المؤلفون: Chen,Shipeng, Li,Mengna, Xue,Changning, Zhou,Xiangting, Wei,Jianxia, Zheng,Lemei, Duan,Yumei, Deng,Hongyu, Tang,Faqing, Xiong,Wei, Xiang,Bo, Zhou,Ming

مصطلحات موضوعية: Drug Design, Development and Therapy

الوصف: Shipeng Chen,1– 3 Mengna Li,1– 3 Changning Xue,1– 3 Xiangting Zhou,1– 3 Jianxia Wei,1– 3 Lemei Zheng,1– 3 Yumei Duan,1– 3 Hongyu Deng,1 Faqing Tang,1 Wei Xiong,1– 3 Bo Xiang,1– 3 Ming Zhou1– 3 1NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People’s Republic of China; 2Cancer Research Institute, Central South University, Changsha, 410078, People’s Republic of China; 3The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, 410078, People’s Republic of ChinaCorrespondence: Ming Zhou; Bo Xiang, Email zhouming2001@163.com; xiangbolin@csu.edu.cnPurpose: Cinobufotalin injection has obvious curative effects on liver cancer patients with less toxicity and fewer side effects than other therapeutic approaches. However, the core ingredients and mechanism underlying these anti-liver cancer effects have not been fully clarified due to its complex composition.Methods: Multidimensional network analysis was used to screen the core ingredients, key targets and pathways underlying the therapeutic effects of cinobufotalin injection on liver cancer, and in vitro and in vivo experiments were performed to confirm the findings.Results: By construction of ingredient networks and integrated analysis, eight core ingredients and ten key targets were finally identified in cinobufotalin injection, and all of the core ingredients are tightly linked with the key targets, and these key targets are highly associated with the cell cycle-related pathways, supporting that both cinobufotalin injection and its core ingredients exert anti-liver cancer roles by blocking cell cycle-related pathways. Moreover, in vitro and in vivo experiments confirmed that either cinobufotalin injection or one of its core ingredients, cinobufagin, significantly inhibited cell proliferation, colony formation, ...

وصف الملف: text/html

العلاقة: https://www.dovepress.com/validation-of-core-ingredients-and-molecular-mechanism-of-cinobufotali-peer-reviewed-fulltext-article-DDDTTest

الإتاحة: https://doi.org/10.2147/DDDT.S443305Test
https://www.dovepress.com/validation-of-core-ingredients-and-molecular-mechanism-of-cinobufotali-peer-reviewed-fulltext-article-DDDTTest

المؤلفون: Wang, Ya, Qiu, Hui, Chen, Shipeng, Li, Dongmei, Zhao, Xu, Guo, Mengmeng, Li, Nana, Chen, Chao, Qin, Ming, Zhou, Ya, Xiao, Daimin, Zhao, Juanjuan, Xu, Lin

المساهمون: National Natural Science Foundation of China

المصدر: Aging Cell ; volume 23, issue 6 ; ISSN 1474-9718 1474-9726

الوصف: Aging is intricately linked to immune system dysfunction. Recent studies have highlighted the biological function of microRNA‐7 (miR‐7) as a novel regulator of immune cell function and related diseases. However, the potential role of miR‐7 in aging remains unexplored. Here, we investigated the contribution of miR‐7 to d ‐gal‐induced aging in mice, focusing on its regulation of senescent Kupffer cells. Our findings revealed that miR‐7 deficiency significantly ameliorated the aging process, characterized by enhanced CD4 + T‐cell activation. However, the adoptive transfer of miR‐7‐deficient CD4 + T cells failed to improve the age‐related phenotype. Further analysis showed that miR‐7 deficiency significantly reduced IL‐1β production in liver tissue, and inhibiting IL‐1β in vivo slowed down the aging process in mice. Notably, IL‐1β is mainly produced by senescent Kupffer cells in the liver tissue of aging mice, and miR‐7 expression was significantly up‐regulated in these cells. Mechanistically, KLF4, a target of miR‐7, was down‐regulated in senescent Kupffer cells in aging mouse model. Furthermore, miR‐7 deficiency also modulated the NF‐κB activation and IL‐1β production in senescent Kupffer cells through KLF4. In conclusion, our findings unveil the role of miR‐7 in d ‐gal‐induced aging in mice, highlighting its regulation of KLF4/NF‐κB/IL‐1β pathways in senescent Kupffer cells. This research may enhance our understanding of miRNA‐based aging immune cells and offer new avenues for new intervention strategies in aging process.

الإتاحة: https://doi.org/10.1111/acel.14145Test

المؤلفون: Chen, Shipeng, Li, Mengna, Xue, Changning, Zhou, Xiangting, Wei, Jianxia, Zheng, Lemei, Duan, Yumei, Deng, Hongyu, Tang, Faqing, Xiong, Wei, Xiang, Bo, Zhou, Ming

المصدر: Drug Design, Development and Therapy ; volume Volume 18, page 1321-1338 ; ISSN 1177-8881

الإتاحة: https://doi.org/10.2147/dddt.s443305Test
https://www.dovepress.com/getfile.php?fileID=98531Test

المؤلفون: Chen, Shipeng, Wang, Hui, Guo, Mengmeng, Zhao, Xu, Yang, Jing, Chen, Longqing, Zhao, Juanjuan, Chen, Chao, Zhou, Ya, Xu, Lin

المساهمون: National Natural Science Foundation of China

المصدر: Cellular Signalling ; volume 117, page 111095 ; ISSN 0898-6568

مصطلحات موضوعية: Cell Biology

الإتاحة: https://doi.org/10.1016/j.cellsig.2024.111095Test
https://api.elsevier.com/content/article/PII:S0898656824000639?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0898656824000639?httpAccept=text/plainTest

المؤلفون: Chen, Shipeng

المصدر: Chen , S 2023 , ' Manipulating immune cells — a therapeutic strategy for cancer and inflammatory disease ' , Doctor of Philosophy , University of Groningen , [Groningen] . https://doi.org/10.33612/diss.822658140Test

الوصف: Despite the increasing application of immunotherapy for a variety of cancers, only a minority of patients obtain durable therapeutic responses. The limited therapeutic efficiency remains a significant challenge for the further application of immunotherapy. One of the reasons could be attributed to the fact that tumors employ diverse strategies to evade tumor-specific immunity. Immunosuppressive cells in the tumor microenvironment play an essential role in protecting the tumor from immune attacks and attenuate the efficacy of immunotherapy. Thus, targeting immunosuppressive cells emerged as a promising strategy to improve the efficacy of cancer immunotherapy. This thesis presents studies on the manipulation of immune cells as a therapeutic strategy to enhance the efficacy of cancer immunotherapy but also as an opposite strategy to resolve inflammatory diseases.

وصف الملف: application/pdf

العلاقة: https://research.rug.nl/en/publications/0bcf25f1-98a9-4511-a6d0-7547b57d4d06Test

الإتاحة: https://doi.org/10.33612/diss.822658140Test
https://hdl.handle.net/11370/0bcf25f1-98a9-4511-a6d0-7547b57d4d06Test
https://research.rug.nl/en/publications/0bcf25f1-98a9-4511-a6d0-7547b57d4d06Test
https://pure.rug.nl/ws/files/822658142/Title_and_contents.pdfTest
https://pure.rug.nl/ws/files/822658144/Chapter_1.pdfTest
https://pure.rug.nl/ws/files/822658148/Chapter_3.pdfTest
https://pure.rug.nl/ws/files/822658152/Chapter_5.pdfTest
https://pure.rug.nl/ws/files/822658154/Chapter_6.pdfTest
https://pure.rug.nl/ws/files/822658156/Chapter_7.pdfTest
https://pure.rug.nl/ws/files/822658158/Appendix.pdfTest

المؤلفون: Wang, Ying, Chen, Shipeng, Xiao, Xiao, Yang, Fan, Wang, Jinhan, Zong, Hui, Gao, Yuzhen, Huang, Chenjun, Xu, Xuewen, Fang, Meng, Zhang, Xiaoyan, Gao, Chunfang

المصدر: Wang , Y , Chen , S , Xiao , X , Yang , F , Wang , J , Zong , H , Gao , Y , Huang , C , Xu , X , Fang , M , Zhang , X & Gao , C 2023 , ' Impact of apolipoprotein A1 on tumor immune microenvironment, clinical prognosis and genomic landscape in hepatocellular carcinoma ' , Precision Clinical Medicine , vol. 6 , no. 3 , pbad021 . https://doi.org/10.1093/pcmedi/pbad021Test

مصطلحات موضوعية: APOA1, HCC, immune cells, NK cell, prognosis, tumor microenvironment

الوصف: Background: Current knowledge on apolipoprotein A1 (APOA1) in hepatocellular carcinoma (HCC) is fragmented and even contradictory. Multi-dimensional analyses are required to comprehensively elucidate its value and underlying mechanism. Methods: We collected 49 RNA-seq datasets, 40 cell line types data and 70 scRNA pan-cancer datasets public available, including 17 HCC datasets (1754 tumor samples), and enrolled 73 pairs of HCC tissue and 516 blood samples independently from our clinics. APOA1 impacting on the HCC tumor microenvironment (TME) was analyzed using intensive data mining. Methylation sequencing, flow cytometry, quantitative PCR, western blot, immunohistochemistry and clinical chemistry assays were conducted for wet experimental investigation. Results: The APOA1 ontology fingerprint indicated that it played various crucial biological roles in HCC, primarily involved in cholesterol efflux. Consistent findings at histology, serology, and clinical follow-up revealed that high APOA1 was a good prognosis indicator of HCC. Hypermethylation in the APOA1 promoter region was found in clinical samples which is in accordance with the reduction of APOA1 in HCC. The cell cycle, DNA replication, mismatch repair pathways, and tumor cell proliferation were less observed in the HCC APOA1high subgroup. The favorable immunoregulatory abilities of APOA1 showed interesting findings: A positive correlation between APOA1 and anti-Tumor immune cells (NK, CD8+ T cells) and a negative association with immune cells exerting immunosuppressive effects, including M2 macrophages. Conclusion: This is an integrative multidimensional exploration of APOA1 using bioinformatics and experiments. Both the prognostic value and anti-Tumor effects based on APOA1 panoramic exploration in the HCC TME demonstrate a new potential clinical target for HCC assessment and intervention in the future.

وصف الملف: application/pdf

العلاقة: https://research.rug.nl/en/publications/5fedfa4d-1f21-4c7e-960c-25b37553d9d6Test

الإتاحة: https://doi.org/10.1093/pcmedi/pbad021Test
https://hdl.handle.net/11370/5fedfa4d-1f21-4c7e-960c-25b37553d9d6Test
https://research.rug.nl/en/publications/5fedfa4d-1f21-4c7e-960c-25b37553d9d6Test
https://pure.rug.nl/ws/files/892747513/Impact_of_apolipoprotein_A1_on_tumor_immune_microenvironment_clinical_prognosis_and_genomic_landscape_in_hepatocellular_carcinoma.pdfTest
http://www.scopus.com/inward/record.url?scp=85174324872&partnerID=8YFLogxKTest

المؤلفون: Zhao, Chunlong, Chen, Shipeng, Chen, Deng, Río-Bergé, Clàudia, Zhang, Jianqiu, Ettema, Petra, Daemen, Toos, Dekker, Frank J

المصدر: Zhao , C , Chen , S , Chen , D , Río-Bergé , C , Zhang , J , Ettema , P , Daemen , T & Dekker , F J 2023 , ' Histone Deacetylase 3-Directed PROTACs Have Anti-inflammatory Potential by Blocking Polarization of M0-like into M1-like Macrophages ' , Angewandte Chemie (International ed. in English) , vol. 62 , no. 42 , e202310059 . https://doi.org/10.1002/anie.202310059Test

الوصف: Macrophage polarization plays a crucial role in inflammatory processes. The histone deacetylase 3 (HDAC3) has deacetylase-independent function that can activate pro-inflammatory gene expression in LPS-stimulated M1-like macrophages and cannot be blocked by traditional small-molecule HDAC3 inhibitors. Here we employ the proteolysis targeting chimera (PROTAC) technology to target the deacetylase-independent function of HDAC3. We developed a potent and selective HDAC3-directed PROTAC, denoted P7, which induces nearly complete HDAC3 degradation at low micromolar concentrations in both THP-1 cells and human primary macrophages. P7 increases the anti-inflammatory cytokine secretion in THP-1 derived M1-like macrophages. Importantly, P7 decreases the secretion of pro-inflammatory cytokines in M1-like macrophages derived from human primary macrophages. This can be explained by the observed inhibition of macrophage polarization from M0-like into M1-like macrophage. In conclusion, we demonstrate that the HDAC3-directed PROTAC P7 has anti-inflammatory activity and blocks macrophage polarization, which demonstrates that this molecular mechanism can be targeted with small molecule therapeutics.

وصف الملف: application/pdf

العلاقة: https://research.rug.nl/en/publications/a77b2b04-13af-4226-8871-939fc9b46ed1Test

الإتاحة: https://doi.org/10.1002/anie.202310059Test
https://hdl.handle.net/11370/a77b2b04-13af-4226-8871-939fc9b46ed1Test
https://research.rug.nl/en/publications/a77b2b04-13af-4226-8871-939fc9b46ed1Test
https://pure.rug.nl/ws/files/827917371/Angew_Chem_Int_Ed_-_2023_-_Zhao_-_Histone_Deacetylase_3_Directed_PROTACs_Have_Anti_inflammatory_Potential_by_Blocking.pdfTest

المؤلفون: Wang, Wei, Song, Qun, Luo, Qiang, Li, Linqian, Huo, Xiaobing, Chen, Shipeng, Li, Jinyang, Li, Yunhong, Shi, Se, Yuan, Yihui, Wang, Ning

الوصف: Hydrogen peroxide (H 2 O 2 ) is a powerful industrial oxidant and potential carbon-neutral liquid energy carrier. Sunlight-driven synthesis of H 2 O 2 from the most earth-abundant O 2 and seawater is highly desirable. However, the solar-to-chemical efficiency of H 2 O 2 synthesis in particulate photocatalysis systems is low. Here, we present a cooperative sunlight-driven photothermal-photocatalytic system based on cobalt single-atom supported on sulfur doped graphitic carbon nitride/reduced graphene oxide heterostructure (Co–CN@G) to boost H 2 O 2 photosynthesis from natural seawater. By virtue of the photothermal effect and synergy between Co single atoms and the heterostructure, Co–CN@G enables a solar-to-chemical efficiency of more than 0.7% under simulated sunlight irradiation. Theoretical calculations verify that the single atoms combined with heterostructure significantly promote the charge separation, facilitate O 2 absorption and reduce the energy barriers for O 2 reduction and water oxidation, eventually boosting H 2 O 2 photoproduction. The single-atom photothermal-photocatalytic materials may provide possibility of large-scale H 2 O 2 production from inexhaustible seawater in a sustainable way.

العلاقة: https://resolver.sub.uni-goettingen.de/purl?gro-2/125397Test; 38211

الإتاحة: https://doi.org/10.1038/s41467-023-38211-3Test
https://resolver.sub.uni-goettingen.de/purl?gro-2/125397Test

المؤلفون: Wei, Jianxia, Li, Mengna, Chen, Shipeng, Xue, Changning, Zheng, Lemei, Duan, Yumei, Deng, Hongyu, Fan, Songqing, Xiong, Wei, Zhou, Ming

المساهمون: National Natural Science Foundation of China, Project 211

المصدر: Cancer Science ; volume 115, issue 1, page 139-154 ; ISSN 1347-9032 1349-7006

الوصف: BRD7 was identified as a tumor suppressor in nasopharyngeal carcinoma (NPC). Circular RNAs (CircRNAs) are involved in the occurrence and development of NPC as oncogenes or tumor suppressors. However, the function and mechanism of the circular RNA forms derived from BRD7 in NPC are not well understood. In this study, we first identified that circBRD7 was a novel circRNA derived from BRD7 that inhibited cell proliferation, migration, invasion of NPC cells, as well as the xenograft tumor growth and metastasis in vivo. Mechanistically, circBRD7 promoted the transcriptional activation and expression of BRD7 by enhancing the enrichment of histone 3 lysine 27 acetylation (H3K27ac) in the promoter region of its host gene BRD7, and BRD7 promoted the formation of circBRD7. Therefore, circBRD7 formed a positive feedback loop with BRD7 to inhibit NPC development and progression. Moreover, restoration of BRD7 expression rescued the inhibitory effect of circBRD7 on the malignant progression of NPC. In addition, circBRD7 demonstrated low expression in NPC tissues, which was positively correlated with BRD7 expression and negatively correlated with the clinical stage of NPC patients. Taken together, circBRD7 attenuates the tumor growth and metastasis of NPC by forming a positive feedback loop with its host gene BRD7, and targeting the circBRD7/BRD7 axis is a promising strategy for the clinical diagnosis and treatment of NPC.

الإتاحة: https://doi.org/10.1111/cas.15998Test

المؤلفون: Wei, Jianxia, Li, Mengna, Xue, Changning, Chen, Shipeng, Zheng, Lemei, Deng, Hongyu, Tang, Faqing, Li, Guiyuan, Xiong, Wei, Zeng, Zhaoyang, Zhou, Ming

المساهمون: National Natural Science Foundation of China, Free Exploration Program of Central South University, the program of Introducing Talents of Discipline to Universities

المصدر: Journal of Experimental & Clinical Cancer Research ; volume 42, issue 1 ; ISSN 1756-9966

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: Circular RNAs (circRNAs) are a novel type of endogenous non-coding RNAs, which are covalently closed loop structures formed by precursor mRNAs (pre-mRNAs) through back-splicing. CircRNAs are abnormally expressed in many tumors, and play critical roles in a variety of tumors as oncogenes or tumor suppressor genes by sponging miRNAs, regulating alternative splicing and transcription, cis-regulating host genes, interacting with RNA binding proteins (RBPs) or encoding polypeptides. Among them, the regulation of circRNAs on their corresponding host genes is a critical way for circRNAs to exit their functions. Accumulating evidence suggests that circRNAs are able to regulate the expression of host genes at the transcriptional level, post-transcriptional level, translational level, post-translational level, or by encoding polypeptides. Therefore, this paper mainly summarized the roles and association of circRNAs and their corresponding host genes in tumorigenesis and tumor progression, generalized the circRNAs that function synergistically or antagonistically with their host genes, and elaborated the mechanisms of mutual regulation between circRNAs and their host genes. More importantly, this review provides specific references for revealing the potential application of circRNAs combined with their host genes in tumor diagnosis, treatment and prognosis.

الإتاحة: https://doi.org/10.1186/s13046-023-02657-6Test