Human Cell最新文献

{"title":"Pathophysiology, molecular mechanisms, and genetics of atrial fibrillation.","authors":"Pan Han, Xinxin Zhao, Xuexun Li, Jing Geng, Shouxiang Ni, Qiao Li","doi":"10.1007/s13577-024-01145-z","DOIUrl":"https://doi.org/10.1007/s13577-024-01145-z","url":null,"abstract":"<p><p>The development of atrial fibrillation (AF) is a highly complex, multifactorial process involving pathophysiologic mechanisms, molecular pathway mechanisms and numerous genetic abnormalities. The pathophysiologic mechanisms including altered ion channels, abnormalities of the autonomic nervous system, inflammation, and abnormalities in Ca2 + handling. Molecular pathway mechanisms including, but not limited to, renin-angiotensin-aldosterone (RAAS), transforming growth factor-β (TGF-β), oxidative stress (OS). Although in clinical practice, the distinction between types of AF such as paroxysmal and persistent determines the choice of treatment options. However, it is the pathophysiologic alterations present in AF that truly determine the success of AF treatment and prognosis, but even more so the molecular mechanisms and genetic alterations that lie behind them. One tiny clue reveals the general trend, and small beginnings show how things will develop. This article will organize the development of these mechanisms and their interactions in recent years.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment and drug resistance characterization of paired organoids using human primary colorectal cancer and matched tumor deposit specimens.","authors":"Jiao Deng, Jerry H Qin, Xiaolan Li, Deding Tao, Yongdong Feng","doi":"10.1007/s13577-024-01139-x","DOIUrl":"10.1007/s13577-024-01139-x","url":null,"abstract":"<p><p>Tumor deposits (TDs) represent a specific form tumor metastasis observed in colorectal cancer (CRC). The lack of successfully established cell lines for TDs, as well as the molecular mechanisms by which TDs occur remain largely unknown. Here, we established paired CRC organoids, including a human primary cancer organoid and its TD organoid, from a 46-year-old male patient with CRC. Further analysis revealed that, compared with primary tumor-derived cells, TD-derived cells exhibited enhanced proliferative, invasive and metastatic capabilities, and increased expression of stemness-related proteins. Furthermore, the present findings also demonstrated that TD-derived cells were more resistant to oxaliplatin or 5-FU. Transcriptomic profiling and qPCR revealed that TD-derived cells exhibited more alterations in fatty acid metabolism signaling and enhanced lipid synthesis ability compared to primary tumor-derived cells. Inhibition of lipid synthesis markedly decreased resistance to oxaliplatin in TD-derived cells. Taken together, the paired organoids established using CRC primary tumor and its TD specimens will provide valuable tools to study tumorigenicity, metastasis and chemoresistance in CRC. Notably, these models will provide novel insights to study tumor heterogeneity and lipid metabolism in CRC.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570121","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":"Establishment and characterization of NCC-SS6-C1: a novel patient-derived cell line of synovial sarcoma.","authors":"Julia Osaki, Rei Noguchi, Takuya Ono, Yuki Adachi, Shuhei Iwata, Yu Toda, Takaya Funada, Shintaro Iwata, Naoki Kojima, Akihiko Yoshida, Akira Kawai, Tadashi Kondo","doi":"10.1007/s13577-024-01122-6","DOIUrl":"10.1007/s13577-024-01122-6","url":null,"abstract":"<p><p>Synovial sarcoma (SS) is identified as a sarcoma with monomorphic blue spindle cells that display variable epithelial differentiation and is characterized by the SS18::SSX fusion gene. SS accounts for approximately 5-10% of all soft tissue sarcomas, making it a relatively common type within this group of tumors. Since SS is generally sensitive to chemotherapy, the standard treatment for SS includes extensive surgical resection, complemented by neoadjuvant chemotherapy with several approved anticancer drugs. However, in advanced and metastatic cases, the efficacy of these drugs is limited, resulting in poor prognoses. This underscores the need for innovative therapeutic strategies. Patient-derived cancer cell lines are essential tools for basic and preclinical research, yet only four SS cell lines are publicly available. To facilitate the studies of SS, we have developed a novel SS cell line, named NCC-SS6-C1, derived from surgically excised tumor tissue of an SS patient. NCC-SS6-C1 cells preserve the SS18::SSX1 fusion gene, consistent with the genetic characteristics of the original tumor. The cells exhibit continuous proliferation, invasiveness, and the ability to form spheroids. Additionally, we confirmed that this cell line was useful for evaluating the efficacy of anticancer drugs. Our results suggest that NCC-SS6-C1 is a useful tool for basic and pre-clinical studies of SS.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABAA receptor modulation by the endocannabinoid system: insights into the regulatory mechanisms involving glutamine synthetase and MAPK mediators.","authors":"Sina Pakkhesal","doi":"10.1007/s13577-024-01126-2","DOIUrl":"10.1007/s13577-024-01126-2","url":null,"abstract":"","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish larvae as a model for studying the impact of oral bacterial vesicles on tumor cell growth and metastasis.","authors":"Marjut Metsäniitty, Saika Hasnat, Carina Öhman, Tuula Salo, Kari K Eklund, Jan Oscarsson, Abdelhakim Salem","doi":"10.1007/s13577-024-01114-6","DOIUrl":"10.1007/s13577-024-01114-6","url":null,"abstract":"<p><p>Oral bacteria naturally secrete extracellular vesicles (EVs), which have attracted attention for their promising biomedical applications including cancer therapeutics. However, our understanding of EV impact on tumor progression is hampered by limited in vivo models. In this study, we propose a facile in vivo platform for assessing the effect of EVs isolated from different bacterial strains on oral cancer growth and dissemination using the larval zebrafish model. EVs were isolated from: wild-type Aggregatibacter actinomycetemcomitans and its mutant strains lacking the cytolethal distending toxin (CDT) or lipopolysaccharide (LPS) O-antigen; and wild-type Porphyromonas gingivalis. Cancer cells pretreated with EVs were xenotransplanted into zebrafish larvae, wherein tumor growth and metastasis were screened. We further assessed the preferential sites for the metastatic foci development. Interestingly, EVs from the CDT-lacking A. actinomycetemcomitans resulted in an increased tumor growth, whereas EVs lacking the lipopolysaccharide O-antigen reduced the metastasis rate. P. gingivalis-derived EVs showed no significant effects. Cancer cells pretreated with EVs from the mutant A. actinomycetemcomitans strains tended to metastasize less often to the head and tail compared to the controls. In sum, the proposed approach provided cost- and labor-effective yet efficient model for studying bacterial EVs in oral carcinogenesis, which can be easily extended for other cancer types. Furthermore, our results support the notion that these nanosized particles may represent promising targets in cancer therapeutics.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976965","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":"Cyclic tensile stress promotes osteogenic differentiation via upregulation of Piezo1 in human dental follicle stem cells.","authors":"Binqing Xie, Xianyi He, Ye Guo, Jie Shen, Binbin Yang, Rui Cai, Junliang Chen, Yun He","doi":"10.1007/s13577-024-01123-5","DOIUrl":"10.1007/s13577-024-01123-5","url":null,"abstract":"<p><p>As periodontal progenitor cells, human dental follicle stem cells (hDFCs) play an important role in regenerative medicine research. Mechanical stimuli exert different regulatory effects on various functions of stem cells. Mechanosensitive ion channels can perceive and transmit mechanical signals. Piezo1 is a novel mechanosensitive cation channel dominated by Ca²⁺ permeation. The yes-associated protein 1 (YAP1) and mitogen-activated protein kinase (MAPK) pathways can respond to mechanical stimuli and play important roles in cell growth, differentiation, apoptosis, and cell cycle regulation. In this study, we demonstrated that Piezo1 was able to transduce cyclic tension stress (CTS) and promote the osteogenic differentiation of hDFCs by applying CTS of 2000 μstrain to hDFCs. Further investigation of this mechanism revealed that CTS activated Piezo1 in hDFCs and resulted in increased levels of intracellular Ca²⁺, YAP1 nuclear translocation, and phosphorylated protein expression levels of extracellular signalling-associated kinase 1/2 (ERK 1/2) and Jun amino-terminal kinase 1/2/3 (JNK 1/3) of the MAPK pathway family. However, when Piezo1 was knocked down in the hDFCs, all these increases disappeared. We conclude that CTS activates Piezo1 expression and promotes its osteogenesis via Ca²⁺/YAP1/MAPK in hDFCs. Appropriate mechanical stimulation promotes the osteogenic differentiation of hDFCs via Piezo1. Targeting Piezo1 may be an effective strategy to regulate the osteogenic differentiation of hDFCs, contributing to MSC-based therapies in the field of bone tissue engineering.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequencing-based study of neural induction of human dental pulp stem cells.","authors":"Shohei Takaoka, Fumihiko Uchida, Hiroshi Ishikawa, Junko Toyomura, Akihiro Ohyama, Hideaki Matsumura, Koji Hirata, Satoshi Fukuzawa, Naomi Ishibashi Kanno, Aiki Marushima, Kenji Yamagata, Toru Yanagawa, Yuji Matsumaru, Eiichi Ishikawa, Hiroki Bukawa","doi":"10.1007/s13577-024-01121-7","DOIUrl":"10.1007/s13577-024-01121-7","url":null,"abstract":"<p><p>Techniques for triggering neural differentiation of embryonic and induced pluripotent stem cells into neural stem cells and neurons have been established. However, neural induction of mesenchymal stem cells, including dental pulp stem cells (DPSCs), has been assessed primarily based on neural-related gene regulation, and detailed studies into the characteristics and differentiation status of cells are lacking. Therefore, this study was aimed at evaluating the cellular components and differentiation pathways of neural lineage cells obtained via neural induction of human DPSCs. Human DPSCs were induced to neural cells in monolayer culture and examined for gene expression and mechanisms underlying differentiation using microarray-based ingenuity pathway analysis. In addition, the neural lineage cells were subjected to single-cell RNA sequencing (scRNA-seq) to classify cell populations based on gene expression profiles and to elucidate their differentiation pathways. Ingenuity pathway analysis revealed that genes exhibiting marked overexpression, post-neuronal induction, such as FABP7 and ZIC1, were associated with neurogenesis. Furthermore, in canonical pathway analysis, axon guidance signals demonstrated maximum activation. The scRNA-seq and cell type annotations revealed the presence of neural progenitor cells, astrocytes, neurons, and a small number of non-neural lineage cells. Moreover, trajectory and pseudotime analyses demonstrated that the neural progenitor cells initially engendered neurons, which subsequently differentiated into astrocytes. This result indicates that the aforementioned neural induction strategy generated neural stem/progenitor cells from DPSCs, which might differentiate and proliferate to constitute neural lineage cells. Therefore, neural induction of DPSCs may present an alternative approach to pluripotent stem cell-based therapeutic interventions for nervous system disorders.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apelin-13 alleviates intrauterine adhesion by inhibiting epithelial-mesenchymal transition of endometrial epithelial cells and promoting angiogenesis.","authors":"Qun Zhao, Yuyan Li, Xingping Zhao, Jiahui Zhou, Yifan Zheng, Zhiyue Li","doi":"10.1007/s13577-024-01117-3","DOIUrl":"10.1007/s13577-024-01117-3","url":null,"abstract":"<p><p>Intrauterine adhesion (IUA) is a common complication of surgical manipulation of the uterine cavity such as abortion. The pathology of IUA is characterized by fibrosis, but the pathogenesis is not fully understood. The function of Apelin-13 in IUA and related mechanisms were investigated in this study. The IUA rat model was established. The pathological changes and fibrosis degree of rat uterine tissues were detected by HE and Masson staining after intraperitoneal injection of Apelin-13. Epithelial-mesenchymal transition (EMT) of endometrial epithelial cells and endothelial-mesenchymal transition (EnMT) of vein endothelial cells were induced by TGF-β1. Tube-forming assay using HUVEC was implemented to detect the effect of Apelin-13 upon angiogenesis. IHC staining, immunofluorescence staining, and Western blot were conducted to detect the expression levels of EMT markers, angiogenesis, and key proteins of the TGF-β1/Smad signaling. Apelin-13 significantly alleviated IUA and fibrosis, and increased endometrial thickness and gland number in IUA rats. In addition, Apelin-13 significantly reversed EMT and EnMT induced by IUA modeling and TGF-β1, promoted the tube-forming ability of HUVEC, and up-regulated the expression of angiogenesis-related proteins. Mechanistically, Apelin-13 significantly suppressed smad2/3 phosphorylation and inhibited the TGF-β1/Smad signaling via its receptor APJ. Apelin-13 might alleviate IUA via repressing the TGF-β1/Smad pathway and is expected to be a potent therapeutic option for the clinical treatment of IUA.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment and characterization of two novel patient-derived cell lines from myxofibrosarcoma: NCC-MFS7-C1 and NCC-MFS8-C1.","authors":"Yuki Adachi, Rei Noguchi, Julia Osaki, Takuya Ono, Shuhei Iwata, Taro Akiyama, Ryuto Tsuchiya, Yu Toda, Sekita Tetsuya, Shintaro Iwata, Eisuke Kobayashi, Naoki Kojima, Akihiko Yoshida, Hideki Yokoo, Akira Kawai, Tadashi Kondo","doi":"10.1007/s13577-024-01124-4","DOIUrl":"10.1007/s13577-024-01124-4","url":null,"abstract":"<p><p>Myxofibrosarcoma (MFS), an aggressive soft tissue sarcoma, presents a significant challenge because of its high recurrence rate, distal metastasis, and complex genetic background. Although surgical resection is the standard treatment for MFS, the outcomes are unsatisfactory and effective non-surgical treatment strategies, including drug therapy, are urgently warranted. MFS is a rare tumor that requires comprehensive preclinical research to develop promising drug therapies; however, only two MFS cell lines are publicly available worldwide. The present study reports two novel patient-derived MFS cell lines, NCC-MFS7-C1 and NCC-MFS8-C1. These cell lines have been extensively characterized for their genetic profile, proliferation, spheroid-forming capacity, and invasive behavior, confirming that they retain MFS hallmarks. Furthermore, we conducted comprehensive drug screening against these cell lines and six others previously established in our laboratory to identify potential therapeutic candidates for MFS. Among the screened agents, actinomycin D, bortezomib, and romidepsin demonstrated considerable antiproliferative effects that were superior to those of doxorubicin, a standard drug, highlighting their potential as novel drugs. In conclusion, NCC-MFS7-C1 and NCC-MFS8-C1 are valuable research resources that contribute to the understanding of the pathogenesis and development of novel therapies for MFS.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of the AP-1/TFPI2 axis contributes to alleviating cerebral ischemia/reperfusion injury by improving blood-brain barrier integrity.","authors":"Yue Cao, Ruixian Xing, Qiushi Li, Yang Bai, Xuewen Liu, Buxian Tian, Xin Li","doi":"10.1007/s13577-024-01125-3","DOIUrl":"10.1007/s13577-024-01125-3","url":null,"abstract":"<p><p>Reperfusion after cerebral ischemia leads to secondary damage to the nervous system, called cerebral ischemia/reperfusion injury (CIRI). The blood-brain barrier (BBB) consists of endothelial cells and tight junction (TJ) proteins, and its disruption aggravates CIRI. Two GSE datasets identified Tissue Factor Pathway Inhibitor 2 (TFPI2) as a differentially upregulated gene (Log2FC > 1, p < 0.01) in the cerebral cortex of ischemic rats, and TFPI2 affects angiogenesis of endothelial cells. Moreover, genes (c-Jun, c-Fos, FosL1) encoding subunits of Activator Protein-1 (AP-1), a transcription factor involved in IRI, were highly expressed in ischemic samples. Thus, the effects of the AP-1/TFPI2 axis on CIRI were explored. We determined increased TFPI2 expression in the cerebral cortex of rats receiving middle cerebral artery occlusion (MCAO) for 90 min and reperfusion (R) for 48 h. Then AAV2-shTFPI2 particles (5 × 10¹⁰ vg) were injected into the right lateral ventricle of rats 3 weeks before MCAO/R. TFPI2 knockdown decreased infarct size and neuronal injury in ischemic rats. It improved BBB integrity, demonstrated by reduced FITC-dextran leakage in brain tissues of MCAO/R-operated rats. Furthermore, it increased the expression of TJ proteins (Occludin, Claudin-5, TJP-1) in the cerebral cortex of rats with CIRI. Consistently, we found that TFPI2 knockdown mitigated cell damage in mouse endothelial bEND.3 cells with oxygen and glucose deprivation (ODG) for 6 h and reoxygenation (R) for 18 h (OGD/R) treatment. High co-expression of c-Jun and c-Fos significantly elevated TFPI2 promoter activity. c-Jun knockdown inhibited TFPI2 expression in OGD/R-treated bEND.3 cell. Collectively, our findings demonstrate that inhibition of the AP-1/TFPI2 axis alleviates CIRI.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}