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Article: A study related to the treatment of gastric cancer with Xiang-Sha-Liu-Jun-Zi-Tang based on network analysis.

Jiang, Ke / Liu, Heli / Ge, Jie / Yang, Bo / Wang, Yu / Wang, Wenbo / Wen, Yuqi / Zeng, Siqing / Chen, Quan / Huang, Jun / Xiong, Xingui

Heliyon

2023 Volume 9, Issue 9, Page(s) e19546

Abstract: Purpose: Xiang-Sha-Liu-Jun-Zi-Tang(XSLJZT) is a common formula for the treatment of Gastric Cancer ...

Abstract	Purpose: Xiang-Sha-Liu-Jun-Zi-Tang(XSLJZT) is a common formula for the treatment of Gastric Cancer(GC) and is widely used in clinical practice, however, there is a lack of investigation into its mechanism. Methods: We collected and organized drug and disease targets, constructed the "XSLJZT-Active Ingredient-Target" visualization network, and performed GO and KEGG functional enrichment analysis of crossover genes, followed by molecular docking of active ingredients and core targets. The best docked monomers were combined with weighted gene co-expression network analysis(WGCNA) and macroscopically analyzed by GO and KEGG enrichment techniques. The results of cluster gene difference analysis, ROC evaluation, and CIBERSORT immune infiltration analysis were evaluated and finally supported by cellular experiments. Results: The main components of XSLJZT are quercetin, stigmasterol, and naringenin, effectively treat GC by targeting STAT3, TP53 and MAPK3, which are involved in IL-17, TNF and HIF-1 signaling pathways. The results of molecular docking showed that quercetin bound better to the core targets. We performed an in-depth analysis of this monomer and found that quercetin acts on the core targets of TP53, MMP9, TIMP1 and MYC, and is involved in two key signaling pathways, TNF and IL-17, thus effectively treating GC. The experimental results are consistent with our analysis that quercetin inhibits the proliferation of GC cells and promotes apoptosis, and TP53, MYC and TIMP1 are the quercetin targets for the treatment of GC. Conclusion: The present study tentatively suggests that quercetin, the main active ingredient in XSLJZT, can exert a therapeutic effect on GC by targeting TIMP1.
Language	English
Publishing date	2023-08-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e19546
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Article ; Online: Cooperation of MLL1 and Jun in controlling H3K4me3 on enhancers in colorectal cancer.

Lin, Xiang / Chen, Ji-Dong / Wang, Chen-Yu / Cai, Zhen / Zhan, Rui / Yang, Chen / Zhang, La-Ying / Li, Lian-Yun / Xiao, Yong / Chen, Ming-Kai / Wu, Min

Genome biology

2023 Volume 24, Issue 1, Page(s) 268

Abstract: ... on the identified Vm3Es. We demonstrate that the transcription factor AP1/JUN interacts with MLL1 and regulates m3E ...

Abstract	Background: Enhancer dysregulation is one of the important features for cancer cells. Enhancers enriched with H3K4me3 have been implicated to play important roles in cancer. However, their detailed features and regulatory mechanisms have not been well characterized. Results: Here, we profile the landscape of H3K4me3-enriched enhancers (m3Es) in 43 pairs of colorectal cancer (CRC) samples. M3Es are widely distributed in CRC and averagely possess around 10% of total active enhancers. We identify 1322 gain variant m3Es and 367 lost variant m3Es in CRC. The target genes of the gain m3Es are enriched in immune response pathways. We experimentally prove that repression of CBX8 and RPS6KA5 m3Es inhibits target gene expression in CRC. Furthermore, we find histone methyltransferase MLL1 is responsible for depositing H3K4me3 on the identified Vm3Es. We demonstrate that the transcription factor AP1/JUN interacts with MLL1 and regulates m3E activity. Application of a small chemical inhibitor for MLL1 activity, OICR-9429, represses target gene expression of the identified Vm3Es, enhances anti-tumor immunity and inhibits CRC growth in an animal model. Conclusions: Taken together, our study illustrates the genome-wide landscape and the regulatory mechanisms of m3Es in CRC, and reveals potential novel strategies for cancer treatment.
MeSH term(s)	Animals ; Colorectal Neoplasms/genetics ; Enhancer Elements, Genetic ; Histones/metabolism ; Myeloid-Lymphoid Leukemia Protein/genetics ; Myeloid-Lymphoid Leukemia Protein/metabolism ; Transcription Factor AP-1/metabolism ; Humans ; Proto-Oncogene Proteins c-jun/genetics ; Proto-Oncogene Proteins c-jun/metabolism
Chemical Substances	histone H3 trimethyl Lys4 ; Histones ; Myeloid-Lymphoid Leukemia Protein (149025-06-9) ; Transcription Factor AP-1 ; KMT2A protein, human ; JUN protein, human ; Proto-Oncogene Proteins c-jun
Language	English
Publishing date	2023-11-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2040529-7
ISSN	1474-760X ; 1474-760X
ISSN (online)	1474-760X
ISSN	1474-760X
DOI	10.1186/s13059-023-03108-3
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Article ; Online: Jun-APOE-LRP1 axis promotes tumor metastasis in colorectal cancer.

He, Lingyuan / Shi, Mengchen / Ren, Shuwei / Zhang, Jingdan / Tian, Yu / Yang, Xiangling / Liu, Huanliang

Biomolecules & biomedicine

2023 Volume 23, Issue 6, Page(s) 1026–1037

Abstract: ... by the transcription factor Jun by activating the proximal promoter region of APOE, and APOE-overexpression reversed ... the metastasis suppression of JUN knockdown. Furthermore, bioinformatics analysis suggested an interaction ... our study suggests that the Jun-APOE-LRP1 axis contributes to tumor metastasis in CRC. ...

Abstract	Apolipoprotein E (apoE) has previously been reported to play vital roles in tumor progression. However, the impact of apoE on colorectal cancer (CRC) metastasis remains largely unexplored. This study aimed to investigate the role of apoE in CRC metastasis and to identify the transcription factor and receptor of apoE involved in regulation of CRC metastasis. Bioinformatic analyses were conducted to examine the expression pattern and prognosis of apolipoproteins. APOE-overexpressing cell lines were utilized to explore the effects of apoE on proliferation, migration and invasion of CRC cells. Additionally, the transcription factor and receptor of apoE were screened via bioinformatics, and further validated through knockdown experiments. We discovered that the mRNA levels of APOC1, APOC2, APOD and APOE were higher in lymphatic invasion group, and a higher apoE level indicated poorer overall survival and progression-free interval. In vitro studies demonstrated that APOE-overexpression did not affect proliferation but promoted the migration and invasion of CRC cells. We also reported that APOE-expression was modulated by the transcription factor Jun by activating the proximal promoter region of APOE, and APOE-overexpression reversed the metastasis suppression of JUN knockdown. Furthermore, bioinformatics analysis suggested an interaction between apoE and low-density lipoprotein receptor-related protein 1 (LRP1). LRP1 was highly expressed in both the lymphatic invasion group and the APOEHigh group. Additionally, we found that APOE-overexpression upregulated LRP1 protein levels, and LRP1 knockdown attenuated the metastasis-promoting function of APOE. Overall, our study suggests that the Jun-APOE-LRP1 axis contributes to tumor metastasis in CRC.
MeSH term(s)	Humans ; Apolipoproteins E/metabolism ; Low Density Lipoprotein Receptor-Related Protein-1/genetics ; Transcription Factors/metabolism ; Cell Movement/genetics ; Carrier Proteins ; Colorectal Neoplasms/genetics
Chemical Substances	Apolipoproteins E ; Low Density Lipoprotein Receptor-Related Protein-1 ; Transcription Factors ; Carrier Proteins ; LRP1 protein, human
Language	English
Publishing date	2023-11-03
Publishing country	Bosnia and Herzegovina
Document type	Journal Article
ISSN	2831-090X
ISSN (online)	2831-090X
DOI	10.17305/bb.2023.9248
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Article ; Online: JunB: a paradigm for Jun family in immune response and cancer.

Ren, Fu-Jia / Cai, Xiao-Yu / Yao, Yao / Fang, Guo-Ying

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1222265

Abstract: Jun B proto-oncogene (JunB) is a crucial member of dimeric activator protein-1 (AP-1) complex ...

Abstract	Jun B proto-oncogene (JunB) is a crucial member of dimeric activator protein-1 (AP-1) complex, which plays a significant role in various physiological processes, such as placental formation, cardiovascular development, myelopoiesis, angiogenesis, endochondral ossification and epidermis tissue homeostasis. Additionally, it has been reported that JunB has great regulatory functions in innate and adaptive immune responses by regulating the differentiation and cytokine secretion of immune cells including T cells, dendritic cells and macrophages, while also facilitating the effector of neutrophils and natural killer cells. Furthermore, a growing body of studies have shown that JunB is involved in tumorigenesis through regulating cell proliferation, differentiation, senescence and metastasis, particularly affecting the tumor microenvironment through transcriptional promotion or suppression of oncogenes in tumor cells or immune cells. This review summarizes the physiological function of JunB, its immune regulatory function, and its contribution to tumorigenesis, especially focusing on its regulatory mechanisms within tumor-associated immune processes.
MeSH term(s)	Female ; Pregnancy ; Humans ; Placenta ; Neoplasms ; Carcinogenesis ; Cell Transformation, Neoplastic ; Immunity ; Tumor Microenvironment ; Transcription Factors
Chemical Substances	JunB protein, human ; Transcription Factors
Language	English
Publishing date	2023-09-04
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1222265
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Article ; Online: c-Jun phosphorylated by JNK is required for protecting Gli2 from proteasomal-ubiquitin degradation by PGE2-JNK signaling axis.

Yang, Jun / Wang, Juan / Zhang, Yu / Huang, Wenjing / Zhang, Shaoqing / Yin, Peihao / Tan, Wenfu

Biochimica et biophysica acta. Molecular cell research

2022 Volume 1870, Issue 3, Page(s) 119418

Abstract: ... signaling pathway. In this study, we showed that c-Jun, a classic substrate of JNK, increased Gli2 protein stability ... after phosphorylated by PGE2. Suppressing the function of c-Jun or JNK indicated that c-Jun prevents ... of Gli2 was detected in colorectal cancer cells treated with PGE2 while suppression of c-Jun restored ...

Abstract	Hedgehog (Hh) signaling pathway includes canonical and non-canonical activation manners. In colorectal cancer, we have previously shown that PGE2-JNK could initiate non-canonical activation of the Hh signaling pathway. In this study, we showed that c-Jun, a classic substrate of JNK, increased Gli2 protein stability after phosphorylated by PGE2. Suppressing the function of c-Jun or JNK indicated that c-Jun prevents Gli2 from protease degradation caused by PGE2-JNK. Moreoer, we revealed that less ubiquitination of Gli2 was detected in colorectal cancer cells treated with PGE2 while suppression of c-Jun restored the ubiquitination of Gli2. In addition, we observed that suppression of c-Jun significantly decreased Gli2 expression no matter when Gli2 remained in phosphorylation or non-phosphorylation state. These phenomena were recapitulated, when the endpoint of Gli2 expression was replaced by Gli2 ubiquitination. Furthermore, we demonstrated that restricting c-Jun function ablated the PGE2-provoked Hh activity and proliferation of colorectal cancer cells. These results elucidated that the evasion of Gli2 with phosphorylation from proteasomal-ubiquitin degradation needed the cooperation of phosphorylated c-Jun by kinase JNK, which contributed to promoting Hh activation and the proliferation of colorectal cancer cells. This study provides a theoretical foundation to target PGE2 downstream for the prevention and treatment of colorectal cancer.
MeSH term(s)	Humans ; Colorectal Neoplasms ; Dinoprostone ; Hedgehog Proteins/metabolism ; Kruppel-Like Transcription Factors/metabolism ; Nuclear Proteins ; Ubiquitin/metabolism ; Zinc Finger Protein Gli2 ; Proto-Oncogene Proteins c-jun/metabolism ; JNK Mitogen-Activated Protein Kinases/metabolism
Chemical Substances	Dinoprostone (K7Q1JQR04M) ; GLI2 protein, human ; Hedgehog Proteins ; Kruppel-Like Transcription Factors ; Nuclear Proteins ; Ubiquitin ; Zinc Finger Protein Gli2 ; Proto-Oncogene Proteins c-jun ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2022-12-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamcr.2022.119418
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Article ; Online: ZBTB7B is a permissive regulator of hepatocellular carcinoma initiation by repressing c-Jun expression and function.

Zhu, Yue / Wang, Qinqin / Xie, Xinyu / Ma, Cuihong / Qiao, Yuemei / Zhang, Yu / Wu, Yanjun / Gao, Yuan / Jiang, Jing / Liu, Xin / Chen, Jianfeng / Li, Chen / Ge, Gaoxiang

Cell death & disease

2024 Volume 15, Issue 1, Page(s) 55

Abstract: ... Integrative multi-omics analyses identify c-Jun as the core signaling node in ZBTB7B-deficient liver cancer ... initiation. c-Jun is a direct target of ZBTB7B essential to accelerated liver cancer initiation in ZBTB7B ... deficient livers. Knockdown of c-Jun expression or dominant negative c-Jun expression delays HCC development ...

Abstract	Hepatocarcinogenesis is a multi-step process. However, the regulators of hepatocellular carcinoma (HCC) initiation are understudied. Adult liver-specific gene expression was globally downregulated in HCC. We hypothesize that adult liver-specific genes, especially adult liver-enriched transcription factors may exert tumor-suppressive functions in HCC. In this study, we identify ZBTB7B, an adult liver-enriched transcription factor as a permissive regulator of HCC initiation. ZBTB7B is highly expressed in hepatocytes in adult livers, compared to fetal livers. To evaluate the functions of ZBTB7B in hepatocarcinogenesis, we performed hepatocyte-specific ZBTB7B knockout in hydrodynamic oncogene transfer-induced mouse liver cancer models. Hepatocyte-specific knockout of ZBTB7B promotes activated Akt and N-Ras-induced HCC development. Moreover, ZBTB7B deficiency sensitizes hepatocytes to a single oncogene Akt-induced oncogenic transformation and HCC initiation, which is otherwise incompetent in inducing HCC. ZBTB7B deficiency accelerates HCC initiation by down-regulating adult liver-specific gene expression and priming livers to a fetal-like state. The molecular mechanism underlying ZBTB7B functions in hepatocytes was investigated by integrated transcriptomic, phosphoproteomic, and chromatin immunoprecipitation-sequencing analyses. Integrative multi-omics analyses identify c-Jun as the core signaling node in ZBTB7B-deficient liver cancer initiation. c-Jun is a direct target of ZBTB7B essential to accelerated liver cancer initiation in ZBTB7B-deficient livers. Knockdown of c-Jun expression or dominant negative c-Jun expression delays HCC development in ZBTB7B-deficient livers. In addition, ZBTB7B competes with c-Jun for chromatin binding. Ectopic ZBTB7B expression attenuates the tumor-promoting functions of c-Jun. Expression of ZBTB7B signature, composed of 140 genes co-regulated by ZBTB7B and c-Jun, is significantly downregulated in early-stage HCCs compared to adjacent normal tissues, correlates to liver-specific gene expression, and is associated with good prognosis in human HCC. Thus, ZBTB7B functions as a permissive regulator of HCC initiation by directly regulating c-Jun expression and function.
MeSH term(s)	Animals ; Humans ; Mice ; Carcinogenesis/genetics ; Carcinoma, Hepatocellular/pathology ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation, Neoplastic ; Liver Neoplasms/pathology ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	DNA-Binding Proteins ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Transcription Factors ; Zbtb7b protein, mouse
Language	English
Publishing date	2024-01-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-024-06441-y
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Article ; Online: Gasdermin E promotes translocation of p65 and c-jun into nucleus in keratinocytes for progression of psoriatic skin inflammation.

Long, Fangyuan / Wei, Xuecui / Chen, Yujie / Li, Min / Lian, Ni / Yu, Shanshan / Chen, Sihan / Yang, Yong / Gu, Heng / Chen, Xu

Cell death & disease

2024 Volume 15, Issue 3, Page(s) 180

Abstract: Gasdermin E (GSDME) has recently been identified as a critical executioner to mediate pyroptosis. While epidermal keratinocytes can initiate GSDME-mediated pyroptosis, the role of keratinocyte GSDME in psoriatic dermatitis remains poorly characterized. ... ...

Abstract	Gasdermin E (GSDME) has recently been identified as a critical executioner to mediate pyroptosis. While epidermal keratinocytes can initiate GSDME-mediated pyroptosis, the role of keratinocyte GSDME in psoriatic dermatitis remains poorly characterized. Through analysis of GEO datasets, we found elevated GSDME levels in psoriatic lesional skin. Additionally, GSDME levels correlated with both psoriasis severity and response to biologics treatments. Single-cell RNA sequencing (scRNA-seq) from a GEO dataset revealed GSDME upregulation in keratinocytes of psoriasis patients. In the imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model, both full-length and cleaved forms of caspase-3 and GSDME were elevated in the epidermis. Abnormal proliferation and differentiation of keratinocytes and dermatitis were attenuated in Gsdme
MeSH term(s)	Animals ; Humans ; Mice ; Dermatitis/metabolism ; Dermatitis/pathology ; Gasdermins/metabolism ; Imiquimod/adverse effects ; Inflammation/pathology ; Keratinocytes/pathology ; Psoriasis/metabolism ; Psoriasis/pathology ; Transcription Factor RelA/metabolism ; Proto-Oncogene Proteins c-jun/metabolism
Chemical Substances	Gasdermins ; Imiquimod (P1QW714R7M) ; GSDME protein, human ; Gsdme protein, mouse ; Transcription Factor RelA ; Proto-Oncogene Proteins c-jun
Language	English
Publishing date	2024-03-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-024-06545-5
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Article ; Online: Shengjihuayu formula ameliorates the oxidative injury in human keratinocytes via blocking JNK/c-Jun/MMPs signaling pathway.

Sun, Lu / Yin, Hao / Li, Yu-Ting / Qiao, Yun-Xiao / Wang, Jie / He, Qing-Yi / Xiao, Zhen-Wei / Kuai, Le / Xiang, Yan-Wei

Journal of ethnopharmacology

2024 Volume 326, Page(s) 117938

Abstract: ... PRDX1, HSP90AA1, HSP90AB1, HSPA8, and TNF-α. Western blot revealed the presence of the JNK/c-Jun/MMPs ...

Abstract	Ethnopharmacological relevance: The reactive oxygen species (ROS) surge in the chronic wound tissue of diabetic ulcers (DUs) aggravates the inflammatory response. The oxidative stress state during inflammation will exacerbate inflammation and cause tissue damage, resulting in prolonged wound healing. Shengjihuayu Formula (SJHYF) is a renowned Chinese medicine prescription for treating chronic wounds in diabetic ulcers. Growing clinical evidence has demonstrated that SJHYF exhibits superior therapeutic efficacy and has a favorable safety profile. However, the underlying mechanisms by which SJHYF ameliorates oxidative damage under pathological conditions of DUs remain unclear. Objective: To investigate the cytoprotective properties of SJHYF on hydrogen peroxide (H Methods: HaCaT cells were incubated with H Results: The application of SJHY at a concentration of 0.25 mg/mL promoted cell proliferation, cell migration, and reduced ROS production. In addition, SJHYF was detected to have a total of 93 active compounds, including key components such as Galloyl-beta-D-glucose, Danshensu, Procyanidin B2, Catechin, and Alkannin. The RNA-seq analysis identified several core targets namely KRT17, TGM1, JUNB, PRDX5, TXNIP, PRDX1, HSP90AA1, HSP90AB1, HSPA8, and TNF-α. Western blot revealed the presence of the JNK/c-Jun/MMPs pathway and its related transcription factors. Conclusion: SJHYF displays significant protective effects on H
MeSH term(s)	Humans ; Reactive Oxygen Species/metabolism ; Hydrogen Peroxide/metabolism ; Ulcer ; Oxidative Stress ; Keratinocytes ; MAP Kinase Signaling System ; Inflammation/metabolism ; Diabetes Mellitus/metabolism ; Apoptosis ; Glucose
Chemical Substances	Reactive Oxygen Species ; Hydrogen Peroxide (BBX060AN9V) ; beta-d-glucose ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2024-02-22
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2024.117938
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Article ; Online: Notch-mediated lactate metabolism regulates MDSC development through the Hes1/MCT2/c-Jun axis.

Zhao, Jun-Long / Ye, Yu-Chen / Gao, Chun-Chen / Wang, Liang / Ren, Kai-Xi / Jiang, Ru / Hu, Si-Jun / Liang, Shi-Qian / Bai, Jian / Liang, Jia-Long / Ma, Peng-Fei / Hu, Yi-Yang / Li, Ben-Chang / Nie, Yong-Zhan / Chen, Yan / Li, Xiao-Fei / Zhang, Wei / Han, Hua / Qin, Hong-Yan

Cell reports

2022 Volume 38, Issue 10, Page(s) 110451

Abstract: ... Jun as a novel intracellular sensor of lactate in myeloid cells using liquid-chromatography ... mass spectrometry (LC-MS) followed by CRISPR-Cas9-mediated gene disruption. Meanwhile, lactate interacts with c-Jun ... between the Notch-MCT2/lactate-c-Jun axis in myeloid cells and tumorigenesis is also confirmed in clinical ...

Abstract	Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) play critical roles in tumorigenesis. However, the mechanisms underlying MDSC and TAM development and function remain unclear. In this study, we find that myeloid-specific activation of Notch/RBP-J signaling downregulates lactate transporter MCT2 transcription via its downstream molecule Hes1, leading to reduced intracellular lactate levels, blunted granulocytic MDSC (G-MDSC) differentiation, and enhanced TAM maturation. We identify c-Jun as a novel intracellular sensor of lactate in myeloid cells using liquid-chromatography-mass spectrometry (LC-MS) followed by CRISPR-Cas9-mediated gene disruption. Meanwhile, lactate interacts with c-Jun to protect from FBW7 ubiquitin-ligase-mediated degradation. Activation of Notch signaling and blockade of lactate import repress tumor progression by remodeling myeloid development. Consistently, the relationship between the Notch-MCT2/lactate-c-Jun axis in myeloid cells and tumorigenesis is also confirmed in clinical lung cancer biopsies. Taken together, our current study shows that lactate metabolism regulated by activated Notch signaling might participate in MDSC differentiation and TAM maturation.
MeSH term(s)	Carcinogenesis/genetics ; Humans ; Lactic Acid ; Myeloid Cells ; Myeloid-Derived Suppressor Cells ; Signal Transduction ; Transcription Factor HES-1
Chemical Substances	Transcription Factor HES-1 ; HES1 protein, human (149348-15-2) ; Lactic Acid (33X04XA5AT)
Language	English
Publishing date	2022-03-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.110451
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Article ; Online: A study related to the treatment of gastric cancer with Xiang-Sha-Liu-Jun-Zi-Tang based on network analysis

Ke Jiang / Heli Liu / Jie Ge / Bo Yang / Yu Wang / Wenbo Wang / Yuqi Wen / Siqing Zeng / Quan Chen / Jun Huang / Xingui Xiong

Heliyon, Vol 9, Iss 9, Pp e19546- (2023)

2023

Abstract: Purpose: Xiang-Sha-Liu-Jun-Zi-Tang(XSLJZT) is a common formula for the treatment of Gastric Cancer ...

Abstract	Purpose: Xiang-Sha-Liu-Jun-Zi-Tang(XSLJZT) is a common formula for the treatment of Gastric Cancer(GC) and is widely used in clinical practice, however, there is a lack of investigation into its mechanism. Methods: We collected and organized drug and disease targets, constructed the “XSLJZT-Active Ingredient-Target” visualization network, and performed GO and KEGG functional enrichment analysis of crossover genes, followed by molecular docking of active ingredients and core targets. The best docked monomers were combined with weighted gene co-expression network analysis(WGCNA) and macroscopically analyzed by GO and KEGG enrichment techniques. The results of cluster gene difference analysis, ROC evaluation, and CIBERSORT immune infiltration analysis were evaluated and finally supported by cellular experiments. Results: The main components of XSLJZT are quercetin, stigmasterol, and naringenin, effectively treat GC by targeting STAT3, TP53 and MAPK3, which are involved in IL-17, TNF and HIF-1 signaling pathways. The results of molecular docking showed that quercetin bound better to the core targets. We performed an in-depth analysis of this monomer and found that quercetin acts on the core targets of TP53, MMP9, TIMP1 and MYC, and is involved in two key signaling pathways, TNF and IL-17, thus effectively treating GC. The experimental results are consistent with our analysis that quercetin inhibits the proliferation of GC cells and promotes apoptosis, and TP53, MYC and TIMP1 are the quercetin targets for the treatment of GC. Conclusion: The present study tentatively suggests that quercetin, the main active ingredient in XSLJZT, can exert a therapeutic effect on GC by targeting TIMP1.
Keywords	XSLJZT ; GC ; Network Pharmacology ; Molecular Docking ; WGCNA ; Mechanism of action ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	004
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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