Biological Procedures Online最新文献

{"title":"TACE responser NDRG1 acts as a guardian against ferroptosis to drive tumorgenesis and metastasis in HCC.","authors":"Bufu Tang,&nbsp;Yajie Wang,&nbsp;Jinyu Zhu,&nbsp;Jingjing Song,&nbsp;Shiji Fang,&nbsp;Qiaoyou Weng,&nbsp;Yang Yang,&nbsp;Jianfei Tu,&nbsp;Zhongwei Zhao,&nbsp;Minjiang Chen,&nbsp;Min Xu,&nbsp;Weiqian Chen,&nbsp;Jiansong Ji","doi":"10.1186/s12575-023-00199-x","DOIUrl":"https://doi.org/10.1186/s12575-023-00199-x","url":null,"abstract":"<p><strong>Background: </strong>The treatment efficacy of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) varies widely between individuals. The aim of this study was to identify subtype landscapes and responser related to TACE, and further clarify the regulatory effect and corresponding mechanism of NDRG1 on HCC tumorgenesis and metastasis.</p><p><strong>Methods: </strong>The principal component analysis (PCA) algorithm was used to construct a TACE response scoring (TRscore) system. The random forest algorithm was applied to identify the TACE response-related core gene NDRG1 of HCC, and its role in the prognosis of HCC was explored. The role of NDRG1 in the progression and metastasis of HCC and functional mechanism were confirmed using several experimental methods.</p><p><strong>Results: </strong>Based on the GSE14520 and GSE104580 cohorts, we identified 2 TACE response-related molecular subtypes for HCC with significant differences in clinical features, and the TACE prognosis of Cluster A was significantly better than that of Cluster B (p < 0.0001). We then established the TRscore system and found that the low TRscore group showed a higher probability of survival and a lower rate of recurrence than the high TRscore group (p < 0.05) in both the HCC and TACE-treated HCC cohorts within the GSE14520 cohort. NDRG1 was determined to be the the hub gene associated with the TACE response of HCC and its high expression suggested a poor prognosis. Furthermore, The suppression of NDRG1 konckdown in tumorgenesis and metastasis of HCC was clarified in both vivo and vitro, which was importantly achieved through inducing ferroptosis in HCC cells, especially contributing to RLS3-induced ferroptosis.</p><p><strong>Conclusion: </strong>The constructed TACE response-related molecular subtypes and TRscores can specifically and accurately predict TACE prognosis for HCC. In addition, the TACE response-related hub gene NDRG1 may act as a guardian against ferroptosis to drive tumorgenesis and metastasis in HCC, which laid a new foundation for the development of new potential targeted therapy strategies to improve disease prognosis in HCC patients.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"25 1","pages":"13"},"PeriodicalIF":6.4,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9498498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: The role of three‑dimensional scaffolds based on polyglycerol sebacate/ polycaprolactone/ gelatin in the presence of Nanohydroxyapatite in promoting chondrogenic differentiation of human adipose‑derived mesenchymal stem cells.","authors":"Pardis Yousefi Talouki,&nbsp;Saeed Hesami Tackallou,&nbsp;Shahrokh Shojaei,&nbsp;Soheila Zamanlui Benisi,&nbsp;Vahabodin Goodarzi","doi":"10.1186/s12575-023-00209-y","DOIUrl":"https://doi.org/10.1186/s12575-023-00209-y","url":null,"abstract":"","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"25 1","pages":"12"},"PeriodicalIF":6.4,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9496334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BPTF in bone marrow provides a potential progression biomarker regulated by TFAP4 through the PI3K/AKT pathway in neuroblastoma.","authors":"Chiyi Jiang,&nbsp;Yeran Yang,&nbsp;Sidou He,&nbsp;Zhixia Yue,&nbsp;Tianyu Xing,&nbsp;Ping Chu,&nbsp;Wenfa Yang,&nbsp;Hui Chen,&nbsp;Xiaoxi Zhao,&nbsp;Yongbo Yu,&nbsp;Xuan Zhang,&nbsp;Yan Su,&nbsp;Yongli Guo,&nbsp;Xiaoli Ma","doi":"10.1186/s12575-023-00200-7","DOIUrl":"https://doi.org/10.1186/s12575-023-00200-7","url":null,"abstract":"<p><strong>Background: </strong>Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, which is highly prone to bone marrow (BM) metastasis. BM can monitor early signs of mild disease and metastasis. Existing biomarkers are insufficient for the diagnosis and treatment of NB. Bromodomain PHD finger transcription factor (BPTF) is an important subunit of the chromatin-remodeling complex that is closely associated with tumors. Here, we evaluated whether BPTF in BM plays an important role in predicting NB progression, and explore the molecular mechanism of BPTF in NB.</p><p><strong>Methods: </strong>The clinical relevance of the BPTF was predicted in the GEO (GSE62564) and TARGET database. The biological function of BPTF in NB was investigated by constructing cell lines and employing BPTF inhibitor AU1. Western blot was used to determine the changes of BPTF, TFAP4, PI3K/AKT signaling and Epithelial-mesenchymal transition (EMT) related markers. A total of 109 children with newly diagnosed NB in Beijing Children's Hospital from January 2018 to March 2021 were included in this study. RT-PCR was used to measure the BPTF and TFAP4 expression in BM. The cut-off level was set at the median value of BPTF expression levels.</p><p><strong>Results: </strong>Databases suggested that BPTF expression was higher in NB and was significantly associated with stage and grade. Proliferation and migration of NB cells were slowed down when BPTF was silenced. Mechanistically, TFAP4 could positively regulate BPTF and promotes EMT process through activating the PI3K/AKT signaling pathway. Moreover, detection of the newly diagnosed BM specimens showed that BPTF expression was significantly higher in high-risk group, stage IV group and BM metastasis group. Children with high BPTF at initial diagnosis were considered to have high risk for disease progression and recurrence. BPTF is an independent risk factor for predicting NB progression.</p><p><strong>Conclusions: </strong>A novel and convenient BPTF-targeted humoral detection that can prompt minimal residual and predict NB progression in the early stages of the disease were identified. BPTF inhibitor AU1 is expected to become a new targeted drug for NB therapy. It's also reveal previously unknown mechanisms of BPTF in NB cell proliferation and metastasis through TFAP4 and PI3K/AKT pathways.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"25 1","pages":"11"},"PeriodicalIF":6.4,"publicationDate":"2023-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9512862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal microRNA-342-5p secreted from adipose-derived mesenchymal stem cells mitigates acute kidney injury in sepsis mice by inhibiting TLR9.","authors":"Wei Liu,&nbsp;Chenghuan Hu,&nbsp;Buyao Zhang,&nbsp;Mingxia Li,&nbsp;Fuxing Deng,&nbsp;Shuangping Zhao","doi":"10.1186/s12575-023-00198-y","DOIUrl":"https://doi.org/10.1186/s12575-023-00198-y","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-related acute kidney injury (AKI) is an inflammatory disease associated with extremely high mortality and health burden. This study explored the possibility of exosomes secreted by adipose-derived mesenchymal stem cells (AMSCs) serving as a carrier for microRNA (miR)-342-5p to alleviate sepsis-related AKI and investigated the possible mechanism.</p><p><strong>Methods: </strong>Serum was obtained from 30 patients with sepsis-associated AKI and 30 healthy volunteers for the measurement of miR-342-5p, blood urea nitrogen (BUN), and serum creatinine (SCr) levels. For in vitro experiments, AMSCs were transfected with LV-miR-342-5p or LV-miR-67 to acquire miR-342-5p-modified AMSCs and miR-67-modified AMSCs, from which the exosomes (AMSC-Exo-342 and AMSC-Exo-67) were isolated. The human renal proximal tubular epithelial cell line HK-2 was induced by lipopolysaccharide (LPS) to construct a cellular model of sepsis. The expression of Toll-like receptor 9 (TLR9) was also detected in AKI cells and mouse models. The interaction between miR-342-5p and TLR9 was predicted by dual luciferase reporter gene assay.</p><p><strong>Results: </strong>Detection on clinical serum samples showed that BUN, SCr, and TLR9 were elevated and miR-342-5p level was suppressed in the serum of patients with sepsis-associated AKI. Transfection with LV-miR-342-5p reinforced miR-342-5p expression in AMSCs and AMSC-secreted exosomes. miR-342-5p negatively targeted TLR9. LPS treatment enhanced TLR9 expression, reduced miR-342-5p levels, suppressed autophagy, and increased inflammation in HK-2 cells, while the opposite trends were observed in LPS-induced HK-2 cells exposed to AMSC-Exo-342, Rapa, miR-342-5p mimic, or si-TLR9. Additionally, the effects of AMSC-Exo-342 on autophagy and inflammation in LPS-induced cells could be weakened by 3-MA or pcDNA3.1-TLR9 treatment. Injection of AMSC-Exo-342 enhanced autophagy, mitigated kidney injury, suppressed inflammation, and reduced BUN and SCr levels in sepsis-related AKI mouse models.</p><p><strong>Conclusion: </strong>miR-342-5p transferred by exosomes from miR-342-5p-modified AMSCs ameliorated AKI by inhibiting TLR9 to accelerate autophagy.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"25 1","pages":"10"},"PeriodicalIF":6.4,"publicationDate":"2023-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9477833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of three-dimensional scaffolds based on polyglycerol sebacate/ polycaprolactone/ gelatin in the presence of Nanohydroxyapatite in promoting chondrogenic differentiation of human adipose-derived mesenchymal stem cells.","authors":"Pardis Yousefi Talouki,&nbsp;Saeed Hesami Tackallou,&nbsp;Shahrokh Shojaei,&nbsp;Soheila Zamanlui Benisi,&nbsp;Vahabodin Goodarzi","doi":"10.1186/s12575-023-00197-z","DOIUrl":"https://doi.org/10.1186/s12575-023-00197-z","url":null,"abstract":"<p><strong>Background: </strong>Tissue engineering for cartilage regeneration has made great advances in recent years, although there are still challenges to overcome. This study aimed to evaluate the chondrogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs) on three-dimensional scaffolds based on polyglycerol sebacate (PGS) / polycaprolactone (PCL) / gelatin(Gel) in the presence of Nanohydroxyapatite (nHA).</p><p><strong>Materials and methods: </strong>In this study, a series of nHA-nanocomposite scaffolds were fabricated using 100:0:0, 60:40:0, and 60:20:20 weight ratios of PGS to PCL: Gel copolymers through salt leaching method. The morphology and porosity of prepared samples was characterized by SEM and EDX mapping analysis. Also, the dynamic contact angle and PBS adsorption tests are used to identify the effect of copolymerization and nanoparticles on scaffolds' hydrophilicity. The hydrolytic degradation properties were also analyzed. Furthermore, cell viability and proliferation as well as cell adhesion are evaluated to find out the biocompatibility. To determine the potential ability of nHA-nanocomposite scaffolds in chondrogenic differentiation, RT-PCR assay was performed to monitor the expression of collagen II, aggrecan, and Sox9 genes as markers of cartilage differentiation.</p><p><strong>Results: </strong>The nanocomposites had an elastic modulus within a range of 0.71-1.30 MPa and 0.65-0.43 MPa, in dry and wet states, respectively. The PGS/PCL sample showed a water contact angle of 72.44 ± 2.2°, while the hydrophilicity significantly improved by adding HA nanoparticles. It was found from the hydrolytic degradation study that HA incorporation can accelerate the degradation rate compared with PGS and PGS/PCL samples. Furthermore, the in vitro biocompatibility tests showed significant cell attachment, proliferation, and viability of adipose-derived mesenchymal stem cells (ADMSCs). RT-PCR also indicated a significant increase in collagen II, aggrecan and Sox9 mRNA levels.</p><p><strong>Conclusions: </strong>Our findings demonstrated that these nanocomposite scaffolds promote the differentiation of hADSCs into chondrocytes possibly by the increase in mRNA levels of collagen II, aggrecan, and Sox9 as markers of chondrogenic differentiation. In conclusion, the addition of PCL, Gelatin, and HA into PGS is a practical approach to adjust the general features of PGS to prepare a promising scaffold for cartilage tissue engineering.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"25 1","pages":"9"},"PeriodicalIF":6.4,"publicationDate":"2023-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10039520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9478036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage-Derived MMP-9 and MMP-2 are Closely Related to the Rupture of the Fibrous Capsule of Hepatocellular Carcinoma Leading to Tumor Invasion.","authors":"Quanwei Cui,&nbsp;Xuben Wang,&nbsp;Yongwei Zhang,&nbsp;Yiqing Shen,&nbsp;Yeben Qian","doi":"10.1186/s12575-023-00196-0","DOIUrl":"https://doi.org/10.1186/s12575-023-00196-0","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor clinical prognosis. Rupture of the fibrous capsule (FC) is a very important clinical phenomenon in the invasion and metastasis of HCC. FC is mainly composed of type I collagen (COL1A1). However, it is not clear what caused the FC rupture. In this study, we aimed to determine whether the rupture of FC in HCC patients was related to macrophage-derived MMP-9 and MMP-2, and their clinical diagnostic value for FC rupture.</p><p><strong>Results: </strong>By performing immunohistochemical and immunofluorescence staining of ruptured FC and intact FC, the results showed that the ruptured area of FC aggregated a large number of macrophages with MMP-9 and MMP-2. Western blot analysis and Quantitative real-time PCR were used to assess the expression of MMP-9 and MMP-2 in the ruptured and relatively intact area of FC in ruptured FC patients, and the results revealed a significantly different expression of MMP-9 and MMP-2. ELISA experiments show that we could discriminate effectively between ruptured FC and intact FC by MMP-9 and MMP-2.</p><p><strong>Conclusions: </strong>Taken together, macrophage-derived MMP-9 and MMP-2 were closely related to the rupture of the FC of HCC and subsequently led to the migration and invasion of the tumor cells through the ruptured area of FC to the para cancer. It is suggested that when performing surgical resection, it is necessary to expand the range of tumor resection for patients with ruptured FC and hence reduce the possibility of recurrence and metastasis in HCC patients.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"25 1","pages":"8"},"PeriodicalIF":6.4,"publicationDate":"2023-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9131299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blocking Abundant RNA Transcripts by High-Affinity Oligonucleotides during Transcriptome Library Preparation.","authors":"Celine Everaert, Jasper Verwilt, Kimberly Verniers, Niels Vandamme, Alvaro Marcos Rubio, Jo Vandesompele, Pieter Mestdagh","doi":"10.1186/s12575-023-00193-3","DOIUrl":"10.1186/s12575-023-00193-3","url":null,"abstract":"<p><strong>Background: </strong>RNA sequencing has become the gold standard for transcriptome analysis but has an inherent limitation of challenging quantification of low-abundant transcripts. In contrast to microarray technology, RNA sequencing reads are proportionally divided in function of transcript abundance. Therefore, low-abundant RNAs compete against highly abundant - and sometimes non-informative - RNA species.</p><p><strong>Results: </strong>We developed an easy-to-use strategy based on high-affinity RNA-binding oligonucleotides to block reverse transcription and PCR amplification of specific RNA transcripts, thereby substantially reducing their abundance in the final sequencing library. To demonstrate the broad application potential of our method, we applied it to different transcripts and library preparation strategies, including YRNAs in small RNA sequencing of human blood plasma, mitochondrial rRNAs in both 3' end sequencing and long-read sequencing, and MALAT1 in single-cell 3' end sequencing. We demonstrate that the blocking strategy is highly efficient, reproducible, specific, and generally results in better transcriptome coverage and complexity.</p><p><strong>Conclusion: </strong>Our method does not require modifications of the library preparation procedure apart from simply adding blocking oligonucleotides to the RT reaction and can thus be easily integrated into virtually any RNA sequencing library preparation protocol.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"25 1","pages":"7"},"PeriodicalIF":3.7,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9092589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YTHDF2 exerts tumor-suppressor roles in gastric cancer via up-regulating PPP2CA independently of m⁶A modification.","authors":"Ying Zhou,&nbsp;Kailing Fan,&nbsp;Ning Dou,&nbsp;Li Li,&nbsp;Jialin Wang,&nbsp;Jingde Chen,&nbsp;Yandong Li,&nbsp;Yong Gao","doi":"10.1186/s12575-023-00195-1","DOIUrl":"https://doi.org/10.1186/s12575-023-00195-1","url":null,"abstract":"<p><strong>Background: </strong>YTHDF2 is one of important readers of N6-methyladenosine (m⁶A) modification on RNA. Growing evidence implicates that YTHDF2 takes an indispensable part in the regulation of tumorigenesis and metastasis in different cancers, but its biological functions and underlying mechanisms remain elusive in gastric cancer (GC).</p><p><strong>Aim: </strong>To investigate the clinical relevance and biological function of YTHDF2 in GC.</p><p><strong>Results: </strong>Compared with matched normal stomach tissues, YTHDF2 expression was markedly decreased in gastric cancer tissues. The expression level of YTHDF2 was inversely associated with gastric cancer patients' tumor size, AJCC classification and prognosis. Functionally, YTHDF2 reduction facilitated gastric cancer cell growth and migration in vitro and in vivo, whereas YTHDF2 overexpression exhibited opposite phenotypes. Mechanistically, YTHDF2 enhanced expression of PPP2CA, the catalytic subunit of PP2A (Protein phosphatase 2A), in an m⁶A-independent manner, and silencing of PPP2CA antagonized the anti-tumor effects caused by overexpression of YTHDF2 in GC cells.</p><p><strong>Conclusion: </strong>These findings demonstrate that YTHDF2 is down-regulated in GC and its down-regulation promotes GC progression via a possible mechanism involving PPP2CA expression, suggesting that YTHDF2 may be a hopeful biomarker for diagnosis and an unrevealed treatment target for GC.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"25 1","pages":"6"},"PeriodicalIF":6.4,"publicationDate":"2023-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10847149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Exosomes on Astrocytes in the Pre-Metastatic Niche of Lung Cancer Brain Metastases.","authors":"Lingyun Ye,&nbsp;Yinfei Wu,&nbsp;Juan Zhou,&nbsp;Mengqing Xie,&nbsp;Zhemin Zhang,&nbsp;Chunxia Su","doi":"10.1186/s12575-023-00192-4","DOIUrl":"https://doi.org/10.1186/s12575-023-00192-4","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the most common cause of cancer-related death globally. There are several reasons for this high mortality rate, including metastasis to multiple organs, especially the brain. Exosomes play a pivotal role in tumor metastasis by remodeling the microenvironment of remote target organs and promoting the pre-metastatic niche's formation. Since astrocytes are indispensable for maintaining the homeostasis of brain microenvironment, it's of great interest to explore the influence of lung cancer cell-derived exosomes on astrocytes to further understand the mechanism of lung cancer brain metastasis.</p><p><strong>Results: </strong>Twenty four h after co-culture of H1299 cell-derived exosomes and SVG P12 cells, the viability of astrocytes decreased and the apoptosis increased. The levels of cytokines in the supernatant including GROα/CXCL1, IFN-γ, IL-3, IL-5, IL-15, LIF, M-CSF, NGF, PDGF, and VEGF were significantly enhanced, while IL-7 secretion was significantly reduced. Meanwhile, apoptosis-related proteins MAP2K1, TUBA1C, RELA, and CASP6 were up-regulated. And the differentially expressed proteins were involved in regulating metabolic pathways.</p><p><strong>Conclusion: </strong>Exosomes of H1299 could induce apoptosis of astrocytes as well as promote their secretion of cytokines that were conducive to the formation of the inflammatory microenvironment and immunosuppressive microenvironment, and affect their metabolic pathways, thus facilitating the formation of pre-metastatic niche in lung cancer brain metastases.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"25 1","pages":"5"},"PeriodicalIF":6.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9976367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10826181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 3D human co-culture to model neuron-astrocyte interactions in tauopathies.","authors":"Kevin L Batenburg,&nbsp;Claudia Sestito,&nbsp;Paulien Cornelissen-Steijger,&nbsp;Jan R T van Weering,&nbsp;Leo S Price,&nbsp;Vivi M Heine,&nbsp;Wiep Scheper","doi":"10.1186/s12575-023-00194-2","DOIUrl":"https://doi.org/10.1186/s12575-023-00194-2","url":null,"abstract":"<p><strong>Background: </strong>Intraneuronal tau aggregation is the major pathological hallmark of neurodegenerative tauopathies. It is now generally acknowledged that tau aggregation also affects astrocytes in a cell non-autonomous manner. However, mechanisms involved are unclear, partly because of the lack of models that reflect the situation in the human tauopathy brain. To accurately model neuron-astrocyte interaction in tauopathies, there is a need for a model that contains both human neurons and human astrocytes, intraneuronal tau pathology and mimics the three-dimensional architecture of the brain.</p><p><strong>Results: </strong>Here we established a novel 100-200 µm thick 3D human neuron/astrocyte co-culture model of tau pathology, comprising homogenous populations of hiPSC-derived neurons and primary human astrocytes in microwell format. Using confocal, electron and live microscopy, we validate the procedures by showing that neurons in the 3D co-culture form pre- and postsynapses and display spontaneous calcium transients within 4 weeks. Astrocytes in the 3D co-culture display bipolar and stellate morphologies with extensive processes that ensheath neuronal somas, spatially align with axons and dendrites and can be found perisynaptically. The complex morphology of astrocytes and the interaction with neurons in the 3D co-culture mirrors that in the human brain, indicating the model's potential to study physiological and pathological neuron-astrocyte interaction in vitro. Finally, we successfully implemented a methodology to introduce seed-independent intraneuronal tau aggregation in the 3D co-culture, enabling study of neuron-astrocyte interaction in early tau pathogenesis.</p><p><strong>Conclusions: </strong>Altogether, these data provide proof-of-concept for the utility of this rapid, miniaturized, and standardized 3D model for cell type-specific manipulations, such as the intraneuronal pathology that is associated with neurodegenerative disorders.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"25 1","pages":"4"},"PeriodicalIF":6.4,"publicationDate":"2023-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9948470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9320089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}