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1.
Front Oncol ; 9: 1187, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31799179

RESUMO

Hepatocellular carcinoma (HCC) is a typical hypervascular solid tumor that requires neoangiogenesis for growth. The vascular endothelial growth factor (VEGF) is the most potent proangiogenic factor in neovascularization. The multifunctional Yin-Yang 1 (YY1) is involved in the regulation of tumor malignancy of HCC. However, the relationship between YY1 and endothelial cell-dependent tumor angiogenesis in HCC remains unclear. In this study, we observed that YY1 is positively correlated with microvessel density (MVD) and poor prognosis in HCC tissues. We further found that YY1 promotes the transcriptional activity of VEGFA by binding its promoter in HCC. The secreted VEGFA from HCC cells activates phosphorylation of VEGFR2 to promotes tube formation, cell migration, and invasion of vascular endothelial cells in vitro, and promotes tumor growth and angiogenesis in vivo. In addition, upregulation of YY1 enhanced resistance of bevacizumab in HCC cells. These results indicate that YY1 plays essential roles in HCC angiogenesis and resistance of bevacizumab by inducing VEGFA transcription and that YY1 may represent a potential molecular target for antiangiogenic therapy during HCC progression.

2.
J Environ Manage ; 255: 109855, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31760301

RESUMO

Air pollution forecasting plays an important role in helping reduce air pollutant emission and guiding people's daily activities and warning the public in advance. Nevertheless, previous articles still have many shortcomings, such as ignoring the importance of outlier point detection and correction of original time series, and random initial parameters of models, and so on. A new hybrid model using outlier detection and correction algorithm and heuristic intelligent optimization algorithm is proposed in this study to address the above mentioned problems. First, data preprocessing algorithms are conducted to detect and correct outliers, excavate the main characteristics of the original time series; second, a widely used heuristic intelligent optimization algorithm is adopted to optimize the parameters of extreme learning machine to obtain the forecasting results of each subseries with improvement in accuracy; finally, experimental results and analysis show that the presented hybrid model provides accurate prediction, outperforming other comparison models, which emphasize the importance of outlier point detection and correction and optimization parameters of models, it also give a new feasible method for air pollution prediction, and contribute to make effective plans for air pollutant emissions.

3.
Cell Death Dis ; 10(9): 630, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431619

RESUMO

Diol-type ginsenosides, such as protopanaxadiol (PPD), exhibit antioxidation, anti-inflammation, and antitumor effects. However, the antitumor effect of these ginsenosides and the mechanism of PPD remain unclear. In this work, the antitumor effects of several derivatives, including PPD, Rg5, Rg3, Rh2, and Rh3, were evaluated in five different cancer cell lines. PPD demonstrated the best inhibitory effects on the proliferation and migration of the five cancer cell lines, especially the hepatocellular carcinoma (HCC) cell lines. Therefore, the mechanism of action of PPD in HCC cells was elucidated. PPD inhibited the proliferation, migration, and invasion ability of HepG2 and PLC/PRF/5 cells in a dose-dependent manner. Western blot and immunofluorescence assay showed that PPD can alter the expression of epithelial-mesenchymal transition markers, increase E-cadherin expression, and decrease vimentin expression. Docking and biacore experiments revealed that STAT3 is the target protein of PPD, which formed hydrogen bonds with Gly583/Leu608/Tyr674 at the SH2 domain of STAT3. PPD inhibited the phosphorylation of STAT3 and its translocation from the cytosol to the nucleus, thereby inhibiting the expression of Twist1. PPD also inhibited tumor volume and tumor lung metastasis in PLC/PRF/5 xenograft model. In conclusion, PPD can inhibit the proliferation and metastasis of HCC cells through the STAT3/Twist1 pathway.

4.
J Immunother Cancer ; 7(1): 231, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462297

RESUMO

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that play an important role in immune evasion, PD-1/PD-L1 inhibitor tolerance and tumour progression. Therefore, MDSCs are potential targets for cancer immunotherapy. In this study, we screened an effective polymorphonuclear MDSC (PMN-MDSC) inhibitor from the Traditional Chinese Medicine Library and evaluated its synergistic antitumour effects with PD-1 inhibitor. METHODS: In the present study, we found that PMN-MDSCs accumulate heavily in the spleen and bone marrow of melanoma (B16-F10) tumour-bearing mice. Then, we determined the top 10 key proteins in the upregulated KEGG pathways of PMN-MDSCs in tumour-bearing mice through proteomics and Cytoscape analysis. The key proteins were then used as targets for the screening of PMN-MDSC inhibitors from the traditional Chinese Medicine Library (20000 compounds) through molecular docking and weight calculation of the docking score. Finally, the inhibitory effect of the inhibitor was verified through proteomics and metabolomics analysis in vitro and melanoma (B16-F10) and triple-negative breast cancer (4 T1) mouse tumour models in vivo. RESULTS: Traditional Chinese medicine saposhnikovia root extract Prim-O-glucosylcimifugin (POG) could bind well to the target proteins and inhibit the proliferation, metabolism and immunosuppressive ability of PMN-MDSCs by inhibiting arginine metabolism and the tricarboxylic acid cycle (TCA cycle). POG could also increase CD8 T-lymphocyte infiltration in the tumours and enhance the antitumour effect of PD-1 inhibitor in B16-F10 and 4 T1 mouse tumour models. CONCLUSIONS: POG was successfully screened from the traditional Chinese Medicine library as a PMN-MDSC inhibitor. POG exhibited a good synergistic antitumour effect with PD-1 inhibitor. This study provided a potential option for enhancing the efficacy of PD-1 inhibitors in clinical applications.

5.
J Exp Clin Cancer Res ; 38(1): 285, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266540

RESUMO

BACKGROUND: Anti-angiogenic therapies demonstrate anti-tumor effects by decreasing blood supply to tumors and inhibiting tumor growth. However, anti-angiogenic therapy may leads to changes in tumor microenvironment and increased invasiveness of tumor cells, which in turn promotes distant metastasis and increased drug resistance. METHODS: The CO-IP assays, N-STORM and cytoskeleton analysis were used to confirm the mechanism that p-VEGFR2/VE-cadherin/ß-catenin/actin complex regulates vascular remodeling and improves the tumor microenvironment. 6-gingerol (6G), the major bioactive component in ginger, stabilized this complex by enhancing the binding of VEGFa to VEGFR2 with non-pathway dependent. Biacore, pull down and molecular docking were employed to confirm the interaction between 6G and VEGFR2 and enhancement of VEGFa binding to VEGFR2. RESULTS: Here, we report that microvascular structural entropy (MSE) may be a prognostic factor in several tumor types and have potential as a biomarker in the clinic. 6G regulates the structural organization of the microvascular bed to decrease MSE via the p-VEGFR2/VE-cadherin/ß-catenin/actin complex and inhibit tumor progression. 6G promotes the normalization of tumor vessels, improves the tumor microenvironment and decreases MSE, facilitating the delivery of chemotherapeutic agents into the tumor core and thereby reducing tumor growth and metastasis. CONCLUSIONS: This study demonstrated the importance of vascular normalization in tumor therapy and elucidated the mechanism of action of ginger, a medicinal compound that has been used in China since ancient times.


Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Catecóis/uso terapêutico , Álcoois Graxos/uso terapêutico , Genes Supressores de Tumor/efeitos dos fármacos , Gengibre/química , Microvasos/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Catecóis/farmacologia , Álcoois Graxos/farmacologia , Feminino , Humanos , Camundongos , Camundongos Nus , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Sensors (Basel) ; 19(4)2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30791597

RESUMO

This paper proposes the maximal ratio transmission (MRT) and maximal ratio combining (MRC) protocols for the power beacon (PB) assisted wireless powered sensor networks and analyzes the impact of the imperfect channel state information (CSI) on the performance using the Markov chain theory. The wireless powered sensor chooses to transmit information to the destination or harvest energy from the PB when its energy can or cannot supply a transmission, respectively. The energy arrival and departure of the sensor is characterized, and the analytical expressions of the network transmit probability, and effective and overall ergodic capacities are formulated and derived. We also optimize the sensor transmit power to maximize the overall ergodic capacity. Our results reveal that the transmit probability and the effective ergodic capacity can be greatly improved with increasing the number of antennas at the PB and the destination, and can also be significantly degraded by decreasing the channel correlation factors. We also demonstrate the effectiveness of the sensor transmit power optimization in improving the overall ergodic capacity.

7.
Sensors (Basel) ; 18(2)2018 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-29364185

RESUMO

In this paper, the secrecy performance of the two-user simultaneous wireless information and power transfer (SWIPT) sensor networks is studied and a novel secure transmission scheme of cooperative zero-forcing (ZF) jamming is proposed. The two sensors opportunistically conduct the SWIPT and cooperative ZF jamming, respectively, where the energy required for jamming the eavesdropper is provided by the SWIPT operation so as to keep the energy balance at the sensors in the long run. By deriving the exact closed-form expressions of the secrecy outage probability and the secrecy throughout, we provide an effective approach to precisely assess the impacts of key parameters on the secrecy performance of the system. It has been shown that the secrecy outage probability is a monotonically increasing function of the growth of secrecy rate ( R s ), and a monotonically decreasing function of the increase of the transmit signal-to-noise ratio ( γ S ), and energy conversion efficiency ( η ). Furthermore, the secrecy throughput could be enhanced when η increases, which becomes especially obvious when a large γ S is provided. Moreover, the existence of an optimum R s maximizing the secrecy throughput is depicted, which also grows with the increase of γ S . Simulations are provided for the validation of the analysis.

8.
Biochim Biophys Acta Mol Cell Res ; 1864(3): 562-571, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28011284

RESUMO

Posttranslational modifications of certain stress granule (SG) proteins are closely related to the assembly of SGs, a type of cytoplasmic foci structure. Our previous studies revealed that the Tudor staphylococcal nuclease (Tudor-SN) protein participates in the formation of SGs. However, the functional significance of potential Tudor-SN modifications during stress has not been reported. In this study, we demonstrated that the Tudor-SN protein was phosphorylated at threonine 103 (T103) upon stimulation with arsenite. In addition, c-Jun N-terminal kinase (JNK) was found to be responsible for Tudor-SN phosphorylation at the T103 site. We further illustrated that either a T103A mutation or the suppression of phosphorylation of T103 by the JNK inhibitor SP600125 inhibited the efficient recruitment of Tudor-SN into SGs. In addition, the T103A mutation could affect the physical binding of Tudor-SN with the G3BP (Ras-GAP SH3 domain-binding protein) protein but not with the HuR (Hu antigen R) protein and AGTR1-3'UTR (3'-untranslated region of angiotensin II receptor, type 1) mRNA cargo. These data suggested that JNK-enhanced Tudor-SN phosphorylation promotes the interaction between Tudor-SN and G3BP and facilitates the efficient recruitment of Tudor-SN into SGs under conditions of sodium arsenite-induced oxidative stress. This finding provides novel insights into the physiological function of Tudor-SN modification.


Assuntos
Proteínas de Transporte/genética , Grânulos Citoplasmáticos/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Nucleares/genética , Processamento de Proteína Pós-Traducional , Antracenos/farmacologia , Arsenitos/farmacologia , Proteínas de Transporte/metabolismo , Grânulos Citoplasmáticos/efeitos dos fármacos , Grânulos Citoplasmáticos/ultraestrutura , DNA Helicases , Proteína Semelhante a ELAV 1/genética , Proteína Semelhante a ELAV 1/metabolismo , Endonucleases , Células HeLa , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Mutação , Proteínas Nucleares/metabolismo , Estresse Oxidativo , Fosforilação/efeitos dos fármacos , Proteínas de Ligação a Poli-ADP-Ribose , Ligação Proteica , Inibidores de Proteínas Quinases/farmacologia , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Compostos de Sódio/farmacologia , Treonina/metabolismo
9.
FEBS Lett ; 590(1): 22-33, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26787461

RESUMO

Malonate, a classic inhibitor of respiratory electron transport chain, induces mitochondrial stress. Stress granules (SGs) are a kind of dynamic foci structure during stress. The study on the connection of mitochondrial stress and SG assembly is still limited. Here, we demonstrated that malonate treatment leads to SG formation and translation inhibition, apart from mitochondrial stress, including enhanced ROS formation, reduced mitochondrial Δψm and ATP level. The phosphorylation levels of eIF2α and 4EBP1 protein were affected upon mitochondrial dysfunction. However, knockdown of 4EBP1 affected SG formation, rather than eIF2α. In addition, an increase of ATP level under mitochondrial stress enhanced malonate-induced SG aggregation. Overall, malonate stimulation triggers mitochondrial stress and induces the assembly of non-canonical cellular SGs via 4EBP1 pathway.


Assuntos
Grânulos Citoplasmáticos/efeitos dos fármacos , Complexo II de Transporte de Elétrons/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Malonatos/farmacologia , Mitocôndrias/efeitos dos fármacos , Biogênese de Organelas , Estresse Oxidativo/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Trifosfato de Adenosina/agonistas , Trifosfato de Adenosina/metabolismo , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Complexo II de Transporte de Elétrons/metabolismo , Fator de Iniciação 2 em Eucariotos/metabolismo , Células HeLa , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , Fosfoproteínas/antagonistas & inibidores , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , Interferência de RNA , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo
10.
Zhongguo Gu Shang ; 29(10): 892-897, 2016 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-29285906

RESUMO

OBJECTIVE: To explore the clinical effects of surgical treatment with cable dragged reduction and cantilever beam internal fixation by posterior approach for odontoid fracture associated with atlantoaxial dislocation. METHODS: The clinical data of 12 patients with odontoid fracture associated with atlantoaxial dislocation from January 2008 to December 2013 were retrospectively analyzed. There were 8 males and 4 females, ranging in age from 21 to 53 years with an average of 37.2 years. Eleven cases were fresh fracture and 1 case was old fracture, all patients complicated with atlantoaxial anterior dislocation. According to Anderson-D' Alonzo typing method modified by Grauer, 3 cases were type IIA, 5 cases were type IIB, 3 cases were type IIC, and 1 case was type IIIA. All patients underwent surgical treatment with cable dragged reduction and cantilever beam internal fixation by posterior approach. JOA score and ADI method were respectively used to evaluate the nerve function and reductive condition of atlantoaxial dislocation. RESULTS: All patients were followed up from 6 months to 2 years with an average of 1 year and 3 months. At 1 week, 6 months after operation, and final follow up, JOA scores were 13.2±1.3, 13.5±1.4, 14.3±1.5, respectively, and these data were obviously better than that of preoperative 8.3±1.4(P<0.05). Postoperative X rays and CT showed satisfactory reduction of atlantoaxial dislocation. At 1 week, 6 months after operation, and final follow up, ADI were (2.2±0.4), (2.4±0.6), (2.3±0.5) mm, respectively, and these data were obviously better than that of preoperative.(5.8±1.2) mm(P<0.05). All screws and cables had good location without looseness and breakage, and bone graft got fusion. CONCLUSIONS: Surgical treatment with cable dragged reduction and cantilever beam internal fixation by posterior approach for odontoid fracture associated with atlantoaxial dislocation is a good method, with advantage of firm fixation and high safety. It could obtain good clinical effects.


Assuntos
Articulação Atlantoaxial/lesões , Fixação Interna de Fraturas/métodos , Luxações Articulares/complicações , Processo Odontoide/lesões , Traumatismos da Coluna Vertebral/cirurgia , Feminino , Humanos , Masculino , Traumatismos da Coluna Vertebral/complicações , Resultado do Tratamento
11.
Nanoscale ; 6(7): 3818-23, 2014 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-24577562

RESUMO

Room temperature liquid-like nanoparticles have emerged as an exciting new research and development area, because their properties could be tailored over a broad range by manipulating geometric and chemical characteristics of the inorganic core and organic canopy. However, related applications are rarely reported due to the multi-step synthesis process and potential toxicity of cadmium based nanomaterials. In this study, we prepared inexpensive and eco-friendly carbon dot fluid by the direct thermal decomposition method. The carbon dot fluid can be excited from UV to near infrared light, and can be prepared as highly concentrated luminescent ink or incorporated into sol-gel derived organically modified silicate glass, suggesting that it has great application potential in the field of printable electronics, solid state lighting and so on.

12.
Neural Regen Res ; 8(12): 1139-45, 2013 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-25206408

RESUMO

Ninety-four patients with lumbar intervertebral disc herniation were enrolled in this study. Of these, 48 were treated with Feng's Spinal Manipulation, hot fomentation, and bed rest (treatment group). The remaining 46 patients were treated with hot fomentation and bed rest only (control group). After 3 weeks of treatment, clinical parameters including the angle of straight-leg raising, visual analogue scale pain score, and Japanese Orthopaedic Association score for low back pain were improved. The treatment group had significantly better improvement in scores than the control group. Magnetic resonance myelography three-dimensional reconstruction imaging of the vertebral canal demonstrated that filling of the compressed nerve root sleeve with cerebrospinal fluid increased significantly in the treatment group. The diameter of the nerve root sleeve was significantly larger in the treatment group than in the control group. However, the sagittal diameter index of the herniated nucleus pulposus and the angle between the nerve root sleeve and the thecal sac did not change significantly in either the treatment or control groups. The effectiveness of Feng's Spinal Manipulation for the treatment of symptoms associated with lumbar intervertebral disc herniation may be attributable to the relief of nerve root compression, without affecting the herniated nucleus pulposus or changing the morphology or position of the nerve root.

14.
Beijing Da Xue Xue Bao Yi Xue Ban ; 39(5): 515-9, 2007 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-17940572

RESUMO

OBJECTIVE: To quantify COX-2 mRNA in lesions of chronic apical periodontitis and relate the findings to the histological findings. METHODS: A total of 13 periapical lesions including 10 periapical granulomas and 3 periapical cysts were obtained. Normal periodontal ligament tissues from extracted third molars were used as control tissues. The expression of COX-2 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR) technique. The relationships between the expression of COX-2 mRNA and histological findings (including the type of histology, the degree of inflammatory infiltrates), the size of radiolucent of the lesions and the clinical findings of the involved tissues were analyzed. The expression of COX-2 at cell level was detected by immunohistochemistry. RESULTS: A significant higher level of COX-2 mRNA was found in periapical granulomas and in periapical cysts , but no significant difference was detected between those two groups. COX-2 mRNA in the group with moderate inflammation cell infiltration was higher than that of light and heavy inflammation cell infiltration (0.76+/-0.11 vs 0.11+/-0.01, 0.76+/-0.11 vs 0.23+/-0.06, P<0.05). The elevated COX-2 mRNA levels were detected in lesions with clinical symptoms. COX-2 -positive cells were detected in the epithelial cells and inflammatory cells. CONCLUSION: COX-2 might play more important roles in the pathogenesis and development of periapical lesions.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Periodontite Periapical/metabolismo , Periodontite Periapical/patologia , Doença Crônica , Ciclo-Oxigenase 2/genética , Células Epiteliais/metabolismo , Humanos , Inflamação , RNA Mensageiro/genética
15.
Lin Chuang Er Bi Yan Hou Ke Za Zhi ; 17(10): 602-3, 2003 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-14727431

RESUMO

OBJECTIVE: Bilateral deafness due to mumps is rare. Here report three cases of bilateral total deafness due to mumps and their outcome of cochlear implantation. METHOD: Three cases of bilateral total deafness due to mumps were reviewed. RESULT: All patients had sudden bilateral total deafness in 3 to 7 days after mumps. 2 had vestibular symptoms. Cochlear implantation has been successful in all 3 patients. Three month after the initial mapping, Case 2 who has been wearing bilateral hearing aids and received one-year language training has the best outcome of hearing and speech than the other two. Case 1 who has been wearing one-side hearing aid and received language training of 6 months has the better outcome than case 3 who has never worn hearing aid and never received language training. CONCLUSION: Hearing loss caused by Mumps is often sudden in onset, conservative therapy have no help. Hearing aid and language training are very important to the outcome of speech perception and speech production after cochlear implantation.


Assuntos
Implante Coclear , Surdez/cirurgia , Caxumba/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Surdez/virologia , Feminino , Auxiliares de Audição , Perda Auditiva Súbita/cirurgia , Perda Auditiva Súbita/virologia , Humanos , Masculino , Resultado do Tratamento
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