Experimental and Molecular Medicine最新文献

{"title":"Golgi condensation causes intestinal lipid accumulation through HIF-1α-mediated GM130 ubiquitination by NEDD4","authors":"Hyunsoo Kim, Channy Park, Xiaofan Wei, Arun Chhetri, Laxman Manandhar, Gyuho Jang, Jaetaek Hwang, Batchingis Chinbold, Chagtsalmaa Chuluunbaatar, Hyug Moo Kwon, Raekil Park","doi":"10.1038/s12276-025-01396-2","DOIUrl":"10.1038/s12276-025-01396-2","url":null,"abstract":"The breakdown of Golgi proteins disrupts lipid trafficking, leading to lipid accumulation in the small intestine. However, the causal mechanism of the effects of Golgi protein degradation on the Golgi structure related to lipid trafficking in the small intestine remains unknown. Here we find that Golgi protein degradation occurs under hypoxic conditions in high-fat-diet-fed mice. Hypoxia-induced degradation promotes structural changes in the Golgi apparatus, termed ‘Golgi condensation’. In addition, hypoxia-inducible factor 1α (HIF-1α) activation enhances Golgi condensation through the ubiquitination and degradation of Golgi matrix protein 130 (GM130), which is facilitated by neural precursor cell expressed developmentally downregulated protein 4 (NEDD4). Golgi condensation upon exposure to hypoxia promotes lipid accumulation, apolipoprotein A1 retention and decreased chylomicron secretion in the intestinal epithelium. Golgi condensation and lipid accumulation induced by GM130 depletion are reversed by exogenous GM130 induction in the intestinal epithelium. Inhibition of either HIF-1α or NEDD4 protects against GM130 degradation and, thereby, rescues cells from Golgi condensation, which further increases apolipoprotein A1 secretion and lipid accumulation both in vivo and in vitro. Furthermore, the HIF-1α inhibitor PX-478 prevents Golgi condensation, which decreases lipid accumulation and promotes high-density lipoprotein secretion in high-fat-diet-fed mice. Overall, our results suggest that Golgi condensation plays a key role in lipid trafficking in the small intestine through the HIF-1α- and NEDD4-mediated degradation of GM130, and these findings highlight the possibility that the prevention of structural modifications in the Golgi apparatus can ameliorate intestinal lipid accumulation in obese individuals. This study explores how low oxygen levels affect the Golgi apparatus, a cell structure involved in processing and packaging proteins and lipids. The study used mice and cell models to investigate these effects. They found that HIF-1α causes the Golgi apparatus to condense or shrink, which disrupts its function. This change is linked to increased lipid accumulation in the small intestine. The researchers discovered that HIF-1α plays a crucial role in this process by promoting the degradation of another protein, GM130, which is essential for maintaining Golgi structure, and NEDD4, a E3 ligase, which contributes on GM130 degradation. The findings suggest that preventing Golgi condensation by inhibiting HIF-1α could reduce lipid buildup in the obese intestine. This research provides new insights into how hypoxia affects lipid metabolism and could lead to potential treatments for obesity-related conditions. 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":"57 2","pages":"349-363"},"PeriodicalIF":9.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-025-01396-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124101","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":"Serotonin attenuates tumor necrosis factor-induced intestinal inflammation by interacting with human mucosal tissue","authors":"Veronika Bosáková, Ioanna Papatheodorou, Filip Kafka, Zuzana Tomášiková, Petros Kolovos, Marcela Hortová Kohoutková, Jan Frič","doi":"10.1038/s12276-025-01397-1","DOIUrl":"10.1038/s12276-025-01397-1","url":null,"abstract":"The intestine hosts the largest immune system and peripheral nervous system in the human body. The gut‒brain axis orchestrates communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Here, using a human three-dimensional in vitro culture model, we investigated the effects of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Serotonin attenuated the tumor necrosis factor-induced proinflammatory response, mostly by affecting the expression of chemokines. Serotonin affected the phenotype and distribution of tissue-migrating monocytes, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, our results show that serotonin plays a crucial role in communication among gut–brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of inflammation. In vivo studies focused on the role of neuromodulators in gut inflammation have shown controversial results, highlighting the importance of human experimental models. Moreover, our results emphasize the importance of human health research in human cell-based models and suggest that the serotonin signaling pathway is a new therapeutic target for inflammatory bowel disease. The gut–brain axis involves communication between the brain and the gut, which is important for maintaining gut health. Here the authors explored this by studying serotonin’s role in gut inflammation using a three-dimensional human cell model. They used intestinal organoids to mimic human gut conditions. These organoids were treated with serotonin and TNF to study their effects on gut cells and immune responses. The researchers found that serotonin reduced TNF-induced inflammation by altering gene expression related to immune cell movement. The study showed that serotonin can decrease the production of certain inflammatory signals in the gut, potentially reducing inflammation. This suggests that targeting serotonin could help treat inflammatory bowel disease (IBD). In conclusion, serotonin plays a role in controlling gut inflammation, offering insights into new treatments for IBD. Future research could explore serotonin’s broader impact on other inflammatory diseases. 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":"57 2","pages":"364-378"},"PeriodicalIF":9.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-025-01397-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081859","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":"Increased oxidative phosphorylation through pyruvate dehydrogenase kinase 2 deficiency ameliorates cartilage degradation in mice with surgically induced osteoarthritis","authors":"Jin Han, Yoon Hee Kim, Seungwoo Han","doi":"10.1038/s12276-025-01400-9","DOIUrl":"10.1038/s12276-025-01400-9","url":null,"abstract":"Chondrocytes can shift their metabolism to oxidative phosphorylation (OxPhos) in the early stages of osteoarthritis (OA), but as the disease progresses, this metabolic adaptation becomes limited and eventually fails, leading to mitochondrial dysfunction and oxidative stress. Here we investigated whether enhancing OxPhos through the inhibition of pyruvate dehydrogenase kinase (PDK) 2 affects the metabolic flexibility of chondrocytes and cartilage degeneration in a surgical model of OA. Among the PDK isoforms, PDK2 expression was increased by IL-1β in vitro and in the articular cartilage of the DMM model in vivo, accompanied by an increase in phosphorylated PDH. Mice lacking PDK2 showed significant resistance to cartilage damage and reduced pain behaviors in the DMM model. PDK2 deficiency partially restored OxPhos in IL-1β-treated chondrocytes, leading to increases in APT and the NAD+/NADH ratio. These metabolic changes were accompanied by a decrease in reactive oxygen species and senescence in chondrocytes, as well as an increase in the expression of antioxidant proteins such as NRF2 and HO-1 after IL-1β treatment. At the signaling level, PDK2 deficiency reduced p38 signaling and maintained AMPK activation without affecting the JNK, mTOR, AKT and NF-κB pathways. p38 MAPK signaling was critically involved in reactive oxygen species production under glycolysis-dominant conditions in chondrocytes. Our study provides a proof of concept for PDK2-mediated metabolic reprogramming toward OxPhos as a new therapeutic strategy for OA. Osteoarthritis is a common joint disease where cartilage breaks down, causing pain and stiffness. Chondrocytes, the cells in cartilage, usually rely on glycolysis for energy production. However, in early OA, they can switch to oxidative phosphorylation as an alternative energy pathway. This study aimed to see if modulating chondrocyte metabolism could slow OA progression. Researchers focused on PDK2, a protein that inactivates PDH, thereby reducing OxPhos activity in chondrocytes. They used mice genetically modified to lack PDK2 and compared them with normal mice with surgically induced OA. They found that, without PDK2, chondrocytes had better energy balance by using OxPhos more effectively and less oxidative stress, which slowed OA progression. This suggests that targeting PDK2 could be a new way to treat OA by improving chondrocyte metabolism. 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":"57 2","pages":"390-401"},"PeriodicalIF":9.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-025-01400-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081901","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: AIVariant: a deep learning-based somatic variant detector for highly contaminated tumor samples","authors":"Hyeonseong Jeon, Junhak Ahn, Byunggook Na, Soona Hong, Lee Sael, Sun Kim, Sungroh Yoon, Daehyun Baek","doi":"10.1038/s12276-025-01405-4","DOIUrl":"10.1038/s12276-025-01405-4","url":null,"abstract":"","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 1","pages":"284-284"},"PeriodicalIF":9.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-025-01405-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061256","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":"RECQL4 requires PARP1 for recruitment to DNA damage, and PARG dePARylation facilitates its associated role in end joining","authors":"Mansoor Hussain, Prabhat Khadka, Komal Pekhale, Tomasz Kulikowicz, Samuel Gray, Alfred May, Deborah L. Croteau, Vilhelm A. Bohr","doi":"10.1038/s12276-024-01383-z","DOIUrl":"10.1038/s12276-024-01383-z","url":null,"abstract":"RecQ helicases, highly conserved proteins with pivotal roles in DNA replication, DNA repair and homologous recombination, are crucial for maintaining genomic integrity. Mutations in RECQL4 have been associated with various human diseases, including Rothmund–Thomson syndrome. RECQL4 is involved in regulating major DNA repair pathways, such as homologous recombination and nonhomologous end joining (NHEJ). RECQL4 has more prominent single-strand DNA annealing activity than helicase activity. Its ability to promote DNA damage repair and the precise role of its DNA annealing activity in DNA repair are unclear. Here we demonstrate that PARP1 interacts with RECQL4, increasing its single-stranded DNA strand annealing activity. PARP1 specifically promoted RECQL4 PARylation at both its N- and C-terminal regions, promoting RECQL4 recruitment to DNA double-strand breaks (DSBs). Inhibition or depletion of PARP1 significantly diminished RECQL4 recruitment and occupancy at specific DSB sites on chromosomes. After DNA damage, PARG dePARylated RECQL4 and stimulated its end-joining activity. RECQL4 actively displaced replication protein A from single-stranded DNA, promoting microhomology annealing in vitro. Furthermore, depletion of PARP1 or RECQL4 substantially impacted classical-NHEJ- and alternative-NHEJ-mediated DSB repair. Consequently, the combined activities of PARP1, PARG and RECQL4 modulate DNA repair. Cells have mechanisms to repair DNA damage, which is crucial for preventing diseases such as cancer. The authors wanted to understand how another protein, PARP1, affects the role of RECQL4 in DNA repair. The study involved laboratory experiments using human cells to see how RECQL4 and PARP1 interact. PARP1 helps recruit RECQL4 to sites of DNA damage and enhances its ability to repair DNA by promoting the strand annealing process. However, when RECQL4 is modified by PARP1 through PARylation, its repair activity is reduced. Another protein, PARG, can reverse this modification, restoring the function of RECQL4. The results suggest that the interaction between RECQL4 and PARP1 is important for efficient DNA repair. This understanding could lead to new strategies for treating diseases related to DNA repair defects, such as cancer. 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":"57 1","pages":"264-280"},"PeriodicalIF":9.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01383-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054148","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":"IFN-γ reprograms cardiac microvascular endothelial cells to mediate doxorubicin transport and influences the sensitivity of mice to doxorubicin-induced cardiotoxicity","authors":"Haoyu Ji, Wenya Ma, Xu Liu, Hongyang Chen, Yining Liu, Zhongyu Ren, Daohong Yin, Ao Cai, Zizhen Zhang, Xin Wang, Wei Huang, Leping Shi, Yanan Tian, Yang Yu, Xiuxiu Wang, Yang Li, Yu Liu, Benzhi Cai","doi":"10.1038/s12276-024-01389-7","DOIUrl":"10.1038/s12276-024-01389-7","url":null,"abstract":"Doxorubicin (DOX) is a first-line chemotherapy agent known for its cardiac toxicity. DOX-induced cardiotoxicity (DIC) severely limits the use for treating malignant tumors and is associated with a poor prognosis. The sensitivity to DIC varies among patients, but the precise mechanisms remain elusive. Here we constructed a mouse model of DIC using DOX to investigate potential mechanisms contributing to the differential susceptibility to DIC. Through surface-enhanced Raman spectroscopy and single-cell RNA sequencing, we explored the mechanisms underlying DIC phenotypic variations. In vitro and in vivo studies with small-molecule drugs were conducted. DIC-insensitive mice displayed preserved ejection fractions, lower DOX levels in cardiac tissues and higher levels in the serum. Single-cell RNA sequencing revealed differences of gene expression in cardiac endothelial cells between DIC-insensitive and DIC-sensitive groups. The expression of IFN-γ pathway-related genes was high in DIC-insensitive mice. IFN-γ administration decreased the DOX distribution in cardiac tissues, whereas PPAR-γ activation increased DIC susceptibility. IFN-γ stimulation upregulated P-glycoprotein expression, leading to increased DOX efflux and DIC insensitivity. Our model provides insights into the mechanisms of DIC sensitivity and potential preventive strategies. Doxorubicin is a powerful cancer drug, but it can harm the heart, leading to a condition called doxorubicin-induced cardiotoxicity (DIC). Some people are more affected by DIC than others, and scientists want to understand why. They found that the heterogeneity observed among endothelial cells (ECs) plays a potential role in determining DIC sensitivity. In mice less sensitive to DIC, reprogramming of ECs increases levels of P-glycoprotein (P-gp), which helps to pump drugs out of cells. They discovered that activating a pathway involving IFN-γ increased P-gp levels, reducing heart damage. Conversely, activating another pathway, PPAR-γ, decreased P-gp levels and increased heart damage. These findings provide new insights into DIC pathogenesis and suggest that boosting P-gp in ECs could be a new strategy to protect against DIC. 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":"57 1","pages":"249-263"},"PeriodicalIF":9.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01389-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025110","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":"Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain","authors":"Chae-Jeong Lee, Seung Hyun Jang, Jiwoo Lim, Hyunju Park, So-Hee Ahn, Seon Young Park, Hyangmi Seo, Soo-Jin Song, Jung-A Shin, Chulhee Choi, Heon Yung Gee, Youn-Hee Choi","doi":"10.1038/s12276-024-01388-8","DOIUrl":"10.1038/s12276-024-01388-8","url":null,"abstract":"Neuroinflammation, a significant contributor to various neurodegenerative diseases, is strongly associated with the aging process; however, to date, no efficacious treatments for neuroinflammation have been developed. In aged mouse brains, the number of infiltrating immune cells increases, and the key transcription factor associated with increased chemokine levels is nuclear factor kappa B (NF-κB). Exosomes are potent therapeutics or drug delivery vehicles for various materials, including proteins and regulatory genes, to target cells. In the present study, we evaluated the therapeutic efficacy of exosomes loaded with a nondegradable form of IκB (Exo-srIκB), which inhibits the nuclear translocation of NF-κB to suppress age-related neuroinflammation. Single-cell RNA sequencing revealed that these anti-inflammatory exosomes targeted macrophages and microglia, reducing the expression of inflammation-related genes. Treatment with Exo-srIκB also suppressed the interactions between macrophages/microglia and T and B cells in the aged brain. We demonstrated that Exo-srIκB successfully alleviates neuroinflammation by primarily targeting activated macrophages and partially modulating the functions of age-related interferon-responsive microglia in the brain. Thus, our findings highlight Exo-srIκB as a potential therapeutic agent for treating age-related neuroinflammation. As we age, our bodies undergo changes that can lead to diseases like Alzheimer’s and Parkinson’s. A key factor in this process is inflammation in the brain, driven by a protein called NF-κB. Researcher explored a new way to reduce this inflammation using tiny particles called exosomes. These exosomes were engineered to carry a special form of a protein that blocks NF-κB, called srIκB. In their study, the team injected these exosomes into mice and observed their effects on neuroinflammation. They used advanced techniques to analyze changes in cells of the brain and found that the exosomes reduced inflammation-related genes and altered immune cell behavior. This suggests that the exosomes can help control inflammation in the aging brain. The results indicate that these engineered exosomes could be a promising treatment for age-related brain diseases. 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":"57 1","pages":"235-248"},"PeriodicalIF":9.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01388-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015501","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: Influencing immunity: role of extracellular vesicles in tumor immune checkpoint dynamics","authors":"Ziyang Ye, Genpeng Li, Jianyong Lei","doi":"10.1038/s12276-025-01394-4","DOIUrl":"10.1038/s12276-025-01394-4","url":null,"abstract":"","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 1","pages":"283-283"},"PeriodicalIF":9.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-025-01394-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015497","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":"mtSTAT3 suppresses rheumatoid arthritis by regulating Th17 and synovial fibroblast inflammatory cell death with IL-17-mediated autophagy dysfunction","authors":"Seon-Yeong Lee, Jeonghyeon Moon, A Ram Lee, Young-Mee Moon, Jeong Won Choi, Chae Rim Lee, Su Been Jeon, Hee Su Sohn, Jeehee Youn, Dongyun Shin, Sung-Hwan Park, Mi-La Cho","doi":"10.1038/s12276-024-01376-y","DOIUrl":"10.1038/s12276-024-01376-y","url":null,"abstract":"Th17 cells are activated by STAT3 factors in the nucleus, and these factors are correlated with the pathologic progression of rheumatoid arthritis (RA). Recent studies have demonstrated the presence of STAT3 in mitochondria, but its function is unclear. We investigated the novel role of mitochondrial STAT3 (mitoSTAT3) in Th17 cells and fibroblast-like synoviocytes (FLSs) and analyzed the correlation of mitoSTAT3 with RA. We used a collagen-induced arthritis (CIA) mouse model to determine the effect of mitochondrial STAT3. We observed changes in the RA mouse model via the use of a mitochondrial STAT3-inducing vector and inhibitor. We observed the accumulation of abnormal autophagosomes, increased inflammatory cell death signaling, and decreased mitoSTAT3 activity in FLSs from both patients with RA and patients with IL-17-treated FLSs. We first discovered that IL-17 increased the accumulation of abnormal autophagosomes and the expression of inflammatory cell death factors in synovial fibroblasts and decreased mitoSTAT3 activation. In a mouse model of CIA, arthritis and joint inflammation were decreased by injection vectors that induced mitoSTAT3 overexpression. The abnormal accumulation of autophagosomes and the expression of inflammatory cell death factors were also decreased in these mice. In mouse and human immune cells, ZnSO4, an inducer of mitochondrial STAT3, decreases the production of reactive oxygen species, the IL-17 concentration, and differentiation into Th17 cells. However, mitoSTAT3 blockade accelerated the development of arthritis, inflammatory cell death, and abnormal autophagosome/autophagolysosome formation. Therefore, this study suggests a novel inhibitory mechanism of RA using mitoSTAT3 via the regulation of autophagy, Th17 differentiation, and inflammatory cell death. Rheumatoid arthritis is a long-term disease where the immune system attacks the joints, causing pain and swelling. Researchers have found that a protein called mitoSTAT3, located in the mitochondria, might help reduce inflammation in RA. Researchers used mice with arthritis and human cells to study mitoSTAT3’s role. They increased mitoSTAT3 levels in mice and observed less joint damage and inflammation and found that mitoSTAT3 helps control a process called autophagy. This is important because poor autophagy can worsen RA. The results showed that boosting mitoSTAT3 reduced inflammation and joint damage in mice. The researchers concluded that mitoSTAT3 could be a new target for RA treatment by improving cell cleanup processes and reducing harmful immune responses. In the future, therapies that increase mitoSTAT3 might help people with RA by reducing inflammation and joint damage. 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":"57 1","pages":"221-234"},"PeriodicalIF":9.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01376-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015513","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":"Advancing pancreatic cancer research and therapeutics: the transformative role of organoid technology","authors":"Jihao Xu, Minh Duc Pham, Vincenzo Corbo, Mariano Ponz-Sarvise, Tobiloba Oni, Daniel Öhlund, Chang-Il Hwang","doi":"10.1038/s12276-024-01378-w","DOIUrl":"10.1038/s12276-024-01378-w","url":null,"abstract":"Research on pancreatic cancer has transformed with the advent of organoid technology, providing a better platform that closely mimics cancer biology in vivo. This review highlights the critical advancements facilitated by pancreatic organoid models in understanding disease progression, evaluating therapeutic responses, and identifying biomarkers. These three-dimensional cultures enable the proper recapitulation of the cellular architecture and genetic makeup of the original tumors, providing insights into the complex molecular and cellular dynamics at various stages of pancreatic ductal adenocarcinoma (PDAC). We explore the applications of pancreatic organoids in dissecting the tumor microenvironment (TME); elucidating cancer progression, metastasis, and drug resistance mechanisms; and personalizing therapeutic strategies. By overcoming the limitations of traditional 2D cultures and animal models, the use of pancreatic organoids has significantly accelerated translational research, which is promising for improving diagnostic and therapeutic approaches in clinical settings, ultimately aiming to improve the outcomes of patients with pancreatic cancer. Pancreatic cancer is a challenging disease to study and treat. This article discusses how researchers have developed pancreatic organoids to better study this cancer. Organoids are created by growing cells in a specialized 3D matrix, allowing them to form structures that resemble tissues found in the body. This method is more effective than traditional 2D cultures because it better replicates the natural environment of the cells. Researchers use these organoids to study cancer progression, test new drugs, and understand genetic changes in tumors. They can be made from small tissue samples, making them useful for studying advanced cancer stages where tissue is scarce. The findings from organoid studies help identify potential new treatments and improve our understanding of pancreatic cancer biology. In conclusion, pancreatic organoids offer a promising tool for advancing cancer research and developing personalized 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":"57 1","pages":"50-58"},"PeriodicalIF":9.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01378-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015493","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}