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1.
Cancer Lett ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32201203

RESUMO

The prevalence of early-stage lung adenocarcinoma (LUAD) has increased alongside increased implementation of lung cancer screenings. Robust discrimination criteria are urgently needed to identify those patients who might benefit from additional systemic therapy. Here, to develop a reliable, individualized immune gene-set-based signature to predict recurrence in early-stage LUAD, a novel recurrence-associated immune signature was identified using a least absolute shrinkage and selection operator model, and a stepwise Cox proportional hazards regression model with a training set comprised of 338 early-stage LUAD samples form TCGA, which was subsequently validated in 226 cases from GSE31210 and an independent set of 68 frozen tumor samples with qRT-PCR data. This new classification system remained strongly predictive of prognoses across clinical subgroups and mutation status. Further analysis revealed that samples from high-risk cases were characterized by active interferon signal transduction, distinctive immune cell proportions and immune checkpoint profiles. Moreover, the signature was identified as an independent prognostic factor. In conclusion, the signature is highly predictive of recurrence in patients with early-stage LUAD, which may serve as a powerful prognostic tool to further optimize immunotherapies for cancer.

2.
ACS Appl Mater Interfaces ; 12(4): 4414-4422, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31909589

RESUMO

Monodisperse CoSn and NiSn nanoparticles were prepared in solution and supported on commercial carbon black. The obtained nanocomposites were applied as anodes for Li- and K-ion batteries. CoSn@C delivered stable average capacities of 850, 650, and 500 mAh g-1 at 0.2, 1.0, and 2.0 A g-1, respectively, well above those of commercial graphite anodes. The capacity of NiSn@C retained up to 575 mAh g-1 at a current of 1.0 A g-1 over 200 continuous cycles. Up to 74.5 and 69.7% pseudocapacitance contributions for Li-ion batteries were measured for CoSn@C and NiSn@C, respectively, at 1.0 mV s-1. CoSn@C was further tested in full-cell lithium-ion batteries with a LiFePO4 cathode to yield a stable capacity of 350 mAh g-1 at a rate of 0.2 A g-1. As electrode in K-ion batteries, CoSn@C composites presented a stable capacity of around 200 mAh g-1 at 0.2 A g-1 over 400 continuous cycles, and NiSn@C delivered a lower capacity of around 100 mAh g-1 over 300 cycles.

3.
Angew Chem Int Ed Engl ; 59(9): 3630-3637, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-31788950

RESUMO

Amorphous metal-organic frameworks (aMOFs) are an emerging family of attractive materials with great application potential, however aMOFs are usually prepared under harsh conditions and aMOFs with complex compositions and structures are rarely reported. In this work, an aMOF-dominated nanocomposite (aMOF-NC) with both structural and compositional complexity has been synthesized using a facile approach. A ligand-competition amorphization mechanism is proposed based on experimental and density functional theory calculation results. The aMOF-NC possesses a core-shell nanorod@nanosheet architecture, including a Fe-rich Fe-Co-aMOF core and a Co-rich Fe-Co-aMOF shell in the core-shell structured nanorod, and amorphous Co(OH)2 nanosheets as the outer layer. Benefiting from the structural and compositional heterogeneity, the aMOF-NC demonstrates an excellent oxygen evolution reaction activity with a low overpotential of 249 mV at 10.0 mA cm-2 and Tafel slope of 39.5 mV dec-1 .

4.
Cancer Manag Res ; 11: 7813-7824, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695486

RESUMO

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors worldwide and the 5-year overall survival rate remains poor. Protein kinase, membrane associated tyrosine/threonine (PKMYT1) is overexpressed in several cancers and participate in tumor progression. However, the mechanism of PKMYT1 in ESCC is unclear. Purpose: The objective of our study was to demonstrate the the expression and role of PKMYT1 in ESCC. Patients and methods:   We detected the expression of PKMYT1 in ESCC patients and analysed the correlation with overall survival time and disease-free survival time. Then we detected PKMYT1 expression in ESCC cell lines and immortalized human esophageal epithelial cell line. Down-regulated PKMYT1 was carried out in KYSE70 and KYSE450 cells to invetigate the mechanism of PKMYT1 in ESCC cells. Results: PKMYT1 was up-regulated in tumor tissues and ESCC cell lines, and higher expression of PKMYT1 correlated with poorer overall survival in ESCC patients. Besides, in ESCC cell lines KYSE70 and KYSE450, knocking down PKMYT1 allowed more cells to skip G2/M checkpoint to complete mitosis, which promoted cell apoptosis, inhibited cell proliferation, and prevented the EMT phenotype in vitro. Meantime, we also observed that down-regulated PKMYT1 in ESCC cells suppressed AKT/mTOR signaling pathway. These results demonstrated PKMYT1 may act as an oncogene in ESCC. Conclusion: PKMYT1 plays an crutial role in ESCC progression, downregulated PKMYT1 might inhibit the development of ESCC by AKT/mTOR signaling pathway, and might be a novel target in the treatment of ESCC.

5.
Chem Asian J ; 14(15): 2676-2684, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31152498

RESUMO

Well-dispersed carbon-coated or nitrogen-doped carbon-coated copper-iron alloy nanoparticles (FeCu@C or FeCu@C-N) in carbon-based supports are obtained using a bimetallic metal-organic framework (Cu/Fe-MOF-74) or a mixture of Cu/Fe-MOF-74 and melamine as sacrificial templates and an active-component precursor by using a pyrolysis method. The investigation results attest formation of Cu-Fe alloy nanoparticles. The obtained FeCu@C catalyst exhibits a catalytic activity with a half-wave potential of 0.83 V for oxygen reduction reaction (ORR) in alkaline medium, comparable to that on commercial Pt/C catalyst (0.84 V). The catalytic activity of FeCu@C-N for ORR (Ehalf-wave =0.87 V) outshines all reported analogues. The excellent performance of FeCu@C-N should be attributed to a change in the energy of the d-band center of Cu resulting from the formation of the copper-iron alloy, the interaction between alloy nanoparticles and supports and N-doping in the carbon matrix. Moreover, FeCu@C and FeCu@C-N show better electrochemical stability and methanol tolerance than commercial Pt/C and are expected to be widely used in practical applications.

6.
Cancer Res ; 79(14): 3737-3748, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31085700

RESUMO

IFNγ is conventionally recognized as an inflammatory cytokine that plays a central role in antitumor immunity. Although it has been used clinically to treat a variety of malignancies, low levels of IFNγ in the tumor microenvironment (TME) increase the risk of tumor metastasis during immunotherapy. Accumulating evidence suggests that IFNγ can induce cancer progression, yet the mechanisms underlying the controversial role of IFNγ in tumor development remain unclear. Here, we reveal a dose-dependent effect of IFNγ in inducing tumor stemness to accelerate cancer progression in patients with a variety of cancer types. Low levels of IFNγ endowed cancer stem-like properties via the intercellular adhesion molecule-1 (ICAM1)-PI3K-Akt-Notch1 axis, whereas high levels of IFNγ activated the JAK1-STAT1-caspase pathway to induce apoptosis in non-small cell lung cancer (NSCLC). Inhibition of ICAM1 abrogated the stem-like properties of NSCLC cells induced by the low dose of IFNγ both in vitro and in vivo. This study unveils the role of low levels of IFNγ in conferring tumor stemness and elucidates the distinct signaling pathways activated by IFNγ in a dose-dependent manner, thus providing new insights into cancer treatment, particularly for patients with low expression of IFNγ in the TME. SIGNIFICANCE: These findings reveal the dose-dependent effect of IFNγ in inducing tumor stemness and elucidate the distinct molecular mechanisms activated by IFNγ in a dose-dependent manner.

7.
Oncoimmunology ; 8(7): 1601478, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31143523

RESUMO

The expression and function of CD163 in glioma are not fully understood. In this report, we collected totally 1323 glioma samples from the Chinese Glioma Genome Atlas (CGGA) dataset, including 325 RNA-seq data and 301 mRNA microarray data, and 697 glioma samples from The Cancer Genome Atlas (TCGA) dataset to characterize the molecular and clinical features of CD163 in glioma by conducting a large-scale study. We found that CD163 expression was positively associated with the grade of malignancy of glioma. CD163 expression was up-regulated in IDH wild-type glioma and mesenchymal subtype. Gene ontology analysis suggested that CD163-related genes were more involved in immune response and angiogenesis in glioma. Moreover, CD163 showed a positive relationship with stromal and immune cell populations. Kaplan-Meier curves analysis revealed that higher CD163 expression indicated significantly poor survival in glioma and glioblastoma multiforme (GBM). Pearson correlation analysis revealed that CD163 was robustly associated with the immune checkpoints and other macrophage markers. These results demonstrated that CD163 predicts poor prognosis in glioma patients. Additionally, combination of CD163 and immune checkpoints may impair angiogenesis and reverse dysfunctional phenotypes of T cells, which suggest that CD163 may be a promising biomarker and target for immunotherapeutic strategies. Abbreviations: CGGA: Chinese Glioma Genome Atlas; TCGA: The Cancer Genome Atlas; TAMs: Tumor associated macrophages; IDH: isocitrate dehydrogenase; GBM: glioblastoma.

8.
Cancer Med ; 8(6): 3059-3071, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31025554

RESUMO

Lung cancer is the leading cause of cancer-related deaths worldwide. Although several therapeutic strategies have been employed to curb lung cancer, the survival rate is still poor owing to the development of drug resistance. The mechanisms underlying drug resistance development are incompletely understood. Here, we aimed to identify the common signaling pathways involved in drug resistance in non-small cell lung cancer (NSCLC). Three published transcriptome microarray data were downloaded from the Gene Expression Omnibus (GEO) database comprising different drug-resistant cell lines and their parental cell lines. Differentially expressed genes (DEGs) were identified and used to perform Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. An overlapping analysis was performed for KEGG pathways enriched from all the three datasets to identify the common signaling pathways. As a result, we found that metabolic pathways, ubiquitin-mediated proteolysis, and mitogen-activated protein kinase (MAPK) signaling were the most aberrantly expressed signaling pathways. The knockdown of nicotinamide phosphoribosyltransferase (NAMPT), the gene involved in metabolic pathways and known to be upregulated in drug-resistant tumor cells, was shown to increase the apoptosis of cisplatin-resistant A549 cells following cisplatin treatment. Thus, our results provide an in-depth analysis of the signaling pathways that are commonly altered in drug-resistant NSCLC cell lines and highlight the potential strategy that facilitates the development of interventions to interfere with upregulated signaling pathways as well as to boost downregulated signaling pathways in drug-resistant tumors for the elimination of multiple resistance of NSCLC.

9.
Inorg Chem ; 58(6): 3916-3924, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30816702

RESUMO

The development of bimetallic transition-metal sulfide and nitrogen-doped carbon composites with unique hollow structure is highly desirable for energy storage applications but is also challenging. In the present work, we demonstrate a facile metal-organic framework engaged strategy for synthesizing bimetallic nickel cobalt sulfide and nitrogen-doped carbon composites with hollow spherical structure (denoted as hollow Ni-Co-S- n/NC composites) and a Ni/Co molar ratio ( n value) that can be easily controlled. When evaluated as electrode materials for both supercapacitors and lithium ion batteries, it is found that the hollow Ni-Co-S-0.5/NC composite with a Ni/Co molar ratio of 0.5 exhibits optimal electrochemical performance. The hollow Ni-Co-S-0.5/NC composite exhibits a high specific capacity of 543.9 C g-1 at 1 A g-1 and maintains a capacity retention of 67.3% when the current density is increased to 20 A g-1. An asymmetric supercapacitor based on the hollow Ni-Co-S-0.5/NC composite is fabricated, which shows good electrochemical performance with a high energy density of 39.6 W h kg-1 at a power density of 808 W kg-1. For lithium storage, the hollow Ni-Co-S-0.5/NC composite manifests a high reversible discharge capacity of 755.0 mA h g-1 at 200 mA g-1 for 200 cycles as well as good rate capability. The excellent electrochemical performance could be attributed to the desirable structural, compositional, and component advantages. This work could offer new insight into the rational design and synthesis of highly efficient electrode materials for both supercapacitors and lithium ion batteries.

10.
ChemSusChem ; 12(7): 1451-1458, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30675996

RESUMO

Co-Sn solid-solution nanoparticles with Sn crystal structure and tuned metal ratios were synthesized by a facile one pot solution-based procedure involving the initial reduction of a Sn precursor followed by incorporation of Co within the Sn lattice. These nanoparticles were used as anode materials for Li-ion batteries. Among the different compositions tested, Co0.7 Sn and Co0.9 Sn electrodes provided the highest capacities with values above 1500 mAh g-1 at a current density of 0.2 A g-1 after 220 cycles, and up to 800 mAh g-1 at 1.0 A g-1 after 400 cycles. Up to 81 % pseudocapacitance contribution was measured for these electrodes at a sweep rate of 1.0 mV s-1 , thereby indicating fast kinetics and long durability. The excellent performance of Co-Sn nanoparticle alloy-based electrodes was attributed to both the small size of the crystal domains and their suitable composition, which buffered volume changes of Sn and contributed to a suitable electrode restructuration.

11.
J Proteome Res ; 18(3): 960-969, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30596429

RESUMO

Mutations in isocitrate dehydrogenase ( IDH) 1 are high-frequency events in low-grade glioma and secondary glioblastoma, and IDH1 mutant gliomas are vulnerable to interventions. Metabolic reprogramming is a hallmark of cancer. In this study, comprehensive metabolism investigation of clinical IDH1 mutant glioma specimens was performed to explore its specific metabolic reprogramming in real microenvironment. Massive metabolic alterations from glycolysis to lipid metabolism were identified in the IDH1 mutant glioma tissue when compared to IDH1 wild-type glioma. Of note, tricarboxylic acid (TCA) cycle intermediates were in similar levels in both groups, with more pyruvate found entering the TCA cycle in IDH1 mutant glioma. The pool of fatty acyl chains was also reduced, displayed as decreased triglycerides and sphingolipids, although membrane phosphatidyl lipids were not changed. The lower fatty acyl pool may be mediated by the lower protein expression levels of long-chain acyl-CoA synthetase 1 (ACSL1), ACSL4, and very long-chain acyl-CoA synthetase 3 (ACSVL3) in IDH1 mutant glioma. Lower ACSL1 was further found to contribute to the better survival of IDH1 mutant glioma patients based on the The Cancer Genome Atlas (TCGA) RNA sequencing data. Our research provides valuable insights into the tissue metabolism of human IDH1 mutant glioma and unravels new lipid-related targets.

12.
Immunol Cell Biol ; 97(5): 457-469, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30575118

RESUMO

Mutations in the isocitrate dehydrogenase (IDH) 1 gene, especially the R132H mutation, have been reported to be associated with a better prognosis in glioma patients. However, the underlying molecular mechanisms are not yet well understood. Many factors may contribute to differences in the survival of IDH1 wild-type and IDH1 mutant glioma patients, in which immune components play a potentially important role. In this study, we analyzed The Cancer Genome Atlas (TCGA), and the Chinese Glioma Genome Atlas (CGGA) databases, as well as glioma patient-derived tumor samples. We found that there was a higher infiltration of natural killer (NK) cells in IDH1 mutant glioma patients, and this was correlated with a better prognosis. We also showed that IDH1-R132 tumor cells had higher expression levels of the chemokine CX3CL1. This arises as a result of the conversion of α-ketoglutarate to R(-)-2-hydroxyglutarate by the IDH1 mutant and the resultant phosphorylation of nuclear factor kappa B. Knockdown of CX3CL1 decreased the migration of NK cells. In addition, the high levels of expression of CX3CL1 were positively correlated with glioma patient survival in the TCGA and CGGA databases, and in the clinical samples. Overall, our data have identified a novel mechanism in which R132H mutation of the IDH1 gene serves as a tumor suppressor by promoting the recruitment of NK cells through CX3CL1/CX3CR1 chemotaxis.


Assuntos
Receptor 1 de Quimiocina CX3C/imunologia , Quimiocina CX3CL1/imunologia , Quimiotaxia , Regulação Neoplásica da Expressão Gênica/imunologia , Glioma , Isocitrato Desidrogenase , Células Matadoras Naturais/imunologia , Mutação de Sentido Incorreto , Proteínas Supressoras de Tumor , Substituição de Aminoácidos , Receptor 1 de Quimiocina CX3C/genética , Linhagem Celular Tumoral , Quimiocina CX3CL1/genética , Quimiotaxia/genética , Quimiotaxia/imunologia , Feminino , Glioma/genética , Glioma/imunologia , Glioma/patologia , Humanos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/imunologia , Células Matadoras Naturais/patologia , Masculino , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/imunologia
13.
Cancer Manag Res ; 10: 6409-6419, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30568502

RESUMO

Background: There is a growing recognition that tumor-associated macrophages (TAMs) are recruited to the glioma environment, facilitating tumor proliferation and migration by creating an immunosuppressive microenvironment. CD68 has been widely reported as a specific marker of TAMs in cancer. Purpose: To clarify the role of CD68 in glioma, we investigated its function at the transcriptome level and relationship with clinical practice. Patients and methods: In total, 325 RNA-seq data from Chinese Glioma Genome Atlas (CGGA) and 697 RNA-seq data from The Cancer Genome Atlas (TCGA) network were enrolled in this study. CD68-specific findings were further analyzed with R language, and the prognostic impacts were validated through analyzing the overall survival (OS). Results: CD68 showed a positive correlation with the WHO grade of malignancy in glioma. Meanwhile, CD68 was predominantly expressed in IDH wide type and mesenchymal subtype. Gene ontology (GO) analysis revealed that CD68-related genes were closely related to inflammatory response and immune response. Moreover, seven cultures of metagenes further confirmed that CD68 was a specific marker for macrophages in inflammatory response and played an important role in suppressing T-cell-mediated immunity. The Pearson correlation test suggested that CD68 showed robust correlation with other markers of macrophages and immune checkpoints, including PD-1 and TIM-3. Clinically, a high expression level of CD68 in tumors exhibited a poor survival in glioma patients. Conclusion: Our results demonstrated that CD68 acted as an immune suppressor and contributed to glioma progression in the tumor microenvironment. These findings may expand our understanding of CD68-specific clinical and immune features in glioma.

14.
Oncoimmunology ; 7(11): e1461303, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30377557

RESUMO

Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases, which is the leading cause of cancer deaths worldwide. IL-17░A, the major effector cytokine derived from Th17 cells, is a key cytokine in tumor pathogenesis and modulates tumor progression. We aimed to identify whether IL-17░A derived from Th17 cells promotes the progression of NSCLC. Here we found that the level of Th17 cells was increased in NSCLC and IL-17░A was mainly produced by CD4+ cells (Th17 cells) in NSCLC. IL-17░A enhanced the migration, invasion and stemness of NSCLC via STAT3/NF-κB/Notch1 signaling. Blockade of this signaling inhibited the migration, invasion and stemness of NSCLC mediated by IL-17░A. Th17 cells in NSCLC were closely associated with poor prognosis of NSCLC patients. Our results indicated that Th17 cell-derived IL-17░A plays an important role in tumor progression of NSCLC via STAT3/NF-κB/Notch1 signaling. Therefore, therapeutic strategies against this pathway would be valuable to be developed for NSCLC treatment.

15.
Oncoimmunology ; 7(11): e1461304, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30377558

RESUMO

Background: B7-H3 is an immune checkpoint member that belongs to B7-CD28 families and plays a vital role in the inhibition of T-cell function. Importantly, B7-H3 is widely overexpressed on solid tumors, making it become an attractive target for cancer immunotherapy. To clarify the expression panel of B7-H3 in glioma, we explored the clinical and immune features of B7-H3 expression in a large-scale study. Methods and patients: Totally, 1323 glioma samples from Chinese Glioma Genome Atlas (CGGA) dataset, including 325 RNAseq data and 301 mRNA microarray data, and The Cancer Genome Atlas (TCGA) dataset, including 697 RNAseq data, were gathered into our research. The statistical analysis and graphical work were mainly realized by R language. Results: B7-H3 expression was found positively correlated with the grade of malignancy, which might be caused by hypomethylation. The expression level of B7-H3 was consistently up-regulated in IDH wild-type glioma and highly enriched in mesenchymal subtype. GSEA analysis suggested that B7-H3 related genes were more involved in immune response and angiogenesis in glioma. Moreover, B7-H3 showed a consistent positive relationship with stromal and immune cell populations. Further analysis confirmed that B7-H3 played an important role in T-cell-mediated immunity, especially in T-cell-mediated immune response to tumor cell. Circos plots revealed that B7-H3 was tightly associated with most B7 members and other immune checkpoints. Univariate and multivariate cox analysis demonstrated that B7-H3 was an independent prognosticator for glioma patients. Conclusion: B7-H3 represents the malignant phenotype of glioma and independently predicted worse prognosis in glioma patients. Moreover, B7-H3 collaborating with other checkpoint members may contribute to the dysfunctional phenotype of T cell. These findings will be helpful for further optimizing immunotherapies for glioma.

16.
Immunol Lett ; 204: 29-37, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30321562

RESUMO

Skeletal muscle injury is a common symptom in daily life. After injury, a distinct population of regulatory T cells (Tregs) will infiltrate skeletal muscle in acute and chronic injury sites. However, the mechanism by which Tregs rapidly accumulate to the site of acute injury remains unclear. BALB/c mice were used to establish a cryo-injured model. Percentage of Tregs in the normal and cryo-injured tissues was detected on different days by flow cytometry. Then, the major factors that contribute to the repair of skeletal muscle by Tregs and the chemokines associated with the chemotaxis of Tregs in the paired muscle were analyzed by qRT-PCR. Finally, Tregs were sorted out by magnetic beads and the transwell analysis was performed in vitro. Compared to the normal muscle, the proportion of Tregs was dramatically-increased in the cryo-injured muscle on day 4. These Tregs produced high level of repair related factors such as amphiregulin (Areg), IL-10 and TGF-ß in the cryo-injured muscle. In addition, we found that CCL3, CCL4, CCL5 were the main chemokines that highly expressed in the injured skeletal muscle compared to the normal skeletal muscle. Simultaneously, their receptors CCR1 and CCR5 were highly expressed on Tregs in cryo-injured muscle compared with the normal muscle. Transwell analysis showed CCL3 can significantly chemotize Tregs and the antibody of CCR1 could reverse the chemotaxis in vitro. These results suggest that Tregs in the cryo-injured muscle play a pivotal role that can promote the regeneration of skeletal muscle and CCL3 may serve as the key chemokine to recruit Tregs to the injury sites.


Assuntos
Quimiocina CCL3/metabolismo , Músculo Esquelético/lesões , Músculo Esquelético/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Cicatrização/imunologia , Animais , Biomarcadores , Quimiotaxia/imunologia , Citocinas/metabolismo , Imunofenotipagem , Camundongos , Músculo Esquelético/patologia , Receptores CCR3/metabolismo , Receptores CCR5/metabolismo
17.
Mol Immunol ; 101: 440-449, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30096583

RESUMO

Granulocytes and natural killer (NK) cells have been linked to brain injury in ischemic stroke. However, their recruitment from peripheral leucocytes in stroke patients is not well understood. Here, the expression of the interleukin 8 (CXCL8) in plasma, and CXC chemokine receptor 2 (CXCR2) in peripheral leucocytes of patients with ischemic stroke were evaluated. Based on the results, CXCR2 expression positively correlated with granulocytes and NK cells, which were in turn attracted by CXCL8. The results also indicated that CXCR2 was a direct target of microRNA (miR)-4437, a negative regulator of CXCR2, which was downregulated in peripheral leucocytes from patients with ischemic stroke. Furthermore, serum CXCL8 levels were associated with the infarct volume and functional outcomes in patients with ischemic stroke. The results of the receiver operating characteristic curve analysis with an optimal cut-off value of 34 pg/mL indicated serum CXCL8 levels could be a prognostic indicator for ischemic stroke. In conclusion, these data highlighted the involvement of the CXCL8-CXCR2 chemotactic axis in the recruitment of granulocytes and NK cells in ischemic stroke. Furthermore, miR-4437 was suggested as a novel target for treating ischemic stroke, while the serum CXCL8 level could be a prognostic factor for ischemic stroke.


Assuntos
Isquemia Encefálica/imunologia , Granulócitos/metabolismo , Interleucina-8/metabolismo , Células Matadoras Naturais/metabolismo , MicroRNAs/metabolismo , Receptores de Interleucina-8B/metabolismo , Acidente Vascular Cerebral/imunologia , Sequência de Bases , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Quimiotaxia , Regulação para Baixo/genética , Feminino , Humanos , Interleucina-8/sangue , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Regulação para Cima/genética
18.
Chem Asian J ; 13(21): 3314-3320, 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30136431

RESUMO

A porous carbon material that was co-doped with copper and phosphorus (Cu-P-C) was synthesized by the direct thermal conversion of [(Ph3 P)2 CuCl2 ] in the channels of an SBA-15 template and found to be an impressive Cu-based electrocatalyst. The prefabricated Cu-Px moieties in the starting [(Ph3 P)2 CuCl2 ] were retained during the preparation process of the catalyst. These Cu-Px active sites effectively catalyzed the oxygen-reduction reaction (ORR). Moreover, the hierarchically porous morphology of the Cu-P-C material, which demonstrated a large specific surface area, allowed for a higher density of the Cu-Px active sites, thereby facilitating mass transfer and further boosting the electrocatalytic activity of the Cu-P-C catalyst. The as-obtained catalyst exhibited surprising catalytic activity, with a halfwave potential of 0.833 V in alkaline medium, which was comparable to that of the commercial Pt/C-JM catalyst, and possessed the highest activity among the reported M-P-C catalysts for the ORR.

19.
J Immunol ; 201(7): 2165-2175, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30150287

RESUMO

MicroRNAs are an important regulator for T cell immune response. In this study, we aimed to identify microRNAs with the potential to regulate T cell differentiation. The influence of miR-143 on differentiation and function of CD8+ T cells from healthy donors were detected, and it was found that miR-143 overexpression could significantly increase the differentiation of central memory T (Tcm) CD8+ cells, decrease cell apoptosis, and increase proinflammatory cytokine secretion. Furthermore, the specific killing of HER2-CAR T cells against esophageal cancer cell line TE-7 was enhanced by miR-143 overexpression. Glucose transporter 1 (Glut-1) was identified as the critical target gene of miR-143 in the role of T cell regulation. By inhibition Glut-1, miR-143 inhibited glucose uptake and glycolysis in T cell to regulated T cell differentiation. Tcm cell populations were also suppressed in parallel with the downregulation of miR-143 in tumor tissues from 13 patients with esophagus cancer. IDO and its metabolite kynurenine in the tumor microenvironment were screened as an upstream regulator of miR-143. IDO small interfering RNA significantly increased the expression of miR-143 and Tcm cell population. In conclusion, our results show that miR-143 enhanced antitumor effects of T cell by promoting memory T cell differentiation and metabolism reprogramming through Glut-1. Our findings will encourage the development of new strategies targeting miR-143 in both cancer cells and T cells.


Assuntos
Plaquetas/fisiologia , Linfócitos T CD8-Positivos/metabolismo , MicroRNAs/genética , Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular , Linhagem Celular Tumoral , Reprogramação Celular , Citocinas/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Humanos , Imunidade/genética , Memória Imunológica , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição/metabolismo
20.
Cancer Immunol Res ; 6(10): 1246-1259, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30082413

RESUMO

Maelstrom (MAEL) is a novel cancer/testis-associated gene, which is not only expressed in the male testicular germ cells among human normal tissues, but is also aberrantly expressed in various cancer tissues. In our study, MAEL was characterized as a tumor-promoting gene and was significantly associated with esophageal squamous cell carcinoma (ESCC) recurrence and unfavorable prognosis. Kaplan-Meier analysis showed that patients with high MAEL expression had a shorter survival time. Functional experiments showed that MAEL promoted tumor cell growth and inhibited cell apoptosis. These results prompted us to investigate the factors affecting the tumorigenicity of MAEL Further experimentation demonstrated that MAEL enhanced the expression of phosphorylated Akt1, with subsequent phosphorylation of nuclear factor kappa B (NF-κB) subunit RelA in tumor cells, and chemoattracted myeloid-derived suppressor cells (MDSCs) by upregulating interleukin-8 (IL8) to accelerate tumor progression in the tumor microenvironment. We also found that TGFß secreted by MDSCs could upregulate MAEL by inducing Smad2/Smad3 phosphorylation. In summary, this study revealed a mechanism by which MAEL could upregulate IL8 through Akt1/RelA to direct MDSCs homing into the tumor, suggesting that MAEL could be an attractive therapeutic target and a prognostic marker against ESCC. Cancer Immunol Res; 6(10); 1246-59. ©2018 AACR.


Assuntos
Proteínas de Transporte/fisiologia , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Interleucina-8/metabolismo , Células Supressoras Mieloides/imunologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição RelA/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Recidiva Local de Neoplasia/genética , Transdução de Sinais , Regulação para Cima
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