The multi-target mechanism of action of Selaginella doederleinii Hieron in the treatment of nasopharyngeal carcinoma: a network pharmacology and multi-omics analysis

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 2, 2025

Nasopharyngeal carcinoma (NPC) presents significant treatment challenges due to its complex etiology and late-stage diagnosis. The traditional Chinese medicine Selaginella doederleinii Hieron (S. doederleinii) has shown potentiality in NPC multi-target, multi-pathway anti-cancer mechanisms. First, we identified related target genes from databases like GeneCards, OMIM, DisGeNET, performed WGCNA analysis on the GSE53819 dataset identify several important gene modules NPC. Active components their targets S. were screened TCMSP other databases, identifying 32 overlapping genes. Gene Ontology (GO) Kyoto Encyclopedia of Genes Genomes (KEGG) pathway revealed that these are primarily involved critical biological processes protein phosphorylation cell cycle regulation. A protein–protein interaction network was constructed, cytoHubba six key (BCL2, MAPK14, ABCB1, PLK1, ATM, HMOX1). Kaplan–Meier immune infiltration further showed closely prognosis microenvironment patients. Single-cell RNA sequencing expression distribution across different types explored roles differentiation process malignant cells through pseudotime trajectory analysis. Molecular docking dynamics simulation results indicated Berberine-MAPK14 Matairesinol-PLK1 complexes have high binding affinity stability. Binding free energy calculations confirmed stability complexes. Based our comprehensive multi-level analysis, active may play a role multi-target synergistic effects.

Язык: Английский

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Tumor-derived erythropoietin acts as an immunosuppressive switch in cancer immunity

Science, Год журнала: 2025, Номер 388(6745)

Опубликована: Апрель 24, 2025

Successful cancer immunotherapy requires a patient to mount an effective immune response against tumors; however, many cancers evade the body’s system. To investigate basis for treatment failure, we examined spontaneous mouse models of hepatocellular carcinoma (HCC) with either inflamed T cell–rich or noninflamed cell–deprived tumor microenvironment (TME). Our studies reveal that erythropoietin (EPO) secreted by cells determines immunotype. Tumor-derived EPO autonomously generates TME interacting its cognate receptor EPOR on tumor-associated macrophages (TAMs). signaling prompts TAMs become immunoregulatory through NRF2-mediated heme depletion. Removing tumor-derived leads and regression independent genotype, owing augmented antitumor cell immunity. Thus, EPO/EPOR axis functions as immunosuppressive switch

Язык: Английский

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Clinical Significance of Heme Oxygenase 1 in Tumor Progression

Antioxidants, Год журнала: 2021, Номер 10(5), С. 789 - 789

Опубликована: Май 17, 2021

Heme oxygenase 1 (HO-1) plays a key role in cell adaptation to stressors through the antioxidant, antiapoptotic, and anti-inflammatory properties of its metabolic products. For these reasons, cancer cells, HO-1 can favor aggressiveness resistance therapies, leading poor prognosis/outcome. Genetic polymorphisms promoter have been associated with an increased risk progression high degree therapy failure. Moreover, evidence from biopsies highlights possible correlation between expression, pathological features, clinical outcome. Indeed, levels tumor specimens often correlate reduced survival rates. Furthermore, modulation has proposed order improve efficacy antitumor therapies. However, contrasting on biology reported. This review focuses as promising biomarker progression; understanding data might guide therapeutic choice outcome patients terms prognosis life quality.

Язык: Английский

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Loss of the intracellular enzyme QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity

Nature Immunology, Год журнала: 2022, Номер 23(4), С. 568 - 580

Опубликована: Март 21, 2022

Язык: Английский

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The capture of extracellular vesicles endogenously released by xenotransplanted tumours induces an inflammatory reaction in the premetastatic niche

Journal of Extracellular Vesicles, Год журнала: 2023, Номер 12(5)

Опубликована: Май 1, 2023

Abstract The capture of tumour‐derived extracellular vesicles (TEVs) by cells in the tumour microenvironment (TME) contributes to metastasis and notably formation pre‐metastatic niche (PMN). However, due challenges associated with modelling release small EVs vivo, kinetics PMN response endogenously released TEVs have not been examined. Here, we studied endogenous mice orthotopically implanted metastatic human melanoma (MEL) neuroblastoma (NB) releasing GFP‐tagged (GFTEVs) their host demonstrate active contribution metastasis. Human GFTEVs captured mouse macrophages vitro resulted transfer GFP exosomal miR‐1246. Mice MEL or NB showed presence blood between 5 28 days after implantation. Moreover, kinetic analysis TEV resident relative arrival outgrowth TEV‐producing organs demonstrated that lung liver precedes homing cells, consistent critical roles formation. Importantly, at future sites was miR‐1246 macrophages, stellate cells. This is first demonstration organotropic as TEV‐capturing only absence non‐metastatic organs. induced dynamic changes inflammatory gene expression which evolved a pro‐tumorigenic reaction progressed state. Thus, our work describes novel approach tracking vivo provides additional insights into role earliest stages progression.

Язык: Английский

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Epigenetics and Metabolism Reprogramming Interplay into Glioblastoma: Novel Insights on Immunosuppressive Mechanisms

Antioxidants, Год журнала: 2023, Номер 12(2), С. 220 - 220

Опубликована: Янв. 18, 2023

The central nervous system represents a complex environment in which glioblastoma adapts skillfully, unleashing series of mechanisms suitable for its efficient development and diffusion. In particular, changes gene expression mutational events that fall within the domain epigenetics interact complexly with metabolic reprogramming stress responses enacted tumor microenvironment, turn fuel genomic instability by providing substrates DNA modifications. aim this review is to analyze interaction consolidates several conditions confer state immunosuppression immunoevasion, making capable escaping attack elimination immune cells therefore invincible against current therapies. progressive knowledge cellular underlie resistance represents, fact, only weapon unmask weak points be exploited plan successful therapeutic strategies.

Язык: Английский

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The Multiple Facets of Iron Recycling

Genes, Год журнала: 2021, Номер 12(9), С. 1364 - 1364

Опубликована: Авг. 30, 2021

The production of around 2.5 million red blood cells (RBCs) per second in erythropoiesis is one the most intense activities body. It continuously consumes large amounts iron, approximately 80% which recycled from aged erythrocytes. Therefore, similar to “making”, “breaking” also very rapid and represents key processes mammalian physiology. Under steady-state conditions, this important task accomplished by specialized macrophages, mostly liver Kupffer (KCs) splenic pulp macrophages (RPMs). relies a extent on engulfment via so-called erythrophagocytosis. Surprisingly, we still understand little about mechanistic details removal processing these macrophages. We have only started uncover signaling pathways that imprint their identity, control functions enable plasticity. Recent findings identify other myeloid cell types capable establish reciprocal cross-talk between intensity erythrophagocytosis cellular activities. Here, aimed review multiple emerging facets iron recycling illustrate how exciting field study currently expanding.

Язык: Английский

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Invasive margin tissue-resident macrophages of high CD163 expression impede responses to T cell-based immunotherapy

Journal for ImmunoTherapy of Cancer, Год журнала: 2023, Номер 11(3), С. e006433 - e006433

Опубликована: Март 1, 2023

Primary and secondary resistance is a major hurdle in cancer immunotherapy. Therefore, better understanding of the underlying mechanisms involved immunotherapy pivotal importance to improve therapy outcome.Here, two mouse models with against therapeutic vaccine-induced tumor regression were studied. Exploration microenvironment by high dimensional flow cytometry combination vivo settings allowed for identification immunological factors driving resistance.Comparison immune infiltrate during early late revealed change from tumor-rejecting toward tumor-promoting macrophages. In concert, rapid exhaustion tumor-infiltrating T cells was observed. Perturbation studies identified small but discernible CD163hi macrophage population, expression several markers functional anti-inflammatory transcriptome profile, not other macrophages, be responsible. In-depth analyses that they localize at invasive margins are more resistant Csf1r inhibition when compared validated activity heme oxygenase-1 as an mechanism resistance. The transcriptomic profile macrophages highly similar human monocyte/macrophage indicating represent target efficacy.In this study, population tissue-resident responsible primary T-cell-based immunotherapies. While these M2 Csf1r-targeted therapies, in-depth characterization allows specific targeting subset thereby creating new opportunities intervention aim overcome

Язык: Английский

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Heme Oxygenase-1 and Its Role in Colorectal Cancer

Antioxidants, Год журнала: 2023, Номер 12(11), С. 1989 - 1989

Опубликована: Ноя. 10, 2023

Heme oxygenase-1 (HO-1) is an enzyme located at the endoplasmic reticulum, which responsible for degradation of cellular heme into ferrous iron, carbon monoxide and biliverdin-IXa. In addition to this main function, involved in many other homeostatic, toxic cancer-related mechanisms. review, we first summarize importance HO-1 physiology pathophysiology with a focus on digestive system. We then detail its structure followed by section regulatory mechanisms that control expression activity. Moreover, HO-2 as important further HO isoform discussed, highlighting similarities differences regard HO-1. Subsequently, describe direct indirect cytoprotective functions breakdown products biliverdin-IXa, but also highlight possible pro-inflammatory effects. Finally, address role cancer particular colorectal cancer. Here, relevant pathways are presented, through impacts tumor induction progression. These include oxidative stress DNA damage, ferroptosis, cell cycle progression apoptosis well migration, proliferation, epithelial-mesenchymal transition.

Язык: Английский

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Ferritin heavy chain supports stability and function of the regulatory T cell lineage

The EMBO Journal, Год журнала: 2024, Номер 43(8), С. 1445 - 1483

Опубликована: Март 18, 2024

Abstract Regulatory T (TREG) cells develop via a program orchestrated by the transcription factor forkhead box protein P3 (FOXP3). Maintenance of TREG cell lineage relies on sustained FOXP3 mechanism involving demethylation cytosine-phosphate-guanine (CpG)-rich elements at conserved non-coding sequences (CNS) in locus. This cytosine is catalyzed ten–eleven translocation (TET) family dioxygenases, and it involves redox reaction that uses iron (Fe) as an essential cofactor. Here, we establish human mouse express Fe-regulatory genes, including encoding ferritin heavy chain (FTH), relatively high levels compared to conventional helper cells. We show FTH expression for immune homeostasis. Mechanistically, supports TET-catalyzed CpG-rich CNS1 2 locus, thereby promoting stability. process, which stability function, limits severity autoimmune neuroinflammation infectious diseases, favors tumor progression. These findings suggest regulation intracellular stable property homeostasis pathological outcomes immune-mediated inflammation.

Язык: Английский

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