Molecular and Cellular Biochemistry最新文献

{"title":"Rhynchophylline alleviates early atherosclerosis by attenuating oxidized low-density lipoprotein-induced foam cell formation and endothelial dysfunction.","authors":"Jeeva Prasannan, Archana Sobha, Abdul Jaleel, Vinod Vikraman Thambi Mohanakumari, Surya Ramachandran","doi":"10.1007/s11010-025-05418-5","DOIUrl":"https://doi.org/10.1007/s11010-025-05418-5","url":null,"abstract":"<p><p>Rhynchophylline (Rhy), a bioactive alkaloid extracted from Uncaria species (Uncaria rhynchophylla and Uncaria tomentosa), has demonstrated therapeutic potential in neurodegenerative and cardiovascular diseases due to its diverse pharmacological effects. However, its role in the development or treatment of atherosclerosis has not yet been studied. In this study, we evaluated the anti-atherosclerotic effects of Rhy using both in vivo and in vitro models. In high-fat diet-fed New Zealand White rabbits, Rhy treatment significantly reduced aortic plaque progression, improved vascular histology, and decreased serum cholesterol levels. In THP-1 macrophages, Rhy inhibited ox-LDL uptake and subsequent foam cell formation by lowering scavenger receptor expression. In endothelial cells, it decreased the expression of adhesion molecules, thereby reducing monocyte adhesion and transendothelial migration. Mechanistically, Rhy suppressed the activation of MAPK and NF-κB signaling pathways, contributing to its anti-inflammatory and antioxidant effects. Overall, these results demonstrate that Rhy offers multi-targeted protective effects against atherosclerosis and could be a promising candidate for its prevention and treatment.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the complexities of epigenetic dysregulation in breast cancer and its implication in therapeutic interventions: a comprehensive overview.","authors":"Swathy Ravindran, Ravindran Vini, Arumugam Rajavelu, Kuzhuvelil B Harikumar, Sreeharshan Sreeja","doi":"10.1007/s11010-025-05415-8","DOIUrl":"https://doi.org/10.1007/s11010-025-05415-8","url":null,"abstract":"<p><p>Breast cancer represents a multifaceted and heterogeneous condition characterized by both genetic and epigenetic alterations. Among these, epigenetic modifications-such as DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs-play pivotal roles in tumor initiation, progression, therapeutic resistance, and immune evasion. These alterations contribute to dysregulation of estrogen signalling, endocrine therapy resistance, and metabolic rewiring, posing challenges for conventional treatment strategies. Notably, our previous findings reveal that 27-hydroxycholesterol, an endogenous selective estrogen modulator, can induce epigenetic changes in (ER)-positive breast cancer cells. This review provides a comprehensive overview of the landscape of epigenetic dysregulation in breast cancer, emphasizing its impact on disease progression and therapeutic resistance. It details the intricate interplay between epigenetic players and the tumor immune microenvironment, which plays a crucial role in shaping treatment responses. In addition, the review highlights the on-going clinical trials and suggests addressing the gaps present in dissecting pathways of epigenetic reprogramming in breast cancer evolution and therapy outcomes. Unraveling these mechanisms reinstates opportunities for potential therapies targeting epigenetic pathways along with the conventional medicine, which is required in transformation of clinical management of breast cancer and potential enhancement of the patient's lifespan.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the therapeutic mechanism of kaempferol in diabetic retinopathy via the P21/Thioredoxin axis.","authors":"Shuyan Zhang, Leilei Wang, Jiajun Wu, Yinjian Zhang","doi":"10.1007/s11010-025-05412-x","DOIUrl":"https://doi.org/10.1007/s11010-025-05412-x","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is an irreversible microvascular complication in individuals with diabetes. Kaempferol, a flavonoid with anti-inflammatory, antioxidant, and hypoglycemic activities, has exhibited therapeutic potential in previous investigations for treating DR. However, its accurate molecular mechanisms remain elusive. This study aimed to elucidate similarity underlying the progression of DR from early to late stages, along with exploring the key targets of kaempferol for DR therapy. Combined with weighted gene co-expression network analysis (WGCNA) and single-cell RNA sequencing (scRNA-seq) analysis, we elucidated hub regulatory genes and cell subpopulations. Molecular docking was conducted to analyze molecular interactions. Evans Blue (EB) leakage assay, Hematoxylin & Eosin (H&E) and Periodic Acid-Schiff (PAS) staining was utilized to assess retinal structural and vascular damage. Additionally, TUNEL staining was applied to evaluate retinal apoptosis. Comprehensive analyses, including enzyme-linked immunosorbent assays (ELISA), immunofluorescence, Western blotting, and real-time PCR were employed to monitor cytokine levels and protein expression. Our findings preliminarily unveiled that kaempferol could modulate the P21/Thioredoxin pathway, and exerted protective effects on DR by regulating metabolism disorder and cellular dysregulation. Moreover, a novel mechanistic connection was established between fibroblasts activity and DR fibrosis progression, underscoring the pivotal role of the VCAM signaling pathway in vascular cell regulation and its contribution to disease pathogenesis. This study provides new perspectives on the therapeutic potential of kaempferol in DR, particularly regulating vascular injury and cellular senescence via the P21/Thioredoxin axis, which expand the horizon of natural compounds in addressing the vision-threatening complications associated with diabetes.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ivermectin modulates macrophage activity and enhances bacterial clearance in Pseudomonas aeruginosa acute pneumonia.","authors":"Thiago Caetano Andrade Belo, Natália Cristina de Melo Santos, Leonardo Pereira de Araújo, Ana Sofia Martelli Chaib Saliba, Severino Matias de Alencar, Graziela Domingues de Almeida Lima, Rômulo Dias Novaes, Flávio Protásio Veras, Giovane Galdino de Souza, Patrícia Paiva Corsetti, Leonardo Augusto de Almeida","doi":"10.1007/s11010-025-05419-4","DOIUrl":"https://doi.org/10.1007/s11010-025-05419-4","url":null,"abstract":"<p><p>The TLR4 receptor, together with the MD-2 co-receptor, is essential for macrophage recognition of LPS from Gram-negative bacteria such as Pseudomonas aeruginosa. Although ivermectin improves survival following LPS challenge in mice, its immunological mechanisms remain poorly understood. In silico molecular docking was performed to evaluate the binding of ivermectin to TLR4/MD-2. In vitro studies were conducted using RAW 264.7 macrophages and bone marrow-derived macrophages (BMDMs) treated with ivermectin and/or TLR4/MD-2 inhibitors, followed by LPS stimulation or infection with P. aeruginosa PA14. In vivo studies were carried out in C57BL/6 wild-type (WT) and TLR4 knockout (KO) mice treated with ivermectin or phosphate-buffered saline and subsequently intratracheally infected with PA14. Docking analysis demonstrated high-affinity binding of ivermectin to the MD-2 component of the TLR4/MD-2 complex. Ivermectin did not affect macrophage viability but impaired bacterial clearance, reduced NO and TNF-α secretion, and enhanced NF-κB activation in LPS-stimulated RAW 264.7 macrophages. These effects were reversed by TLR4/MD-2 complex inhibition with LPS/RS. In vivo, ivermectin treatment reduced the pulmonary bacterial load in TLR4 KO mice. Additionally, ivermectin decreased inflammatory infiltrates IL-6 and TNF-α levels while increasing IL-17 and IFN-γ production in infected lungs, with more pronounced effects in TLR4 KO mice. Ivermectin binds to MD-2 and suppresses macrophage microbicidal activity in vitro. In vivo, however-particularly in TLR4-deficient mice-ivermectin improved bacterial clearance, lung histopathology, and cytokine modulation. These findings highlight a complex, context-dependent immunomodulatory role of ivermectin.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-150-5p attenuates heart failure by targeting MMP14 to regulate vascular smooth muscle cell function.","authors":"Xu Yu, Yang Zhao, Qikui Wang, Xin Jiang, Liang Zhang","doi":"10.1007/s11010-025-05417-6","DOIUrl":"https://doi.org/10.1007/s11010-025-05417-6","url":null,"abstract":"<p><p>MiR-150-5p is a microRNA that plays an important role in the heart diseases. However, its specific role and molecular mechanism in heart failure (HF) remain unclear. In this study, we found that miR-150-5p was downregulated in patients with HF, while the expression of MMP14 was elevated. In vitro experiments have shown that miR-150-5p directly targets MMP14 and inhibits its expression in human aortic smooth muscle cells (HASMCs). Functionally, miR-150-5p promotes the proliferation, migration and apoptosis of HASMC, which is a key process in the progression of HF. In the HF mouse model induced by transverse aortic contraction (TAC), overexpression of miR-150-5p can improve cardiac function, reduce hypertrophy and fibrosis, while its inhibition aggravates these effects. These findings determined that miR-150-5p is a protective regulator in HF, functioning by inhibiting MMP14, and indicated its potential as a therapeutic target for HF treatment.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CIITA was involved in regulating ACSL4-dependent ferroptosis in gastric cancer cells.","authors":"Ping Zhang, Tian Wang, Na Zhu, Feifei Zhuang, Daihong Ding, Ping Wang","doi":"10.1007/s11010-025-05411-y","DOIUrl":"https://doi.org/10.1007/s11010-025-05411-y","url":null,"abstract":"<p><p>In this study, we discussed the impact of CIITA on the occurrence and development of gastric cancer, as well as its potential mechanisms. In this study, N87-C and AGS were used as in vitro research subjects. After knocking down and overexpressing CIITA, CCK8, ELISA, reactive oxygen species (ROS), JC-1, immunofluorescence and western blot were used to assess the effect of CIITA on ferroptosis. To further validate the potential mechanism of CIITA, we continued to transfect lentiviruses cloned with ACSL4 knockdown into cells and repeated the above experiment. In addition, we constructed a subcutaneous transplant tumor model to validate the results of in vitro experiments. In vitro experiments showed that overexpressed CIITA promoted ferroptosis in gastric cancer cells, manifested as the decreased cell viability, increased ROS production, decreased mitochondrial membrane potential, and changes in the expression of ferroptosis-related proteins and secreted factors. After knocking down CIITA, the above results were reversed, inhibiting ferroptosis. In addition, we confirmed that the effect of CIITA on ferroptosis was related to ACSL4. In vitro experiments also confirmed that CIITA overexpression promoted ferroptosis and inhibited tumor growth, while low CIITA had the opposite effect. Overexpressed CIITA promoted ferroptosis and inhibited gastric cancer growth by upregulating ACSL4. CIITA may be a potential therapeutic target for gastric cancer and may have certain predictive value in future clinical applications.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irisin protects against atherosclerosis in ApoE^-/- mice by suppressing the migration of vascular smooth muscle cell via PI3K-Akt-cofilin.","authors":"Junshu Wang, Yihang Cai, Mohammad Ismail Hajary Sagor, Yunqi Chu, Fang Liu, Tingjun Wang","doi":"10.1007/s11010-025-05414-9","DOIUrl":"https://doi.org/10.1007/s11010-025-05414-9","url":null,"abstract":"<p><p>Irisin, a myokine secreted by the skeletal muscles during exercise, exerts atheroprotective effects. However, the precise molecular mechanisms that underlie these effects remain incompletely elucidated. This study aimed to investigate the effect of irisin on atherosclerosis and vascular smooth muscle cell (VSMC) migration, and to explore the role of cofilin-mediated cytoskeletal remodeling in the atheroprotective effect of irisin. In vivo, irisin was administered to high-fat diet-fed ApoE^-/- mice. Dyslipidemia in these mice was alleviated by irisin treatment. Atherosclerotic lesion assessment via Oil Red O staining, Masson's trichrome staining, and alpha-smooth muscle actin (a-SMA) immunofluorescence staining revealed that irisin significantly attenuated atherosclerotic plaque burden, necrotic core size, and VSMC area within the aortic tissue of ApoE^-/- mice. However, the atheroprotective effect of irisin was partially reversed when ApoE^-/- mice were cotreated with an integrin αVβ5 inhibitor. In vitro, irisin supplementation decreased platelet-derived growth factor (PDGF)-induced VSMC migration, determined by wound healing assay and transwell migration assay. Furthermore, irisin treatment reversed the elevated expression of p-PI3K and p-Akt as well as the decreased expression of p-cofilin observed both in the aorta of ApoE^-/- mice and in PDGF-stimulated VSMCs. The effects of irisin on p-PI3K, p-Akt, and p-cofilin expression were partially blocked by cotreatment with an integrin αVβ5 inhibitor or PI3K activator. The decreased expression of p-cofilin in PDGF-stimulated VSMCs was partially blocked by PI3K inhibitor. Systemic irisin administration confers protection against atherosclerosis in ApoE^-/- mice. Mechanistically, this beneficial effect involves suppression of the PI3K-Akt signaling pathway, which modulates cofilin-mediated cytoskeletal remodeling to regulate VSMC migration.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2X7 receptor: a potential therapeutic target for chronic respiratory diseases.","authors":"Ping Huang, Xichen Pang, Xiaoju Liu","doi":"10.1007/s11010-025-05408-7","DOIUrl":"https://doi.org/10.1007/s11010-025-05408-7","url":null,"abstract":"<p><p>The purinergic ligand-gated ion channel 7 receptor (P2X7R) is a non-selective ion channel activated by extracellular adenosine triphosphate. It promotes intracellular signal transduction by inducing Na⁺ and Ca²⁺ influx and K⁺ efflux. Moreover, this receptor is involved in the regulation of the inflammatory response, oxidative stress, cell death, and immune response. P2X7R is associated with the onset and progression of various chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, pulmonary arterial hypertension, and pulmonary tuberculosis. In this review, we comprehensively summarize the structure and functions of P2X7R as well as its roles and potential molecular mechanisms in chronic respiratory diseases. Additionally, we explored the application of P2X7R antagonists in clinical practice. In summary, targeting P2X7R may be a new strategy for treating chronic respiratory diseases, but we should still pay attention to its dual roles, especially in lung cancer.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Journey through the gut-inflammation axis in polycystic ovary syndrome: the microbiota's role in shaping inflammatory pathways.","authors":"Ujjawal Sharma, Anidrisha Sahu, Neelam Thakur, Ranjay Kumar Choudhary, Himanshu Shekhar, Shafiul Haque, Hardeep Singh Tuli, Aygul Toktasynovna Aubakirova, Bunty Sharma","doi":"10.1007/s11010-025-05409-6","DOIUrl":"https://doi.org/10.1007/s11010-025-05409-6","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine disease in women in their reproductive phase of life. It could be characterized by irregularity in menstrual cycles, abnormal levels of androgen, and multiple cyst formations in the ovaries. It involves a complex and multifaceted pathophysiology including endocrine and metabolic irregularity, genetic and epigenetic abnormality, inflammation, and gut microbiota dysbiosis. PCOS interferes with the fertility of the patient directly due to irregular ovulation caused by hormonal imbalances. Further, this condition is also associated with increased risk for other health conditions such as type2 diabetes and cardiovascular disease, as well as psychological conditions such as anxiety and depression. Among various other factors, metabolic profiles and gut health also play a crucial role in PCOS pathogenesis. Various recent studies have reported an association of gut microbiota dysbiosis with PCOS. gut microbiota: The microbial population residing in the host organism influences our health status, and their diversity and balance are crucial to maintaining the healthy status of the body. There is growing evidence of the involvement of gut microbe dysbiosis in different diseases, including PCOS. Further inflammation is another key hallmark of PCOS. The inflammatory status of the host body depends on various factors; gut microbe dysbiosis is one such factor that can modulate the inflammatory status and thus contribute to various health conditions such as PCOS. In the present article, we have thoroughly reviewed the current status of research on the involvement of gut microbiota dysbiosis in PCOS pathogenesis and the inflammatory mechanism by which it leads to PCOS, including MCP-1/IL-2 mediated cytokine signaling, LPS-induced leaky gut inflammation, JNK/NF-KB and IKK pathways, tight junction disruption, and oxidative stress. Further, we have also discussed the factors affecting gut microbe dysbiosis and the current status of therapeutic interventions targeting gut dysbiosis in PCOS. These insights emphasize the clinical potential of targeting gut dysbiosis and associated inflammatory pathways to improve the metabolic, reproductive, and psychological outcomes in women with PCOS.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of LSD1 enhances T cells anti-tumor immunity by promoting TNFSF14 expression in gastric cancer.","authors":"Xueqing Xie, Wei Lu, Qingling Yin, Meijun Hou, Jingjing Tian, Xunsheng Chen, Yuanling Zhang, Lili Zeng, Jie Ding","doi":"10.1007/s11010-025-05403-y","DOIUrl":"https://doi.org/10.1007/s11010-025-05403-y","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs), especially anti-PD-1 immunotherapy, offer a new treatment option for tumor patients. However, its efficacy is limited in the most of patients with immunologically \"cold\" tumors. An important histone demethylase, histone lysine-specific demethylase 1 (LSD1/KDM1A), plays a significant role in T cell regulation. Combining LSD1 inhibitors with anti-PD-1 mAb has shown improved anti-tumor effects in various solid tumors. Specifically, in gastric cancer (GC), LSD1 knockdown boosts T cell-mediated anti-tumor immunity. Nevertheless, currently, this effect is only related to PD-L1 in exosomes. Therefore, further research on the molecular mechanisms of LSD1 in regulating T cells in GC is needed. Using TIMER 2.0 and GEPIA 2 databases, we analyzed LSD1 expression in GC and its gene correlations. Lentiviral transfection was utilized to construct a control cell line (shControl) and an LSD1 knockdown cell line (shLSD1). The mRNA and protein levels of LSD1 and immune-related cytokines were measured through real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western blotting. We examined the role of LSD1 knockdown in regulating T cell anti-tumor immunity via transcriptome sequencing (RNA-seq). Mouse subcutaneous graft tumor models and in vitro conditioned culture models were established, and the altered functional phenotypes of T cells in mice and in vitro were assessed by RT-qPCR and flow cytometry. Genetic inhibition of LSD1 in GC cells increased T cell proliferation, CD8⁺ activation, and chemotaxis in vitro. Pharmacological inhibition of LSD1 curbed tumor growth in vivo. Remarkably, the combination LSD1 inhibitors with PD-1/PD-L1 blockers led to greater efficacy. At the molecular level, LSD1 knockdown induced the transcription of tumor necrosis factor ligand superfamily member 14 (TNFSF14). As a result, T cell-mediated anti-tumor immunity was improved. Inhibiting LSD1 in GC upregulates TNFSF14 expression, which in turn promotes T cell proliferation, CD8⁺ activation, and chemotaxis. This enhancement of T cell-mediated anti-tumor immunity is further amplified when LSD1 inhibitors are used alongside PD-(L)1 blockers, facilitating the activation of CD8⁺ T cells in the spleen and improving leukocyte infiltration in the tumor.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}