Cytojournal最新文献

{"title":"Tumor necrosis factor receptor-associated factor 5 enhances perianal fistulizing Crohn's disease through epithelial-mesenchymal transition.","authors":"Xiaomei Sun, Hairui Gao, Lu Lu, Qianqian Wang, Youran Li, Yunfei Gu","doi":"10.25259/Cytojournal_148_2024","DOIUrl":"10.25259/Cytojournal_148_2024","url":null,"abstract":"<p><strong>Objective: </strong>Crohn's disease (CD) is a chronic inflammatory condition of the bowel that remarkably impairs a patient's quality of life and often has a poor prognosis. Perianal fistulizing CD (PFCD) is one of the most common parenteral symptoms of CD and a huge challenge for the management of this illness. This study aimed to elucidate the molecular mechanisms underlying PFCD and identify potential biomarkers to advance our understanding and management of this condition.</p><p><strong>Material and methods: </strong>Transcriptome sequencing was performed using the control and PFCD groups to investigate the mechanisms of PFCD development. The expression of tumor necrosis factor receptor-associated factor 5 (TRAF5), nuclear factor-kappa B (NF-κB), and interleukin 13 (IL-13) messenger ribonucleic acid (mRNAs) was detected by quantitative polymerase chain reaction (qPCR). Pathological morphology was observed using hematoxylin and eosin staining. The expression of TRAF5, Epithelial Cadherin (E-cadherin), Snail family transcriptional repressor 1 (SNAIL1), and vimentin protein was detected by immunohistochemistry. Following the knockdown of TRAF5 in human tumor-29 (HT-29) cells, the effects on cell proliferation and migration were assessed using the cell counting kit-8 and Transwell assays. The expression levels of crucial markers were analyzed by qPCR, Western blot, and immunohistochemistry.</p><p><strong>Results: </strong>Transcriptomic sequencing revealed a significant upregulation of TRAF5 in the PFCD group, accompanied by elevated mRNA levels of NF-κB and IL-13 compared with those in the control group. In addition, the PFCD group exhibited increased expression of TRAF5, SNAIL, and vimentin and marked reduction in E-cadherin levels, indicating that PFCD may facilitate epithelial-mesenchymal transition (EMT). Knocking down TRAF5 in HT-29 cells reduced cell proliferation and migration; inhibited NF-κB and IL-13 mRNAs, SNAIL1, and vimentin levels; and promoted E-cadherin levels.</p><p><strong>Conclusions: </strong>The development of PFCD was associated with EMT, and TRAF5 was a key gene of PFCD. Knocking down TRAF5 alleviated the EMT promotion of PFCD, indicating that TRAF5 drove the development of PFCD through EMT.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"82"},"PeriodicalIF":2.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FTO-mediated regulation of Kupffer cell polarization and interleukin-6 secretion promotes biliary epithelial cell proliferation in intrahepatic bile duct stones.","authors":"Lixiang Li, Hui Peng, Ziyi Li, Fuhai Zhou, Qingsheng Yu","doi":"10.25259/Cytojournal_193_2024","DOIUrl":"10.25259/Cytojournal_193_2024","url":null,"abstract":"<p><strong>Objective: </strong>Intrahepatic cholangiolithiasis (Intrahepatic bile duct stones, IBDSs) is a common hepatobiliary disease characterized by bile duct obstruction and inflammation, often leading to severe complications such as cholangitis, cirrhosis, and cholangiocarcinoma. This study investigates the role of fat mass and obesity-associated (FTO) protein, an RNA demethylase, in regulating Kupffer cell (KC) polarization, interleukin (IL)-6 secretion, and subsequent human intrahepatic biliary epithelial cell (HiBEC) proliferation in IBDS.</p><p><strong>Material and methods: </strong>Liver tissues from patients with IBDS were analyzed for FTO expression, KC M2 polarization, and IL-6 levels. <i>In vitro</i> experiments with FTO silencing in KCs were conducted to examine the effects on M2 polarization, IL-6 production, and HiBEC proliferation. Mechanistic analysis focused on the c-Jun N-terminal kinase (JNK)/p38 and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways.</p><p><strong>Results: </strong>The patients with IBDS showed significantly higher KC M2 polarization, elevated FTO expression, and increased IL-6 levels relative to the controls. Without FTO silencing, IL-6 secretion and HiBEC proliferation remained at high baseline levels. However, FTO silencing reduced M2 polarization, IL-6 secretion, and HiBEC proliferation through the JNK/p38 pathway. Activating the PI3K/AKT pathway partially reversed these inhibitory effects.</p><p><strong>Conclusion: </strong>FTO plays a critical role in IBDS by promoting the M2 polarization of KCs, which leads to increased IL-6 secretion and induced pathological HiBEC proliferation. Targeting FTO may represent a novel therapeutic strategy for managing IBDS and preventing disease progression.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"83"},"PeriodicalIF":2.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of minichromosome maintenance proteins in the exfoliated cells supplement sputum cytology in the diagnosis of lung cancer.","authors":"Neeraja Panakkal, Asha Lekshmi, K M Jagathnath Krishna, Veena Vemadevan Saraswathy, Kunjuraman Sujathan","doi":"10.25259/Cytojournal_115_2024","DOIUrl":"10.25259/Cytojournal_115_2024","url":null,"abstract":"<p><strong>Objective: </strong>Sputum cytology is recognized as a straightforward and noninvasive way to diagnose lung cancer, although its clinical utility has not yet been investigated. The objective of the study was to detect and classify cancerous cells in sputum by examining their expression of minichromosome maintenance proteins (MCM2 and MCM7). In addition, the study attempted to evaluate these proteins' potential as biomarkers of lung cancer lesions and their relationships with clinicopathological characteristics.</p><p><strong>Material and methods: </strong>MCM2 and MCM7 expression in sputum samples was evaluated using immunocytochemistry in sputum cell blocks (<i>n</i> = 97), and their correlation with clinicopathological features was examined. Diagnostic performance was evaluated as a function of sensitivity and specificity.</p><p><strong>Results: </strong>Immunoexpression of MCM2 and MCM7 was confined to the nuclei of malignant cells alone, suggesting its potential as a differential diagnostic marker. They showed significant correlations with tumor cytology (<i>P</i> < 0.001), while MCM7 alone exhibited a significant correlation with tumor stage (<i>P</i> = 0.014). The overexpression of these markers was notably pronounced in lung adenocarcinoma compared to other subtypes. In terms of characterizing malignant cells, MCM7 protein demonstrated the highest sensitivity at 92% with an area under the curve (AUC) of 0.961, whereas MCM2 had a sensitivity of 80% and AUC of 0.901.</p><p><strong>Conclusion: </strong>This study presents the inaugural use of MCM7 immunocytochemistry on exfoliated cells in sputum samples, proposing that analyzing immunocytochemical markers in sputum could serve as a cost-effective approach for diagnosing lung cancer. Integrating these assessed markers into routine cytopathology laboratories could augment traditional morphological evaluations, thereby improving the sensitivity of sputum cytology.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"81"},"PeriodicalIF":2.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of fine-needle aspiration cytology combined with flow cytometry in extramedullary hematolymphoid lesions - A cross-sectional study.","authors":"Roobashri Murugan, Prabhu Manivannan, Debasis Gochhait, Rakhee Kar, Neelaiah Siddaraju, Sushya Sahadevan","doi":"10.25259/Cytojournal_109_2023","DOIUrl":"10.25259/Cytojournal_109_2023","url":null,"abstract":"<p><strong>Objective: </strong>Flow cytometry (FC) can be an adjunct to fine-needle aspiration cytology (FNAC) in the diagnosis and subclassification of hematolymphoid lesions. This study evaluates the utility of FC in diagnosing extramedullary hematolymphoid lesions in fine-needle aspirate samples.</p><p><strong>Material and methods: </strong>This cross-sectional study enrolled patients who presented to the FNAC clinic and suspected to have hematolymphoid lesions (nodal and extra nodal lesions) from August 2020 to June 2022. Sixty-seven cases of hematolymphoid malignancies and 67 cases without hematolymphoid malignancies were included. The combined FNAC/FC diagnosis was compared with the gold standard: Biopsy, cell block, or peripheral blood/bone marrow aspirate FC.</p><p><strong>Results: </strong>Of 67 lymphoma cases, 63 were of the primary type and 4 were diagnosed with suspected recurrence/residual disease. Moreover, 57 cases were nodal, and 10 were extranodal. Four of the patients had discordant findings between FNAC and FC. The gold standard was available only in 56 cases, of which 5 had discordant findings between combined FNAC/FC and the gold standard. We subclassified 34 cases based on combined FNAC/FC. The five cases included anaplastic large cell lymphoma (1/5), classic Hodgkin lymphoma (3/5), and one case of atypical lymphoid hyperplasia. Non-contributory FC was attributed to the presence of large cells/necrosis/nodular lymphocyte predominant Hodgkin lymphoma/metastasis/Castleman disease/technical problem.</p><p><strong>Conclusion: </strong>Combining FC with FNAC enhances diagnostic accuracy and helps subclassify lymphoma. Future works should explore whether it can replace excision biopsy, especially in recurrent cases.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"79"},"PeriodicalIF":2.5,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geniposide alleviates post-myocardial infarction-induced pyroptosis by modulating the thioredoxin-interacting protein/NLRP3 signaling pathway.","authors":"Youqin Jiang, Yao Su, Chen Li, Weiwei Jiang, Yang Wei, Guanglei Chang, Ya Liu, Honghong He","doi":"10.25259/Cytojournal_139_2024","DOIUrl":"10.25259/Cytojournal_139_2024","url":null,"abstract":"<p><strong>Objective: </strong>Geniposide (GP) provides myocardial cells with protection against pyroptosis-induced damage. However, the mechanisms governing GP's effect on the thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathway remain unclear. This study aimed to explore how GP alleviates post-myocardial infarction (MI)-induced pyroptosis through regulation of the TXNIP/NLRP3 pathway.</p><p><strong>Material and methods: </strong><i>In vivo</i> studies: MI models were established, mouse body weight, heart rate, and blood glucose levels were monitored, and methods, such as cardiac ultrasound, hematoxylin-eosin staining, triphenyltetrazolium chloride staining, terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling staining, quantitative polymerase chain reaction (qPCR), and Western blot (WB), were used to explore the effect of GP on myocardial cell pyroptosis. We explored the role of NLRP3 in GP's antimyocardial cell pyroptosis through qPCR, WB, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and other methods. <i>In vitro</i> studies: A chronic hypoxia (CH) cell model was established, and detection methods, such as cell counting kit-8 assay, transmission electron microscopy, ELISA, and immunological assays, were used to explore the effects of GP on CH myocardial cell pyroptosis and GP's inhibition of the TXNIP/NLRP3 signaling pathway to resist CH myocardial cell pyroptosis.</p><p><strong>Results: </strong><i>In vivo</i> studies revealed that after the treatment with GP, the infarct area of mice's hearts significantly decreased, cardiac structure and function notably improved, fibroblast proliferation in cardiac tissues decreased significantly, and the pyroptosis level of myocardial cells decreased. GP treatment significantly downregulated the expression levels of type I collagen (Col I), Col III, TXNIP NLRP3, caspase-1, and gasdermin D N-terminal (GSDMD-N). The inhibition of NLRP3 also reduced the expressions of NLRP3, TXNIP, caspase-1, and GSDMD-N in the cardiac tissue, which is concomitant with a decline in reactive oxygen species (ROS) production. In addition, <i>in vitro</i> studies unveiled that GP effectively alleviated pyroptosis in CH myocardial cells, reducing pyroptosis rates, interleukin (IL)-1β, IL-18, lactate dehydrogenase, and creatine kinase-muscle/brain levels. This protective effect was achieved by inhibiting the TXNIP/NLRP3 signaling pathway.</p><p><strong>Conclusion: </strong>GP greatly diminishes the extent of infarcted myocardial tissue and mitigates pyroptosis, which improves cardiac structure and function through modulation of the TXNIP/NLRP3 pathway. Furthermore, the inhibition of NLRP3 lowers the expressions of factors associated with pyroptosis in the cardiac tissue and reduces ROS production.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"80"},"PeriodicalIF":2.5,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PR/SET domain 1 targeting glutathione peroxidase 4 regulates chronic hepatitis B liver fibrosis through ferroptosis.","authors":"Wenjun Wu, Wenhai Ke, Weiping Shi, Ting Lin, Shenglong Lin, Minghua Lin, Huaxi Ma, Haibing Gao","doi":"10.25259/Cytojournal_123_2024","DOIUrl":"10.25259/Cytojournal_123_2024","url":null,"abstract":"<p><strong>Objective: </strong>Addressing the inhibition and reversal of chronic hepatitis B fibrosis is an urgent global challenge, which highlights the critical need to understand its underlying mechanisms. Inhibiting the activation of hepatic stellate cells (HSCs) is an important strategy for fibrosis reversal. In particular, the induction of ferroptosis in HSCs presents a promising avenue for curtailing liver fibrosis. Therefore, this study explores the influence of PR/SET domain 1 (PRDM1), which is a transcriptional regulator, on the progression of liver fibrosis by regulating HSC ferroptosis through glutathione peroxidase 4 (GPX4).</p><p><strong>Material and methods: </strong>We used protein-protein interaction databases to analyze the interacting proteins of GPX4. The messenger ribonucleic acid levels of PRDM1 and GPX4 in liver tissues with varying degrees of fibrosis were examined using quantitative polymerase chain reaction. Cell lines with interference and overexpression of PRDM1/GPX4 were established. Reactive oxygen species (ROS) activity, malondialdehyde (MDA) concentration, cell proliferation capacity, as well as the expression levels of GPX4, a-smooth muscle actin, vimentin, and desmin, were assessed to investigate the relationship between PRDM1 and hepatic fibrosis, as well as its impact on ferroptosis in HSCs.</p><p><strong>Results: </strong>A significant negative correlation was observed between the transcriptional regulator PRDM1 and GPX4. As the degree of fibrosis worsened, PRDM1 decreased significantly, whereas GPX4 increased significantly. The overexpression of PRDM1 markedly increased ROS and MDA concentrations, but it decreased cell proliferation capacity, GPX4 expression levels, and activation marker protein levels. Interference with PRDM1 yielded opposite results. The expression level of GPX4 did not affect PRMD1 expression levels. Compared with cells with single interference of PRDM1, simultaneous interference with PRDM1 and GPX4 significantly inhibited the activity and proliferation capacity of HSCs. It also elevated ROS activity and MDA concentrations. When ferroptosis inhibitors were added, ROS activity and MDA concentrations decreased, and the proliferation capacity and activity of HSCs increased. Opposite results were obtained when PRDM1 and GPX4 were overexpressed simultaneously.</p><p><strong>Conclusion: </strong>PRDM1 is implicated in the occurrence and progression of hepatic fibrosis. It may act as an upstream regulatory factor of GPX4, which exerts control over ferroptosis by suppressing the transcription of GPX4. Ultimately, the activation of HSCs is promoted.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"78"},"PeriodicalIF":2.5,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the role of exosomal microRNA-5703 in modulating tumor-associated endothelial cells in lung cancer.","authors":"Bing Wen, Rancen Tao, Yuyu Liu, Zhenfa Zhang","doi":"10.25259/Cytojournal_99_2024","DOIUrl":"10.25259/Cytojournal_99_2024","url":null,"abstract":"<p><strong>Objective: </strong>Lung cancer, as a prevalent malignancy, continues to be a considerable clinical challenge. This study aimed to elucidate the role of microRNA-5703 (miR-5703) in lung cancer progression and to assess the effect of exosomal miR-5703 on tumor-associated endothelial cells (TAECs).</p><p><strong>Material and methods: </strong>We analyzed Gene Expression Omnibus datasets and performed quantitative real-time polymerase chain reaction to determine miR-5703 expression levels in lung cancer tissues. Exosomes derived from lung cancer cells were identified, and the effects of miR-5703 inhibitors or mimics on malignant biological behavior were evaluated in the lung cancer cells. Moreover, to understand these effects on TAECs, we assessed angiogenesis, endothelial-mesenchymal transition (EndMT), and barrier function after treatment with miR- 5703 inhibitors or the exosome-assimilated inhibitor cytochalasin D. Tumor-bearing mouse models were used in validating the tumor-promoting effects of exosomes derived from lung cancer cells, and the markers of angiogenesis, EndMT, and barrier function were examined.</p><p><strong>Results: </strong>Our results showed that miR-5703 was up-regulated in the lung cancer cells and patient-derived exosomes. miR-5703 facilitated cell growth, migration, invasion, in LC cells, and impaired the barrier function, which promoted angiogenesis and EndMT of TAECs by carrying in exosomes through targeting inhibitor of growth family member 4 (ING4) was identified as target of miR-5703 (<i>P</i> < 0.05). <i>In vivo</i>, the tumor-promoting effects of lung cancer cell-derived exosomes were rescued by miR-5703 inhibitors, leading to the up-regulation of ING4 expression and reduction in vascular distribution in the tumor tissues (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>miR-5703 operates as an oncogenic factor in lung cancer. After being taken up by TAECs, exosomal miR-5703 promotes angiogenesis, EndMT, and barrier damage by targeting ING4. Hence, miR-5703 is a potential target in the lung cancer microenvironment.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"77"},"PeriodicalIF":2.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knocking-down annexin A3 suppresses inflammation, oxidative stress, apoptosis, and endoplasmic reticulum stress to attenuate sepsis-induced acute kidney injury in HK2 cells.","authors":"Jie Su, Lantao Wang, Xiaoying Guan, Nan Li, Lixiao Sun","doi":"10.25259/Cytojournal_64_2024","DOIUrl":"10.25259/Cytojournal_64_2024","url":null,"abstract":"<p><strong>Objective: </strong>Sepsis-induced acute kidney injury (AKI) is considered as a life-threatening complication of sepsis. The purpose of this study is to clarify the involvement of annexin A3 (ANXA3) in sepsis-related AKI.</p><p><strong>Material and methods: </strong>Lipopolysaccharide (LPS) was used to establish a cell model based on HK2 cells. ANXA3 expression was quantified through quantitative real-time polymerase chain reaction. Cell proliferative capacities were assessed through 5-ethynyl-2'-deoxyuridine proliferation, cell counting kit-8, and colony formation experiments. Flow cytometry was utilized to analyze apoptotic cells. Inflammatory and oxidative stress indicators were measured by employing corresponding commercial assay kits. Endoplasmic reticulum (ER) stress markers were quantified through western blot analysis.</p><p><strong>Results: </strong>ANXA3 levels were significantly elevated in HK2 cells treated with LPS and in serum samples obtained from patients with AKI and sepsis (<i>P</i> < 0.001). LPS treatment exacerbated cellular damage, leading to increased ER and oxidative stresses, apoptosis, and inflammation, whereas knocking down ANXA3 significantly reversed these changes (<i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>Interference with ANXA3 protected HK2 cells from LPS-induced cell injury through inhibiting inflammation, oxidative stress, apoptosis, and ER stress.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"75"},"PeriodicalIF":2.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of sodium ferulate on neutrophil extracellular traps-platelet activation-mediated endothelial dysfunction in immune small vasculitis.","authors":"Xiaoli Zhou, Zhuojun Wang, Weixiang Liao, Qianlu Yin, Chuan Xiong, Yuhang Zheng, Wei Peng","doi":"10.25259/Cytojournal_153_2024","DOIUrl":"10.25259/Cytojournal_153_2024","url":null,"abstract":"<p><strong>Objective: </strong>Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease that is challenging to treat. This study aimed to identify the effect of sodium ferulate on endothelial dysfunction mediated by neutrophil extracellular trap (NET)-platelet activation in AAV to provide potential strategies for AAV treatment.</p><p><strong>Material and methods: </strong>An animal model of myeloperoxidase (MPO)-AAV passive immune vasculitis was established using anti-MPO immunoglobulin G and Rag2 knockout mice. The efficacy and mechanism of action of sodium ferulate in AAV were explored in cultured and isolated endothelial progenitor cells (EPCs), and messenger ribonucleic acid gene expression, relative protein expression, and protein fluorescence intensity were determined through quantitative polymerase chain reaction, Western blotting, and immunofluorescence, respectively. Serum antibody concentrations were determined by enzyme-linked immunosorbent assay, and flow cytometry was used in determining the expression levels of platelet-selectin (CD62p) and procaspase-activating compound-1 (PAC-1) on the surfaces of the platelets. The EPCs' ultramicroscopic structure was observed through transmission electron microscopy.</p><p><strong>Results: </strong>The expression levels of ANCA, histone H3 citrullinated, and MPO protein fluorescence intensity in MPO-AAV mice were inhibited by sodium ferulate, and the expression levels of CD62p and PAC-1 on the cell surface were reduced. The relative expression levels of β-trace protein (β-TG), soluble thrombomodulin, inducible nitric oxide synthase (iNOS), and tumor necrosis factor α decreased. We found that sodium ferulate inhibited NETs' free DNA and mitigated damage in EPCs. In addition, relative expression levels of von Willebrand Factor, β-TG, and iNOS and serum concentrations of PAC-1, β-TG, and iNOS were inhibited.</p><p><strong>Conclusion: </strong>Sodium ferulate can treat AAV by inhibiting NET release and platelet activation and reducing endothelial cell damage.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"76"},"PeriodicalIF":2.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes derived from cancer-associated fibrolasts mediated ciplatin resistance.","authors":"Yiyu Meng, Hui Shao, Lijun Wu","doi":"10.25259/Cytojournal_149_2024","DOIUrl":"10.25259/Cytojournal_149_2024","url":null,"abstract":"<p><strong>Objective: </strong>Nasopharyngeal carcinoma (NPC), a highly invasive form of head and neck cancer, carries a significant risk of distant metastasis. NPC is particularly prevalent in Asia and has a high incidence in southern China. Cisplatin-diamminedichloroplatinum (DDP), a chemotherapy agent, is commonly employed in NPC treatment. Despite DDP's efficacy, many patients eventually develop resistance to it over the course of their therapy, which significantly hinders treatment outcomes. Cancer-associated fibroblasts (CAFs) are key components of the tumor micro-environment and contribute to tumor progression and chemotherapy resistance. Exosomes secreted by CAFs serve as crucial mediators of intercellular communication and participate in modulating diverse biological processes. This study aimed to explore how exosomes derived from CAFs contribute to DDP resistance in NPC.</p><p><strong>Material and methods: </strong>An <i>in vitro</i> coculture system was used to simulate the interaction between CAFs and NPC cells, and exosomes secreted by CAFs were isolated and characterized. The expression of autophagy hallmark proteins was detected by Western blot and quantitative real-time polymerase chain reaction. Autophagy intensity was quantified using monodansylcadaverine staining, and cell proliferation was assessed by colony formation assays and methylthiazolyldiphenyl-tetrazolium assays. NPC cells were treated with autophagy inducers (rapamycin), and the expression of Ras homologue enriched in brain (Rheb), mammalian target of rapamycin complex (mTORC1), and UNC51-like kinase was detected. Immunofluorescence was used to determine the cellular localization and expression intensity of mTORC1, and the effect on DDP sensitivity was evaluated through cell proliferation rates. In addition, the exosome-mediated resistance mechanism was further validated using an <i>in vivo</i> xenograft tumor model.</p><p><strong>Results: </strong>Coculture of CAFs with NPC cells significantly promoted the proliferation of NPC cells (<i>P</i> < 0.01), significantly elevated the IC50 value of DDP (<i>P</i> < 0.01), and elevated the resistance of NPC cells to DDP. CAF-derived exosomes elevated autophagy hallmark proteins light chain 3B-II, Beclin, and increased the autophagy intensity (<i>P</i> < 0.01). CAF-derived exosomes promoted autophagy by inhibiting mTORC1 (<i>P</i> < 0.01). In the <i>in vitro</i> model, exosomes promoted the growth of tumor tissues (<i>P</i> < 0.01), and the inhibition of exosome secretion reversed the promotion effect of autophagy (<i>P</i> < 0.01) and elevated the sensitivity of NPC cells to DDP.</p><p><strong>Conclusion: </strong>CAF-derived exosomes promote protective autophagy in NPC cells through the Rheb/mTOR axis, and result in DDP resistance in NPC.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"74"},"PeriodicalIF":2.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}