International Journal of Biological Sciences最新文献

{"title":"Probiotic-facilitated cytokine-induced killer cells suppress peritoneal carcinomatosis and liver metastasis in colorectal cancer cells.","authors":"Hong-Hwa Chen, Chi-Wen Luo, Yi-Ling Chen, John Y Chiang, Chi-Ruei Huang, Yi-Ting Wang, Chih-Hung Chen, Jun Guo, Hon-Kan Yip","doi":"10.7150/ijbs.101051","DOIUrl":"10.7150/ijbs.101051","url":null,"abstract":"<p><p><b>Background:</b> This study tested the hypothesis that combined therapy with probiotics and cytokine-induced killer (CIK) cells was superior to merely one on suppressing the peritoneal carcinomatosis and liver metastasis of colorectal cancer (CRC) cells in nude mice. <b>Methods and Results:</b> The <i>in vitro</i> study revealed that in HCT 116/SW620 CRC cell lines, cell viability, proliferation, colony formation, migratory ability, wound healing, and protein expression of PD-L1 and FAK were significantly and comparably suppressed and that apoptosis was significantly and comparably increased by probiotics and CIK cells, and these effects were further significantly enhanced by combined probiotics + CIK cell therapy (all p<0.001). Nude mice were categorized into Groups 1 (SC), 2 (HCT 116), 3 (HCT 116 + probiotics), 4 (HCT 116 + CIK cells), and 5 (HCT 116 + probiotics + CIK cells). CRC cells were intraperitoneally implanted into Groups 2 to 5, and the animals were euthanized by Day 28. The results demonstrated that the abdominal dissemination of CRC cells, tumor numbers, tumor weights, liver weights, liver necrosis areas and the expression of γ-H2AX/PD-L1/FAK in harvested liver tumors were lowest in Group 1, highest in Group 2, and significantly and progressively decreased in Groups 3 to 5 (all p<0.0001). The protein expression levels of apoptotic and DNA damage biomarkers (Bax/c-caspase 3/c-PARP/γ-H2AX), a metastatic biomarker (FAK) and three tumor proliferation and survival signaling biomarkers (JAK-STAT1, PI3K/Akt/m-TOR and Ras/Raf/MEK/ERK) exhibited identical patterns to that of a tumor immune escape biomarker (PD-L1) among the groups (all p<0.0001). <b>Conclusion:</b> The combination of probiotics and CIK cells was superior to either therapy alone in suppressing CRC cell growth, proliferation, liver metastasis and survival, mainly through downregulating cell proliferation and survival signaling pathways.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"20 15","pages":"6162-6180"},"PeriodicalIF":8.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Annexin-V binds subpopulation of immune cells altering its interpretation as an <i>in vivo</i> biomarker for apoptosis in the retina.","authors":"Kiyoharu Joshua Miyagishima, Francisco Manuel Nadal-Nicolás, Wenxin Ma, Wei Li","doi":"10.7150/ijbs.102551","DOIUrl":"10.7150/ijbs.102551","url":null,"abstract":"<p><p>In cells undergoing apoptosis phosphatidylserine, a major component of the plasma membrane, translocates to the outer leaflet where it provides eat-me signals for phagocytic recognition and is bound by annexin-V, an apoptotic marker. The need to track retinal ganglion cell death (RGC) in response to glaucomatous damage or optic neuropathy has led to the development of DARC (detection of apoptosing retinal cells) imaging, providing non-invasive, <i>in vivo</i> assessment of RGC death. Although the eye is an immune privileged site, resident and infiltrating immune cells are known to respond quickly to trauma or infection. Some immune cells have binding sites for annexin homologs; thus, their presence may confound estimates of apoptosis measured by annexin-V labeling. The purpose of this study was to re-examine the accuracy of annexin-V apoptotic labeling in the posterior eye and to temporally characterize contributions of non-apoptotic labeling in response to optic nerve (ON) injury. Here, we found annexin-V labeling consists of two phases. Initially, there is a rapid phase matching the time course of apoptotic cell death indicated by cleaved caspase-3 immunostaining observed <i>ex vivo</i>. This is followed by a sustained plateau phase that persists long after the peak of degeneration. We demonstrate that annexin-V binds to a specific subpopulation of myeloid cells in the retina, which were identified using simultaneous confocal scanning laser ophthalmoscopy. Optical coherence tomography and confocal imaging reveal these cells occupy the posterior hyaloid space above the retinal nerve fiber layer and at various retinal depths. Our results highlight the cellular morphological heterogeneity of non-apoptotic annexin-V labeling of retinal microglia. Accordingly, pharmacological depletion of microglia abolishes annexin-V labeling of elongated microglia <i>in vivo</i> revealing fainter labeling of round RGCs. Thus, consideration should be given to the time course of the immune response when interpreting fluorescently labeled annexin-V to visualize retinal cell apoptosis for clinical diagnosis.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"20 15","pages":"6073-6089"},"PeriodicalIF":8.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IKBKE regulates renal cell carcinoma progression and sunitinib resistance through the RRM2-AKT pathway.","authors":"Shiwei Liu, Junhong Li, Junyu Zhang, Fangning Wan, Zongyuan Hong, Zhe Hong, Bo Dai","doi":"10.7150/ijbs.102666","DOIUrl":"10.7150/ijbs.102666","url":null,"abstract":"<p><p>Tyrosine kinase inhibitors (TKIs), such as sunitinib, have emerged as promising agents in renal cell carcinoma (RCC) treatment, particularly in patients at advanced/metastatic clinical stages. However, acquired resistance to sunitinib is common following prolonged clinical treatment in RCC. Increasing evidence has demonstrated a strong correlation between inhibitor of nuclear factor kappa B kinase subunit epsilon (IKBKE) and cancer progression as well as drug resistance. Here, we found that IKBKE is upregulated in RCC tissues and sunitinib-resistant RCC cells. High IKBKE expression is positively correlated with advanced clinical staging and a poor prognosis in RCC. Silencing IKBKE downregulates ribonucleotide reductase M2 (RRM2) and induces cell cycle arrest at G2/M phase, suppressing RCC progression and enhancing sunitinib sensitivity to RCC cells. Mechanistically, IKBKE interacts with and phosphorylates RRM2 to activate the AKT signaling pathway to promotes RCC progression and sunitinib resistance. Notably, the IKBKE inhibitor CYT387 restores sunitinib sensitivity in RCC cells by downregulating RRM2 expression. Collectively, these results indicate that inhibition of IKBKE restrains RCC progression and enhances sunitinib sensitivity by downregulating RRM2 through the RRM2-AKT pathway, suggesting that IKBKE may be a potential therapeutic target for RCC.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"20 15","pages":"6146-6161"},"PeriodicalIF":8.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PFKP silencing suppresses tumor growth via the AXL-MET axis.","authors":"Huijie Zhao, Yuze Sun, Huijing Feng, Jing Cai, Yue Liu, Yu Li, Sijie Chen, Zhiqing Zhou, Yuhui Du, Xiaofei Zeng, Huan Ren, Wenmei Su, Qi Mei, Guoan Chen","doi":"10.7150/ijbs.100525","DOIUrl":"10.7150/ijbs.100525","url":null,"abstract":"<p><p>PFKP <b>(</b>Phosphofructokinase, Platelet Type isoform), as an essential metabolic enzyme, contributes to the high glycolysis rates seen in cancers while its role in oncogenic pathways, especially from a non-metabolic aspect, is not fully understood. We found that PFKP was highly expressed in NSCLC and was related to poor patient survival. Knockdown of PFKP significantly inhibited cell proliferation, colony formation, invasion, and migration of NSCLC cells. Nanoparticles-mediated PFKP silencing can inhibit tumor growth <i>in vivo</i>. Mechanistically, we found that PFKP can bind with AXL and promote its phosphorylation at Y779, thus activating the AXL signaling pathway and promoting MET phosphorylation. In addition, several glycolysis, glutaminolysis, and TCA cycle proteins were downregulated following PFKP silencing. PFKP has an oncogenic role in cancer progression <i>in vitro</i> and <i>in vivo</i>. Beyond its known role in glycolysis, PFKP also has a non-metabolic function in affecting lung cancer progression by interacting with the AXL-MET axis, thus indicating a potential therapeutic target for lung cancer.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"20 15","pages":"6056-6072"},"PeriodicalIF":8.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing of the Antipsychotic Trifluoperazine Induces SLC7A11/GPX4- Mediated Ferroptosis of Oral Cancer via the ROS/Autophagy Pathway.","authors":"Sheng-Chieh Tsai, Po-Chih Chang, Yu Tong Lin, Po-Tsang Huang, Jeff Yi-Fu Chen, Chang-Shen Lin, Bin-Nan Wu, Hui-Min Chang, Wan-Ju Wu, Chi-I Chang, Chien-Hsing Lee","doi":"10.7150/ijbs.99859","DOIUrl":"10.7150/ijbs.99859","url":null,"abstract":"<p><p>Ferroptosis, a mode of cell death characterized by iron-dependent phospholipid peroxidation, has a substantial therapeutic potential for the treatment of various cancers. This study investigated the effects of trifluoperazine (TFP), an FDA-approved drug traditionally utilized for mental health disorder, on oral cancer cells, with a particular focus on the mechanisms involved in its potential anti-tumor properties. Our findings indicate that TFP significantly elevates the levels of lipid-derived reactive oxygen species (ROS) and induces ferroptotic cell death in oral cancer cells through pathways involving autophagy, the SLC7A11/GPX4 axis, and mitochondrial damage. Additionally, molecular docking analyses revealed that TFP acts as an inhibitor of GPX4. The elevated expression level of GPX4 in oral cancer biopsies was also found to correlate with a poor prognosis. Together, these results provide evidence that TFP selectively induces GPX4-mediated, autophagy-dependent ferroptosis, thereby exerting anti-cancer effects against oral cancer and preventable death.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"20 15","pages":"6090-6113"},"PeriodicalIF":8.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SCGN recruits macrophages by regulating chemokine secretion in clear cell renal cell carcinoma.","authors":"Tuanjie Guo, Xinchao Zhang, Xuan Wang, Heting Tang, Yang Liu, Siteng Chen, Zhengchuan Niu, Chaofu Wang, Xu Wang, Xiang Wang","doi":"10.7150/ijbs.103252","DOIUrl":"10.7150/ijbs.103252","url":null,"abstract":"<p><p>Immunotherapy is considered to be one of the most promising curative modalities for cancer, and the effectiveness of immunotherapy depends on the abundance of immune cells in the tumor microenvironment (TME). Immunotherapy tends to be more effective in \"hot tumors\" characterized by a high abundant immune cells. Our previous studies found that secretagogin (SCGN) showed intranuclear aggregation in the early stages of clear cell renal cell carcinoma (ccRCC) development. However, with tumor progression and distant metastasis of the ccRCC, the expression of SCGN is gradually absent. In this study, we found that SCGN did not affect the malignant phenotype of cancer cells, but could regulate cytokine/chemokine secretion and immune cell migration by performing gene function assays and RNA-seq analyses after overexpressing SCGN in cell lines of ccRCC. Bioinformatics analysis, Transwell and co-culture experiments confirmed that ccRCC cells overexpressing SCGN could recruit M1-type macrophages. Mechanistically, SCGN initiates downstream cytokine/chemokine expression and secretion through the NF-κB signal pathway. This study provides a comprehensive understanding of the function of SCGN in ccRCC. Continuous forced expression of SCGN at different stages may be a potential approach for the treatment of ccRCC.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"20 15","pages":"5925-5938"},"PeriodicalIF":8.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid-Derived Suppressor Cells Induce Exhaustion-Like CD8⁺ T Cells during JEV Infection.","authors":"Weijia Zhang, Qing Yu, Xiaochen Gao, Haowei Chen, Jie Su, Yanru Chen, Yanling Li, Nan Zhang, Zhenfang Fu, Min Cui","doi":"10.7150/ijbs.102372","DOIUrl":"10.7150/ijbs.102372","url":null,"abstract":"<p><p>Japanese encephalitis (JE), caused by Japanese encephalitis virus (JEV), is a mosquito-borne zoonotic disease and a leading cause of viral encephalitis worldwide. While JEV has the ability to traverse the blood-brain barrier (BBB), the precise mechanisms by which it inhibits the immune response prior to penetrating the BBB remain unclear, presenting obstacles in the development of efficacious therapeutic interventions. This study investigated the impact of JEV on CD8⁺ T cell responses, with a particular focus on the dysfunction of CD8⁺ T cells during JEV infection. Our results demonstrated that JEV infection significantly elevated the expression of PD-1 and TIM-3 on CD8⁺ T cells, which are markers of T cell exhaustion, leading to inhibited function and impaired differentiation, resulting in a poorer prognosis in mice. Compared with nondiseased mice, symptomatic mice presented a greater proportion of exhaustion-like CD8⁺ T cells. <i>In vitro</i> experiments further demonstrated that MDSCs induced an exhaustion-like state in CD8⁺ T cells, characterized by significant upregulation of PD-1 and TIM-3 expression. Notably, blocking TIM-3 or depleting MDSCs restored CD8⁺ T cell functionality by rescuing the expression of IFN-γ and TNF-α. Furthermore, the depletion of MDSCs not only alleviated T cell exhaustion-like phenotypes but also improved survival rates in JEV-infected mice. These findings suggest that JEV promotes immune evasion through MDSC-induced CD8⁺ T cell exhaustion-like states and identify TIM-3 as a promising therapeutic target for JE treatment.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"20 15","pages":"5959-5978"},"PeriodicalIF":8.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of miR-4763-3p expression activates the PI3K/mTOR/Bcl2 autophagy signaling pathway to ameliorate cognitive decline.","authors":"Wenxin Qi, Yiwei Ying, Peiru Wu, Naijun Dong, Wenjun Fu, Qian Liu, Natalie Ward, Xin Dong, Robert Chunhua Zhao, Jiao Wang","doi":"10.7150/ijbs.103225","DOIUrl":"10.7150/ijbs.103225","url":null,"abstract":"<p><p>Cognitive decline and memory impairment are subsequently result in neuronal apoptosis and synaptic damage. Aberrant regulation of microRNAs has been implicated in the pathogenesis of Alzheimer's disease (AD) and may play a pivotal role in the early stages of the disease. In this study, we identified the critical role of miR-4763-3p in AD pathogenesis, focusing on early-stage mild cognitive impairment (AD-MCI). Leveraging fluorescence <i>in situ</i> hybridization, we observed miR-4763-3p upregulation in AD hippocampal tissue, colocalizing with Aβ and Tau. Antagomir-mediated inhibition of miR-4763-3p ameliorated cognitive decline in AD-MCI mice. RNA-seq and functional assays revealed that miR-4763-3p targets ATP11A, and antagomir enhancing inward flipping of the \"eat me\" phosphatidylserine signal on the surface of neuronal cells, autophagy, and clearance of Aβ/lipofuscin, while reducing neuroinflammation and neuronal apoptosis. Mechanistically, miR-4763-3p modulates the PI3K/AKT/mTOR/Bcl2 pathway, thereby promoting neuronal autophagy and reducing apoptotic crosstalk. These findings underscore miR-4763-3p as a therapeutic target for AD-MCI, offering a novel strategy to enhance neuronal autophagy, alleviate inflammation, and improve cognitive function.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"20 15","pages":"5999-6017"},"PeriodicalIF":8.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty Acid Metabolism Disruptions: A Subtle yet Critical Factor in Adverse Pregnancy Outcomes.","authors":"Xiao-Yan Cao, Meng-Ying Li, Chang-Xiang Shao, Jia-Lu Shi, Tao Zhang, Feng Xie, Ting Peng, Ming-Qing Li","doi":"10.7150/ijbs.103404","DOIUrl":"10.7150/ijbs.103404","url":null,"abstract":"<p><p>The establishment and maintenance of pregnancy encompass a series of complex and high-energy-consuming physiological processes, resulting in a significant energy demand. Fatty acids, one of the most essential nutrients, play a crucial role in energy supply via oxidation and perform critical biological functions such as anti-inflammatory and anti-oxidant effects, which substantially impact human health. Disordered fatty acid metabolism can cause anomalies in fetal growth and development, as well as a range of pregnancy problems, which can influence the health of both the mother and the fetus. In this review, we innovatively explore the relationship between fatty acid metabolism abnormalities and pregnancy complications, emphasizing the potential of dietary interventions with polyunsaturated fatty acids in improving pregnancy outcomes. These findings provide important evidence for clinical interventions and enhance the understanding and practical application of health management during pregnancy.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"20 15","pages":"6018-6037"},"PeriodicalIF":8.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement C1q is a key player in tumor-associated macrophage-mediated CD8⁺ T cell and NK cell dysfunction in malignant pleural effusion.","authors":"Feng-Shuang Yi, Xin Qiao, Shu-Feng Dong, Qing-Yu Chen, Rui-Qi Wei, Ming-Ming Shao, Huan-Zhong Shi","doi":"10.7150/ijbs.100607","DOIUrl":"10.7150/ijbs.100607","url":null,"abstract":"<p><p>Macrophages play a crucial role in malignant pleural effusion (MPE), a frequent complication of advanced cancer. While C1q⁺ macrophages have been identified as a pro-tumoral cluster, direct evidence supporting the role of C1q-mediated macrophages remains to be elucidated. This study employed global and macrophage-specific knockout mice to investigate the role of C1q in MPE. The data demonstrated that C1q deficiency in macrophages suppressed MPE and prolonged mouse survival. scRNA-seq analysis of the C1qa^-/- mouse MPE model revealed that C1q deficiency significantly decreased the proportion of M2 macrophages in MPE. <i>In vitro</i> experiments suggested that C1q expression was gradually upregulated during M2 polarization, which was C1q-dependent, as was antigen presentation. Deficiency of C1q in macrophages rescued the exhausted status of CD8⁺ T cells and enhanced the immune activity of CD8⁺ T cells and NK cells in both MPE and pleural tumors. Cell-to-cell interaction analysis demonstrated that C1q deficiency attenuated the immunoinhibitory effects of macrophages on NK cells by downregulating the CCR2-CCL2 signaling axis. Metabolomic analysis revealed significantly elevated hippuric acid levels in C1q-deficient mouse MPE. Treatment with either hippuric acid or a CCR2 antagonist inhibited MPE and tumor growth, with an even more pronounced effect observed when both treatments were combined.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"20 15","pages":"5979-5998"},"PeriodicalIF":8.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}