Immunogenic shift of arginine metabolism triggers systemic metabolic and immunological reprogramming to prevent HER2+ breast cancer DOI Creative Commons
Vandana Sharma, Veani Fernando,

Xunzhen Zheng

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 26, 2024

Abstract Arginine metabolism in tumors is often shunted into the pathway producing pro-tumor and immune suppressive polyamines (PAs), while downmodulating alternative nitric oxide (NO) synthesis pathway. Aiming to correct arginine tumors, deprivation therapy inhibitors of PA have been developed. Despite some therapeutic advantages, these approaches yielded severe side effects, making it necessary explore an strategy. We previously reported that supplementing SEP, endogenous precursor BH 4 (the essential NO synthase cofactor), could tumor cells tumor-associated macrophages (TAMs) induce their metabolic phenotypic reprogramming. saw oral SEP treatment effectively suppressed growth HER2-positive mammary animals. also has no dose-dependent toxicity clinical trials for disorders. In present study, we report a long-term use animals susceptible prevented occurrence. These SEP-treated had undergone reprogramming systemic immunity, elevating total T cell counts circulation bone marrow. Given marrow-resident are mostly memory cells, plausible chronic promoted formation, leading potent prevention. findings suggest possible roles SEP/BH /NO axis promoting formation its potential utility preventing breast cancer.

Язык: Английский

Single-cell RNA sequencing highlights the role of distinct natural killer subsets in sporadic amyotrophic lateral sclerosis DOI Creative Commons

Esther Álvarez‐Sánchez,

Álvaro Carbayo,

Natalia Valle‐Tamayo

и другие.

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Янв. 23, 2025

Neuroinflammation plays a major role in amyotrophic lateral sclerosis (ALS), and cumulative evidence suggests that systemic inflammation the infiltration of immune cells into brain contribute to this process. However, no study has investigated peripheral blood ALS pathophysiology using single-cell RNA sequencing (scRNAseq). We aimed characterize from identify ALS-related alterations at resolution. For purpose, mononuclear (PBMC) were isolated 14 patients cognitively unimpaired healthy individuals (HC), matched by age gender, cryopreserved until library preparation scRNAseq. analyzed differences proportions PBMC, gene expression, cell-cell communication patterns between HC, as well their association with plasma neurofilament light (NfL) concentrations, surrogate biomarker for neurodegeneration. Flow cytometry was used validate cell type proportions. identified expansion CD56dim natural killer (NK) (fold change = 2; adj. p-value 0.0051), mainly driven specific subpopulation, NK_2 3.12; 0.0001), which represent mature cytotoxic NK subset. Our results revealed extensive expression cells, pointing towards activation response (adj. 9.2 × 10− 11) regulation lymphocyte proliferation 6.46 6). also changes other such classical monocytes, distinct CD8 + effector memory T suggested enhanced antigen presentation via histocompatibility class-II 1.23 8) ALS. The inference demonstrated interaction HLA-E CD94:NKG2C different lymphocytes is unique compared HC. Finally, regression analysis proportion CD56bright along ALSFRS-r, disease duration, explained up 76.4% variance NfL levels. reveal signature relevant occurring underscore proportion, signaling terminally differentiated subpopulation (NK_2), possible

Язык: Английский

Процитировано

0
Impact of Mlkl or Ripk3 deletion on age-associated liver inflammation, metabolic health, and lifespan DOI Creative Commons

Sabira Mohammed,

Phoebe Ohene-Marfo, Chao Jiang

и другие.

GeroScience, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Abstract Chronic, low-grade inflammation is a hallmark of aging and various age-related diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). The prevalence steatohepatitis (MASH), an advanced form MASLD, increases with age contributes to morbidity mortality among the elderly. This study investigates role necroptosis, programmed cell death pathway that promotes inflammation, in inflammaging age-associated MASLD by utilizing genetic ablation models two key necroptosis proteins, Mlkl or Ripk3. absence Ripk3 significantly reduced steatosis, fibrosis aged male mice, supporting MASLD. Additionally, deletion impacted other non-necroptotic cellular processes drive such as senescence, apoptosis, autophagy liver. Levels plasma TNFα IL6, proinflammatory cytokines associated inflammaging, are −/− systemic effect inhibition on inflammation. Proteomic analysis tissues emphasizes critical lipid immune regulatory maintaining homeostasis when absent While did not affect lifespan shortened it. deficiency improved insulin sensitivity, whereas exacerbated glucose intolerance mice. Thus, selective Mlkl, Ripk3, represents potential therapeutic avenue for mitigating enhancing outcomes

Язык: Английский

Процитировано

0
GTSE1-expressed osteoblastic cells facilitate formation of pro-metastatic tumor microenvironment in osteosarcoma DOI Creative Commons
Linzhu Wang, Wenyue Li,

Weihang Ji

и другие.

Genes & Diseases, Год журнала: 2025, Номер unknown, С. 101591 - 101591

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Immunogenic shift of arginine metabolism triggers systemic metabolic and immunological reprogramming to suppress HER2 + breast cancer DOI Creative Commons
Vandana Sharma, Veani Fernando,

Xunzhen Zheng

и другие.

Cancer & Metabolism, Год журнала: 2025, Номер 13(1)

Опубликована: Март 20, 2025

Arginine metabolism in tumors is often shunted into the pathway producing pro-tumor and immune suppressive polyamines (PAs), while downmodulating alternative nitric oxide (NO) synthesis pathway. Aiming to correct arginine tumors, deprivation therapy inhibitors of PA have been developed. Despite some therapeutic advantages, these approaches yielded severe side effects, making it necessary explore an strategy. We previously reported that supplementing sepiapterin (SEP), endogenous precursor tetrahydrobiopterin (BH4, essential NO synthase cofactor), could tumor cells tumor-associated macrophages (TAMs) induce their metabolic phenotypic reprogramming. saw oral SEP treatment effectively suppressed growth HER2-positive mammary animals. also has no dose-dependent toxicity clinical trials for disorders. In present study, we tested our hypothesis a long-term administration individuals susceptible would protect them against occurrence. administered SEP, comparison control DMSO, MMTV-neu mice 8 months starting at pre-pubertal stage. monitored onsets determine rate tumor-free survival. After treatment, grouped animals DMSO with or without tumors. analyzed blood metabolites, PBMC, bone marrow vs. treated found use These SEP-treated had undergone reprogramming systemic immunity, elevating total T cell counts circulation marrow. Given marrow-resident are mostly memory cells, plausible chronic promoted formation, leading potent prevention. findings suggest possible roles SEP/BH4/NO axis promoting formation its potential utility preventing breast cancer.

Язык: Английский

Процитировано

0
In vivo synergistic enhancement of MIF‐mediated inflammation in acute lung injury by the plant ortholog ArabidopsisMDL1 DOI Creative Commons
Lukas Spiller, Lin Zhang, Simona Gerra

и другие.

The FASEB Journal, Год журнала: 2025, Номер 39(6)

Опубликована: Март 26, 2025

Abstract Recent research has uncovered Arabidopsis thaliana proteins that are similar to the human inflammatory cytokine MIF. Plant MIF/D‐dopachrome tautomerase (D‐DT)‐like (MDLs) can interact with MIF, yet significance of these findings in living organisms not been investigated. Given MIF's key role acute respiratory distress syndrome promoting pulmonary inflammation, pathology, and leukocyte infiltration, here we set out investigate interplay between MIF MDL1, one three A. orthologs, an vivo mouse model MIF‐induced lung injury (ALI). Human MDL1 were administered C57BL/6 mice via inhalation, individually or combination. Inhalation promoted various parameters as evaluated by flow cytometry, immunofluorescence microscopy, RT‐qPCR, ELISA, while inhalation alone had no effect. Intriguingly, combined treatment synergistically enhanced infiltration neutrophils monocytic cells, accompanied upregulation pro‐inflammatory genes. Thus, plant‐derived ortholog potentiates inflammation ALI. These data support growing evidence interactions compounds mediators illustrate how they may impact health.

Язык: Английский

Процитировано

0
Integration of bulk RNA-seq and scRNA-seq reveals transcriptomic signatures associated with deep vein thrombosis DOI Creative Commons
Bin Pan, Mingjun Jiang, Liming Deng

и другие.

Frontiers in Genetics, Год журнала: 2025, Номер 16

Опубликована: Апрель 24, 2025

Deep vein thrombosis (DVT) is a prevalent peripheral vascular disease. The intricate and multifaceted nature of the associated mechanisms hinders comprehensive understanding disease-relevant targets. This study aimed to identify examine most distinctive genes linked DVT. In this study, bulk RNA sequencing (bulk RNA-seq) analysis was conducted on whole blood samples from 11 DVT patients six control groups. Topology performed using seven protein-protein interaction (PPI) network algorithms. combination weighted correlation (WGCNA) clinical prediction models employed validate hub DEGs. Furthermore, single-cell (scRNA-seq) 3 three groups probe cellular localization target genes. Based same methodology as internal test set, 12 were collected construct an external set validated machine learning (ML) algorithms immunofluorescence (IF). Concurrently, examination pathways in disparate cell populations basis CellChat pathway. A total 193 DEGs identified set. Additionally, eight highly characteristic (including TLR1, TLR7, TLR8, CXCR4, DDX58, TNFSF10, FCGR1A CD36) by PPI algorithm. accordance with WGCNA model, aforementioned all situated within blue core module, exhibiting coefficient 0.84. model demonstrated notable disparities TLR8 (P = 0.018, AUC 0.847), CXCR4 0.00088, 1.000), TNFSF10 0.00075, 0.958), 0.00022, 0.986). scRNA-seq that B cells, T cells monocytes play active role validation potential ML algorithm IF. context pathway, it indicated MIF - (CD74 + CXCR4) plays role. findings indicate may serve genetic marker for DVT, potentially implicated regulatory underlying

Язык: Английский

Процитировано

0
Human and Mouse Bone Marrow CD45+ Erythroid Cells Have a Constitutive Expression of Antibacterial Immune Response Signature Genes DOI Creative Commons
Roman Perik-Zavodskii, Olga Perik-Zavodskaia, Julia Shevchenko

и другие.

Biomedicines, Год журнала: 2025, Номер 13(5), С. 1218 - 1218

Опубликована: Май 17, 2025

Introduction: Recent studies have shown that Erythroid progenitor cells exhibit a distinct immunosuppressive and immunoregulatory phenotype associated with the response to bacteria. Methods: The objective of this study was comprehensively explore traits human bone marrow through protein–protein interaction network analysis using cytokine secretion analysis, single-cell immunoproteomic flow cytometry, as well re-analysis publicly available mouse Erythroid-cell transcriptomic data. Results: Our protein-coding genes identified enrichment in immune lipopolysaccharide, Calprotectin Cathepsin G being main factors. We then mapped CD45+ both humans mice via scRNA-seq Additionally, we observed secrete cytokines chemokines, such IL-1b, IL-8, IL-18, which are also mainly involved lipopolysaccharide. found conditional media inhibit bacterial growth vitro. Discussion: These findings suggest possess potential combat pathogenic microbes thus play role innate antimicrobial immunity. Conclusions: potent cell population mice.

Язык: Английский

Процитировано

0
Exploring T Cell and NK Cell Involvement in Ankylosing Spondylitis Through Single‐Cell Sequencing DOI Creative Commons
Tianyou Chen, Shipeng Ning, Jichong Zhu

и другие.

Journal of Cellular and Molecular Medicine, Год журнала: 2024, Номер 28(24)

Опубликована: Дек. 1, 2024

ABSTRACT To uncover the complex immune mechanisms driving inflammation in ankylosing spondylitis and lay groundwork for identifying new therapeutic targets innovative approaches, we conducted 10× single‐cell sequencing on bone marrow cell samples collected from vertebrae of three AS patients non‐AS patients. Using data, analysed expression differentially expressed genes (DEGs) by comparing with Key among related DEGs were identified through protein–protein interaction networks hub gene screening further validated using immunohistochemistry. We performed clustering annotation data externally findings GSE232131 dataset. By integrating transcriptome assessed differential cells AS. Finally, explored interactions between communication analysis. The upregulated CD74 was as a T Further research revealed important relationship NK fundamental processes Additionally, found that macrophage migration inhibitory factor signalling pathway is prominently various types

Язык: Английский

Процитировано

1
Surfactant Protein-C Regulates Alveolar Type 2 Epithelial Cell Lineages via the CD74 Receptor DOI
Krishan Gopal Jain, Yang Liu,

Runzhen Zhao

и другие.

Deleted Journal, Год журнала: 2024, Номер 1(4), С. 10017 - 10017

Опубликована: Янв. 1, 2024

Deficiency of surfactant protein-C (SPC) increases susceptibility to lung infections and injury, suppressed expression SPC has been associated with the severity acute respiratory distress syndrome (ARDS). Alveolar type 2 epithelial cells (AT2) are critical for maintenance repair lung. However, role in regulation AT2 cell lineage underlying mechanisms not completely understood.

Язык: Английский

Процитировано

0
Immunogenic shift of arginine metabolism triggers systemic metabolic and immunological reprogramming to prevent HER2+ breast cancer DOI Creative Commons
Vandana Sharma, Veani Fernando,

Xunzhen Zheng

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 26, 2024

Abstract Arginine metabolism in tumors is often shunted into the pathway producing pro-tumor and immune suppressive polyamines (PAs), while downmodulating alternative nitric oxide (NO) synthesis pathway. Aiming to correct arginine tumors, deprivation therapy inhibitors of PA have been developed. Despite some therapeutic advantages, these approaches yielded severe side effects, making it necessary explore an strategy. We previously reported that supplementing SEP, endogenous precursor BH 4 (the essential NO synthase cofactor), could tumor cells tumor-associated macrophages (TAMs) induce their metabolic phenotypic reprogramming. saw oral SEP treatment effectively suppressed growth HER2-positive mammary animals. also has no dose-dependent toxicity clinical trials for disorders. In present study, we report a long-term use animals susceptible prevented occurrence. These SEP-treated had undergone reprogramming systemic immunity, elevating total T cell counts circulation bone marrow. Given marrow-resident are mostly memory cells, plausible chronic promoted formation, leading potent prevention. findings suggest possible roles SEP/BH /NO axis promoting formation its potential utility preventing breast cancer.

Язык: Английский

Процитировано

0