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ENPP3 drives ccRCC progression by cGAMP hydrolysis and STING-IFN suppression.
[OBJECTIVE] Clear-cell renal cell carcinoma (ccRCC) is an immune-desert tumor. This study investigates the role of ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) as a potential therapeutic target and immune-checkpoint enzyme in …
FULLTEXT: nuclear function -
Prednisolone modulates CD8⁺ and regulatory T-cell activity to dampen response to immune checkpoint inhibitor therapy in melanoma.
Immune checkpoint inhibitors (ICIs) have transformed the treatment of advanced melanoma, yet their efficacy is limited by high-grade immune-related adverse events that often require treatment with systemic corticosteroids. Although corticos…
FULLTEXT: nuclear function -
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Gut microbial -demethylation has been reported for plant-derived dietary compounds containing -methylated aromatic(s). However, the significance of gut microbial -demethylation in drug metabolism and disposition remains unexplored. This stu…
FULLTEXT: nuclear function -
Discovery of novel murine PML isoforms.
Promyelocytic leukemia protein (PML) orchestrates the formation of PML nuclear bodies (PML NBs), membraneless organelles with diverse regulatory roles. Despite their importance, the specific functions of individual PML splicing variants rem…
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Sialic acid -ligand dynamics modulate Siglec-7 and -9 function and affect Siglec-7/9 co-blockade to potentiate natural killer cell anti-tumor activity.
The glyco-immune checkpoints Siglec-7 and Siglec-9 have received considerable interest as targets for cancer immunotherapy. How Siglec-7/9-sialic acid -interactions on immune cells influence -signaling induced by tumor cells and whether Sig…
FULLTEXT: nuclear function -
VGLL4 regulates the Wnt/β-catenin signaling pathway and acts as an oncogenic factor in acute myeloid leukemia.
[OBJECTIVE] To investigate the expression, function, and underlying mechanism of VGLL4 in AML. [METHODS] Bioinformatic analysis of TCGA data by GEPIA website was performed. VGLL4 protein expression was analyzed by Western blot. We then per…
FULLTEXT: nuclear function -
Spatial transcriptomics unveils immune cellular ecosystems associated with patient survival in diffuse large B-cell lymphoma.
Diffuse large B-cell Lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin's lymphoma for which current therapeutic strategies remain insufficient, in part owing to heterogeneity in tumor biology and the immune microenvironment. The…
FULLTEXT: nuclear function -
XPO1 inhibitor selinexor suppresses homologous recombination by inhibiting E2F7 nuclear export in acute myeloid leukemia.
[OBJECTIVES] Aberrant nucleocytoplasmic transport mediated by Exportin 1 (XPO1) contributes to leukemogenesis, yet the molecular basis underlying the limited efficacy of the XPO1 inhibitor Selinexor in acute myeloid leukemia (AML) remains u…
FULLTEXT: nuclear function -
Sex determines the natural killer cell-mediated immunity against pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) ranks among the most aggressive malignancies and exhibits a higher prevalence and poorer prognosis in male patients. While both the importance of natural killer (NK) cells in anti-tumor immunity and s…
FULLTEXT: nuclear function -
activates histone lactylation to promote gastric cancer progression and immune evasion through the HAS2/c-MYC/PD-L1 axis.
[BACKGROUND] Metabolic reprogramming and epigenetic alterations play important roles in driving tumor microenvironment (TME) remodeling and immune evasion in gastric cancer (GC). Histone lactylation links glycolytic metabolism to transcript…
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outer membrane protein Amuc_0904 modulates intestinal homeostasis by promoting goblet cell differentiation.
is recognized as a promising probiotic that improves the symptoms of a variety of diseases. However, the role and mechanism of in regulating intestinal homeostasis remain to be explored. Here, we discovered that was dramatically increased…
FULLTEXT: nuclear function -
metaFun: An analysis pipeline for metagenomic big data with fast and unified functional searches.
Metagenomic approaches offer unprecedented opportunities to characterize microbial community structure and function, yet several challenges remain unresolved. Inconsistent genome quality impairs reliability of metagenome-assembled genomes, …
FULLTEXT: nuclear function -
Novel bacterium sp. M3 promotes colorectal tumorigenesis via the production of the carcinogen styrene.
[BACKGROUND] The bacterial marker 'm3' shows promise for the non-invasive diagnosis of colorectal cancer (CRC) and adenomas. However, the m3-harboring bacterium (M3) had not been successfully cultured. [OBJECTIVE] This study aims to elucid…
FULLTEXT: nuclear function -
Monocytes acquire a tumor-associated IL1B program upon encountering patient-derived colon cancer organoids.
Tumor-associated macrophages (TAMs) and monocytes that accumulate in colorectal cancer (CRC) play a crucial role in shaping the tumor microenvironment (TME) and anti-tumor immune responses. Although TAMs have been linked to both pro- and an…
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TNF-α deficiency underlies NK cell dysfunction in colorectal cancer.
Natural killer (NK) cells are central to innate antitumor immunity, yet their function is systemically compromised in colorectal cancer (CRC). We show that CRC patients exhibit early and pronounced alterations in peripheral blood NK cells, …
FULLTEXT: nuclear function -
PD-1 genetic fate mapping uncovers immune cell diversity mediating the efficacy of combined PD-1 blockade and chemotherapy.
Combined cytotoxic chemotherapy and immune checkpoint inhibition (ICI) improves outcomes in PD-L1-low lung cancer, but transient and broad PD-1 expression across immune cells complicates the understanding of the underlying mechanisms. We ge…
FULLTEXT: nuclear function -
Downregulation of the lncRNA PGM5P4-AS1 predicts poor prognosis and drives breast cancer progression through miR-3664-5p/KLF9.
[BACKGROUND] Accumulating evidence suggests that deregulated long non-coding RNAs (lncRNAs) drive breast cancer (BRCA) progression. This study investigated the expression profile and mechanism of PGM5P4 antisense RNA 1 (PGM5P4-AS1) in BRCA.…
FULLTEXT: nuclear function -
Passive nuclear transport deviates from Fickian behavior in prostate and breast cell types.
Nuclear trafficking is essential for cellular function and biomedical applications such as nucleus-targeted drug delivery; however, how passive nuclear transport varies across cell types and phenotypic states remains poorly understood. Here…
FULLTEXT: nuclear function -
IL-37/IL-1R8 axis: a novel major mechanism of control at the interface between tumor and immune cells.
Interleukin (IL)-37 is one of the "youngest" IL-1 family members and one of the few molecules exerting anti-inflammatory activity. Upon inflammasome activation, the cytokine precursor is converted into its mature form, which acts intracellu…
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Killing cancer takes guts: lessons learned from the manipulation of gut microbiome and immunotherapy for the future of urothelial carcinoma.
Urothelial carcinoma (UC) remains a common cancer with significant morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) have helped revolutionize the treatment of UC, and there is growing evidence suggesting the crucial ro…
FULLTEXT: nuclear function