Cell Biology and Toxicology最新文献_第4页

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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}

引用次数: 0

TRAF6 promotes spinal microglial M1 polarization to aggravate neuropathic pain by activating the c-JUN/NF-kB signaling pathway. TRAF6 通过激活 c-JUN/NF-kB 信号通路，促进脊髓小胶质细胞 M1 极化，从而加重神经病理性疼痛。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-07-12 DOI: 10.1007/s10565-024-09900-6

Yu Zhao, Tiegang Li, Lichun Zhang, Jun Yang, Feng Zhao, Yu Wang, Yi Ouyang, Jiahui Liu

{"title":"TRAF6 promotes spinal microglial M1 polarization to aggravate neuropathic pain by activating the c-JUN/NF-kB signaling pathway.","authors":"Yu Zhao, Tiegang Li, Lichun Zhang, Jun Yang, Feng Zhao, Yu Wang, Yi Ouyang, Jiahui Liu","doi":"10.1007/s10565-024-09900-6","DOIUrl":"10.1007/s10565-024-09900-6","url":null,"abstract":"Background: The neuropathic pain with complex networks of neuroinflammatory activation severely limits clinical therapeutic research. TNF receptor-associated factor 6 (TRAF6) is associated with multiple inflammatory diseases. However, there remains confusion about the effects and mechanisms of TRAF6 in neuropathic pain.Methods: A chronic constriction injury (CCI) model was developed to simulate neuralgia in vivo. We overexpressed or knocked down TRAF6 in CCI mice, respectively. Activation of microglia by TRAF6, the inflammatory response, and disease progression were inspected using WB, qRT-PCR, immunofluorescence, flow cytometry, and ELISA assays. Moreover, the mechanism of M1/M2 polarization activation of microglia by TRAF6 was elaborated in BV-2 cells.Results: TRAF6 was enhanced in the spinal neurons and microglia of the CCI mice model compared with the sham operation group.. Down-regulation of TRAF6 rescued the expression of Iba-1. In response to mechanical and thermal stimulation, PWT and PWL were improved after the knockdown of TRAF6. Decreased levels of pro-inflammatory factors were observed in TRAF6 knockdown groups. Meanwhile, increased microglial M1 markers induced by CCI were limited in mice with TRAF6 knockdown. In addition, TRAF6 overexpression has the precise opposite effect on CCI mice or microglia polarization. We also identifed that TRAF6 activated the c-JUN/NF-kB pathway signaling; the inhibitor of c-JUN/NF-kB could effectively alleviate the neuropathic pain induced by upregulated TRAF6 in the CCI mice model.Conclusion: In summary, this study indicated that TRAF6 was concerned with neuropathic pain, and targeting the TRAF6/c-JUN/NF-kB pathway may be a prospective target for treating neuropathic pain.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589678","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

Mechanistic and therapeutic perspectives of non-coding RNA-modulated apoptotic signaling in diabetic retinopathy. 非编码 RNA 调节糖尿病视网膜病变中细胞凋亡信号转导的机制和治疗前景。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-07-06 DOI: 10.1007/s10565-024-09896-z

Qin Wu, Chunlei Liu, Xiangwen Shu, Lian Duan

{"title":"Mechanistic and therapeutic perspectives of non-coding RNA-modulated apoptotic signaling in diabetic retinopathy.","authors":"Qin Wu, Chunlei Liu, Xiangwen Shu, Lian Duan","doi":"10.1007/s10565-024-09896-z","DOIUrl":"10.1007/s10565-024-09896-z","url":null,"abstract":"Diabetic retinopathy (DR), a significant and vision-endangering complication associated with diabetes mellitus, constitutes a substantial portion of acquired instances of preventable blindness. The progression of DR appears to prominently feature the loss of retinal cells, encompassing neural retinal cells, pericytes, and endothelial cells. Therefore, mitigating the apoptosis of retinal cells in DR could potentially enhance the therapeutic approach for managing the condition by suppressing retinal vascular leakage. Recent advancements have highlighted the crucial regulatory roles played by non-coding RNAs (ncRNAs) in diverse biological processes. Recent advancements have highlighted that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), act as central regulators in a wide array of biogenesis and biological functions, exerting control over gene expression associated with histogenesis and cellular differentiation within ocular tissues. Abnormal expression and activity of ncRNAs has been linked to the regulation of diverse cellular functions such as apoptosis, and proliferation. This implies a potential involvement of ncRNAs in the development of DR. Notably, ncRNAs and apoptosis exhibit reciprocal regulatory interactions, jointly influencing the destiny of retinal cells. Consequently, a thorough investigation into the complex relationship between apoptosis and ncRNAs is crucial for developing effective therapeutic and preventative strategies for DR. This review provides a fundamental comprehension of the apoptotic signaling pathways associated with DR. It then delves into the mutual relationship between apoptosis and ncRNAs in the context of DR pathogenesis. This study advances our understanding of the pathophysiology of DR and paves the way for the development of novel therapeutic strategies.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544559","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

Delivery of miR-15b-5p via magnetic nanoparticle-enhanced bone marrow mesenchymal stem cell-derived extracellular vesicles mitigates diabetic osteoporosis by targeting GFAP. 通过磁性纳米粒子增强骨髓间充质干细胞衍生的细胞外囊泡输送 miR-15b-5p 可通过靶向 GFAP 缓解糖尿病骨质疏松症。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-07-05 DOI: 10.1007/s10565-024-09877-2

Chen Xu, Zhaodong Wang, Yajun Liu, Keyou Duan, Jianzhong Guan

{"title":"Delivery of miR-15b-5p via magnetic nanoparticle-enhanced bone marrow mesenchymal stem cell-derived extracellular vesicles mitigates diabetic osteoporosis by targeting GFAP.","authors":"Chen Xu, Zhaodong Wang, Yajun Liu, Keyou Duan, Jianzhong Guan","doi":"10.1007/s10565-024-09877-2","DOIUrl":"10.1007/s10565-024-09877-2","url":null,"abstract":"Diabetic osteoporosis (DO) presents significant clinical challenges. This study aimed to investigate the potential of magnetic nanoparticle-enhanced extracellular vesicles (GMNPE-EVs) derived from bone marrow mesenchymal stem cells (BMSCs) to deliver miR-15b-5p, thereby targeting and downregulating glial fibrillary acidic protein (GFAP) expression in rat DO models. Data was sourced from DO-related RNA-seq datasets combined with GEO and GeneCards databases. Rat primary BMSCs, bone marrow-derived macrophages (BMMs), and osteoclasts were isolated and cultured. EVs were separated, and GMNPE targeting EVs were synthesized. Bioinformatic analysis revealed a high GFAP expression in DO-related RNA-seq and GSE26168 datasets for disease models. Experimental results confirmed elevated GFAP in rat DO bone tissues, promoting osteoclast differentiation. miR-15b-5p was identified as a GFAP inhibitor, but was significantly downregulated in DO and enriched in BMSC-derived EVs. In vitro experiments showed that GMNPE-EVs could transfer miR-15b-5p to osteoclasts, downregulating GFAP and inhibiting osteoclast differentiation. In vivo tests confirmed the therapeutic potential of this approach in alleviating rat DO. Collectively, GMNPE-EVs can effectively deliver miR-15b-5p to osteoclasts, downregulating GFAP expression, and hence, offering a therapeutic strategy for rat DO.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533764","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

Zinc oxide nanoparticles induces cell death and consequently leading to incomplete neural tube closure through oxidative stress during embryogenesis. 纳米氧化锌颗粒会诱导细胞死亡，从而在胚胎发育过程中通过氧化应激导致神经管闭合不全。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-07-03 DOI: 10.1007/s10565-024-09894-1

Yu Yan, Wenyi Huang, Xiaoting Lu, Xianxian Chen, Yingyi Shan, Xin Luo, Yu Li, Xuesong Yang, Chun Li

{"title":"Zinc oxide nanoparticles induces cell death and consequently leading to incomplete neural tube closure through oxidative stress during embryogenesis.","authors":"Yu Yan, Wenyi Huang, Xiaoting Lu, Xianxian Chen, Yingyi Shan, Xin Luo, Yu Li, Xuesong Yang, Chun Li","doi":"10.1007/s10565-024-09894-1","DOIUrl":"10.1007/s10565-024-09894-1","url":null,"abstract":"The implementation of Zinc oxide nanoparticles (ZnO NPs) raises concerns regarding their potential toxic effects on human health. Although more and more researches have confirmed the toxic effects of ZnO NPs, limited attention has been given to their impact on the early embryonic nervous system. This study aimed to explore the impact of exposure to ZnO NPs on early neurogenesis and explore its underlying mechanisms. We conducted experiments here to confirm the hypothesis that exposure to ZnO NPs causes neural tube defects in early embryonic development. We first used mouse and chicken embryos to confirm that ZnO NPs and the Zn2+ they release are able to penetrate the placental barrier, influence fetal growth and result in incomplete neural tube closure. Using SH-SY5Y cells, we determined that ZnO NPs-induced incomplete neural tube closure was caused by activation of various cell death modes, including ferroptosis, apoptosis and autophagy. Moreover, dissolved Zn2+ played a role in triggering widespread cell death. ZnO NPs were accumulated within mitochondria after entering cells, damaging mitochondrial function and resulting in the over production of reactive oxygen species, ultimately inducing cellular oxidative stress. The N-acetylcysteine (NAC) exhibits significant efficacy in mitigating cellular oxidative stress, thereby alleviating the cytotoxicity and neurotoxicity brought about by ZnO NPs. These findings indicated that the exposure of ZnO NPs in early embryonic development can induce cell death through oxidative stress, resulting in a reduced number of cells involved in early neural tube closure and ultimately resulting in incomplete neural tube closure during embryo development. The findings of this study could raise public awareness regarding the potential risks associated with the exposure and use of ZnO NPs in early pregnancy.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491017","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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