Tumor cell-intrinsic BIN1 deficiency promotes the immunosuppression and impedes ferroptosis of non-small cell lung cancer via G3BP1-mediated degradation of STAT1 DOI
Jiali Wang,

Yunlong Jia,

Tianxu Liu

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 21, 2025

Abstract Background Tumors often evade immune surveillance by limiting T cell infiltration. In non-small lung cancer (NSCLC), increased infiltration of CD8+ cells is associated with a favorable response to immunotherapy. While BIN1 recognized as tumor suppressor gene, its role in shaping the microenvironment NSCLC has yet be fully clarified. Methods To investigate relationship between expression and CD8+T NSCLC, we performed comprehensive data analysis utilizing clinical information from patients. levels tissues were evaluated, their correlation patient survival outcomes was examined. Loss-of-function strategies targeting applied syngeneic mouse models assess functional significance. Tumor growth monitored, populations analyzed terms frequency functionality through mass cytometry flow techniques. Cytokine secretion profiled using multiplex assays. Additionally, RNA sequencing, immunoprecipitation-mass spectrometry, molecular docking employed confirm direct interactions cytokine-encoding genes. Finally, regulatory ferroptosis explored metabolomics analysis, ROS measurement, MDA detection. Results We observed that downregulated tissues, reduced strongly advanced disease progression poor prognosis. Bioinformatics human samples revealed positive Furthermore, prognostic impact on patients linked level models, knockout significantly inhibited impaired cytotoxic function, facilitating evasion. Mechanistically, demonstrated directly interacts G3BP1, stabilizes G3BP1. This, turn, promotes STAT1 degradation reduces cell-recruiting chemokines such CXCL10 CCL5. our findings reveal influences G3BP1/STAT1/GSH pathway, thereby regulating proliferation, migration, invasion. Conclusion This study highlights crucial BIN1/G3BP1/STAT1/CD8+ tumor-infiltrating lymphocyte signaling pathway mechanisms fundings lay foundation for development BIN1-targeted therapies aimed at improving immunogenicity transforming immunologically “cold” into more responsive disease.

Язык: Английский

QingGan LiDan capsules improved alcoholic liver injury by regulating liver lipid transport and oxidative stress in mice DOI Creative Commons
Zhiwen Fu, Jiafeng Zhou,

Hongye Pan

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 26, 2025

Background The QingGan LiDan capsule (QGLD) consists of five traditional Chinese herbs, which have been used for hepatobiliary diseases such as jaundice. However, the effects and mechanisms by QGLD prevent alcoholic liver (ALD) remain unknown. Aim study Investigate therapeutic potential Lidan in alleviating alcohol-induced injury. Materials Methods Acute injury model chronic Binge ethanol Feeding Model (NIAAA) were established. Mice administered (360, 720, 1,440 mg/kg) or vehicle. Liver function indicators (ALT, AST), serum lipid (TC, TG), antioxidant markers (SOD, GSH, MDA), metabolism/transport genes relative expression levels, ileal villus morphology analyzed. Network pharmacology analysis was also performed to identify targets pathways QGLD. Results reduced ALT, AST, hepatic TC, TG, droplet accumulation both models. It upregulated enzymes GSH) downregulated MDA. regulated mRNA levels related NRF2/KEAP1 pathway transport. identified 221 targets. Conclusion mitigates reducing accumulation, regulating transport enhancing capacity. This supports its application ALD management.

Язык: Английский

Процитировано

0
Glutathione Metabolism in Ferroptosis and Cancer Therapy DOI
Xiangfei Xue, Manyuan Wang,

Jiangtao Cui

и другие.

Cancer Letters, Год журнала: 2025, Номер unknown, С. 217697 - 217697

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Linezolid administration to lactating Wistar rats affects the health of their offspring DOI Creative Commons

Aya G Hamouda,

Entsar R. Abd‐Allah,

A. Mahmoud

и другие.

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 12, 2025

Lactational exposure to antibacterial medications may affect the normal development of newborns during this crucial stage and later in adult life. Linezolid (LNZ) is an oxazolidinone drug that effective against drug-resistant Gram-positive bacteria multidrug-resistant Mycobacterium tuberculosis. Although it relatively toxic, there insufficient data about LNZ use lactation. This study aimed elucidate impact linezolid administration lactation on Wistar rats' offspring. Eighteen lactating female rats were separated into three groups (n = 6): control, therapeutic, low dose groups. The therapeutic group received 61.66 mg/kg (equivalent human dose), while 15.41 (1/4 dose) by gavage twice daily. All dams their offspring died four days after receiving a dose. In group, significantly reduced body weight females pups. liver tissue pups showed considerable increase malondialdehyde levels, along with decrease catalase, glutathione, superoxide dismutase activities accompanied moderate histological alterations like congestion, infiltration, DNA fragmentation as indicated comet assay. Microscopic examination renal revealed glomeruli deterioration, cellular intratubular protein deposits. conclusion, highlights potential risks pose infants postpartum. Therefore, need for preweaning monitoring caution should be taken breastfeeding.

Язык: Английский

Процитировано

0
Homogeneous electrochemiluminescence sensor based on novel Ru-MOF nanosheets for highly sensitive and efficient detection of glutathione without immobilization DOI
Xin Wang, Zhaojiang Yin, Binghui Li

и другие.

Microchimica Acta, Год журнала: 2025, Номер 192(5)

Опубликована: Апрель 12, 2025

Язык: Английский

Процитировано

0
Tumor cell-intrinsic BIN1 deficiency promotes the immunosuppression and impedes ferroptosis of non-small cell lung cancer via G3BP1-mediated degradation of STAT1 DOI
Jiali Wang,

Yunlong Jia,

Tianxu Liu

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 21, 2025

Abstract Background Tumors often evade immune surveillance by limiting T cell infiltration. In non-small lung cancer (NSCLC), increased infiltration of CD8+ cells is associated with a favorable response to immunotherapy. While BIN1 recognized as tumor suppressor gene, its role in shaping the microenvironment NSCLC has yet be fully clarified. Methods To investigate relationship between expression and CD8+T NSCLC, we performed comprehensive data analysis utilizing clinical information from patients. levels tissues were evaluated, their correlation patient survival outcomes was examined. Loss-of-function strategies targeting applied syngeneic mouse models assess functional significance. Tumor growth monitored, populations analyzed terms frequency functionality through mass cytometry flow techniques. Cytokine secretion profiled using multiplex assays. Additionally, RNA sequencing, immunoprecipitation-mass spectrometry, molecular docking employed confirm direct interactions cytokine-encoding genes. Finally, regulatory ferroptosis explored metabolomics analysis, ROS measurement, MDA detection. Results We observed that downregulated tissues, reduced strongly advanced disease progression poor prognosis. Bioinformatics human samples revealed positive Furthermore, prognostic impact on patients linked level models, knockout significantly inhibited impaired cytotoxic function, facilitating evasion. Mechanistically, demonstrated directly interacts G3BP1, stabilizes G3BP1. This, turn, promotes STAT1 degradation reduces cell-recruiting chemokines such CXCL10 CCL5. our findings reveal influences G3BP1/STAT1/GSH pathway, thereby regulating proliferation, migration, invasion. Conclusion This study highlights crucial BIN1/G3BP1/STAT1/CD8+ tumor-infiltrating lymphocyte signaling pathway mechanisms fundings lay foundation for development BIN1-targeted therapies aimed at improving immunogenicity transforming immunologically “cold” into more responsive disease.

Язык: Английский

Процитировано

0