Acta biochimica et biophysica Sinica最新文献_第10页

Combined treatment with cetuximab and STA9090 has synergistic anticancer effects on human non-small cell lung cancer. 西妥昔单抗和 STA9090 联合治疗对人类非小细胞肺癌具有协同抗癌作用。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-05-30 DOI: 10.3724/abbs.2024069

Wanjun Lu, Lixia Liu, Xiang Kang, Kangkang Ren, Ye Huang, Minzhang Cheng, Xiaolei Li, Fei Xu, Xinping Xu

{"title":"Combined treatment with cetuximab and STA9090 has synergistic anticancer effects on human non-small cell lung cancer.","authors":"Wanjun Lu, Lixia Liu, Xiang Kang, Kangkang Ren, Ye Huang, Minzhang Cheng, Xiaolei Li, Fei Xu, Xinping Xu","doi":"10.3724/abbs.2024069","DOIUrl":"10.3724/abbs.2024069","url":null,"abstract":"Cetuximab (CET), a human murine chimeric IgG monoclonal antibody and an inhibitor of epidermal growth factor receptor (EGFR), has been shown to be effective in treating various types of cancer. However, its use is hindered by limitations such as resistance development, variability in patient response, side effects, and challenges in biomarker identification. Therefore, CET is often combined with other targeted therapies or chemotherapies to enhance its effectiveness. In this study, we investigate the anticancer effects and underlying mechanisms of the combination of CET, an EGFR inhibitor, and STA9090, an inhibitor of heat shock protein 90 (Hsp90), in both in vitro and in vivo models of non-small cell lung cancer (NSCLC). The results demonstrate significantly stronger effects on NSCLC cells in response to combination therapy than to treatment with either agent alone, indicating that the combination of CET and STA9090 has potential synergistic effects. Additionally, the combination therapy inhibits tumor growth in a xenograft nude mouse model more effectively than treatment with either agent alone, suggesting improved efficacy when used together. Furthermore, the synergistic effects of the combination therapy are likely due to inactivation of the receptor tyrosine kinase (RTK) pathway, which is overly activated in cancer and contributes to tumor growth, angiogenesis, and metastasis. Consequently, our findings suggest that STA9090 has potent direct antitumor activity and synergizes with CET against NSCLC tumors. It is highly likely that these synergistic effects are mediated through RTK pathway inactivation caused by the combination. Therefore, our findings strongly and consistently support the potential synergistic effect of STA9090, an RTK inhibitor, in combination with EGFR-targeting agents.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178652","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}

引用次数: 0

Identification of RACK1 as a novel regulator of non-structural protein 4 of chikungunya virus. 鉴定 RACK1 是基孔肯雅病毒非结构蛋白 4 的新型调节因子。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-05-29 DOI: 10.3724/abbs.2024073

Yao Yan, Fengyuan Zhang, Meng Zou, Hongyu Chen, Jingwen Xu, Shuaiyao Lu, Hongqi Liu

{"title":"Identification of RACK1 as a novel regulator of non-structural protein 4 of chikungunya virus.","authors":"Yao Yan, Fengyuan Zhang, Meng Zou, Hongyu Chen, Jingwen Xu, Shuaiyao Lu, Hongqi Liu","doi":"10.3724/abbs.2024073","DOIUrl":"10.3724/abbs.2024073","url":null,"abstract":"Chikungunya virus (CHIKV) is a neglected arthropod-borne and anthropogenic alphavirus. Over the past two decades, the CHIKV distribution has undergone significant changes worldwide, from the original tropics and subtropics regions to temperate regions, which has attracted global attention. However, the interactions between CHIKV and its host remain insufficiently understood, which dampens the need for the development of an anti-CHIKV strategy. In this study, on the basis of the optimal overexpression of non-structural protein 4 (nsP4), we explore host interactions of CHIKV nsP4 using mass spectrometry-based protein-protein interaction approaches. The results reveal that some cellular proteins that interact with nsP4 are enriched in the ubiquitin-proteasome pathway. Specifically, the scaffold protein receptor for activated C kinase 1 (RACK1) is identified as a novel host interactor and regulator of CHIKV nsP4. The inhibition of the interaction between RACK1 and nsP4 by harringtonolide results in the reduction of nsP4, which is caused by the promotion of degradation but not the inhibition of nsP4 translation. Furthermore, the decrease in nsP4 triggered by the RACK1 inhibitor can be reversed by the proteasome inhibitor MG132, suggesting that RACK1 can protect nsP4 from degradation through the ubiquitin-proteasome pathway. This study reveals a novel mechanism by which the host factor RACK1 regulates CHIKV nsP4, which could be a potential target for developing drugs against CHIKV.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174091","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}

引用次数: 0

Aminophylline suppresses chronic renal failure progression by activating SIRT1/AMPK/mTOR-dependent autophagy. 氨茶碱通过激活SIRT1/AMPK/mTOR依赖性自噬抑制慢性肾功能衰竭的进展。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-05-28 DOI: 10.3724/abbs.2024049

Xin Liao, Jieyi Lu, Zhifeng Huang, Jinai Lin, Miao Zhang, Huanru Chen, Xiaoqing Lin, Xia Gao, Sitang Gong

{"title":"Aminophylline suppresses chronic renal failure progression by activating SIRT1/AMPK/mTOR-dependent autophagy.","authors":"Xin Liao, Jieyi Lu, Zhifeng Huang, Jinai Lin, Miao Zhang, Huanru Chen, Xiaoqing Lin, Xia Gao, Sitang Gong","doi":"10.3724/abbs.2024049","DOIUrl":"10.3724/abbs.2024049","url":null,"abstract":"Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160024","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}

引用次数: 0

Highly sensitive detection of a long-COVID-related SNP in LZTFL1 allele with Pyrococcus furiosus Argonaute in point-of-care settings. 用 Pyrococcus furiosus Argonaute 在护理点环境中高灵敏地检测 LZTFL1 等位基因中与长 COVID 相关的 SNP。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-05-27 DOI: 10.3724/abbs.2024071

Yixin Tang, Miao Xu, Bo Luo, Yue Wang, Yukang Chen, Guangxi Yu, Guang Yang, Song Gao, Pei Wang

引用次数: 0

EZH2 inhibition induces senescence via ERK1/2 signaling pathway in multiple myeloma. EZH2 抑制通过 ERK1/2 信号通路诱导多发性骨髓瘤衰老

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-05-27 DOI: 10.3724/abbs.2024077

Shushan Guo, Qiongwei Tang, Xuejie Gao, Liangning Hu, Ke Hu, Hui Zhang, Qikai Zhang, Yue Lai, Yujie Liu, Zhuning Wang, Shuaikang Chang, Yifei Zhang, Huifang Hu, Dong An, Yu Peng, Haiyan Cai, Jumei Shi

{"title":"EZH2 inhibition induces senescence via ERK1/2 signaling pathway in multiple myeloma.","authors":"Shushan Guo, Qiongwei Tang, Xuejie Gao, Liangning Hu, Ke Hu, Hui Zhang, Qikai Zhang, Yue Lai, Yujie Liu, Zhuning Wang, Shuaikang Chang, Yifei Zhang, Huifang Hu, Dong An, Yu Peng, Haiyan Cai, Jumei Shi","doi":"10.3724/abbs.2024077","DOIUrl":"10.3724/abbs.2024077","url":null,"abstract":"Epigenetic modifications play an important role in cellular senescence, and enhancer of zeste homolog 2 (EZH2) is a key methyltransferase involved in epigenetic remodeling in multiple myeloma (MM) cells. We have previously demonstrated that GSK126, a specific EZH2 inhibitor, exhibits anti-MM therapeutic efficacy and safety in vivo and in vitro; however, its specific mechanism remains unclear. This study shows that GSK126 induces cellular senescence in MM, which is characterized by the accumulation of senescence-associated heterochromatin foci (SAHF) and p21, and increased senescence-associated β galactosidase activity. Furthermore, EZH2 is inhibited in ribonucleotide reductase regulatory subunit M2 (RRM2)-overexpressing OCI-MY5 and RPMI-8226 cells. RRM2 overexpression inhibits the methyltransferase function of EZH2 and promotes its degradation through the ubiquitin-proteasome pathway, thereby inducing cellular senescence. In this senescence model, Lamin B1, a key component of the nuclear envelope and a marker of senescence, does not decrease but instead undergoes aberrant accumulation. Meanwhile, phosphorylation of extracellular signal-regulated protein kinase (ERK1/2) is significantly increased. The inhibition of ERK1/2 phosphorylation in turn partially restores Lamin B1 level and alleviates senescence. These findings suggest that EZH2 inhibition increases Lamin B1 level and induces senescence by promoting ERK1/2 phosphorylation. These data indicate that EZH2 plays an important role in MM cellular senescence and provide insights into the relationships among Lamin B1, p-ERK1/2, and cellular senescence.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157433","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}

引用次数: 0

FOXP3 targets KIF5A to increase lactate production and promote docetaxel resistance in lung adenocarcinoma. FOXP3 靶向 KIF5A 增加乳酸生成，促进肺腺癌对多西他赛的耐药性。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-05-26 DOI: 10.3724/abbs.2024082

Liangliang Dong, Chan Feng, Wenwen Cheng, Aihua Huang, Kejing Ying

{"title":"FOXP3 targets KIF5A to increase lactate production and promote docetaxel resistance in lung adenocarcinoma.","authors":"Liangliang Dong, Chan Feng, Wenwen Cheng, Aihua Huang, Kejing Ying","doi":"10.3724/abbs.2024082","DOIUrl":"10.3724/abbs.2024082","url":null,"abstract":"A prominent cause of cancer-related fatalities with a poor prognosis is lung adenocarcinoma (LUAD). KIF5A, a crucial member of the kinesin superfamily, is linked to drug resistance in malignancies. This work aims to investigate the mechanism of KIF5A in docetaxel (DTX) resistance in LUAD cells. The results of bioinformatics analysis, qRT-PCR and western blot analysis show that KIF5A, which is involved in the glycolysis pathway, is highly expressed in LUAD and is positively correlated with glycolysis-related genes. We further verify that silencing of KIF5A inhibits DTX resistance, glycolysis, and lactate production in LUAD cells via cell counting kit-8 (CCK-8), flow cytometry, Seahorse XFe 96, lactate, and glucose assays. Mechanistically, KIF5A promotes DTX resistance in LUAD, and this effect is attenuated upon the addition of an LDHA inhibitor. Chromatin immunoprecipitation and dual-luciferase reporter assays reveal that FOXP3 transcriptionally activates KIF5A. Knockdown of FOXP3 reduces lactate production and enhances DTX sensitivity in LUAD, which is restored upon simultaneous overexpression of KIF5A. Our findings reveal that FOXP3 increases DTX resistance in LUAD cells by enhancing lactate production through the upregulation of KIF5A level. In conclusion, our study provides a novel treatment target for improving chemosensitivity in LUAD.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155086","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}

引用次数: 0

Integrated network pharmacology and experimental verification to explore the potential mechanism of San Ying decoction for treating triple-negative breast cancer. 综合网络药理学和实验验证，探索三英煎治疗三阴性乳腺癌的潜在机制。

IF 3.7 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-05-25 DOI: 10.3724/abbs.2024015

Xiaojuan Yang, Feifei Li, Youyang Shi, Yuanyuan Wu, Rui Yang, Xiaofei Liu, Yang Zhang, Guangtao Zhang, Mei Ma, Zhanyang Luo, Xianghui Han, Ying Xie, Sheng Liu

{"title":"Integrated network pharmacology and experimental verification to explore the potential mechanism of San Ying decoction for treating triple-negative breast cancer.","authors":"Xiaojuan Yang, Feifei Li, Youyang Shi, Yuanyuan Wu, Rui Yang, Xiaofei Liu, Yang Zhang, Guangtao Zhang, Mei Ma, Zhanyang Luo, Xianghui Han, Ying Xie, Sheng Liu","doi":"10.3724/abbs.2024015","DOIUrl":"10.3724/abbs.2024015","url":null,"abstract":"Traditional Chinese medicine (TCM) has been used to treat triple-negative breast cancer (TNBC), a breast cancer subtype with poor prognosis. Clinical studies have verified that the Sanyingfang formula (SYF), a TCM prescription, has obvious effects on inhibiting breast cancer recurrence and metastasis, prolonging patient survival, and reducing clinical symptoms. However, its active ingredients and molecular mechanisms are still unclear. In this study, the active ingredients of each herbal medicine composing SYF and their target proteins are obtained from the Traditional Chinese Medicine Systems Pharmacology database. Breast cancer-related genes are obtained from the GeneCards database. Major targets and pathways related to SYF treatment in breast cancer are identified by analyzing the above data. By conducting molecular docking analysis, we find that the active ingredients quercetin and luteolin bind well to the key targets KDR1, PPARG, SOD1, and VCAM1. In vitro experiments verify that SYF can reduce the proliferation, migration, and invasion ability of TNBC cells. Using a TNBC xenograft mouse model, we show that SYF could delay tumor growth and effectively inhibit the occurrence of breast cancer lung metastasis in vivo. PPARG, SOD1, KDR1, and VCAM1 are all regulated by SYF and may play important roles in SYF-mediated inhibition of TNBC recurrence and metastasis.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11177106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183453","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}

引用次数: 0

Corrigendum to: Huperzine A ameliorates neurological deficits after spontaneous subarachnoid hemorrhage through endothelial cell pyroptosis inhibition. 更正：Huperzine A 通过抑制内皮细胞的热蛋白沉积改善自发性蛛网膜下腔出血后的神经功能缺损。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-05-25 DOI: 10.3724/abbs.2024067

Qiang Hu, Rong Zhang, Xiaoqiao Dong, Dingbo Yang, Quan Du, Wenhua Yu

引用次数: 0

The recent advancement of TCR-T cell therapies for cancer treatment. TCR-T 细胞疗法治疗癌症的最新进展。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-05-25 DOI: 10.3724/abbs.2024034

Xiang Zhao, Shuai Shao, Lanxin Hu

{"title":"The recent advancement of TCR-T cell therapies for cancer treatment.","authors":"Xiang Zhao, Shuai Shao, Lanxin Hu","doi":"10.3724/abbs.2024034","DOIUrl":"10.3724/abbs.2024034","url":null,"abstract":"Adoptive cell therapies involve infusing engineered immune cells into cancer patients to recognize and eliminate tumor cells. Adoptive cell therapy, as a form of living drug, has undergone explosive growth over the past decade. The recognition of tumor antigens by the T-cell receptor (TCR) is one of the natural mechanisms that the immune system used to eliminate tumor cells. TCR-T cell therapy, which involves introducing exogenous TCRs into patients' T cells, is a novel cell therapy strategy. TCR-T cell therapy can target the entire proteome of cancer cells. Engineering T cells with exogenous TCRs to help patients combat cancer has achieved success in clinical trials, particularly in treating solid tumors. In this review, we examine the progress of TCR-T cell therapy over the past five years. This includes the discovery of new tumor antigens, protein engineering techniques for TCR, reprogramming strategies for TCR-T cell therapy, clinical studies on TCR-T cell therapy, and the advancement of TCR-T cell therapy in China. We also propose several potential directions for the future development of TCR-T cell therapy.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334293","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}

引用次数: 0

Maslinic acid alleviates intervertebral disc degeneration by inhibiting the PI3K/AKT and NF-κB signaling pathways. 马斯林酸通过抑制 PI3K/AKT 和 NF-κB 信号通路缓解椎间盘退变。

IF 3.3 2区生物学

Acta biochimica et biophysica Sinica Pub Date : 2024-05-25 DOI: 10.3724/abbs.2024027

Yichen Que, Chipiu Wong, Jincheng Qiu, Wenjie Gao, Youxi Lin, Hang Zhou, Bo Gao, Pengfei Li, Zhihuai Deng, Huihong Shi, Wenjun Hu, Song Liu, Yan Peng, Peiqiang Su, Caixia Xu, Anjing Liang, Xianjian Qiu, Dongsheng Huang

{"title":"Maslinic acid alleviates intervertebral disc degeneration by inhibiting the PI3K/AKT and NF-κB signaling pathways.","authors":"Yichen Que, Chipiu Wong, Jincheng Qiu, Wenjie Gao, Youxi Lin, Hang Zhou, Bo Gao, Pengfei Li, Zhihuai Deng, Huihong Shi, Wenjun Hu, Song Liu, Yan Peng, Peiqiang Su, Caixia Xu, Anjing Liang, Xianjian Qiu, Dongsheng Huang","doi":"10.3724/abbs.2024027","DOIUrl":"10.3724/abbs.2024027","url":null,"abstract":"Intervertebral disc degeneration (IDD) is the cause of low back pain (LBP), and recent research has suggested that inflammatory cytokines play a significant role in this process. Maslinic acid (MA), a natural compound found in olive plants ( Olea europaea), has anti-inflammatory properties, but its potential for treating IDD is unclear. The current study aims to investigate the effects of MA on TNFα-induced IDD in vitro and in other in vivo models. Our findings suggest that MA ameliorates the imbalance of the extracellular matrix (ECM) and mitigates senescence by upregulating aggrecan and collagen II levels as well as downregulating MMP and ADAMTS levels in nucleus pulposus cells (NPCs). It can also impede the progression of IDD in rats. We further find that MA significantly affects the PI3K/AKT and NF-κB pathways in TNFα-induced NPCs determined by RNA-seq and experimental verification, while the AKT agonist Sc-79 eliminates these signaling cascades. Furthermore, molecular docking simulation shows that MA directly binds to PI3K. Dysfunction of the PI3K/AKT pathway and ECM metabolism has also been confirmed in clinical specimens of degenerated nucleus pulposus. This study demonstrates that MA may hold promise as a therapeutic agent for alleviating ECM metabolism disorders and senescence to treat IDD.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142564","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}

引用次数: 0