative P-wave velocity inversion with active measurements and passive acoustic emission data using the fast-marching method were conducted, and new Green's functions established based on the tomography results. The resolved fault plane solution rotated only 3.5° when using the new Green's functions, but the presence of spurious isotropic and compensated linear vector dipole components was not completely eliminated. It is concluded that the cooperative inversion is capable of greatly improving the accuracy of the fault plane solutions and reducing the spurious components in the full moment tensor solution.

3.
Biochem Biophys Res Commun ; 558: 134-140, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-33910127

RESUMO

Previous studies have shown that secreted protein acidic and rich in cysteine (SPARC) proteins can inhibit the development of cancer cells in various ways, such as by inhibiting angiogenesis and inhibiting cell proliferation. In fact, SPARC proteins may have an effect on the chemoresistance of gastric cancer cells to 5-Fluorouracil (5-FU), which needs further research in the future. Therefore, the purpose of this study was to explore the relationship between SPARC proteins and the chemosensitivity of gastric cancer cells to 5-FU. In vitro, after SPARC protein levels were regulated by plasmid, siRNA and human recombinant SPARC protein transfection in MGC-803, SGC-7901 and BGC-823 cells, we detected epithelial-mesenchymal transition (EMT), apoptosis markers and cell viability after 5-FU treatment. In vivo, we implanted BGC-823 cells with stable SPARC overexpression into nude mice. Tumour size was measured to assess the effect of SPARC protein on tumour formation and 5-FU chemosensitivity. In SGC-7901 and BGC-823 cells, both endogenous and exogenous upregulation of SPARC protein levels decreased cell viability, destroyed cytoskeletal F-actin, inhibited cell migration, and downregulated a series of transcription factors to inhibit cell EMT; it also upregulated cell apoptosis-related proteins to promote cell apoptosis. However, we obtained opposite results in SPARC knockdown MGC-803 cells. In vivo, compared with the control group, the group engrafted with BGC-823 cells stably overexpressing SPARC had a significant smaller tumour size. After 5-FU treatment, the new tumour gradually decreased in size. Our results show that the SPARC protein could enhance 5-FU chemosensitivity in gastric cancer cell lines by inhibiting EMT and promoting cell apoptosis.


Assuntos
Fluoruracila/farmacologia , Osteonectina/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Actinas/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/fisiologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Osteonectina/antagonistas & inibidores , Osteonectina/genética , Poli(ADP-Ribose) Polimerases/metabolismo , RNA Interferente Pequeno/genética , Neoplasias Gástricas/patologia , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
4.
BMC Cancer ; 21(1): 645, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059009

RESUMO

BACKGROUND: Breast cancer (BRCA) is a malignant tumor with high morbidity and mortality, which is a threat to women's health worldwide. Ferroptosis is closely related to the occurrence and development of breast cancer. Here, we aimed to establish a ferroptosis-related prognostic gene signature for predicting patients' survival. METHODS: Gene expression profile and corresponding clinical information of patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. The Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis model was utilized to construct a multigene signature. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes, Genomes (KEGG) pathway and single-sample gene set enrichment analysis (ssGSEA) were performed for patients between the high-risk and low-risk groups divided by the median value of risk score. RESULTS: We constructed a prognostic signature consisted of nine ferroptosis-related genes (ALOX15, CISD1, CS, GCLC, GPX4, SLC7A11, EMC2, G6PD and ACSF2). The Kaplan-Meier curves validated the fine predictive accuracy of the prognostic signature (p < 0.001). The area under the curve (AUC) of the ROC curves manifested that the ferroptosis-related signature had moderate predictive power. GO and KEGG functional analysis revealed that immune-related responses were largely enriched, and immune cells, including activated dendritic cells (aDCs), dendritic cells (DCs), T-helper 1 (Th1), were higher in high-risk groups (p < 0.001). Oppositely, type I IFN response and type II IFN response were lower in high-risk groups (p < 0.001). CONCLUSION: Our study indicated that the ferroptosis-related prognostic signature gene could serve as a novel biomarker for predicting breast cancer patients' prognosis. Furthermore, we found that immunotherapy might play a vital role in therapeutic schedule based on the level and difference of immune-related cells and pathways in different risk groups for breast cancer patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Mama/mortalidade , Ferroptose/genética , Antineoplásicos Imunológicos/farmacologia , Biomarcadores Tumorais/antagonistas & inibidores , Mama/imunologia , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/terapia , Conjuntos de Dados como Assunto , Feminino , Ferroptose/efeitos dos fármacos , Ferroptose/imunologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/genética , Curva ROC , Medição de Risco/métodos
5.
J Vasc Res ; 57(5): 276-290, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32610319

RESUMO

INTRODUCTION: CD4-positive T lymphocytes (CD4 cells) play a significant role in human abdominal aortic aneurysm (AAA). However, we know little about the role of the different CD4 subtypes. OBJECTIVE: We aimed to discover the circulatory CD4 phenotypic marker profile and the roles of the newly found T helper cell 9 (Th9) and follicular helper T cells (Tfh) and that of inflammasomes in CD4 cells from AAA patients. METHODS: We extracted CD4 cells from 30 AAA patients and 21 age-matched controls. Phenotype-specific transcription factors (TFs) and inflammasomes were analyzed with qRT-PCR. RESULTS: Th17-, Th1-, Th9-, and Tfh-specific TFs and inflammasome components NLRP1 (NLR family pyrin domain-containing 1), NLRP3, NLRC4, AIM2 (absent in melanoma 2), PYCARD (apoptosis speck-like protein containing a CARD), and CASP1 (caspase 1) were upregulated, and T regulatory cell- and Th2-specific TFs were downregulated in the patients' peripheral blood CD4 cells. Homocysteine was involved in Tfh and Th17 imbalance by AIM2 and NLRP1 inflammasome upregulation. Blood total cholesterol level correlated positively with NLRP1 expression, and blood low-density lipoprotein level correlated negatively with FOXP3 expression. CONCLUSIONS: Inflammasome-induced CD4 cell imbalance was involved in AAA. We thought that AAA might be a consequence of synergism between systemic immune imbalance and local autoimmunity.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Aneurisma da Aorta Abdominal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ligação a DNA/metabolismo , Homocisteína/farmacologia , Imunidade Humoral/efeitos dos fármacos , Inflamassomos/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Idoso , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/imunologia , Estudos de Casos e Controles , Colesterol/sangue , Feminino , Fatores de Transcrição Forkhead/metabolismo , Homocisteína/sangue , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Células Jurkat , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Proteínas NLR , Fenótipo , Transdução de Sinais , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Células THP-1 , Regulação para Cima
6.
J Cardiovasc Pharmacol ; 75(3): 229-239, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31821190

RESUMO

Abdominal aortic aneurysms (AAA) is a multifactorial vascular disease with a high rate of mortality and brings heavy burden to both human and society. The pathological process behind AAA is complex. Elastin degradation, chronic inflammation, and vascular smooth muscle cell phenotypic modulation are involved in AAA formation. Apigenin (API) has gained much attention due to its specific properties, such as anti-inflammation, antioxidant, and anti-cancer effects. Previous studies have demonstrated that API exert beneficial effects on prevention of cardiovascular diseases. However, the effects of API on AAA are still unknown. Here, we for the first time evaluated API-related effects on AAA formation using a Cacl2-induced AAA model. Compared with the AAA group, treatment with API reduced the incidence of AAA, attenuated pathological expansion of the aorta, and preserved elastic fiber in a dose-dependent manner. In addition, API attenuated vascular inflammation by inhibiting activation of matrix metalloproteinase and modulated vascular smooth muscle cell contractile phenotypic transition. The preventative effect of API on AAA might be associated with the downregulation of nuclear factor-kappa B (NF-κB) activity via the IKK-dependent signaling pathway. Our findings firstly revealed that API could suppress AAA formation in a dose-dependent manner by inhibiting the NF-κB signaling pathway, and API should be considered as a promising therapeutic drug in prevention of AAA.


Assuntos
Anti-Inflamatórios/farmacologia , Aorta Abdominal/efeitos dos fármacos , Aneurisma da Aorta Abdominal/prevenção & controle , Apigenina/farmacologia , NF-kappa B/metabolismo , Remodelação Vascular/efeitos dos fármacos , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/fisiopatologia , Dilatação Patológica , Modelos Animais de Doenças , Tecido Elástico/efeitos dos fármacos , Tecido Elástico/metabolismo , Tecido Elástico/patologia , Quinase I-kappa B/metabolismo , Proteínas I-kappa B/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Ratos Sprague-Dawley , Transdução de Sinais
7.
Sensors (Basel) ; 20(16)2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32824347

RESUMO

To explore the potential precursors of rock instability, it is necessary to clarify the mechanism of micro-crack from fracturing to failure, which involves the evolution of fracture size, orientation, source model, and their relationships to the loading. The waveforms of acoustic emission (AE) recorded by the sensor network attached rock sample during laboratory tests provide a data basis for solving these problems, since these observations are directly related to the characteristics of the fracturing sources. Firstly, we investigated the source mechanism, looking at the rise angle and the average frequency (RA-AF) trends during five loading stages in a uniaxial compression test. Results show that the proportion of shear events significantly increases when approaching instability. Secondly, we calculated the moment tensor for each event, considering the uncertainties of P-wave polarity, azimuth, and the takeoff angles of the rays. Moment tensor solutions suggest that there are obviously more crack events than shear events in all loading stages. Moment tensor evolutions confirmed that the decreasing of isotropic component and the increment of double-couple can be used as precursors of rock fracturing development. Considering the limitations of these two methods, it is suggested that we should be concerned more about the proportions of individual failure components and their evolutions over time, instead of absolutely classifying the events into a certain source type.

8.
J Am Chem Soc ; 141(38): 15423-15432, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31469556

RESUMO

The presence of labile bulky insulating hydrocarbon ligands in halide perovskite nanocrystals (NCs) passivates surface traps but concurrently makes charge transport difficult in optoelectronic devices. Early efforts routinely rely on the replacement of long-chain ligands with short-chain cousins, leading to notable changes in NC's sizes and photophysical properties and thus making it hard to obtain devices with nearly designed emissions. Here we report a general solution-phase ligand-exchange strategy to produce organic-ligand-lacking halide perovskite NCs with high photoluminescence (PL) quantum yields and good stability in ambient air. We demonstrate that the ligand exchange can be achieved by a well-controlled mild reaction of thionyl halide with the carboxylic and amine groups on the NC's surface, resulting in nearly dry NCs with well-passivated surfaces and almost unaltered emission characteristics. Consequently, we achieve exceptionally high-performance blue perovskite NC light-emitting diodes (LEDs) with an external quantum efficiency of up to 1.35% and an extremely narrow full width at half-maximum of 14.6 nm. Our work provides a systematic framework for preparing high-quality organic-ligand-lacking perovskite NC inks that can be directly cast as films featuring effective charge transport, thereby providing the foundation for further development of a wide range of efficient perovskite optoelectronic devices.

9.
Cancer Cell Int ; 19: 137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31139014

RESUMO

BACKGROUND: The aim of the present study was to clarify the correlations between SPARC expression in gastric cancer-associated fibroblasts (GCAFs) and the prognosis of patients with gastric cancer and to elucidate the role of GCAF-derived SPARC in stemness transformation and 5-fluorouracil resistance in gastric cancer. METHODS: One hundred ninety-two patients were enrolled in the present study. SPARC expression levels were evaluated by immunohistochemical staining. Primary GCAFs were obtained and cultured from cancer patients for in vitro study, and a lentivirus infection method was employed to knock down SPARC expression in GCAFs. The stemness phenotype and 5-fluorouracil (5-FU) response of gastric cancer cells were assessed via a 3D co-culture model. The apoptotic status and stemness alterations were monitored by flow cytometry and western blotting. Additionally, label-free quantification proteomics was used to identify the differentially expressed proteins and potential pathways in gastric cancer cells treated with GCAF-derived SPARC. RESULTS: Low expression of GCAF-derived SPARC was associated with decreased differentiation and reduced 5-year overall survival and was an independent predictive factor for prognosis in gastric cancer. The 3D tumour growth and 5-FU resistance abilities of gastric cancer cells were elevated after treatment with GCAFs with SPARC knockdown relative to these abilities in negative control cells. Additionally, suppressing SPARC expression in GCAFs facilitated the phenotypic alteration of gastric cancer cells towards CD44+/CD24- cancer stem cell (CSC)-like cells. Quantification proteomics analysis revealed that the differentially expressed proteins in gastric cancer cells were mainly involved in the AKT/mTOR and MEK/ERK signalling pathways. CONCLUSIONS: SPARC expression in GCAFs is a useful prognostic factor in patients with gastric cancer. Low expression of GCAF-derived SPARC can lead to CSC transformation and 5-FU resistance. Additionally, the AKT/mTOR and MEK/ERK signalling pathways may participate in the malignant process.

10.
Chemistry ; 25(55): 12842-12848, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31376189

RESUMO

Aurivillius phases have been routinely known as excellent ferroelectrics and have rarely been deemed as materials that luminesce in the near-infrared (NIR) region. Herein, it is shown that the Aurivillius phases can demonstrate broadband NIR luminescence that covers telecommunication and biological optical windows. Experimental characterization of the model system Bi2.14 Sr0.75 Ta2 O9-x , combined with theoretical calculations, help to establish that the NIR luminescence originates from defective [Bi2 O2 ]2+ layers. Importantly, the generality of this finding is validated based on observations of a rich bank of NIR luminescence characteristics in other Aurivillius phases. This work highlights that incorporating defects into infinitely repeating [Bi2 O2 ]2+ layers can be used as a powerful tool to space-selectively impart unusual luminescence emitters to Aurivillius-phase ferroelectrics, which not only offers an optical probe for the examination of defect states in ferroelectrics, but also provides possibilities for coupling of the ferroelectric property with NIR luminescence.

11.
Mediators Inflamm ; 2019: 5796491, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354386

RESUMO

Escherichia coli Nissle 1917 (EcN), a kind of probiotic, has been reported to have a protective effect on the intestinal barrier function and can ameliorate certain gastrointestinal disorders. In this study, the potential protective effect of EcN on the intestinal barrier function in a septic mouse model induced by cecal ligation and puncture (CLP) operation was investigated. FITC-Dextran 4,000 Da (FD-4) flux and the expression levels of tight junction (TJ) proteins were measured to evaluate the protective effect of EcN on the intestinal barrier function. Then, Caco-2 monolayers were utilized to further investigate the protective effect of the EcN supernatant (EcNsup) on the barrier dysfunction induced by TNF-α and IFN-γ in vitro; the plasma level of both the cytokines increased significantly during sepsis. Transepithelial electrical resistance (TEER) and FD-4 transmembrane flux were measured, and the localization of ZO-1 and Occludin was investigated by immunofluorescence. The expression of MLCK and the phosphorylation of MLC were detected by western blot. The activation of NF-κB was explored by immunofluorescence, and CHIP assays were performed to investigate the conjunction of NF-κB with the promoter of MLCK. The results indicated that EcN protected the intestinal barrier function in sepsis by ameliorating the altered expression and localization of TJ proteins and inhibiting the NF-κB-mediated activation of the MLCK-P-MLC signaling pathway which might be one of the mechanisms underlying the effect of EcN.


Assuntos
Escherichia coli/fisiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , NF-kappa B/metabolismo , Animais , Western Blotting , Células CACO-2 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/metabolismo , Fosforilação/fisiologia , Sepse/metabolismo , Transdução de Sinais , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo , Fator de Transcrição RelA/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(2): 194-202, 2019 Apr 28.
Artigo em Zh | MEDLINE | ID: mdl-31060674

RESUMO

Objective To determine the effect of denticleless E3 ubiquitin protein ligase(DTL)on the proliferation and clone formation of multiple myeloma(MM)cells and investigate the related mechanism. Methods Mononuclear cells were extracted from 34 MM patients.Mononuclear cells harvested from 14 healthy volunteers were used as controls.Quantitative polymerase chain reaction was used to detect the change of DTL at mRNA level.Furthermore,12 MM patients and 2 controls were selected,in whom the change of DTL at protein level was detected by Western blot.Human MM cell line RPMI8226 was divided into control(CON)group and DTL-short hairpin RNA(DTL-shRNA)group,which was infected with the CON and DTL-shRNA virus,respectively,for 48 hours.The infection efficiency was detected by using flow cytometry,the knock-down efficiencies at mRNA and protein levels were detected by quantitative polymerase chain reaction and Western blot,the change of cell counts in the next 0,24,48,72,96 hours were measured with CCK8 assay.The CON and DTL-shRNA cells were cultured in semisolid medium.Ten days later,inverted phase microscopy was used to measure the number of colones that contain more than 50 cells,annexin V/propidium iodide double staining to detect apoptosis,and propidium iodide staning to detect cell cycle.Finally,Western blot was empoyed to detect the phosphorylation of P65 and inhibitory subunit-κBα(IκBα)in nuclear factor-κB(NF-κB)pathway and electrophoretic mobility shift assay(EMSA)to detect the NF-κB transcriptional ability. Results The DTL expression was(1.00±0.12)and(9.36±3.71),respectively in the bone marrow mononuclear cells of healthy volunteers and in the CD138+cells of MM patients(t=3.65,P=0.0024).DTL was also highly expressed in MM CD138+positive cells at protein level.After RPMI8226 was infected by CON and DTL-shRNA virus for 48 hours,green fluorescent protein-positive cells accounted for more than 90%.The relative expression of DTL was(1.00±0.01)and(0.21±0.04)(t=33.19,P<0.0001)at mRNA level and(0.52±0.13)and(0.11±0.02)at protein level(t=5.399,P=0.0057).CCK8 revealed that CON and DTL-shRNA cells proliferated by(1.00±0.03)vs.(1.00±0.02),(2.19±0.28)vs.(1.47±0.13),(3.50±0.14)vs.(2.24±0.19),(5.43±0.41)vs.(3.08±0.14),(7.42±0.17)vs.(4.29±013)after 0,24,48,72,and 96 hours(F=24.58,P=0.001).The number of colone containing more than 50 cells was in 76±4 in CON group and 0 in DTL-shRNA group(P<0.01).The proportion of G1 stage cells was(28.61±8.64)% in CON group and(57.25±10.37)% in DTL-shRNA group(t=3.675,P=0.0213).The proportion of annexin V+in CON and DTL-shRNA groups was(3.21±0.89)% vs.(34.71±18.68)%(t=2.895,P=0.0443).After RPMI8226 was infected with CON or DTL-shRNA virus for 48 hours,the relative expression of phosphorylation P65 was(1.52±0.14)vs.(0.82±0.11)(t=6.81,P=0.0024),the P65 relative expression was(0.25±0.04)vs.(0.24±0.08)(t=0.19,P=0.85),the CON and DTL-shRNA phosphorylation-IκBα relative expression was(0.19±0.03)vs.(0.13±0.02)(t=2.882,P=0.0449),and the IκBα was(0.22±0.05)vs.(1.01±0.06)(t=17.52,P<0.0001).Detection of the transcriptional ability of DTL-shRNA NF-κB by EMSA further confirmed the down-regulation of DTL suppressed the NF-κB transcriptional ability. Conclusions DTL is highly expressed in MM cells,and down-regulation of DTL suppresses the cell proliferation,inhibit the colony formation,and induce cell apoptosis and cell cycle arrest.The effect of DTL on the biological functions of MM cells is related to the change of NF-κB pathway.


Assuntos
Proliferação de Células , Mieloma Múltiplo/patologia , Ubiquitina-Proteína Ligases/metabolismo , Apoptose , Estudos de Casos e Controles , Linhagem Celular Tumoral , Humanos , NF-kappa B/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas
13.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(2): 175-182, 2019 Apr 28.
Artigo em Zh | MEDLINE | ID: mdl-31060671

RESUMO

Objective To identify the expression of ribosomal protein S9(RPS9)in multiple myeloma(MM)and explore its effect on the biological characteristics of myeloma cells and the corresponding mechanisms. Methods Bone marrow mononuclear cells were harvested in 10 healthy volunteers(CON group)and bone marrow CD138 +cells from 30 MM patients(CD138+group).Quantitative polymerase chain reaction(qPCR)was performed to detect RPS9 expression at mRNA level.In three cases from CON group and 11 cases from CD138+group,Western blot was performed to detect RPS9 at protein level.GSE19784 dataset was employed to detect the relationships of RPS9 expression with the overall survival rate,nuclear factor-κB(NF-κB),small ubiquitin-like modifier(SUMO),and ubiquitin pathway.After the RPS9 knock-down vector was constructed,flow cytometry was performed to detect the infection efficiency and qPCR and Western blot to detect the knock-down efficiency.RPMI8226 was divided into CON group and RPS9-short hairpin RNA(shRNA)group,in which annexin V allophycocyanin/propidium iodide(PI)double staining was performed to detect the change of apoptosis,CCK8 to detect the proliferation change,and PI staining to detect cell cycle change.After sentrin-specific protease 1(SENP1)overexpression vector was constructed,Western blot was performed to detect the phosphorylation of P65 and inhibitory subunit-κBα(IκBα)from NF-κB pathway in CON,RPS9-shRNA,and RPS9-shRNA-SENP1 cells;in addition,annexin V/PI double staining was also performed to detect the apoptosis in these three cells. Results The relative expression of RPS9 in CON group and CD138+group was(1.00±0.12)and(5.45±0.71),respectively(t=4.291,P=0.0036).Western blot showed RPS9 expression was high in most myeloma CD138+cells.The high expression of RPS9 was associated with both extramedullary invasion and overall survival in GSE19784 dataset.After RPMI8226 was infected with CON or RPS9-shRNA lentivirus for 48 hours,flow cytometry confirmed that the infection efficiencies were above 90% in both groups.qPCR and Western blot confirmed that RPS9 expression was inhibited at both mRNA and protein levels.After RPMI8226 CON and RPS9-shRNA infected with virus for 48 hours,the proportion of annexin V-positive cells in CON and RPS9-shRNA cells was(3.47±0.37)% and(18.60±64.00)%(t=9.015,P=0.0008).The proliferation index significantly differed between CON group and RPS9-shRNA group at 72 hours(t=6.846,P=0.0024).When CON and RPS9-shRNA were infected with virus for 48 hours,the proportion of G2 phase cells was(29.28±3.42)% and(10.43±1.43)%,respectively(t=9.329,P=0.0007).The RPS9 expression was positively correlated with SENP1 in GSE19784 dataset and negatively correlated with IκBα coding gene NFKBIA.Western blot further confirmed that RPS9 knockdown inhibited the expression of SENP1,inhibited the phosphorylation of NF-κB subunit P65 and inhibitor IκBα,and promoted the expression of IκBα.Overexpression of SENP1 not only impeded this effect but also reduced RPS9-induced apoptosis. Conclusions RPS9 is highly expressed in MM CD138+cells and is associated with overall survival and extramedullary infiltration.Inhibition of RPS9 can promote apoptosis,cell cycle arrest,and proliferation of myeloma cells.RPS9 can affect the activation of NF-κB pathway and cell apoptosis through SENP1,suggesting that SENP1 may be a key factor in the biological effect of RPS9.


Assuntos
Cisteína Endopeptidases/metabolismo , Mieloma Múltiplo/metabolismo , Proteínas Ribossômicas/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Proteína S9 Ribossômica , Transdução de Sinais
14.
J Am Chem Soc ; 140(31): 9942-9951, 2018 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-30008218

RESUMO

All-inorganic perovskite nanocrystals (NCs) have emerged as a new generation of low-cost semiconducting luminescent system for optoelectronic applications. The room-temperature photoluminescence quantum yields (PLQYs) of these NCs in the green and red spectral range approach unity. However, their PLQYs in the violet are much lower, and an insightful understanding of such poor performance remains missing. We report a general strategy for the synthesis of all-inorganic violet-emitting perovskite NCs with near-unity PLQYs through engineering local order of the lattice by nickel ion doping. A broad range of experimental characterizations, including steady-state and time-resolved luminescence spectroscopy, X-ray absorption spectra, and magic angle spinning nuclear magnetic resonance spectra, reveal that the low PLQY in undoped NCs is associated with short-range disorder of the lattice induced by intrinsic defects such as halide vacancies and that Ni doping can substantially eliminate these defects and result in increased short-range order of the lattice. Density functional theory calculations reveal that Ni doping of perovskites causes an increase of defect formation energy and does not introduce deep trap states in the band gap, which is suggested to be the main reason for the improved local structural order and near-unity PLQY. Our ability to obtain violet-emitting perovskite NCs with near-perfect properties opens the door for a range of applications in violet-emitting perovskite-based devices such as light-emitting diodes, single-photon sources, lasers, and beyond.

15.
Cancer Cell Int ; 18: 104, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30038550

RESUMO

BACKGROUND: Cancer-associated fibroblasts (CAFs) play important roles in tumor progression. However, the behaviors of activated CAFs in gastric cancer remain to be determined. The aim of the present study was to investigate the correlations between activated gastric CAFs and the prognosis of patients with gastric cancer, and to determine the effects of activated CAFs on the malignant phenotype and 5-fluorouracil resistance in this cancer. METHODS: Ninety-five patients with primary gastric cancer were enrolled in this study. Activation states of gastric CAFs were evaluated by immunohistochemistry. A modified method for the primary culture of gastric CAFs was employed. Types of CAFs and activation states were identified by immunocytochemical and immunofluorescent staining. Cell co-culture and gastric CAF conditioned medium transfer models were established to investigate the paracrine effects of activated CAFs on the migration and invasion of gastric cell lines. The half maximal inhibitory concentration of 5-fluorouracil and levels of cell apoptosis were examined using cell viability assay and flow cytometry, respectively. Protein expression levels of associated molecules were measured by Western blotting. RESULTS: Kaplan-Meier survival curves showed that activated gastric CAFs identified via fibroblast activation protein were significantly related to poorer cumulative survival in gastric cancer patients. Five strains of CAFs were successfully cultured via the modified culture method, and three gastric CAFs strains were identified as activated gastric CAFs. The migration and invasion abilities of gastric cells were significantly enhanced in both the co-culture group and the conditioned medium group. The half maximal inhibitory concentration for 5-fluorouracil in BGC-823 cells was elevated after treatment with conditioned medium, and early apoptosis was inhibited. Additionally, an obvious elevation of epithelial-mesenchymal transition level was observed in the conditioned medium group. CONCLUSIONS: Activated gastric CAFs correlate with a poor prognosis of cancer patients and may contribute to the malignant phenotype and the development of resistance to 5-fluorouracil via paracrine action in gastric cancer. Gastric CAFs with a specific activation state might be used as a tumor biomarker within the microenvironment for prognosis and as a new therapeutic target for chemoresistant gastric cancer.

16.
Chemistry ; 24(35): 8875-8882, 2018 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-29655241

RESUMO

Engineering oxygen coordination environments of cations in oxides has received intense interest thanks to the opportunities for the discovery of novel oxides with unusual properties. Herein, the synthesis of stoichiometric layered BaBiO2.5 by a nontopotactic phase transformation of perovskite BaBiO3 is presented. By analyzing the synchrotron X-ray diffraction data by the maximum-entropy method/Rietveld technique, it was found that Bi is involved in an unusual chemical bonding situation with four oxygen atoms featuring one ionic bond and three covalent bonds, which results in an asymmetric coordination geometry. Photophysical characterization revealed that this peculiar structure shows near-infrared luminescence differing from that of conventional Bi-containing compounds. Experimental and theoretical results led to the proposal of an excitonic nature of the luminescence. This work highlights that synthesizing materials with uncommon Bi-O bonding and Bi coordination geometry provides a pathway to the discovery of systems with new functionalities. This could inspire interest in the exploration of a range of materials containing heavier p-block elements with prospects for finding systems with unusual properties.

17.
Chemistry ; 24(39): 9976-9982, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29683534

RESUMO

The synthesis of luminescent polyoxometalates (POMs) typically relies on the assembly of POM ligands with rare earth or transition metals, placing significant constraints on the composition, structure, and hence the luminescence properties of the resultant systems. Herein, we show that the ion-exchange strategy can be used for the synthesis of novel POM-based luminescent materials. We demonstrate that introducing bismuth ions into an ion-exchangeable, microporous POM compound yields an unconventional system luminescing in the near-infrared region. Experimental characterization, coupled with quantum chemical calculations, confirms that bismuth ions site-specifically occupy an off-center site in the lattice, and have an asymmetric coordination geometry unattainable by other means, thus giving rise to peculiar emission. Our findings offer an effective strategy for the synthesis of POM-based luminescent materials, and the design concept may potentially be adapted to the creation of POM-based systems with other functionalities.

18.
Chin J Traumatol ; 19(6): 371-372, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28088945

RESUMO

From January 2013 to January 2015, 19 patients of traumatic hemothorax with hemorrhagic shock were treated in our department by thoracoscopic surgery combined with autologous blood transfusion. This study retrospectively analyzed the therapeutic effect and shared our experience. The average amount of blood transfused back was 662.41 ml ± 269.15 ml. None of the patients developed transfusion reaction and were all discharged uneventfully. Thoracoscopic surgery combined with autologous blood trans- fusion is effective in the rescue of patients with progressive hemothorax and hemorrhagic shock. When corresponding indications are well managed, treatment for these patients is quicker, safer, and more effective.


Assuntos
Transfusão de Sangue Autóloga , Hemotórax/cirurgia , Traumatismos Torácicos/cirurgia , Toracoscopia/métodos , Feminino , Humanos , Masculino , Estudos Retrospectivos
19.
Biochem Biophys Res Commun ; 468(1-2): 130-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26523511

RESUMO

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been reported to inhibit proliferation and migration of multiple types of cancer cells. However, the mechanism underlying its anti-metastasis effect is not fully illustrated. In this study, the effect of 1,25(OH)2D3 on TGF-ß1/ß2-induced epithelial-mesenchymal transition (EMT) is tested in colon cancer cells. The results suggest that 1,25(OH)2D3 inhibited TGF-ß1/ß2-induced increased invasion and migration of in SW-480 and HT-29 cells. 1,25(OH)2D3 also inhibited the cadherin switch in SW-480 and HT-29 cells. TGF-ß1/ß2-induced increased expression of EMT-related transcription factors was also inhibited by 1,25(OH)2D3. 1,25(OH)2D3 also inhibited the secretion of MMP-2 and MMP-9 and increased expression of F-actin induced by TGF-ß1/ß2 in SW-480 cells. Taken together, this study suggests that the suppression of EMT might be one of the mechanisms underlying the anti-metastasis effect of 1,25(OH)2D3 in colon cancer cells.


Assuntos
Calcitriol/farmacologia , Colo/patologia , Neoplasias do Colo/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Invasividade Neoplásica/prevenção & controle , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Vitaminas/farmacologia , Actinas/metabolismo , Caderinas/metabolismo , Movimento Celular/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Células HT29 , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica/patologia
20.
J Neurosci Res ; 93(2): 253-67, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25250856

RESUMO

The superfamily of importin-ß-related proteins is the largest class of nuclear transport receptors and can be generally divided into importins and exportins according to their transport directions. Eleven importins and seven exportins have been identified, and the expression patterns of both classes are important for their functions in nucleocytoplasmic transport activities. This study demonstrates that all of the importins (importin-ß; transportin-1, -2, and -3; and importin-4, -5, -7, -8, -9, -11, and -13) and all the exportins (exportin-1, -2, -4, -5, -6, -7, and -t) are differentially expressed in the cerebral cortex, cerebellum, hippocampus, and brainstem and in primary cultures of cerebral cortical astrocytes and neurons. For astrocytes, we observed that different importins and exportins displayed different expression changes during 0-6 hr of ischemia treatment, especially an increase of both the mRNA and the protein of exportin-7. Immunostaining showed that exportin-7 accumulated inside the nucleus and around the nuclear envelope. In addition, we noticed an increased cytoplasmic distribution of one of the cargo proteins of exportin-7, LKB1, an important element in maintaining energy homeostasis. This increased cytoplasmic distribution was accompanied by an increased expression of exportin-7 under ischemia in astrocytes. We demonstrate that exportin-7 responds to ischemia in astrocytes and that this response involves translocation of LKB1, a protein that plays important roles during metabolic stress, from the nucleus to the cytoplasm.


Assuntos
Astrócitos/metabolismo , Astrócitos/ultraestrutura , Isquemia Encefálica/patologia , Regulação da Expressão Gênica/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteína ran de Ligação ao GTP/metabolismo , Proteínas Quinases Ativadas por AMP , Animais , Hipóxia Celular/fisiologia , Núcleo Celular/metabolismo , Células Cultivadas , Embrião de Mamíferos , Regulação da Expressão Gênica/genética , Carioferinas/genética , Carioferinas/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neurônios/citologia , Neurônios/metabolismo , Fotodegradação , Proteínas Serina-Treonina Quinases/genética , Transporte Proteico/genética , Transporte Proteico/fisiologia , RNA Mensageiro/metabolismo , beta Carioferinas/genética , beta Carioferinas/metabolismo , Proteína ran de Ligação ao GTP/genética
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