Pub Date : 2024-12-02DOI: 10.1038/s12276-024-01365-1
Kibong Sung, Min-Jae Jeong, Taesik Yoo, Jung Hoon Jung, Sumin Kang, Jong-Yeon Yoo, Hyun Jin Kim, Kyunghyun Park, Jung Hyun Pyo, Hyun-Yong Lee, Noah Koo, Soo-Hee Choi, Joung-Hun Kim
Post-traumatic stress disorder (PTSD) often arises after exposure to traumatic events and is characterized by dysregulated fear responses. Although the associations of erb-b2 receptor tyrosine kinase 4 (ErbB4) with various neuropsychiatric diseases, including schizophrenia and bipolar disorder, have been widely examined, the physiological roles of ErbB4 in PTSD and fear responses remain unclear. Using Cre-dependent ErbB4 knockout (KO) mice, we observed that PTSD-like fear behaviors emerged in ErbB4-deficient mice, particularly in inhibitory neurons. Specifically, the loss of ErbB4 in somatostatin-expressing (SST+) neurons was sufficient to induce PTSD-like fear responses. We also adopted the CRISPR/Cas9 system for region-specific KO of ErbB4, which revealed that ErbB4 deletion in SST+ neurons of the lateral division of the amygdala (CeL) caused elevated anxiety and PTSD-like fear generalization. Consistent with its physiological role, ErbB4 expression was diminished in CeLSST neurons from mice that exhibited PTSD-like phenotypes. While fear On and Off cells identified in the CeL displayed distinct responses to conditioned and novel cues, as previously shown, the selectivity of those On and Off cells was compromised in SSTErbB4-/- and stressed mice, which displayed strong fear generalization. Therefore, the bimodal activity that CeL On/Off cells display is likely required for proper discrimination of fearful stimuli from ambient stimuli, which should be sustained by the presence of ErbB4. Taken together, our data substantiate the correlation between PTSD-like fear responses and ErbB4 expression in CeLSST neurons and further underscore the functional effects of ErbB4 in CeLSST neurons, supporting the bimodal responses of CeL neurons. Post-traumatic stress disorder is a mental health condition that can develop after experiencing traumatic events. Researchers tried to understand the biological basis of PTSD using animal models. The researchers investigated the role of a protein called ErbB4 in fear responses related to PTSD. They used mice to study how deleting ErbB4 in specific brain cells affects fear behavior. They focused on somatostatin(SST)-expressing neurons in a brain region called the central amygdala, which is involved in processing fear. The study involved genetic modification, behavioral tests, and in vivo recording to observe changes in fear responses. The findings showed that removing ErbB4 from SST+ neurons led to increased anxiety and generalized fear, like PTSD symptoms, with specific alteration of neuronal activity. This suggests that ErbB4 helps regulate fear responses, and its absence may contribute to PTSD-like behaviors. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"ErbB4 precludes the occurrence of PTSD-like fear responses by supporting the bimodal activity of the central amygdala","authors":"Kibong Sung, Min-Jae Jeong, Taesik Yoo, Jung Hoon Jung, Sumin Kang, Jong-Yeon Yoo, Hyun Jin Kim, Kyunghyun Park, Jung Hyun Pyo, Hyun-Yong Lee, Noah Koo, Soo-Hee Choi, Joung-Hun Kim","doi":"10.1038/s12276-024-01365-1","DOIUrl":"10.1038/s12276-024-01365-1","url":null,"abstract":"Post-traumatic stress disorder (PTSD) often arises after exposure to traumatic events and is characterized by dysregulated fear responses. Although the associations of erb-b2 receptor tyrosine kinase 4 (ErbB4) with various neuropsychiatric diseases, including schizophrenia and bipolar disorder, have been widely examined, the physiological roles of ErbB4 in PTSD and fear responses remain unclear. Using Cre-dependent ErbB4 knockout (KO) mice, we observed that PTSD-like fear behaviors emerged in ErbB4-deficient mice, particularly in inhibitory neurons. Specifically, the loss of ErbB4 in somatostatin-expressing (SST+) neurons was sufficient to induce PTSD-like fear responses. We also adopted the CRISPR/Cas9 system for region-specific KO of ErbB4, which revealed that ErbB4 deletion in SST+ neurons of the lateral division of the amygdala (CeL) caused elevated anxiety and PTSD-like fear generalization. Consistent with its physiological role, ErbB4 expression was diminished in CeLSST neurons from mice that exhibited PTSD-like phenotypes. While fear On and Off cells identified in the CeL displayed distinct responses to conditioned and novel cues, as previously shown, the selectivity of those On and Off cells was compromised in SSTErbB4-/- and stressed mice, which displayed strong fear generalization. Therefore, the bimodal activity that CeL On/Off cells display is likely required for proper discrimination of fearful stimuli from ambient stimuli, which should be sustained by the presence of ErbB4. Taken together, our data substantiate the correlation between PTSD-like fear responses and ErbB4 expression in CeLSST neurons and further underscore the functional effects of ErbB4 in CeLSST neurons, supporting the bimodal responses of CeL neurons. Post-traumatic stress disorder is a mental health condition that can develop after experiencing traumatic events. Researchers tried to understand the biological basis of PTSD using animal models. The researchers investigated the role of a protein called ErbB4 in fear responses related to PTSD. They used mice to study how deleting ErbB4 in specific brain cells affects fear behavior. They focused on somatostatin(SST)-expressing neurons in a brain region called the central amygdala, which is involved in processing fear. The study involved genetic modification, behavioral tests, and in vivo recording to observe changes in fear responses. The findings showed that removing ErbB4 from SST+ neurons led to increased anxiety and generalized fear, like PTSD symptoms, with specific alteration of neuronal activity. This suggests that ErbB4 helps regulate fear responses, and its absence may contribute to PTSD-like behaviors. 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":"2703-2713"},"PeriodicalIF":9.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01365-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774463","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}
Pub Date : 2024-12-02DOI: 10.1038/s12276-024-01354-4
Soon Sang Park, Young-Kyoung Lee, Young Hwa Kim, So Hyun Park, Hee Young Kang, Jin Cheol Kim, Dong Jun Kim, Su Bin Lim, Gyesoon Yoon, Jang-Hee Kim, Yong Won Choi, Tae Jun Park
Cellular senescence, recognized as a key hallmark of aging, leads to the accumulation of senescent cells in various tissues over time. While the detrimental effects of these cells on age-related pathological conditions are well-documented, there is still limited information about how senescent cells are distributed in normal tissues of both young and aged organs. Our research indicates that fully senescent p16INK4A+ cells are rarely identified in the parenchyma of organic tissues and in the stromal cells crucial for structural maintenance, such as fibroblasts and smooth muscle cells. Instead, p16INK4A+ cells are more commonly found in immune cells, whether they reside in the organ or are infiltrating. Notably, p16INK4A+ senescent T cells have been observed to induce apoptosis and inflammation in colonic epithelial cells through Granzyme A-PARs signaling, compromising the integrity of the epithelial lining. This study showed that the senescence of immune cells could affect the phenotypical change of the parenchymal cells in the elderly and suggests that targeting immunosenescence might be a strategy to control functional decline in this population. Cellular senescence accumulates in tissues as we age, causing dysfunction and inflammation. However, the specific cell types that become senescent and their removal are not well understood. Researchers aimed to map senescent cells in young and elderly tissues, creating a “Senescence Atlas.” This study involved analyzing human tissues and mouse tissues using immunohistochemistry and single-cell RNA-sequencing. They focused on p16INK4A and found that senescent cells were rare in both young and elderly tissues. However, immune cells, especially T cells, showed increased senescence in elderly tissues. Results showed that senescent T cells release granzyme A, which activates protease-activated receptors in epithelial cells, leading to inflammation and cell death. This suggests that targeting senescent immune cells could improve organ function in the elderly. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"Distribution and impact of p16INK4A+ senescent cells in elderly tissues: a focus on senescent immune cell and epithelial dysfunction","authors":"Soon Sang Park, Young-Kyoung Lee, Young Hwa Kim, So Hyun Park, Hee Young Kang, Jin Cheol Kim, Dong Jun Kim, Su Bin Lim, Gyesoon Yoon, Jang-Hee Kim, Yong Won Choi, Tae Jun Park","doi":"10.1038/s12276-024-01354-4","DOIUrl":"10.1038/s12276-024-01354-4","url":null,"abstract":"Cellular senescence, recognized as a key hallmark of aging, leads to the accumulation of senescent cells in various tissues over time. While the detrimental effects of these cells on age-related pathological conditions are well-documented, there is still limited information about how senescent cells are distributed in normal tissues of both young and aged organs. Our research indicates that fully senescent p16INK4A+ cells are rarely identified in the parenchyma of organic tissues and in the stromal cells crucial for structural maintenance, such as fibroblasts and smooth muscle cells. Instead, p16INK4A+ cells are more commonly found in immune cells, whether they reside in the organ or are infiltrating. Notably, p16INK4A+ senescent T cells have been observed to induce apoptosis and inflammation in colonic epithelial cells through Granzyme A-PARs signaling, compromising the integrity of the epithelial lining. This study showed that the senescence of immune cells could affect the phenotypical change of the parenchymal cells in the elderly and suggests that targeting immunosenescence might be a strategy to control functional decline in this population. Cellular senescence accumulates in tissues as we age, causing dysfunction and inflammation. However, the specific cell types that become senescent and their removal are not well understood. Researchers aimed to map senescent cells in young and elderly tissues, creating a “Senescence Atlas.” This study involved analyzing human tissues and mouse tissues using immunohistochemistry and single-cell RNA-sequencing. They focused on p16INK4A and found that senescent cells were rare in both young and elderly tissues. However, immune cells, especially T cells, showed increased senescence in elderly tissues. Results showed that senescent T cells release granzyme A, which activates protease-activated receptors in epithelial cells, leading to inflammation and cell death. This suggests that targeting senescent immune cells could improve organ function in the elderly. 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":"2631-2641"},"PeriodicalIF":9.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01354-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774297","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}
Pub Date : 2024-12-02DOI: 10.1038/s12276-024-01350-8
Pengpeng Yue, Xiaoyan Lv, Hankun Cao, Yongkang Zou, Jian You, Jun Luo, Zhongshan Lu, Hao Chen, Zhongzhong Liu, Zibiao Zhong, Yan Xiong, Xiaoli Fan, Qifa Ye
The use of fatty livers in liver transplantation has emerged as a crucial strategy to expand the pool of donor livers; however, fatty livers are more sensitive to ischemia‒reperfusion injury (IRI). Excessive congenital inflammatory responses are crucial in IRI. Hypothermic oxygenated perfusion (HOPE) is a novel organ preservation technique that may improve marginal donor liver quality by reducing the inflammatory response. Tissue factor pathway inhibitor-2 (TFPI2) and CAP-Gly domain-containing linker protein 1 (CLIP1) exhibit modulatory effects on the inflammatory response. However, the underlying mechanisms of HOPE in fatty liver and the effects of TFPI2 and CLIP1 in fatty liver IRI remain unclear. Here, we aimed to explore the impact of HOPE on the inflammatory response in a rat model of fatty liver IRI and the mechanisms of action of TFPI2 and CLIP1. HOPE significantly reduces liver injury, especially the inflammatory response, and alleviates damage to hepatocytes and endothelial cells. Mechanistically, HOPE exerts its effects by inhibiting TFPI2, and CLIP1 can rescue the damaging effects of TFPI2. Moreover, HOPE promoted the ubiquitination and subsequent degradation of Toll/interleukin-1 receptor domain-containing adapter protein (TIRAP) by regulating the binding of R24 of the KD1 domain of TFPI2 with CLIP1, thereby negatively regulating the TLR4/NF-κB-mediated inflammatory response and reducing IRI. Furthermore, TFPI2 expression increased and CLIP1 expression decreased following cold ischemia in human fatty livers. Overall, our results suggest that targeting the inflammatory response by modulating the TFPI2/CLIP1/TIRAP signaling pathway via HOPE represents a potential therapeutic approach to ameliorate IRI during fatty liver transplantation. Liver transplantation is the only effective treatment for end-stage liver disease, but donor organ shortages limit its progress. Researchers found that fatty livers, which make up 15-30% of donations, are more prone to damage during transplantation. In this study, the researchers used a rat model to explore how hypothermic oxygenated perfusion (HOPE) affects fatty liver transplants. HOPE is a technique where the liver is preserved at low temperatures with oxygenated fluid. They divided rats into three groups: sham, cold storage (CS), and HOPE. Results showed that HOPE significantly reduces liver injury, especially the inflammatory response, and alleviates oxidative stress to improve liver function. The researchers concluded that HOPE can protect fatty livers during transplantation by inhibiting inflammation. Future studies could explore HOPE’s potential in human liver transplants. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"Hypothermic oxygenated perfusion inhibits CLIP1-mediated TIRAP ubiquitination via TFPI2 to reduce ischemia‒reperfusion injury of the fatty liver","authors":"Pengpeng Yue, Xiaoyan Lv, Hankun Cao, Yongkang Zou, Jian You, Jun Luo, Zhongshan Lu, Hao Chen, Zhongzhong Liu, Zibiao Zhong, Yan Xiong, Xiaoli Fan, Qifa Ye","doi":"10.1038/s12276-024-01350-8","DOIUrl":"10.1038/s12276-024-01350-8","url":null,"abstract":"The use of fatty livers in liver transplantation has emerged as a crucial strategy to expand the pool of donor livers; however, fatty livers are more sensitive to ischemia‒reperfusion injury (IRI). Excessive congenital inflammatory responses are crucial in IRI. Hypothermic oxygenated perfusion (HOPE) is a novel organ preservation technique that may improve marginal donor liver quality by reducing the inflammatory response. Tissue factor pathway inhibitor-2 (TFPI2) and CAP-Gly domain-containing linker protein 1 (CLIP1) exhibit modulatory effects on the inflammatory response. However, the underlying mechanisms of HOPE in fatty liver and the effects of TFPI2 and CLIP1 in fatty liver IRI remain unclear. Here, we aimed to explore the impact of HOPE on the inflammatory response in a rat model of fatty liver IRI and the mechanisms of action of TFPI2 and CLIP1. HOPE significantly reduces liver injury, especially the inflammatory response, and alleviates damage to hepatocytes and endothelial cells. Mechanistically, HOPE exerts its effects by inhibiting TFPI2, and CLIP1 can rescue the damaging effects of TFPI2. Moreover, HOPE promoted the ubiquitination and subsequent degradation of Toll/interleukin-1 receptor domain-containing adapter protein (TIRAP) by regulating the binding of R24 of the KD1 domain of TFPI2 with CLIP1, thereby negatively regulating the TLR4/NF-κB-mediated inflammatory response and reducing IRI. Furthermore, TFPI2 expression increased and CLIP1 expression decreased following cold ischemia in human fatty livers. Overall, our results suggest that targeting the inflammatory response by modulating the TFPI2/CLIP1/TIRAP signaling pathway via HOPE represents a potential therapeutic approach to ameliorate IRI during fatty liver transplantation. Liver transplantation is the only effective treatment for end-stage liver disease, but donor organ shortages limit its progress. Researchers found that fatty livers, which make up 15-30% of donations, are more prone to damage during transplantation. In this study, the researchers used a rat model to explore how hypothermic oxygenated perfusion (HOPE) affects fatty liver transplants. HOPE is a technique where the liver is preserved at low temperatures with oxygenated fluid. They divided rats into three groups: sham, cold storage (CS), and HOPE. Results showed that HOPE significantly reduces liver injury, especially the inflammatory response, and alleviates oxidative stress to improve liver function. The researchers concluded that HOPE can protect fatty livers during transplantation by inhibiting inflammation. Future studies could explore HOPE’s potential in human liver transplants. 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":"2588-2601"},"PeriodicalIF":9.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01350-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774469","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}
Pub Date : 2024-12-02DOI: 10.1038/s12276-024-01352-6
Su-hyang Han, Je Yeong Ko, Sungju Jung, Sumin Oh, Do Yeon Kim, Eunseo Kang, Myung Sup Kim, Kyung-Hee Chun, Kyung Hyun Yoo, Jong Hoon Park
Early tumor recurrence in hepatocellular carcinoma (HCC) remains a challenging area, as the mechanisms involved are not fully understood. While microvascular invasion is linked to early recurrence, established biomarkers for diagnosis and prognostication are lacking. In this study, our objective was to identify DNA methylation sites that can predict the outcomes of liver cancer patients and elucidate the molecular mechanisms driving HCC aggressiveness. Using DNA methylome data from HCC patient samples from the CGRC and TCGA databases, we pinpointed hypermethylated CpG sites in HCC. Our analysis revealed that cg02746869 acts as a crucial regulatory site for VIM-AS1 (vimentin antisense RNA1), a 1.8 kb long noncoding RNA. RNA sequencing of HCC cells with manipulated VIM-AS1 expression revealed EPHA3 as a pathogenic target of VIM-AS1, which performs an oncogenic function in HCC. Hypermethylation-induced suppression of VIM-AS1 significantly impacted HCC cell dynamics, particularly impairing motility and invasiveness. Mechanistically, reduced VIM-AS1 expression stabilized EPHA3 mRNA by enhancing the binding of IGF2BP1 to EPHA3 mRNA, leading to increased expression of EPHA3 mRNA and the promotion of HCC progression. In vivo experiments further confirmed that the VIM-AS1‒EPHA3 axis controlled tumor growth and the tumor microenvironment in HCC. These findings suggest that the downregulation of VIM-AS1 due to hypermethylation at cg02746869 increased EPHA3 mRNA expression via a m6A-dependent mechanism to increase HCC aggressiveness. Despite advancements in treatment, cancer remains a life-threatening disease that can recur (come back) and metastasize. Researchers found a knowledge gap in understanding how DNA methylation affects cancer progression. Researchers conducted an experiment to identify DNA methylation markers related to liver cancer prognosis. They used human liver cancer cell lines and analyzed DNA methylation and gene expression. The researchers discovered that hypermethylation of a specific DNA region in the VIM-AS1 gene is linked to poor prognosis in liver cancer. They concluded that DNA methylation affects gene expression and cancer cell behavior. This finding could lead to new diagnostic and treatment strategies for liver cancer. Future research may explore how to target these epigenetic changes for better cancer therapies. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"VIM-AS1, which is regulated by CpG methylation, cooperates with IGF2BP1 to inhibit tumor aggressiveness via EPHA3 degradation in hepatocellular carcinoma","authors":"Su-hyang Han, Je Yeong Ko, Sungju Jung, Sumin Oh, Do Yeon Kim, Eunseo Kang, Myung Sup Kim, Kyung-Hee Chun, Kyung Hyun Yoo, Jong Hoon Park","doi":"10.1038/s12276-024-01352-6","DOIUrl":"10.1038/s12276-024-01352-6","url":null,"abstract":"Early tumor recurrence in hepatocellular carcinoma (HCC) remains a challenging area, as the mechanisms involved are not fully understood. While microvascular invasion is linked to early recurrence, established biomarkers for diagnosis and prognostication are lacking. In this study, our objective was to identify DNA methylation sites that can predict the outcomes of liver cancer patients and elucidate the molecular mechanisms driving HCC aggressiveness. Using DNA methylome data from HCC patient samples from the CGRC and TCGA databases, we pinpointed hypermethylated CpG sites in HCC. Our analysis revealed that cg02746869 acts as a crucial regulatory site for VIM-AS1 (vimentin antisense RNA1), a 1.8 kb long noncoding RNA. RNA sequencing of HCC cells with manipulated VIM-AS1 expression revealed EPHA3 as a pathogenic target of VIM-AS1, which performs an oncogenic function in HCC. Hypermethylation-induced suppression of VIM-AS1 significantly impacted HCC cell dynamics, particularly impairing motility and invasiveness. Mechanistically, reduced VIM-AS1 expression stabilized EPHA3 mRNA by enhancing the binding of IGF2BP1 to EPHA3 mRNA, leading to increased expression of EPHA3 mRNA and the promotion of HCC progression. In vivo experiments further confirmed that the VIM-AS1‒EPHA3 axis controlled tumor growth and the tumor microenvironment in HCC. These findings suggest that the downregulation of VIM-AS1 due to hypermethylation at cg02746869 increased EPHA3 mRNA expression via a m6A-dependent mechanism to increase HCC aggressiveness. Despite advancements in treatment, cancer remains a life-threatening disease that can recur (come back) and metastasize. Researchers found a knowledge gap in understanding how DNA methylation affects cancer progression. Researchers conducted an experiment to identify DNA methylation markers related to liver cancer prognosis. They used human liver cancer cell lines and analyzed DNA methylation and gene expression. The researchers discovered that hypermethylation of a specific DNA region in the VIM-AS1 gene is linked to poor prognosis in liver cancer. They concluded that DNA methylation affects gene expression and cancer cell behavior. This finding could lead to new diagnostic and treatment strategies for liver cancer. Future research may explore how to target these epigenetic changes for better cancer therapies. 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":"2617-2630"},"PeriodicalIF":9.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01352-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774495","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}
Pub Date : 2024-12-02DOI: 10.1038/s12276-024-01356-2
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
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.
{"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}
Pub Date : 2024-12-02DOI: 10.1038/s12276-024-01353-5
Joonsu Han, Hua Wang
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.
{"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}
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.
{"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}
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.
{"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}
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.
{"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}
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