Experimental and Molecular Medicine最新文献

{"title":"A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response","authors":"Jumpei Ogura, Koji Yamanoi, Kentaro Ishida, Eijiro Nakamura, Shinji Ito, Naoki Aoyama, Yuki Nakanishi, Toshi Menju, Kosuke Kawaguchi, Yuko Hosoe, Mana Taki, Ryusuke Murakami, Ken Yamaguchi, Junzo Hamanishi, Masaki Mandai","doi":"10.1038/s12276-024-01356-2","DOIUrl":"10.1038/s12276-024-01356-2","url":null,"abstract":"Fatty acids are known to have significant effects on the properties of cancer cells. Therefore, these compounds have been incorporated into therapeutic strategies. However, few studies have examined the effects of individual fatty acids and their interactions in depth. This study analyzed the effects of various fatty acids on cancer cells and revealed that stearic acid, an abundant saturated fatty acid, had a stronger inhibitory effect on cell growth than did palmitic acid, which is also an abundant saturated fatty acid, by inducing DNA damage and apoptosis through the unfolded protein response (UPR) pathway. Intriguingly, the negative effects of stearate were reduced by the presence of oleate, a different type of abundant fatty acid. We combined a stearate-rich diet with the inhibition of stearoyl-CoA desaturase-1 to explore the impact of diet on tumor growth. This intervention significantly reduced tumor growth in both ovarian cancer models and patient-derived xenografts (PDXs), including those with chemotherapy resistance, notably by increasing stearate levels while reducing oleate levels within the tumors. Conversely, the negative effects of a stearate-rich diet were mitigated by an oleate-rich diet. This study revealed that dietary stearate can directly inhibit tumor growth through mechanisms involving DNA damage and apoptosis mediated by the UPR pathway. These results suggest that dietary interventions, which increase stearic acid levels while decreasing oleic acid levels, may be promising therapeutic strategies for cancer treatment. These results could lead to the development of new cancer treatment strategies. Obesity, characterized by excessive body fat, is linked to higher cancer risks. Researchers explored how specific fatty acids impact cancer growth. The study focused on palmitate, stearate, and oleate, using various cancer cell lines and patient derived xenograft. They found that stearate significantly inhibited cancer cell growth more than palmitate. This was a controlled experiment involving human cancer cell lines and mice fed specialized diets. Results showed that stearate induced DNA damage and cancer cell death, while oleate reduced these effects. The researchers concluded that dietary stearate could suppress tumor growth, especially when combined with inhibitors of fatty acid conversion. Future research could explore dietary interventions as potential cancer treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 12","pages":"2659-2672"},"PeriodicalIF":9.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01356-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773927","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}

{"title":"Cytokine-overexpressing dendritic cells for cancer immunotherapy","authors":"Joonsu Han, Hua Wang","doi":"10.1038/s12276-024-01353-5","DOIUrl":"10.1038/s12276-024-01353-5","url":null,"abstract":"Dendritic cells (DCs), the main type of antigen-presenting cells in the body, act as key mediators of adaptive immunity by sampling antigens from diseased cells for the subsequent priming of antigen-specific T and B cells. While DCs can secrete a diverse array of cytokines that profoundly shape the immune milieu, exogenous cytokines are often needed to maintain the survival, proliferation, and differentiation of DCs, T cells, and B cells. However, conventional cytokine therapies for cancer treatment are limited by their low therapeutic benefit and severe side effects. The overexpression of cytokines in DCs, followed by paracrine release or membrane display, has emerged as a viable approach for controlling the exposure of cytokines to interacting DCs and T/B cells. This approach can potentially reduce the necessary dose of cytokines and associated side effects to achieve comparable or enhanced antitumor efficacy. Various strategies have been developed to enable the overexpression or chemical conjugation of cytokines on DCs for the subsequent modulation of DC–T/B-cell interactions. This review provides a brief overview of strategies that enable the overexpression of cytokines in or on DCs via genetic engineering or chemical modification methods and discusses the promise of cytokine-overexpressing DCs for the development of new-generation cancer immunotherapy. Cancer immunotherapy has transformed cancer treatment, particularly with immune checkpoint blockades and CAR T cell therapy. However, cancer vaccines have been less effective. Researchers investigated ways to improve cancer vaccines by targeting dendritic cells and cytokines. DCs are immune cells that present antigens to T and B cells, starting immune responses. The study involved genetically or chemically modifying DCs to produce more cytokines like IL-2 and IL-12. This aimed to better activate T cells and enhance the immune response against tumors. Results showed that these modified DCs significantly increased T cell responses and reduced tumor growth in mice. Researchers concluded this could improve cancer vaccine effectiveness and reduce side effects. Future studies may refine cytokine combinations and delivery methods for clinical use. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 12","pages":"2559-2568"},"PeriodicalIF":9.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01353-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773968","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}

{"title":"Astrocyte–neuron crosstalk through extracellular vesicle-shuttled miRNA-382-5p promotes traumatic brain injury","authors":"Qing Hu, Xun Wu, Chengxuan Guo, Tinghao Wang, Hao Guo, Jin Wang, Bodong Wang, Wenxing Cui, Hao Bai, Jinpeng Zhou, Leiyang Li, Liying Han, Liang Cao, Shunnan Ge, Guodong Gao, Ting Wang, Zhenyong Wu, Wei Guo, Yan Qu, Jing Feng, Haixiao Liu","doi":"10.1038/s12276-024-01355-3","DOIUrl":"10.1038/s12276-024-01355-3","url":null,"abstract":"Although astrocytes undergo functional changes in response to brain injury and may be the driving force of subsequent neuronal death, the underlying mechanisms remain incompletely elucidated. Here, we showed that extracellular vesicle (EV)-shuttled miRNA-382-5p may serve as a biomarker for the severity of traumatic brain injury (TBI), as the circulating EV-miRNA-382-5p level was significantly increased in both human patients and TBI model mice. Mechanistically, astrocyte-derived EVs delivered the shuttled miRNA-382-5p to mediate astrocyte–neuron communication, which promoted neuronal mitochondrial dysfunction by inhibiting the expression of optic atrophy-1 (OPA1). Consistent with these findings, genetic ablation of neuronal OPA1 exacerbated mitochondrial damage and neuronal apoptosis in response to TBI. Moreover, engineered RVG-miRNA-382-5p inhibitor-EVs, which can selectively deliver a miRNA-382-5p inhibitor to neurons, significantly attenuated mitochondrial damage and improved neurological function after TBI. Taken together, our data suggest that EV-shuttled miRNA-382-5p may be a critical mediator of astrocyte-induced neurotoxicity under pathological conditions and that targeting miRNA-382-5p-OPA1 signaling has potential for clinical translation in the treatment of traumatic brain injury. Traumatic brain injury often results in long-term disabilities. This study investigates how astrocytes contribute to nerve cell damage after TBI, focusing on extracellular vesicles and microRNAs, specifically miRNA-382-5p. The research involved blood samples from TBI patients and healthy people, and mouse experiments, to study the effects of astrocyte-derived EVs carrying miRNA-382-5p on nerve cells. The study found that after TBI, astrocytes release EVs with miRNA-382-5p, which disrupts mitochondrial function in nerve cells, causing damage. The study concludes that astrocyte-derived EVs carrying miRNA-382-5p significantly contribute to nerve cell damage after TBI. By inhibiting miRNA-382-5p, such damage can be reduced, offering a new TBI treatment approach. This research enhances our understanding of TBI and offers potential for targeted therapies. Future implications include using miRNA-382-5p as a diagnostic tool or treatment target to improve TBI outcomes. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 12","pages":"2642-2658"},"PeriodicalIF":9.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01355-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773956","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}

{"title":"IL33-induced neutrophil extracellular traps (NETs) mediate a positive feedback loop for synovial inflammation and NET amplification in rheumatoid arthritis","authors":"Jifeng Tang, Jinfang Xia, Huali Gao, Renquan Jiang, Lianbo Xiao, Huiming Sheng, Jinpiao Lin","doi":"10.1038/s12276-024-01351-7","DOIUrl":"10.1038/s12276-024-01351-7","url":null,"abstract":"This study investigated the mechanisms driving the induction and sustained presence of neutrophil extracellular traps (NETs) in the synovial microenvironment of rheumatoid arthritis (RA). Synovial tissue and fluid samples were collected from patients with RA and osteoarthritis (OA), and NET levels and cytokine concentrations were measured using a cytometric bead array and enzyme-linked immunosorbent assay (ELISA). The ability of interleukin-33 (IL-33) to induce NET formation was evaluated using quantitative assays, immunofluorescence staining, live-cell imaging, and electron microscopy. Coincubation experiments of NETs with fibroblast-like synovial cells (FLSs) were conducted, and a modified Transwell migration assay was designed to assess neutrophil migration. The role of IL-33 and NETs in RA progression was further investigated using a collagen antibody-induced arthritis (CAIA) mouse model. The results revealed an increase in NETs and IL-33 levels in the synovial fluid of RA patients, with a significant positive correlation between them. NET formation assays confirmed that IL-33 activates neutrophils to produce NETs and that neutrophils from RA patients exhibit increased responsiveness to IL-33 stimulation. Both in vitro and in vivo evidence has demonstrated that NETs stimulate FLSs to secrete IL-33 and the chemokine CXCL8 via Toll-like receptor 9, promoting further neutrophil recruitment and increasing NET production within the RA synovium. This study reveals a novel positive feedback loop involving NETs and FLSs that is mediated by IL-33 that increases NET accumulation in RA. Targeting IL-33 or NET formation and amplification may offer new therapeutic strategies for managing RA. Rheumatoid arthritis is a disease where the body’s defense system wrongly attacks the joints, leading to swelling and pain. This research explores the role of neutrophil extracellular traps in RA. NETs are net-like structures released by a type of white blood cell to catch harmful germs but in RA, NETs can harm the body’s own tissues. The team collected samples from 120 RA patients, comparing them with samples from osteoarthritis patients and healthy people. They studied how certain proteins, particularly IL-33, affect NET formation in RA patients’ joints. They found that IL-33 greatly increases NET production, suggesting a cycle where IL-33 and NETs continue the inflammation in RA. This highlights IL-33’s potential as a target for RA treatment, providing new understanding of this disabling disease. Future treatments might aim to break this cycle to ease RA symptoms. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 12","pages":"2602-2616"},"PeriodicalIF":9.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01351-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774479","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}

{"title":"Noncoding RNA as a crucial epigenetic modulator in the degeneration of the ligamentum flavum","authors":"Yongzhao Zhao, Qian Xiang, Shuo Tian, Zhenquan Wu, Jialiang Lin, Longjie Wang, Zhuoran Sun, Weishi Li","doi":"10.1038/s12276-024-01348-2","DOIUrl":"10.1038/s12276-024-01348-2","url":null,"abstract":"Ligamentum flavum degeneration, including hypertrophy and ossification of the ligamentum flavum, leads to degenerative spinal stenosis in older adults. However, the underlying mechanisms of ligamentum flavum degeneration remain unclear, and therapeutic strategies are limited. Noncoding RNAs include microRNAs, circular RNAs, and long noncoding RNAs. As important epigenetic modifications, noncoding RNAs are involved in the progression of several age-related diseases, including ligamentum flavum degeneration. Previous studies have shown that noncoding RNAs can regulate the osteogenic differentiation and fibrosis of ligamentum flavum cells by regulating the expression of related genes. In this review, we discuss noncoding RNAs and their role in ligamentum flavum degeneration. Degenerative Spinal Stenosis (DSS), a common condition in older adults causing numbness and muscle weakness, is often caused by the breakdown of the ligamentum flavum, a spinal structure. Despite DSS’s commonness, the role of non-coding RNAs, molecules that don’t code for proteins but regulate gene activity, in LF breakdown is not well understood. Researchers reviewed the biological functions of ncRNAs in LF breakdown, focusing on microRNAs, circular RNAs, and long non-coding RNAs, aiming to provide new insights. They identified specific ncRNAs contributing to LF degeneration, suggesting their potential as treatment targets. This research could guide future studies towards non-surgical treatments for DSS. The findings reveal that manipulating these ncRNAs could offer new treatment options. This could lead to targeted therapies addressing DSS’s underlying causes, offering hope for less invasive treatments in the future. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 12","pages":"2551-2558"},"PeriodicalIF":9.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01348-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774430","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}

{"title":"Author Correction: Sorcin can trigger pancreatic cancer-associated new-onset diabetes through the secretion of inflammatory cytokines such as serpin E1 and CCL5","authors":"Jiali Gong, Xiawei Li, Zengyu Feng, Jianyao Lou, Kaiyue Pu, Yongji Sun, Sien Hu, Yizhao Zhou, Tianyu Song, Meihua Shangguan, Kai Zhang, Wenjie Lu, Xin Dong, Jian Wu, Hong Zhu, Qiaojun He, Hongxia Xu, Yulian Wu","doi":"10.1038/s12276-024-01363-3","DOIUrl":"10.1038/s12276-024-01363-3","url":null,"abstract":"","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 11","pages":"2549-2549"},"PeriodicalIF":9.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01363-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741172","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}

{"title":"Author Correction: 3C methods in cancer research: recent advances and future prospects","authors":"Insoo Yoon, Uijin Kim, Kyung Oh Jung, Yousuk Song, Taesoo Park, Dong-Sung Lee","doi":"10.1038/s12276-024-01349-1","DOIUrl":"10.1038/s12276-024-01349-1","url":null,"abstract":"","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 11","pages":"2548-2548"},"PeriodicalIF":9.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01349-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689426","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}

{"title":"Influencing immunity: role of extracellular vesicles in tumor immune checkpoint dynamics","authors":"Ziyang Ye, Genpeng Li, Jianyong Lei","doi":"10.1038/s12276-024-01340-w","DOIUrl":"10.1038/s12276-024-01340-w","url":null,"abstract":"Immune checkpoint proteins (ICPs) serve as critical regulators of the immune system, ensuring protection against damage due to overly activated immune responses. However, within the tumor environment, excessive ICP activation weakens antitumor immunity. Despite the development of numerous immune checkpoint blockade (ICB) drugs in recent years, their broad application has been inhibited by uncertainties about their clinical efficacy. A thorough understanding of ICP regulation in the tumor microenvironment is essential for advancing the development of more effective and safer ICB therapies. Extracellular vesicles (EVs), which are pivotal mediators of cell–cell communication, have been extensively studied and found to play key roles in the functionality of ICPs. Nonetheless, a comprehensive review summarizing the current knowledge about the crosstalk between EVs and ICPs in the tumor environment is lacking. In this review, we summarize the interactions between EVs and several widely studied ICPs as well as their potential clinical implications, providing a theoretical basis for further investigation of EV-related ICB therapeutic approaches. In 1991, the finding of CTLA4 led to extensive studies on immune checkpoint proteins, key in controlling immune reactions. This review explores the role of extracellular vesicles—small particles released by cells carrying proteins, RNA, and lipids, affecting various cell functions—in immune checkpoint control. The research focuses on how EVs influence immune checkpoints, especially in cancer, where they can change immune cell function and affect therapy results. The authors aim to discover new treatment strategies by studying the interaction between EVs and immune checkpoints. This detailed review highlights the potential of targeting EV-related pathways to improve cancer treatment effectiveness and safety. The results emphasize the need for more research into EVs and immune checkpoints, potentially leading to significant progress in cancer treatment. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 11","pages":"2365-2381"},"PeriodicalIF":9.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01340-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631734","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}

{"title":"Sorcin can trigger pancreatic cancer-associated new-onset diabetes through the secretion of inflammatory cytokines such as serpin E1 and CCL5","authors":"Jiali Gong, Xiawei Li, Zengyu Feng, Jianyao Lou, Kaiyue Pu, Yongji Sun, Sien Hu, Yizhao Zhou, Tianyu Song, Meihua Shangguan, Kai Zhang, Wenjie Lu, Xin Dong, Jian Wu, Hong Zhu, Qiaojun He, Hongxia Xu, Yulian Wu","doi":"10.1038/s12276-024-01346-4","DOIUrl":"10.1038/s12276-024-01346-4","url":null,"abstract":"A rise in blood glucose is an early warning sign of underlying pancreatic cancer (PC) and may be an indicator of genetic events in PC progression. However, there is still a lack of mechanistic research on pancreatic cancer-associated new-onset diabetes (PCAND). In the present study, we identified a gene SRI, which possesses a SNP with the potential to distinguish PCAND and Type 2 diabetes mellitus (T2DM), by machine learning on the basis of the UK Biobank database. In vitro and in vivo, sorcin overexpression induced pancreatic β-cell dysfunction. Sorcin can form a positive feedback loop with STAT3 to increase the transcription of serpin E1 and CCL5, which may directly induce β-cell dysfunction. In 88 biopsies, the expression of sorcin was elevated in PC tissues, especially in PCAND samples. Furthermore, plasma serpin E1 levels are higher in peripheral blood samples from PCAND patients than in those from T2DM patients. In conclusion, sorcin may be the key driver in PCAND, and further study on the sorcin-STAT3-serpin E1/CCL5 signaling axis may help us better understand the pathogenesis of PCAND and identify potential biomarkers. Pancreatic cancer, a lethal disease with a low survival rate, can be better managed with early detection. Researchers investigated the connection between pancreatic cancer and newly developed diabetes, pinpointing the SRI gene and its protein, sorcin, as crucial elements. They used machine learning to examine genetic data from the UK Biobank, focusing on Single Nucleotide Polymorphisms to differentiate between diabetes associated with pancreatic cancer and type 2 diabetes. The research included lab and live experiments to understand how sorcin impacts pancreatic β-cells and contributes to diabetes in pancreatic cancer patients. Researchers believe that focusing on the sorcin-STAT3 pathway could provide new possibilities for early diagnosis and treatment of pancreatic cancer. This study is a significant advancement in understanding the molecular links between pancreatic cancer and diabetes, potentially leading to earlier detection and better patient outcomes. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 11","pages":"2535-2547"},"PeriodicalIF":9.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01346-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631737","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}

{"title":"The muscle–intervertebral disc interaction mediated by L-BAIBA modulates extracellular matrix homeostasis and PANoptosis in nucleus pulposus cells","authors":"Tianyu Qin, Ming Shi, Chao Zhang, Jiajun Wu, Zhengqi Huang, Xiaohe Zhang, Shuangxing Li, Yuliang Wu, Weitao Han, Bo Gao, Kang Xu, Song Jin, Wei Ye","doi":"10.1038/s12276-024-01345-5","DOIUrl":"10.1038/s12276-024-01345-5","url":null,"abstract":"Upon engaging in physical activity, skeletal muscle synthesizes myokines, which not only facilitate crosstalk with various organs, including the brain, adipose tissue, bone, liver, gut, pancreas, and skin but also promote intramuscular signaling. Crosstalk is vital for maintaining various physiological processes. However, the specific interactions between skeletal muscle and intervertebral discs remain largely unexplored. β-Aminoisobutyric acid (BAIBA), an exercise-induced myokine and a metabolite of branched-chain amino acids in skeletal muscle, has emerged as a key player in this context. Our study demonstrated that exercise significantly elevates BAIBA levels in skeletal muscle, plasma, and nucleus pulposus (NP) tissues. Moreover, exercise enhances extracellular matrix (ECM) synthesis in NP tissues and upregulates L-BAIBA synthase in skeletal muscle. Both in vivo and in vitro evidence revealed that L-BAIBA impedes PANoptosis and ECM degradation in NP cells by activating the AMPK/NF-κB signaling pathway. These findings suggest that exercise, coupled with the resulting increase in L-BAIBA, may serve as an effective intervention to decelerate the progression of intervertebral disc degeneration (IDD). Consequently, L-BAIBA, which originates from skeletal muscle, is a promising new therapeutic approach for IDD. Intervertebral disc degeneration affects many people globally. Researchers investigated how exercise and a muscle-produced molecule, L-BAIBA, can slow IDD. They used human tissue samples, cell cultures, and rat models to study how exercise affects IDD and how L-BAIBA protects disc cells. The study combined lab and animal research, using human disc tissues and rats to understand disc degeneration and exercise effects. They found exercise increases L-BAIBA production, which benefits disc cells by promoting essential disc components and reducing cell death, a degeneration contributor. This could lead to non-invasive IDD treatments using the body’s exercise responses. The results showed exercise and L-BAIBA improved disc health by increasing essential disc components and reducing cell death. They suggest L-BAIBA could be a new IDD treatment, using exercise benefits at a molecular level. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 11","pages":"2503-2518"},"PeriodicalIF":9.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01345-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607422","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}