Cell Biology and Toxicology最新文献_第5页

Novel therapeutic targets: bifidobacterium-mediated urea cycle regulation in colorectal cancer 新的治疗目标：双歧杆菌介导的结直肠癌尿素循环调节

IF 6.1 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-03 DOI: 10.1007/s10565-024-09889-y

Xusheng Nie, Tingting Zhang, Xiumei Huang, Chongqi Gu, Wei Zuo, Li-Juan Fu, Yiping Dong, Hao Liu

{"title":"Novel therapeutic targets: bifidobacterium-mediated urea cycle regulation in colorectal cancer","authors":"Xusheng Nie, Tingting Zhang, Xiumei Huang, Chongqi Gu, Wei Zuo, Li-Juan Fu, Yiping Dong, Hao Liu","doi":"10.1007/s10565-024-09889-y","DOIUrl":"https://doi.org/10.1007/s10565-024-09889-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background and purpose</h3>Colorectal cancer (CRC) is a widespread malignancy with a complex and not entirely elucidated pathogenesis. This study aims to explore the role of Bifidobacterium in the urea cycle (UC) and its influence on the progression of CRC, a topic not extensively studied previously.<h3 data-test=\"abstract-sub-heading\">Experimental approach</h3>Utilizing both bioinformatics and experimental methodologies, this research involved analyzing bacterial abundance in CRC patients in comparison to healthy individuals. The study particularly focused on the abundance of BA. Additionally, transcriptomic data analysis and cellular experiments were conducted to investigate the impact of Bifidobacterium on ammonia metabolism and mitochondrial function, specifically examining its regulation of the key UC gene, ALB.<h3 data-test=\"abstract-sub-heading\">Key results</h3>The analysis revealed a significant decrease in Bifidobacterium abundance in CRC patients. Furthermore, Bifidobacterium was found to suppress ammonia metabolism and induce mitochondrial dysfunction through the regulation of the ALB gene, which is essential in the context of UC. These impacts contributed to the suppression of CRC cell proliferation, a finding corroborated by animal experimental results.<h3 data-test=\"abstract-sub-heading\">Conclusions and implications</h3>This study elucidates the molecular mechanism by which Bifidobacterium impacts CRC progression, highlighting its role in regulating key metabolic pathways. These findings provide potential targets for novel therapeutic strategies in CRC treatment, emphasizing the importance of microbiota in cancer progression.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"54 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141884099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FOXC1 transcriptionally suppresses ABHD5 to inhibit the progression of renal cell carcinoma through AMPK/mTOR pathway. FOXC1通过AMPK/mTOR途径转录抑制ABHD5，从而抑制肾细胞癌的进展。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-02 DOI: 10.1007/s10565-024-09899-w

Jianfa Li, Shuangchen Chen, Jing Xiao, Jiayuan Ji, Chenchen Huang, Ge Shu

{"title":"FOXC1 transcriptionally suppresses ABHD5 to inhibit the progression of renal cell carcinoma through AMPK/mTOR pathway.","authors":"Jianfa Li, Shuangchen Chen, Jing Xiao, Jiayuan Ji, Chenchen Huang, Ge Shu","doi":"10.1007/s10565-024-09899-w","DOIUrl":"10.1007/s10565-024-09899-w","url":null,"abstract":"Background: Increased activity of the transcription factor FOXC1 leads to elevated transcription of target genes, ultimately facilitating the progression of various cancer types. However, there are currently no literature reports on the role of FOXC1 in renal cell carcinoma.Methods: By using RT-qPCR, immunohistochemistry and Western blotting, FOXC1 mRNA and protein expression was evaluated. Gain of function experiments were utilized to assess the proliferation and metastasis ability of cells. A nude mouse model was created for transplanting tumors and establishing a lung metastasis model to observe cell proliferation and spread in a living organism. Various techniques including biological analysis, CHIP assay, luciferase assay, RT-qRCR and Western blotting experiments were utilized to investigate how FOXC1 contributes to the transcription of ABHD5 on a molecular level. FOXC1 was assessed by Western blot for its impact on AMPK/mTOR signaling pathway.Results: FOXC1 is down-regulated in RCC, causing unfavorable prognosis of patients with RCC. Further experiments showed that forced FOXC1 expression significantly restrains RCC cell growth and cell metastasis. Mechanically, FOXC1 promotes the transcription of ABHD5 to activate AMPK signal pathway to inhibit mTOR signal pathway. Finally, knockdown of ABHD5 recovered the inhibitory role of FOXC1 overexpression induced cell growth and metastasis suppression.Conclusion: In general, our study demonstrates that FOXC1 exerts its tumor suppressor role by promoting ABHD5 transcription to regulating AMPK/mTOR signal pathway. FOXC1 could serve as both a diagnostic indicator and potential treatment focus for RCC.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"62"},"PeriodicalIF":5.3,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the hidden dangers: a review of non-apoptotic programmed cell death in anesthetic-induced developmental neurotoxicity. 揭开隐藏危险的面纱：回顾麻醉剂诱发的发育神经毒性中的非凋亡性程序性细胞死亡。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-02 DOI: 10.1007/s10565-024-09895-0

Haiyan Sun, Yisi Shan, Liyan Cao, Xiping Wu, Jiangdong Chen, Rong Yuan, Min Qian

{"title":"Unveiling the hidden dangers: a review of non-apoptotic programmed cell death in anesthetic-induced developmental neurotoxicity.","authors":"Haiyan Sun, Yisi Shan, Liyan Cao, Xiping Wu, Jiangdong Chen, Rong Yuan, Min Qian","doi":"10.1007/s10565-024-09895-0","DOIUrl":"10.1007/s10565-024-09895-0","url":null,"abstract":"Anesthetic-induced developmental neurotoxicity (AIDN) can arise due to various factors, among which aberrant nerve cell death is a prominent risk factor. Animal studies have reported that repeated or prolonged anesthetic exposure can cause significant neuroapoptosis in the developing brain. Lately, non-apoptotic programmed cell deaths (PCDs), characterized by inflammation and oxidative stress, have gained increasing attention. Substantial evidence suggests that non-apoptotic PCDs are essential for neuronal cell death in AIDN compared to apoptosis. This article examines relevant publications in the PubMed database until April 2024. Only original articles in English that investigated the potential manifestations of non-apoptotic PCD in AIDN were analysed. Specifically, it investigates necroptosis, pyroptosis, ferroptosis, and parthanatos, elucidating the signaling mechanisms associated with each form. Furthermore, this study explores the potential relevance of these non-apoptotic PCDs pathways to the pathological mechanisms underlying AIDN, drawing upon their distinctive characteristics. Despite the considerable challenges involved in translating fundamental scientific knowledge into clinical therapeutic interventions, this comprehensive review offers a theoretical foundation for developing innovative preventive and treatment strategies targeting non-apoptotic PCDs in the context of AIDN.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"63"},"PeriodicalIF":5.3,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Let's make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment. 让我们把它变成个人的：利用CRISPR工具操纵细胞死亡途径以治疗癌症。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-07-29 DOI: 10.1007/s10565-024-09907-z

Mobina Bayat, Javid Sadri Nahand

{"title":"Let's make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment.","authors":"Mobina Bayat, Javid Sadri Nahand","doi":"10.1007/s10565-024-09907-z","DOIUrl":"10.1007/s10565-024-09907-z","url":null,"abstract":"Advancements in the CRISPR technology, a game-changer in experimental research, have revolutionized various fields of life sciences and more profoundly, cancer research. Cell death pathways are among the most deregulated in cancer cells and are considered as critical aspects in cancer development. Through decades, our knowledge of the mechanisms orchestrating programmed cellular death has increased substantially, attributed to the revolution of cutting-edge technologies. The heroic appearance of CRISPR systems have expanded the available screening platform and genome engineering toolbox to detect mutations and create precise genome edits. In that context, the precise ability of this system for identification and targeting of mutations in cell death signaling pathways that result in cancer development and therapy resistance is an auspicious choice to transform and accelerate the individualized cancer therapy. The concept of personalized cancer therapy stands on the identification of molecular characterization of the individual tumor and its microenvironment in order to provide a precise treatment with the highest possible outcome and minimum toxicity. This study explored the potential of CRISPR technology in precision cancer treatment by identifying and targeting specific cell death pathways. It showed the promise of CRISPR in finding key components and mutations involved in programmed cell death, making it a potential tool for targeted cancer therapy. However, this study also highlighted the challenges and limitations that need to be addressed in future research to fully realize the potential of CRISPR in cancer treatment.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"61"},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteasome activity inhibition mediates endoplasmic reticulum stress-apoptosis in triptolide/lipopolysaccharide-induced hepatotoxicity. 蛋白酶体活性抑制在三苯氧胺/脂多糖诱导的肝毒性中介导内质网应激-凋亡。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-07-29 DOI: 10.1007/s10565-024-09903-3

Ruohan Cheng, Yihan Jiang, Yue Zhang, Mohammed Ismail, Luyong Zhang, Zhenzhou Jiang, Qinwei Yu

{"title":"Proteasome activity inhibition mediates endoplasmic reticulum stress-apoptosis in triptolide/lipopolysaccharide-induced hepatotoxicity.","authors":"Ruohan Cheng, Yihan Jiang, Yue Zhang, Mohammed Ismail, Luyong Zhang, Zhenzhou Jiang, Qinwei Yu","doi":"10.1007/s10565-024-09903-3","DOIUrl":"10.1007/s10565-024-09903-3","url":null,"abstract":"Triptolide (TP) is a major active and toxic composition of the Chinese medicine Tripterygium wilfordii Hook. F. (TWHF), exhibiting various therapeutic bioactivities. Among the toxic effects, the hepatotoxicity of TP deserves serious attention. Previously, our research group proposed a new view of TP-related hepatotoxicity: hepatic hypersensitivity under lipopolysaccharide (LPS) stimulation. However, the mechanism of TP/LPS-induced hepatic hypersensitivity remains unclear. In this study, we investigated the mechanism underlying TP/LPS-induced hypersensitivity from the perspective of the inhibition of proteasome activity, activated endoplasmic reticulum stress (ERS)-related apoptosis, and the accumulation of reactive oxygen species (ROS). Our results showed that N-acetylcysteine (NAC), a common ROS inhibitor, decreased the expression of cleaved caspase-3 and cleaved PARP, which are associated with FLIP enhancement. Moreover, 4-phenylbutyric acid (4-PBA), an ERS inhibitor, was able to alleviate TP/LPS-induced hepatotoxicity by reducing ERS-related apoptosis protein expression (GRP78, p-eIF2α/eIF2α, ATF4, CHOP, cleaved caspase-3 and cleaved PARP) and ROS levels, with ATF4 being an indispensable mediator. In addition, the proteasome activity inhibitor MG-132 further aggravated ERS-related apoptosis, which indicated that the inhibition of proteasome activity also plays an important role in TP/LPS-related liver injuries. In summary, we propose that TP/LPS may upregulate the activation of ERS-associated apoptosis by inhibiting proteasome activity and enhancing ROS production through ATF4.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"60"},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adenosine kinase protects against acetaminophen-induced acute liver injury by activating autophagy in hepatocytes. 腺苷激酶通过激活肝细胞自噬保护肝细胞免受对乙酰氨基酚诱发的急性肝损伤。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-07-27 DOI: 10.1007/s10565-024-09906-0

Chuanxin Zhang, Xuehao Liu, Xilong Liu, Rui Hua, Han Liu, Jiaxin Ma, Dan Zou, Guangmei Wang, Qiuhuan Yuan, Bailu Wang, Shujian Wei, Yuguo Chen

{"title":"Adenosine kinase protects against acetaminophen-induced acute liver injury by activating autophagy in hepatocytes.","authors":"Chuanxin Zhang, Xuehao Liu, Xilong Liu, Rui Hua, Han Liu, Jiaxin Ma, Dan Zou, Guangmei Wang, Qiuhuan Yuan, Bailu Wang, Shujian Wei, Yuguo Chen","doi":"10.1007/s10565-024-09906-0","DOIUrl":"10.1007/s10565-024-09906-0","url":null,"abstract":"Acute liver injury (ALI) is a common life-threatening condition with a high mortality rate due to liver disease-related death. However, current therapeutic interventions for ALI remain ineffective, and the development of effective novel therapies is urgently needed. Liver samples from patients with drug-induced ALI were collected to detect adenosine kinase (ADK) expression. Male C57BL/6 J mice, hepatocyte-specific ADK knockout (ADKHKO) mice, and their controls (ADKf/f) were exposed to acetaminophen (APAP) and other treatments to investigate the mechanisms of APAP-related ALI. ADK expression was significantly decreased in APAP-injured livers. Hepatocyte-specific ADK deficiency exacerbated APAP-induced ALI, while a gain-of-function approach delivering AAV-ADK, markedly alleviated APAP-induced ALI, as indicated by changes in alanine aminotransferases (ALT) levels, aspartate aminotransferase (AST) levels, neutrophil infiltration and hepatocyte death. This study showed that ADK played a critical role in ALI by activating autophagy through two signaling pathways, the adenosine monophosphate-activated protein kinase (AMPK)-mTOR pathway and the adenosine receptor A1 (ADORA1)-Akt-mTOR pathway. Furthermore, we found that metformin upregulated ADK expression in hepatocytes and protected against APAP-induced ALI. These results demonstrate that ADK is critical in protecting against APAP-induced ALI and that developing therapeutics targeting ADK-adenosine-ADORA1 is a new approach for ALI treatment. Metformin is a potential candidate for preventing ALI by upregulating ADK.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"59"},"PeriodicalIF":5.3,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KIAA1429 increases FOXM1 expression through YTHDF1-mediated m6A modification to promote aerobic glycolysis and tumorigenesis in multiple myeloma. KIAA1429 通过 YTHDF1 介导的 m6A 修饰增加 FOXM1 的表达，从而促进多发性骨髓瘤的有氧糖酵解和肿瘤发生。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-07-26 DOI: 10.1007/s10565-024-09904-2

Yue Wu, Yi Luo, Xingchen Yao, Xiangjun Shi, Ziyu Xu, Jie Re, Ming Shi, Meng Li, Junpeng Liu, Youzhi He, Xinru Du

{"title":"KIAA1429 increases FOXM1 expression through YTHDF1-mediated m6A modification to promote aerobic glycolysis and tumorigenesis in multiple myeloma.","authors":"Yue Wu, Yi Luo, Xingchen Yao, Xiangjun Shi, Ziyu Xu, Jie Re, Ming Shi, Meng Li, Junpeng Liu, Youzhi He, Xinru Du","doi":"10.1007/s10565-024-09904-2","DOIUrl":"10.1007/s10565-024-09904-2","url":null,"abstract":"Objective: Multiple myeloma (MM) is a deadly plasma cell malignancy with elusive pathogenesis. N6-methyladenosine (m6A) is critically engaged in hematological malignancies. The function of KIAA1429, the largest component of methyltransferases, is unknown. This study delved into the mechanism of KIAA1429 in MM, hoping to offer novel targets for MM therapy.Methods: Bone marrow samples were attained from 55 MM patients and 15 controls. KIAA1429, YTHDF1, and FOXM1 mRNA levels were detected and their correlation was analyzed. Cell viability, proliferation, cell cycle, and apoptosis were testified. Glycolysis-enhancing genes (HK2, ENO1, and LDHA), lactate production, and glucose uptake were evaluated. The interaction between FOXM1 mRNA and YTHDF1, m6A-modified FOXM1 level, and FOXM1 stability were assayed. A transplantation tumor model was built to confirm the mechanism of KIAA1429.Results: KIAA1429 was at high levels in MM patients and MM cells and linked to poor prognoses. KIAA1429 knockdown restrained MM cell viability, and proliferation, arrested G0/G1 phase, and increased apoptosis. KIAA1429 mRNA in plasma cells from MM patients was positively linked with to glycolysis-enhancing genes. The levels of glycolysis-enhancing genes, glucose uptake, and lactate production were repressed after KIAA1429 knockdown, along with reduced FOXM1 levels and stability. YTHDF1 recognized KIAA1429-methylated FOXM1 mRNA and raised FOXM1 stability. Knockdown of YTHDF1 curbed aerobic glycolysis and malignant behaviors in MM cells, which was nullified by FOXM1 overexpression. KIAA1429 knockdown also inhibited tumor growth in animal experiments.Conclusion: KIAA1429 knockdown reduces FOXM1 expression through YTHDF1-mediated m6A modification, thus inhibiting MM aerobic glycolysis and tumorigenesis.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"58"},"PeriodicalIF":5.3,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ADAR1 prevents ZBP1-dependent PANoptosis via A-to-I RNA editing in developmental sevoflurane neurotoxicity. 在七氟烷神经毒性发育过程中，ADAR1通过A-to-I RNA编辑防止ZBP1依赖性PAN凋亡

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-07-25 DOI: 10.1007/s10565-024-09905-1

Huiling Yang, Sen Xu, Xinya Hong, Yusi Liu, Shaojie Qian, Yifei Lou, Wenyuan Wang

{"title":"ADAR1 prevents ZBP1-dependent PANoptosis via A-to-I RNA editing in developmental sevoflurane neurotoxicity.","authors":"Huiling Yang, Sen Xu, Xinya Hong, Yusi Liu, Shaojie Qian, Yifei Lou, Wenyuan Wang","doi":"10.1007/s10565-024-09905-1","DOIUrl":"10.1007/s10565-024-09905-1","url":null,"abstract":"It is well established that sevoflurane exposure leads to widespread neuronal cell death in the developing brain. Adenosine deaminase acting on RNA-1 (ADAR1) dependent adenosine-to-inosine (A-to-I) RNA editing is dynamically regulated throughout brain development. The current investigation is designed to interrogate the contributed role of ADAR1 in developmental sevoflurane neurotoxicity. Herein, we provide evidence to show that developmental sevoflurane priming triggers neuronal pyroptosis, apoptosis and necroptosis (PANoptosis), and elicits the release of inflammatory factors including IL-1β, IL-18, TNF-α and IFN-γ. Additionally, ADAR1-P150, but not ADAR1-P110, depresses cellular PANoptosis and inflammatory response by competing with Z-DNA/RNA binding protein 1 (ZBP1) for binding to Z-RNA in the presence of sevoflurane. Further investigation demonstrates that ADAR1-dependent A-to-I RNA editing mitigates developmental sevoflurane-induced neuronal PANoptosis. To restore RNA editing, we utilize adeno-associated virus (AAV) to deliver engineered circular ADAR-recruiting guide RNAs (cadRNAs) into cells, which is capable of recruiting endogenous adenosine deaminases to promote cellular A-to-I RNA editing. As anticipated, AAV-cadRNAs diminishes sevoflurane-induced cellular Z-RNA production and PANoptosis, which could be abolished by ADAR1-P150 shRNA transfection. Moreover, AAV-cadRNAs delivery ameliorates developmental sevoflurane-induced spatial and emotional cognitive deficits without influence on locomotor activity. Taken together, these results illustrate that ADAR1-P150 exhibits a prominent role in preventing ZBP1-dependent PANoptosis through A-to-I RNA editing in developmental sevoflurane neurotoxicity. Application of engineered cadRNAs to rectify the compromised ADAR1-dependent A-to-I RNA editing provides an inspiring direction for possible clinical preventions and therapeutics.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"57"},"PeriodicalIF":5.3,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade. PD-L2通过RGMB/NFκB/CCL20级联介导吸烟诱导的调节性T细胞招募。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-07-23 DOI: 10.1007/s10565-024-09892-3

Hua Guo, Chen Zhang, Yu-Ke Shen, Jian-Dong Zhang, Fu-Ying Yang, Fan Liang, Wei Wang, Yu-Tao Liu, Gui-Zhen Wang, Guang-Biao Zhou

{"title":"PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade.","authors":"Hua Guo, Chen Zhang, Yu-Ke Shen, Jian-Dong Zhang, Fu-Ying Yang, Fan Liang, Wei Wang, Yu-Tao Liu, Gui-Zhen Wang, Guang-Biao Zhou","doi":"10.1007/s10565-024-09892-3","DOIUrl":"10.1007/s10565-024-09892-3","url":null,"abstract":"Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"56"},"PeriodicalIF":5.3,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HMGB1 as an extracellular pro-inflammatory cytokine: Implications for drug-induced organic damage. 作为细胞外促炎细胞因子的 HMGB1：对药物诱导的有机损伤的影响

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-07-15 DOI: 10.1007/s10565-024-09893-2

JianYe Yuan, Lin Guo, JiaTing Ma, HeJian Zhang, MingXuan Xiao, Ning Li, Hui Gong, Miao Yan

{"title":"HMGB1 as an extracellular pro-inflammatory cytokine: Implications for drug-induced organic damage.","authors":"JianYe Yuan, Lin Guo, JiaTing Ma, HeJian Zhang, MingXuan Xiao, Ning Li, Hui Gong, Miao Yan","doi":"10.1007/s10565-024-09893-2","DOIUrl":"10.1007/s10565-024-09893-2","url":null,"abstract":"Drug-induced organic damage encompasses various intricate mechanisms, wherein HMGB1, a non-histone chromosome-binding protein, assumes a significant role as a pivotal hub gene. The regulatory functions of HMGB1 within the nucleus and extracellular milieu are interlinked. HMGB1 exerts a crucial regulatory influence on key biological processes including cell survival, inflammatory regulation, and immune response. HMGB1 can be released extracellularly from the cell during these processes, where it functions as a pro-inflammation cytokine. HMGB1 interacts with multiple cell membrane receptors, primarily Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE), to stimulate immune cells and trigger inflammatory response. The excessive or uncontrolled HMGB1 release leads to heightened inflammatory responses and cellular demise, instigating inflammatory damage or exacerbating inflammation and cellular demise in different diseases. Therefore, a thorough review on the significance of HMGB1 in drug-induced organic damage is highly important for the advancement of pharmaceuticals, ensuring their effectiveness and safety in treating inflammation as well as immune-related diseases. In this review, we initially outline the characteristics and functions of HMGB1, emphasizing their relevance in disease pathology. Then, we comprehensively summarize the prospect of HMGB1 as a promising therapeutic target for treating drug-induced toxicity. Lastly, we discuss major challenges and propose potential avenues for advancing the development of HMGB1-based therapeutics.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"55"},"PeriodicalIF":5.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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