Communications Biology最新文献_第2页

Infection with novel duck reovirus induces stress granule and methylation-mediated host translational shutoff in Muscovy ducklings. 新型鸭再病毒感染会诱导雏鸭体内的应激颗粒和甲基化介导的宿主翻译关闭。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-21 DOI: 10.1038/s42003-024-07259-2

Tao Yun, Jionggang Hua, Liu Chen, Weicheng Ye, Zheng Ni, Yinchu Zhu, Cun Zhang

{"title":"Infection with novel duck reovirus induces stress granule and methylation-mediated host translational shutoff in Muscovy ducklings.","authors":"Tao Yun, Jionggang Hua, Liu Chen, Weicheng Ye, Zheng Ni, Yinchu Zhu, Cun Zhang","doi":"10.1038/s42003-024-07259-2","DOIUrl":"10.1038/s42003-024-07259-2","url":null,"abstract":"The recently identified novel duck reovirus (NDRV) is a waterfowl reovirus that can seriously harm or kill various waterfowl species. However, how NDRV interacts with host cells in Muscovy ducklings beyond the typical pathogenesis resulting from a viral infection is unknown. The current study examined the global translation efficiency of the Fabricius bursa of Muscovy ducklings infected with NDRV HN10 using mass spectrometry and ribosome footprint sequencing. Protein-protein interactions were investigated using immunogold labeling, transmission electron microscopy, and immunocytochemistry. An analysis of the relationship between m6A and translation was performed using RNA immunoprecipitation and m6A methylation immunoprecipitation. We found that both in vivo and in vitro, the translation efficiency of RNA modified with m6A could be significantly reduced by σB, a structural protein component of NDRV HN10. Furthermore, σB might simultaneously interact with the stress granule complex CAPRIN1 and G3BP1 and the m6A reader protein YTHDF1/3. Significant overlap was observed between m6A-modified and G3BP1-enriched RNA, indicating that granule stress could capture m6A-methylated RNA. We discovered a new function for NDRV HN10 in translational shutoff by recruiting m6A-modified RNA into stress granules located in the Fabricius bursa of Muscovy ducklings.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1549"},"PeriodicalIF":5.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasmodium berghei liver stage parasites exploit host GABARAP proteins for TFEB activation. 疟原虫肝阶段寄生虫利用宿主 GABARAP 蛋白激活 TFEB。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-21 DOI: 10.1038/s42003-024-07242-x

Jacqueline Schmuckli-Maurer, Annina F Bindschedler, Rahel Wacker, Oliver M Würgler, Ruth Rehmann, Timothy Lehmberg, Leon O Murphy, Thanh N Nguyen, Michael Lazarou, Jlenia Monfregola, Andrea Ballabio, Volker T Heussler

{"title":"Plasmodium berghei liver stage parasites exploit host GABARAP proteins for TFEB activation.","authors":"Jacqueline Schmuckli-Maurer, Annina F Bindschedler, Rahel Wacker, Oliver M Würgler, Ruth Rehmann, Timothy Lehmberg, Leon O Murphy, Thanh N Nguyen, Michael Lazarou, Jlenia Monfregola, Andrea Ballabio, Volker T Heussler","doi":"10.1038/s42003-024-07242-x","DOIUrl":"10.1038/s42003-024-07242-x","url":null,"abstract":"Plasmodium, the causative agent of malaria, infects hepatocytes prior to establishing a symptomatic blood stage infection. During this liver stage development, parasites reside in a parasitophorous vacuole (PV), whose membrane acts as the critical interface between the parasite and the host cell. It is well-established that host cell autophagy-related processes significantly impact the development of Plasmodium liver stages. Expression of genes related to autophagy and lysosomal biogenesis is orchestrated by transcription factor EB (TFEB). In this study, we explored the activation of host cell TFEB in Plasmodium berghei-infected cells during the liver stage of the parasite. Our results unveiled a critical role of proteins belonging to the Gamma-aminobutyric acid receptor-associated protein subfamily (GABARAP) of ATG8 proteins (GABARAP/L1/L2 and LC3A/B/C) in recruiting the TFEB-blocking FLCN-FNIP (Folliculin-Folliculin-interacting protein) complex to the PVM. Remarkably, the sequestration of FLCN-FNIP resulted in a robust activation of TFEB, reliant on conjugation of ATG8 proteins to single membranes (CASM) and GABARAP proteins. Our findings provide novel mechanistic insights into host cell signaling occurring at the PVM, shedding light on the complex interplay between Plasmodium parasites and the host cell during the liver stage of infection.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1554"},"PeriodicalIF":5.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential bone morphology and hypoxia activity in skeletal metastases of ER⁺ and ER^- breast cancer. ER+和ER-乳腺癌骨骼转移中不同的骨形态和缺氧活性。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-21 DOI: 10.1038/s42003-024-07247-6

Anindita Das, Megan M Barry, Cheyenne A Ernst, Renuka Dahiya, Minhyung Kim, Spencer R Rosario, Hin Ching Lo, Cuijuan Yu, Tao Dai, Zbigniew Gugala, Jianmin Zhang, Subhamoy Dasgupta, Hai Wang

{"title":"Differential bone morphology and hypoxia activity in skeletal metastases of ER+ and ER- breast cancer.","authors":"Anindita Das, Megan M Barry, Cheyenne A Ernst, Renuka Dahiya, Minhyung Kim, Spencer R Rosario, Hin Ching Lo, Cuijuan Yu, Tao Dai, Zbigniew Gugala, Jianmin Zhang, Subhamoy Dasgupta, Hai Wang","doi":"10.1038/s42003-024-07247-6","DOIUrl":"10.1038/s42003-024-07247-6","url":null,"abstract":"Bone metastases occur in the majority of advanced breast cancer patients, and the most common complications are osteolytic bone metastases. However, due to the limitations of models and methodologies for bone metastasis studies, the intricacies of bone metastasis have not been fully acknowledged and revealed in prior work. Our earlier study indicated that certain breast cancer cells undergo a pre-osteolytic stage before the establishment of overt metastatic lesions. Here, we further identify a differential bone morphology between ER (estrogen receptor)+ and ER- breast cancer. Specifically, we observe a more pronounced osteolytic phenotype in the bone metastatic lesions of ER- cells investigated, linked to elevated hypoxia signaling that stimulates the secretion of osteolytic inducers from cancer cells. In the in vivo mouse model, the application of the hypoxia-inducible factor (HIF) inhibitor 2-methoxyestradiol demonstrates a promising efficacy in suppressing tumor growth and osteoclast differentiation in the bone lesions established by bone-tropic subpopulation of ER- MDA-MB-231 cell. Overall, our findings explore the complexity of phenotype and morphology in bone metastatic lesions of ER+ and ER- breast cancer, which offers a compelling rationale for leveraging HIF inhibitors to the treatment targeting skeletal complications of breast cancer bone metastases, especially for ER- tumors.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1545"},"PeriodicalIF":5.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Age-dependent effects of vaping on the prefrontal cortex, ventral tegmental area, and nucleus accumbens. 吸烟对前额叶皮层、腹侧被盖区和伏隔核的影响与年龄有关。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-21 DOI: 10.1038/s42003-024-07272-5

Brandon J Henderson, Lauren E Young, Nathan A Olszewski, Samuel Tetteh-Quarshie, Sarah K Maddox, M Alex Simpkins, Mathew C Dudich, M Sage McGlauglin, Zoie C Weinsweig, Skylar Y Cooper

{"title":"Age-dependent effects of vaping on the prefrontal cortex, ventral tegmental area, and nucleus accumbens.","authors":"Brandon J Henderson, Lauren E Young, Nathan A Olszewski, Samuel Tetteh-Quarshie, Sarah K Maddox, M Alex Simpkins, Mathew C Dudich, M Sage McGlauglin, Zoie C Weinsweig, Skylar Y Cooper","doi":"10.1038/s42003-024-07272-5","DOIUrl":"10.1038/s42003-024-07272-5","url":null,"abstract":"Electronic nicotine delivery systems (ENDS) are unique from combustible cigarettes due to the availability of flavor options which make these devices popular among adolescents. However, there are no preclinical investigations into the impact of vaporized nicotine on late-developing brain regions such as the prefrontal cortex. Here, we investigated how neuronal function and drug self-administration differed between adult-exposed and adolescent-exposed mice. Male and female adolescent and adult C57BL/6J mice were used in a 20-session e-Vape® self-administration (EVSA) assay. Brains were then extracted and acute slices were used for either patch-clamp electrophysiology or fast-scan cyclic voltammetry. Adolescent-exposed males exhibited greater reinforcement-related behavior compared to their adult-exposed counterparts. However, adolescent-exposed and adult-exposed females exhibited similar levels of reinforcement-related behavior. Adolescent-exposed mice exhibited significant increases in intrinsic excitability of medial prefrontal cortex (mPFC) pyramidal neurons. Additionally, reinforcement-related behavior observed during EVSA assays correlated with adolescent-exposed mPFC neuronal excitability. This did not occur in adult-exposed mice. In the ventral tegmental area (VTA), we observed that upregulation of nicotinic acetylcholine receptors (nAChRs) only correlated with nicotine self-administration in adult and not adolescent-exposed mice. The relationship between self-administration and changes in neuronal excitability in adolescent mice indicates that the mPFC may be important for adolescent nicotine dependence.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1553"},"PeriodicalIF":5.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modality-specific and modality-general representations of subjective value in frontal cortex. 额叶皮层中主观价值的特定模式表征和一般模式表征。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-21 DOI: 10.1038/s42003-024-07253-8

Shilpa Dang, Jessica Emily Antono, Igor Kagan, Arezoo Pooresmaeili

{"title":"Modality-specific and modality-general representations of subjective value in frontal cortex.","authors":"Shilpa Dang, Jessica Emily Antono, Igor Kagan, Arezoo Pooresmaeili","doi":"10.1038/s42003-024-07253-8","DOIUrl":"10.1038/s42003-024-07253-8","url":null,"abstract":"Neuroeconomics theories propose that the value associated with diverse rewards or reward-predicting stimuli is encoded along a common reference scale, irrespective of their sensory properties. However, in a dynamic environment with changing stimulus-reward pairings, the brain must also represent the sensory features of rewarding stimuli. The mechanism by which the brain balances these needs-deriving a common reference scale for valuation while maintaining sensitivity to sensory contexts-remains unclear. To investigate this, we conducted an fMRI study with human participants engaged in a dynamic foraging task, which required integrating the reward history of auditory or visual choice options and updating the subjective value for each sensory modality. Univariate fMRI analysis revealed modality-specific value representations in the orbitofrontal cortex (OFC) and modality-general value representations in the ventromedial prefrontal cortex (vmPFC), confirmed by an exploratory multivariate pattern classification approach. Crucially, modality-specific value representations were absent when the task involved instruction-based rather than value-based choices. Effective connectivity analysis showed that modality-specific value representations emerged from selective bidirectional interactions across the auditory and visual sensory cortices, the corresponding OFC clusters, and the vmPFC. These results illustrate how the brain enables a valuation process that is sensitive to the sensory context of rewarding stimuli.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1550"},"PeriodicalIF":5.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

E. coli and S. aureus resist silver nanoparticles via an identical mechanism, but through different pathways. 大肠杆菌和金黄色葡萄球菌抵抗纳米银粒子的机制相同，但途径不同。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-21 DOI: 10.1038/s42003-024-07266-3

Lucie Hochvaldová, David Panáček, Lucie Válková, Renata Večeřová, Milan Kolář, Robert Prucek, Libor Kvítek, Aleš Panáček

{"title":"E. coli and S. aureus resist silver nanoparticles via an identical mechanism, but through different pathways.","authors":"Lucie Hochvaldová, David Panáček, Lucie Válková, Renata Večeřová, Milan Kolář, Robert Prucek, Libor Kvítek, Aleš Panáček","doi":"10.1038/s42003-024-07266-3","DOIUrl":"10.1038/s42003-024-07266-3","url":null,"abstract":"Nanostructured materials with antibacterial activity face the same threat as conventional antibiotics - bacterial resistance, which reduces their effectiveness. However, unlike antibiotics, research into the emergence and mechanisms of bacterial resistance to antibacterial nanomaterials is still in its early stages. Here we show how Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria develop resistance to silver nanoparticles, resulting in an increase in the minimum inhibitory concentration from 1.69 mg/L for S. aureus and 3.38 mg/L for E. coli to 54 mg/L with repeated exposure over 12 and 6 cultivation steps, respectively. The mechanism of resistance is the same for both types of bacteria and involves the aggregation of silver nanoparticles leading to the formation of black precipitates. However, the way in which Gram-positive and Gram-negative bacteria induce aggregation of silver nanoparticles is completely different. Chemical analysis of the surface of the silver precipitates shows that aggregation is triggered by flagellin production in E. coli and by bacterial biofilm formation in S. aureus. However, resistance in both types of bacteria can be overcome by using pomegranate rind extract, which inhibits both flagellin and biofilm production, or by stabilizing the silver nanoparticles by covalently binding them to a composite material containing graphene sheets, which protects the silver nanoparticles from aggregation induced by the bacterial biofilm produced by S. aureus. This research improves the understanding of bacterial resistance mechanisms to nanostructured materials, which differ from resistance mechanisms to conventional antibiotics, and provides potential strategies to combat bacterial resistance and develop more effective antimicrobial treatments.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1552"},"PeriodicalIF":5.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

YeeE-like bacterial SoxT proteins mediate sulfur import for oxidation and signal transduction. 类 YeeE 细菌 SoxT 蛋白介导氧化和信号转导的硫输入。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-21 DOI: 10.1038/s42003-024-07270-7

Jingjing Li, Fabienne Göbel, Hsun Yun Hsu, Julian Nikolaus Koch, Natalie Hager, Wanda Antonia Flegler, Tomohisa Sebastian Tanabe, Christiane Dahl

{"title":"YeeE-like bacterial SoxT proteins mediate sulfur import for oxidation and signal transduction.","authors":"Jingjing Li, Fabienne Göbel, Hsun Yun Hsu, Julian Nikolaus Koch, Natalie Hager, Wanda Antonia Flegler, Tomohisa Sebastian Tanabe, Christiane Dahl","doi":"10.1038/s42003-024-07270-7","DOIUrl":"10.1038/s42003-024-07270-7","url":null,"abstract":"Many sulfur-oxidizing prokaryotes oxidize sulfur compounds through a combination of initial extracytoplasmic and downstream cytoplasmic reactions. Facultative sulfur oxidizers adjust transcription to sulfur availability. While sulfur-oxidizing enzymes and transcriptional repressors have been extensively studied, sulfur import into the cytoplasm and how regulators sense external sulfur are poorly understood. Addressing this gap, we show that SoxT1A and SoxT1B, which resemble YeeE/YedE-family thiosulfate transporters and are encoded alongside sulfur oxidation and transcriptional regulation genes, fulfill these roles in the Alphaproteobacterium Hyphomicrobium denitrificans. SoxT1A mutants are sulfur oxidation-negative despite high transcription levels of sulfur oxidation genes, showing that SoxT1A delivers sulfur to the cytoplasm for its further oxidation. SoxT1B serves as a signal transduction unit for the transcriptional repressor SoxR, as SoxT1B mutants are sulfur oxidation-negative due to low transcription unless SoxR is also absent. Thus, SoxT1A and SoxT1B play essential but distinct roles in oxidative sulfur metabolism and its regulation.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1548"},"PeriodicalIF":5.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Finding the sweet spot in the deep ocean. 在深海中寻找甜蜜点

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-21 DOI: 10.1038/s42003-024-07220-3

Linn Hoffmann

引用次数: 0

Collateral nuclease activity of TnpB triggered by high temperature enables fast and sensitive nucleic acid detection. 高温引发的 TnpB 附带核酸酶活性可实现快速、灵敏的核酸检测。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-20 DOI: 10.1038/s42003-024-07123-3

Ying Xu, Wen Yin, Yibin Cheng, Wei Zeng, Wenqiang Li, Wanping Chen, Fei Wang, Nan Peng, Lixin Ma, Tao Liu

{"title":"Collateral nuclease activity of TnpB triggered by high temperature enables fast and sensitive nucleic acid detection.","authors":"Ying Xu, Wen Yin, Yibin Cheng, Wei Zeng, Wenqiang Li, Wanping Chen, Fei Wang, Nan Peng, Lixin Ma, Tao Liu","doi":"10.1038/s42003-024-07123-3","DOIUrl":"10.1038/s42003-024-07123-3","url":null,"abstract":"TnpB proteins encoded in the IS200/IS605 family are RNA-guided endonuclease which can be harnessed in genome editing. However, the collateral nuclease activity of TnpB remains poorly understood, which limits the development of TnpB-based diagnostic tools. Here we showed that TnpB from a thermophilic archaeon exhibits enhanced collateral ssDNA cleavage activity (trans-cleavage) activated by high temperature. Mutations either in the TAM or seed sequences of the target DNA impair the trans-cleavage activity, which indicates its potential to be employed in molecular diagnostic. Importantly, by optimizing the length and the sequences of the collateral substrates, we have developed a new nucleic acid detection method based on TnpB with a sensitivity of 29 cp μl-1 in 30 min, which we name it TESD (TnpB Enable fast and Sensitive Detection). In summary, our findings illustrate the collateral nuclease activity of a TnpB from thermophiles and provide a novel platform for molecular diagnostics.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1541"},"PeriodicalIF":5.2,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PLGA/BK microspheres targeting the bradykinin signaling pathway as a therapeutic strategy to delay intervertebral disc degeneration. 以缓激肽信号通路为靶点的 PLGA/BK 微球是一种延缓椎间盘退变的治疗策略。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-20 DOI: 10.1038/s42003-024-07196-0

Xiaoming Qiu, Yizhi Zhang, Ziyan Wei, Zhangbin Luo, Zhuanping Wang, Xuewen Kang

{"title":"PLGA/BK microspheres targeting the bradykinin signaling pathway as a therapeutic strategy to delay intervertebral disc degeneration.","authors":"Xiaoming Qiu, Yizhi Zhang, Ziyan Wei, Zhangbin Luo, Zhuanping Wang, Xuewen Kang","doi":"10.1038/s42003-024-07196-0","DOIUrl":"10.1038/s42003-024-07196-0","url":null,"abstract":"Intervertebral disc degeneration(IVDD) is a common spinal condition with limited effective treatments available. This study aims to investigate the impact of poly(lactic-co-glycolic acid)/Bradykinin (PLGA/BK) microspheres on IVDD and its underlying mechanisms. We collected nucleus pulposus samples from both healthy and degenerated human intervertebral disks and conducted immunohistochemical analyses, revealing reduced BK expression in degenerated tissues. Subsequently, we used BK to treat nucleus pulposus cells and conducted Bulk RNA sequencing (RNA-seq), identifying BK's involvement in cellular senescence, extracellular matrix metabolism, and the PI3K signaling pathway. Further experiments using tert-butyl hydroperoxide (TBHP)-induced cell senescence showed that BK treatment reduced senescence, enhanced extracellular matrix synthesis, and inhibited degradation, along with activation of the PI3K pathway. These effects were mediated through B2R (BK receptor 2) and the downstream PI3K pathway. Following this, we developed sustained-release BK microspheres with an optimized manufacturing process. In vitro co-culture experiments showed no observable toxicity. We established an IVDD model in rat tail vertebrae through fine needle puncture, administering local injections of BK sustained-release microspheres. Using various experimental methods, including X-ray, MRI, histopathology, and immunohistochemistry, we found that these microspheres could slow the progression of IVDD. This study highlights the potential of injectable PLGA/BK microspheres to regulate cellular senescence and extracellular matrix metabolism via the B2R and PI3K pathways, ultimately delaying IVDD.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1540"},"PeriodicalIF":5.2,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0