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| 2. |
- Li, Yifei, et al.
(författare)
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Can Nup88 expression be associated with atypical endometrial hyperplasia and endometrial cancer? A preliminary study
- 2016
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Ingår i: Pathology, Research and Practice. - : ELSEVIER GMBH, URBAN & FISCHER VERLAG. - 0344-0338 .- 1618-0631. ; 212:4, s. 274-278
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nup88 is overexpressed in a number of types of carcinomas and is associated with myometrial invasion, but its exact expression pattern in endometrial cancer and premalignant lesions is unknown. Aims: To evaluate the role of Nup88 in endometrial cancers and atypical endometrial hyperplasia and its clinicopathological significance. Methods: Nup88 expression was examined by immunohistochemistry in samples from 104 endometrial cancers, 21 atypical endometrial hyperplasia lesions, and 40 normal endometria. All samples were from patients who underwent surgery at the First Hospital of Hebei Medical University (Shijiazhuang, China) between April 2006 and December 2009. Nup88 expression was compared between the groups and associations were assessed between Nup88 and clinicopathological characteristics of the subjects. Results: Nup88 expression in cancer (76% of samples) and atypical hyperplasia (91%) was significantly higher compared to normal endometrium (33%, both P < 0.001), but there was no significant difference between endometrial cancer and atypical hyperplasia (P = 0.237). The expression of Nup88 increased significantly with increasing exposure time to estrogen (P = 0.033). Conclusions: Nup88 may be related to the occurrence of endometrial cancers and premalignant lesions. Nup88 might be a useful biomarker for pre-malignant lesions and early-stage endometrial cancer. (C) 2016 Elsevier GmbH. All rights reserved.
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| 3. |
- Chen, Zhipeng, et al.
(författare)
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Design, Synthesis, and Structure-Activity Relationship of N-Aryl-N'-(thiophen-2-yl) thiourea Derivatives as Novel and Specific Human TLR1/2 Agonists for Potential Cancer Immunotherapy
- 2021
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Ingår i: Journal of Medicinal Chemistry. - Washington, DC : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:11, s. 7371-7389
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Tidskriftsartikel (refereegranskat)abstract
- The previous virtual screening of ten million compounds yielded two novel nonlipopeptide-like chemotypes as TLR2 agonists. Herein, we present the chemical optimization of our initial hit, 1-phenyl-3-(thiophen-2-yl) urea, which resulted in the identification of SMU-C80 (EC50 = 31.02 ± 1.01 nM) as a TLR2-specific agonist with a 370-fold improvement in bioactivity. Mechanistic studies revealed that SMU-C80, through TLR1/2, recruits the adaptor protein MyD88 and triggers the NF-κB pathway to release cytokines such as TNF-α and IL-1β from human, but not murine, cells. To the best of our knowledge, it is the first species-specific TLR1/2 agonist reported until now. Moreover, SMU-C80 increased the percentage of T, B, and NK cells ex vivo and activated the immune cells, which suppressed cancer cell growth in vitro. In summary, we obtained a highly efficient and specific human TLR1/2 agonist that acts through the MyD88 and NF-κB pathway, facilitating cytokine release and the simultaneous activation of immune cells that in turn affects the apoptosis of cancer cells. © 2021 American Chemical Society
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| 4. |
- He, Shijun, et al.
(författare)
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GLP-1 Receptor Activation Abrogates β-Cell Dysfunction by PKA Cα-Mediated Degradation of Thioredoxin Interacting Protein
- 2019
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide 1 receptor (GLP-1R) agonist (Exendin-4) is a well-known agent used to improve β-cell dysfunctions via protein kinase A (PKA), but the detailed downstream molecular mechanisms are still elusive. We have now found that PKA Cα mediated- TXNIP phosphorylation and degradation played a vital role in the β-cell protective role of exendin-4. After PKA activator (Exendin-4 or FSK) treatment, PKA Cα could directly interact with TXNIP by bimolecular fluorescence complementation and Co-IP assays in INS-1 cells. And PKA Cα overexpression decreased TXNIP level, whereas TXNIP level was largely increased in PKA Cα-KO β-cells by CRISPR-Cas9. Interestingly, TXNIP overexpression or PKA Cα-KO has impaired β-cell functions, including loss of insulin secretion and activation of inflammation. PKA Cα directly phosphorylated TXNIP at Ser307 and Ser308 positions, leading to its degradation via activation of cellular proteasome pathway. Consistent with this observation, TXNIP (S307/308A) mutant resisted the degradation effects of PKA Cα. However, exendin-4 neither affected TXNIP level in TXNIP (S307/308A) mutant overexpressed β-cells nor in PKA Cα-KO β-cells. Moreover, exendin-4 treatment reduced the inflammation gene expression in TXNIP overexpressed β-cells, but exendin-4 treatment has no effect on the inflammation gene expression in TXNIP (S307/308A) overexpressed β-cells. In conclusion, our study reveals the integral role of PKA Cα/TXNIP signaling in pancreatic β-cells and suggests that PKA Cα-mediated TXNIP degradation is vital in β-cell protective effects of exendin-4.
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| 5. |
- Li, Yifei, et al.
(författare)
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Expression and clinical significance of FXYD3 in endometrial cancer
- 2014
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 8:2, s. 517-522
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Tidskriftsartikel (refereegranskat)abstract
- FXYD3 expression is upregulated in numerous cancer cell types. The present study compared the FXDY3 expression in normal endometrium, premalignant lesion and endometrial cancer tissue samples, and investigated the correlation between FXDY3 expression and clinicopathological features. FXYD3 expression was analyzed by streptavidin-peroxidase immunohistochemistry in 21 normal endometrial tissue samples, 18 atypical endometrial hyperplasia samples and 50 tissues obtained from patients diagnosed with endometrial cancer. The percentage of FXYD3-positive cell expression in the normal endometrium, atypical hyperplasia and endometrial cancer tissues samples was 0, 22, and 26%, respectively. The differences between the atypical hyperplasia and endometrial cancer groups were statistically significant when compared with the normal group (P=0.007 and P=0.037, respectively). There was no significant difference between the atypical hyperplasia and endometrial cancer groups. The percentage of FXYD3-positive cells correlated with the fertility frequency (Pless than0.05). In conclusion, FXYD3 is a potential biomarker for endometrial cancer, and its upregulation may be an early event in endometrial carcinoma progression. In addition, FXYD3 expression in endometrial carcinoma correlates with fertility frequency.
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| 6. |
- Ma, Shuwen, et al.
(författare)
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CD163 as a Potential Biomarker in Colorectal Cancer for Tumor Microenvironment and Cancer Prognosis : A Swedish Study from Tissue Microarrays to Big Data Analyses
- 2022
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:24
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary: Through the analysis of tissue microarray (TMA) samples from colorectal cancer (CRC) patients and bioinformatical analyses of public databases and our clinical dataset, this study identifies the different expressions of CD163 in various tissues, the presence of the receptor in TME, the interaction with other biological processes and a positive correlation between CD163 dysfunction and worse prognosis. Therefore, CD163 can be used as a new biomarker to predict patient prognosis.(1) Background: CD163, a specific macrophage receptor, affects the progression of malignant tumors. Unfortunately, the regulation and expression of CD163 are poorly understood. In this study, we determined the expressions of CD163 in TMA samples from CRC patients and combined them with patient data from several Swedish hospitals.(2) Methods: The expressions of CD163 in tissue samples from CRC patients were examined. After combining 472 CRC patients' gene expression and 438 CRC patients' clinical data with the TCGA database, 964 cases from the GEO database, and experimental expression data from 1247 Swedish CRC patients, we selected four genes (PCNA, LOX, BCL2, and CD163) and analyzed the tumor-infiltrating immune cells (TICs) and CRC prognosis.(3) Results: Based on histopathological TMA analysis, CD163 was strongly expressed in the stroma of both normal and cancer tissues, and the expressions in normal and cancer cells varied from negative to strong. The results from public databases show decreased expression of CD163 in cancer tissue compared to normal mucosa (|log FC| > 1 and FDR < 0.01), and it is a negative prognostic factor for CRC patients (p-value < 0.05). Through tumor microenvironment (TME) analysis, we found a potential influence of CD163 on immune cell infiltration. Furthermore, the enrichment analysis indicated the possible interaction with other proteins and biological pathways.(4) Conclusions: CD163 is expressed differently in CRC tissue and is a negative prognostic factor. Its expression is associated with the TME and tumor purity of CRC. Considering all results, CD163 has the potential to be a predictive biomarker in the investigation of CRC.
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| 7. |
- Tian, Kai, et al.
(författare)
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Comprehensive Characterization of the 4H-SiC Planar and Trench Gate MOSFETs From Cryogenic to High Temperature
- 2019
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Ingår i: IEEE Transactions on Electron Devices. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0018-9383 .- 1557-9646. ; 66:10, s. 4279-4286
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Tidskriftsartikel (refereegranskat)abstract
- In this article, the static, dynamic, and short-circuit properties of 1.2-kV commercial 4H-SiC planar and trench gate metal-oxide-semiconductor field-effect transistors (MOSFETs) are compared and analyzed in a wide temperature range from 90 to 493 K. The temperature-dependent specific ON-resistance (Rsp-ON) and threshold voltage (V-th) are analyzed in relation to the density of the interface state. The turn-on rise and turn-off fall times (T-r and T-f) and the corresponding energy loss (E-r and E-f) are extracted from a double-pulse test from cryogenic to high temperature and analyzed. The short-circuit capability of the two structures is studied at low temperature for the first time. The comprehensive comparison and analysis of the planar and trench gate MOSFET versus temperature in this work show the importance to study applications with SiC MOSFETs in a wide temperature range, especially for the cryogenic temperatures.
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| 8. |
- Yao, Xingang, et al.
(författare)
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Inhibition of dengue viral infection by diasarone-I is associated with 2'O methyltransferase of NS5
- 2018
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Ingår i: European Journal of Pharmacology. - Amsterdam : Elsevier. - 0014-2999 .- 1879-0712. ; 821, s. 11-20
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Tidskriftsartikel (refereegranskat)abstract
- Dengue virus (DENV) is the most prevalent mosquito borne viral pathogen worldwide. However, antiviral drugs against this infection are not available. To identify novel anti-DENV compound from traditional Chinese medicine, we discovered the ethanol extract of Acorus tatarinowii Schott containing potent anti-DENV activity and diasarone-I was isolated from this extract. Diasarone-I has antiviral effect with half maximal effective concentration (EC50) of 4.5μM and half maximal cytotoxicity concentration (CC50) of >80μM. Time of drug addition assay suggested that this compound inhibited at RNA replication step in the DENV life cycle. Further, in silico analysis indicated that diasarone-I might act as an inhibitor of 2'O Methyltransferase of NS5. Diasarone-I has also decreased the DENV2-induced STAT1 phosphorylation and ISGs. In summary, we suggest that diasarone-I may be a 2'O Methyltransferase inhibitor and might serve as a potential candidate for the treatment of DENV2 infections. © 2017 Elsevier B.V.
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| 9. |
- Yao, Xingang, et al.
(författare)
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Q63, a novel DENV2 RdRp non-nucleoside inhibitor, inhibited DENV2 replication and infection
- 2018
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Ingår i: Journal of Pharmacological Sciences. - Amsterdam : Elsevier. - 1347-8613 .- 1347-8648. ; 138:4, s. 247-256
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Tidskriftsartikel (refereegranskat)abstract
- Dengue virus (DENV) annually infects 400 million people worldwide. Unfortunately, there is lack ofwidely protective vaccine or drugs against DENV. The viral RNA-dependent RNA polymerase (RdRp) ofNS5 protein is highly conserved among different DENV subtypes, thus presenting itself as an attractivetarget for drug design. In the current research, SPRi was performed to screen compounds against DENV2RdRp and 5(1H)-Quinazolinone,2-(4-bromophenyl)-2,3,4,6,7,8-hexahydro-7,7-dimethyl-1,3-diphenyl(Q63) was successfully screened out with a KD of 0.9 mM. Then, ITC and molecular docking assay wasperformed to access the binding mechanism between Q63 and DENV2 RdRp. Meanwhile, Q63 alsodecreased the intermediate dsRNA production, which was the product of RdRp. Further the antiviraleffects of Q63 were evaluated on mosquito C6/36 cells and mammalian BHK-21 cells. Q63 reduced CPEand cell toxicity effect after DENV2 infection on C6/36 and BHK-21 cells, with an EC50 of 2.08 mM. Time ofaddition assay revealed that Q63 affected the early genome RNA replication stage, including genome RNAreplication. In addition, Q63 down-regulated STAT1 phosphorylation, ISG15 and ISG54 after DENV2infection. In summary, Q63 was found to be a novel RdRp non-nucleoside inhibitor and a potential leadcompound for coping with DENV infectious disease in the future. © 2018 The Authors.
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| 10. |
- Yao, Xingang, et al.
(författare)
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Tatanan A from the Acorus calamus L. root inhibited dengue virus proliferation and infections
- 2018
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Ingår i: Phytomedicine. - München : Elsevier. - 0944-7113 .- 1618-095X. ; 42, s. 258-267
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acorus calamus l. (Acoraceae) is a well-known traditional Chinese medicinal plant, whose root are historically mainly used to treat neurodegenerative diseases, and for cholera treatment. This datum strongly indicates the antimicrobial activity of A. calamus.PURPOSE: Our goal is to find the active constituents of A. calamus to treat dengue virus (DENV) infections, and to study the effects and mechanisms of these active substances.METHODS: The root of A. calamus was extracted by ethanol. Mosquito larva C6/36 cells were used for DENV2 replication and transfection host. Mouse kidney fibroblast cells (BHK-21) were used as a host cell to study the infection ability of the virus. DENV2-induced cytopathic effect (CPE) and plaque assay were used to evaluate the inhibitory effect of A. calamus extracts on DENV2 infectivity inhibition. The levels of E and NS1 protein expression were measured by real-time PCR and western blot assays.RESULTS: 12 compounds were isolated from ethanol extract of A. calamus root, tatanan A showed the best anti-DENV ability among these 12 compounds, which significantly alleviated DENV2-induced CPE and cytotoxicity effects, with an EC50 of 3.9 µM. In addition, RNA replication assay further confirmed the antivirus ability of tatanan A. Time-addition assay showed that tatanan A affected the early stage of viral RNA replication, which in turn inhibited mRNA and protein levels of DENV2.CONCLUSIONS: These results demonstrated the anti-DENV2 effect of tatanan A, in inhibiting DENV2 RNA replication and infections. In summary, tatanan A was found to be a novel natural DENV inhibitor and a potential candidate for the treatment of DENV infectious disease.
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