BioFactors最新文献

{"title":"Construction of lysosome-related prognostic signature to predict the survival outcomes and selecting suitable drugs for patients with HNSCC.","authors":"Bing Cao, Shanshan Gu, Zhisen Shen, Yuna Zhang, Yiming Shen","doi":"10.1002/biof.2140","DOIUrl":"https://doi.org/10.1002/biof.2140","url":null,"abstract":"<p><p>Lysosomes are digestive organelles responsible for endocytosis and autophagy. Recently, the malignancy and invasiveness head and neck squamous cell carcinoma (HNSCC) has been increasingly studied with the role of lysosomes. A list of lysosome-related genes were obtained from MSigDB. A Spearman correlation and univariate Cox regression analyses combined with differential expression analysis were conducted to detect differentially expressed lysosome-related genes related to prognosis. The prediction of prognostic signature was evaluated by plotting survival curve, ROC, and by developing a nomogram. Immune subtypes, infiltration of immune cells, GSVA, TIDE, IC₅₀ of common chemotherapy and targeted therapy, GO, and KEGG function enrichment analyses were carried out to explore the immune microenvironment of the signature. We constructed a lysosome-related prognostic signature that could function as an independent prognostic indicator for patients with HNSCC. High-risk patients were better suited to receive Doxorubicin, Mitomycin C, Pyrimethamine, anti-PD-L1 and anti-CTLA-4 immunotherapy, whereas low-risk patients had sensitivity to Lapatinib. GO functional enrichment analysis showed that prognostic features were strongly associated with epidermis-related functions (e.g., epidermal cell differentiation, epidermal development, and keratinization). In addition, a KEGG function enrichment analysis revealed a potential relationship between the risk assessment model and cardiomyopathy. We constructed a prognostic signature based on lysosome-related genes and successfully predicted the survival outcome of HNSCC patients, which not only provides potential guidance for personalized treatment but also provides a new idea for precision treatment of HNSCC.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567700","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":"Machine learning models reveal ARHGAP11A's impact on lymph node metastasis and stemness in NSCLC.","authors":"Xiaoli Wang, Yan Zhou, Xiaomin Lu, Lili Shao","doi":"10.1002/biof.2141","DOIUrl":"https://doi.org/10.1002/biof.2141","url":null,"abstract":"<p><p>Most patients with non-small cell lung cancer (NSCLC) are diagnosed at an advanced stage of the disease, which complicates treatment due to a heightened risk of metastasis. Consequently, the timely identification of biomarkers associated with lymph node metastasis is essential for improving the clinical management of NSCLC patients. In this research, the WGCNA algorithm was utilized to pinpoint genes linked to lymph node metastasis in NSCLC. A cluster analysis was carried out to investigate how these genes correlate with the prognosis and the outcomes of immunotherapy for NSCLC patients. Following this, diagnostic and prognostic models were created and validated through various machine learning methodologies. The random forest technique highlighted the importance of ARHGAP11A, leading to an in-depth examination of its role in NSCLC. By analyzing 78 tissue chip samples from NSCLC patients, the study confirmed the association between ARHGAP11A expression, patient prognosis, and lymph node metastasis. Finally, the influence of ARHGAP11A on NSCLC cells was assessed through cell function experiments. This research utilized the WGCNA technique to identify 25 genes that are related to lymph node metastasis, clarifying their connections with tumor invasion, growth, and the activation of stemness pathways. Cluster analysis revealed significant associations between these genes and lymph node metastasis in NSCLC, especially concerning immunotherapy and targeted treatments. A diagnostic system that combines various machine learning approaches demonstrated strong efficacy in forecasting both the diagnosis and prognosis of NSCLC. Importantly, ARHGAP11A was identified as a key prognostic gene associated with lymph node metastasis in NSCLC. Molecular docking analyses suggested that ARHGAP11A has a strong affinity for targeted therapies within NSCLC. Additionally, immunohistochemical assessments confirmed that higher levels of ARHGAP11A expression correlate with unfavorable outcomes for NSCLC patients. Experiments on cells showed that reducing ARHGAP11A expression can hinder the proliferation, metastasis, and stemness traits of NSCLC cells. This investigation reveals the novel insight that ARHGAP11A may function as a potential biomarker connected to lymph node metastasis in NSCLC. Moreover, reducing the expression of ARHGAP11A has demonstrated the ability to diminish tumor stemness characteristics, presenting a promising opportunity for improving treatment strategies for this condition.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557082","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":"The carcinogenesis of esophageal squamous cell cancer is positively regulated by USP13 through WISP1 deubiquitination.","authors":"An Wang, Youbo Wang, Qinyun Ma, Xiaofeng Chen","doi":"10.1002/biof.2139","DOIUrl":"https://doi.org/10.1002/biof.2139","url":null,"abstract":"<p><p>The objective was to determine whether USP13 stabilizes WISP1 protein and contributes to tumorigenicity and metastasis in ESCC through the Wnt/CTNNB1 signaling pathway. ESCC cell lines (KYSE150 and TE10) were treated with the proteasome inhibitor MG-132, followed by siRNA screening of deubiquitinases (DUBs) to identify regulators of WISP1. Mass spectrometry, immunoprecipitation, and in vitro functional assays were conducted to explore the interaction between USP13 and WISP1 and to assess the effects of USP13 downregulation on cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and apoptosis. Additionally, in vivo experiments using mouse models were performed to evaluate the impact of USP13 knockdown on tumor growth and metastasis. USP13 was identified as a key regulator of WISP1, stabilizing its protein levels through deubiquitination. Downregulation of USP13 resulted in reduced WISP1 protein stability, decreased cell proliferation, migration, and EMT, and increased apoptosis in vitro. In vivo, USP13 knockdown significantly inhibited tumor growth and lung metastasis. WISP1 overexpression in USP13-knockdown cells partially rescued these phenotypes, confirming the functional role of the USP13/WISP1 axis. Furthermore, knockdown of USP13 or WISP1 impaired the activation of the Wnt/CTNNB1 signaling pathway and reduced immune checkpoint marker expression, indicating a mechanism by which USP13 promotes immune evasion in ESCC. USP13 stabilizes WISP1 through deubiquitination, enhancing ESCC progression by activating the Wnt/CTNNB1 pathway and promoting immune evasion, making USP13 a potential therapeutic target in ESCC.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520905","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":"Piperine: an emerging biofactor with anticancer efficacy and therapeutic potential.","authors":"Hesti Lina Wiraswati, Ilma Fauziah Ma'ruf, Javad Sharifi-Rad, Daniela Calina","doi":"10.1002/biof.2134","DOIUrl":"https://doi.org/10.1002/biof.2134","url":null,"abstract":"<p><p>Anticancer drug discovery needs serious attention to overcome the high mortality rate caused by cancer. There are still many obstacles to treating this disease, such as the high cost of chemotherapeutic drugs, the resulting side effects from the drug, and the occurrence of multidrug resistance. Herbaceous plants are a reservoir of natural compounds that can be anticancer drugs with novel mechanisms of action. Piperine, a bioactive compound derived from Piper species, is gaining attention due to its unique dual role in directly inhibiting tumor growth and enhancing the bioavailability of chemotherapeutic drugs. Unlike conventional treatments, Piperine exhibits a novel mechanism of action by modulating multiple signaling pathways, including apoptosis and autophagy, with low toxicity. Additionally, Piperine acts as a bioenhancer by improving the absorption and effectiveness of other anticancer agents, reducing the required dosage, and minimizing side effects. Therefore, this review aims to visualize a summary of Piperine sources, phytochemistry, chemical structure-anticancer activity relationship, anticancer activities of semi-synthetic derivatives, pharmacokinetic and bioavailability, in vitro and in vivo preclinical studies, mechanism of antitumor action, human clinical trials, toxicity, side effects, and safety of Piperine. References were collected from the Pubmed/MedLine database (https://pubmed.ncbi.nlm.nih.gov/) with the following keywords: \"Piperine anticancer,\" \"Piperine derivatives,\" \"Piperine antitumor mechanism\" and \"Piperine pharmacokinetic and bioavailability,\" after filter process by inclusion and exclusion criteria, 101 were selected from 444 articles. From 2013 to 2023, there were numerous studies regarding preclinical studies of Piperine of various cell lines, including breast cancer, prostate cancer, lung cancer, melanoma, cervical cancer, gastric cancer, osteosarcoma, colon cancer, hepatocellular carcinoma, ovarian cancer, leukemia, colorectal cancer, and hypopharyngeal carcinoma. In vivo, the anticancer study has also been conducted on some animal models, such as Ehrlich carcinoma-bearing mice, Ehrlich ascites carcinoma cells-bearing Balbc mice, hepatocellular carcinoma-bearing Wistar rat, A375SM cells-bearing mice, A375P cells-bearing mice, SNU-16 cells-bearing BalbC mice, and HGC-27-bearing baby mice. Treatment with this compound leads to cell proliferation inhibition and induction of apoptosis. Piperine has been used for clinical trials of diseases, but no cancer patient report exists. Various semi-synthetic derivatives of Piperine show efficacy as an anticancer drug across multiple cell lines. Piperine shows promise for use in cancer clinical trials, either as a standalone treatment or as a bioenhancer. Its bioenhancer properties may enhance the efficacy of existing chemotherapeutic agents, providing a valuable foundation for developing new anticancer therapies.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520904","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":"Construction of mitochondrial quality regulation genes-related prognostic model based on bulk-RNA-seq analysis in multiple myeloma.","authors":"Xiaohui Li, Ling Zhang, Chengcheng Liu, Yi He, Xudong Li, Yichuan Xu, Cuiyin Gu, Xiaozhen Wang, Shuoting Wang, Jingwen Zhang, Jiajun Liu","doi":"10.1002/biof.2135","DOIUrl":"https://doi.org/10.1002/biof.2135","url":null,"abstract":"<p><p>Mitochondrial quality regulation plays an important role in affecting the treatment sensitivity of multiple myeloma (MM). We aimed to develop a mitochondrial quality regulation genes (MQRGs)-related prognostic model for MM patients. The Genomic Data Commons-MM of bulk RNA-seq, mutation, and single-cell RNA-seq (scRNA-seq) dataset were downloaded, and the MQRGs gene set was collected previous study. \"maftools\" and CIBERSORT were used for mutation and immune-infiltration analysis. Subsequently, the \"ConsensusClusterPlus\" was used to perform the unsupervised clustering analysis, \"survminer\" and \"ssGSEA\" R package was used for the Kaplan-Meier survival and enrichment analysis, \"limma\" R, univariate and Least Absolute Shrinkage and Selection Operator Cox were used for RiskScore model. The \"timeROC\" R package was used for Receiver Operating Characteristic Curve analysis. Finally, the \"Seurat\" R package was used for scRNA-seq analysis. These MQRGs are mainly located on chromosome-1,2,3,7, and 22 and had significant expression differences among age, gender, and stage groups, in which PPARGC1A and PPARG are the high mutation genes. Most MQRGs expression are closely associated with the plasma cells infiltration and can divide the patients into 2 different prognostic clusters (C1, C2). Then, 8 risk models were screened from 60 DEGs for RiskScore, which is an independent prognostic factor and effectively divided the patients into high and low risk groups with significant difference of immune checkpoint expression. Nomogram containing RiskScore can accurately predict patient prognosis, and a series of specific transcription factor PRDM1 and IRF1 were identified. We described the based molecular features and developed a high effective MQRGs-related prognostic model in MM.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494157","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":"CXC chemokine receptor 4 - mediated immune modulation and tumor microenvironment heterogeneity in gastric cancer: Utilizing multi-omics approaches to identify potential therapeutic targets.","authors":"Jing Tang, Wei Wei, Yaoqing Xu, Kexin Chen, Yaping Miao, Weining Fan, Zhi Huang, Jie Liu, Ping Chen, Honghao Luo, Lexin Wang","doi":"10.1002/biof.2130","DOIUrl":"https://doi.org/10.1002/biof.2130","url":null,"abstract":"<p><p>G-protein-coupled receptors (GPRs) are critical regulators of various biological behaviors, and their role in gastric cancer (GC) progression is gaining increasing attention. Among them, the immune regulatory mechanisms mediated by chemokine receptor 4 (CXCR4) remain insufficiently understood. This study aims to explore the immune regulatory functions of CXCR4 and the heterogeneity of the tumor microenvironment (TME) by examining GPR-related gene expression in GC. Through multi-omics approaches, including spatial transcriptomics and single-cell RNA sequencing, we investigated the oncogenic mechanisms of CXCR4, particularly its role in T cell immune exhaustion. In vitro experiments, including ELISA, PCR, CCK8 assays, cell scratch assays, and colony formation assays, were used to validate the role of CXCR4 in the migration and invasion of AGS and SNU-1 cell lines. CXCR4 silencing using siRNA further demonstrated its regulatory effects on these cellular processes. Our results revealed a strong correlation between elevated CXCR4 expression and increased exhaustion of regulatory T cells (Tregs) in the TME. Furthermore, heightened CXCR4 expression was linked to increased TME heterogeneity, driven by oxidative stress and activation of the NF-κB pathway, promoting immune evasion and tumor progression. Silencing CXCR4 significantly inhibited the invasive and proliferative abilities of AGS and SNU-1 cells, while also reducing the expression of pro-inflammatory cytokines IL-1β and interleukin-6, thus alleviating chronic inflammation and improving TME conditions. In conclusion, our comprehensive investigation highlights CXCR4 as a key mediator of TME dynamics and immune modulation in GC. Targeting CXCR4 presents a promising therapeutic strategy to slow tumor progression by reducing Tregs-mediated immune exhaustion and TME heterogeneity, positioning it as a novel therapeutic target in GC treatment.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457159","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":"Delphinidin or α-amyrin attenuated liver steatosis and metabolic disarrangement in rats fed a high-fat diet.","authors":"Bassam Mohamed Ali, Eman M Elbaz, Asmaa K Al-Mokaddem, Soad Z El-Emam, Magdy M Awny","doi":"10.1002/biof.2133","DOIUrl":"https://doi.org/10.1002/biof.2133","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is a liver pathology concomitant with metabolic disarrangement. This study assessed the therapeutic impacts of delphinidin, an anthocyanin, or α-amyrin, a pentacyclic triterpenoid, on NAFLD in rats and the underlying mechanisms involved. NAFLD was established by feeding a high-fat diet (HFD) for 10 weeks, either alone or in combination with delphinidin (40 mg/kg, oral) or α-amyrin (20 mg/kg, oral). Delphinidin or α-amyrin ameliorated the metabolic and histopathological perturbations induced by HFD. These compounds markedly attenuated NAFLD-induced hepatic steatosis, as evidenced by a substantial decrease in body weight, insulin resistance, and liver and adipose tissue indices. Alongside normalization of the atherogenic index, both improved HFD-mediated abnormalities in serum lipids, liver enzymes, leptin, and ghrelin levels. Moreover, their intervention activated the NFE2 like bZIP transcription factor 2 and heme oxygenase 1 pathways and abrogated HFD-triggered activation of mitogen-activated protein kinase 1 signaling. These remedies inhibited hepatic apoptosis and modulated the gene expression of lipogenic enzymes. Furthermore, histological analysis corroborated the suppression of lipid accumulation and amelioration of hepatic architecture in the treated rats. Our findings highlight the hepatoprotective value of delphinidin or α-amyrin against NAFLD and related metabolic diseases through their insulin-sensitizing, anti-inflammatory, antioxidant, and antiapoptotic effects.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457160","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":"Machine learning-derived peripheral blood transcriptomic biomarkers for early lung cancer diagnosis: Unveiling tumor-immune interaction mechanisms.","authors":"Xiaohua Li, Xuebing Li, Jiangyue Qin, Lei Lei, Hua Guo, Xi Zheng, Xuefeng Zeng","doi":"10.1002/biof.2129","DOIUrl":"https://doi.org/10.1002/biof.2129","url":null,"abstract":"<p><p>Lung cancer continues to be the leading cause of cancer-related mortality worldwide. Early detection and a comprehensive understanding of tumor-immune interactions are crucial for improving patient outcomes. This study aimed to develop a novel biomarker panel utilizing peripheral blood transcriptomics and machine learning algorithms for early lung cancer diagnosis, while simultaneously providing insights into tumor-immune crosstalk mechanisms. Leveraging a training cohort (GSE135304), we employed multiple machine learning algorithms to formulate a Lung Cancer Diagnostic Score (LCDS) based on peripheral blood transcriptomic features. The LCDS model's performance was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) in multiple validation cohorts (GSE42834, GSE157086, and an in-house dataset). Peripheral blood samples were obtained from 20 lung cancer patients and 10 healthy control subjects, representing an in-house cohort recruited at the Sixth People's Hospital of Chengdu. We employed advanced bioinformatics techniques to explore tumor-immune interactions through comprehensive immune infiltration and pathway enrichment analyses. Initial screening identified 844 differentially expressed genes, which were subsequently refined to 87 genes using the Boruta feature selection algorithm. The random forest (RF) algorithm demonstrated the highest accuracy in constructing the LCDS model, yielding a mean AUC of 0.938. Lower LCDS values were significantly associated with elevated immune scores and increased CD4+ and CD8+ T-cell infiltration, indicative of enhanced antitumor-immune responses. Higher LCDS scores correlated with activation of hypoxia, peroxisome proliferator-activated receptor (PPAR), and Toll-like receptor (TLR) signaling pathways, as well as reduced DNA damage repair pathway scores. Our study presents a novel, machine learning-derived peripheral blood transcriptomic biomarker panel with potential applications in early lung cancer diagnosis. The LCDS model not only demonstrates high accuracy in distinguishing lung cancer patients from healthy individuals but also offers valuable insights into tumor-immune interactions and underlying cancer biology. This approach may facilitate early lung cancer detection and contribute to a deeper understanding of the molecular and cellular mechanisms underlying tumor-immune crosstalk. Furthermore, our findings on the relationship between LCDS and immune infiltration patterns may have implications for future research on therapeutic strategies targeting the immune system in lung cancer.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457162","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":"Investigate the metabolic changes in intestinal diseases by employing a ¹H-NMR-based metabolomics approach on Caco-2 cells treated with cedrol.","authors":"Mo-Rong Xu, Chia-Hsin Lin, Chung Hsuan Wang, Sheng-Yang Wang","doi":"10.1002/biof.2132","DOIUrl":"https://doi.org/10.1002/biof.2132","url":null,"abstract":"<p><p>Mitochondrial dysfunction may precipitate intestinal dysfunction, while inflammatory bowel disease manifests as a chronic inflammatory ailment affecting the gastrointestinal tract. This condition disrupts the barrier function of the intestinal epithelium and alters metabolic products. Increasing mitochondrial adenosine triphosphate (ATP) synthesis in intestinal epithelial cells presents a promising avenue for colitis treatments. Nevertheless, the impact of cedrol on ATP and the intestinal barrier remains unexplored. Hence, this study is dedicated to examining the cedrol's protective effect on an inflammatory cocktail (IC)-induced intestinal epithelial barrier dysfunction in Caco-2 cells. The finding reveals that cedrol enhances ATP content and the transepithelial electrical resistance value in the intestinal epithelial barrier. Moreover, cedrol mitigates the IC-induced decrease in the messenger ribonucleic acid (mRNA) expression of tight junction proteins (ZO-1, Occludin, and Claudin-1), thereby ameliorating intestinal epithelial barrier dysfunction. Furthermore, nuclear magnetic resonance (NMR)-based metabolomic analysis indicated that IC-exposed Caco-2 cells are restored by cedrol treatments. Notably, cedrol elevates metabolites such as amino acids, thereby enhancing the intestinal barrier. In conclusion, cedrol alleviates IC-induced intestinal epithelial barrier dysfunction by promoting ATP-dependent proliferation of Caco-2 cells and bolstering amino acid levels to sustain tight junction messenger ribonucleic acid expression.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457161","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":"O-GlcNAcylation regulates osteoblast differentiation through the morphological changes in mitochondria, cytoskeleton, and endoplasmic reticulum.","authors":"Yao Weng, Ziyi Wang, Heriati Sitosari, Mitsuaki Ono, Hirohiko Okamura, Toshitaka Oohashi","doi":"10.1002/biof.2131","DOIUrl":"https://doi.org/10.1002/biof.2131","url":null,"abstract":"<p><p>To explore the potential mechanisms which O-linked-N-acetylglucosaminylation (O-GlcNAcylation) regulates osteogenesis, a publicly RNA-seq dataset was re-analyzed with literature-mining and showed the primary targets of O-GlcNAcylation in osteoblasts are mitochondria/cytoskeleton. Although the O-GlcNAcylation-regulated mitochondria/cytoskeleton has been extensively studied, its specific role during osteogenesis remains unclear. To address this, we knocked out Ogt (Ogt-KO) in MC3T3-E1 osteoblastic cells. Then, significantly reduced osteoblast differentiation, motility, proliferation, mitochondria-endoplasmic reticulum (Mito-ER) coupling, volume of ER, nuclear tubulins, and oxygen metabolism were observed in Ogt-KO cells. Through artificial intelligence (AI)-predicted cellular structures, the time-lapse live cells imaging with reactive-oxygen-species/hypoxia staining showed that lower cell proliferation and altered oxygen metabolism in the Ogt-KO cells were correlated with the Mito-ER coupling. Bioinformatics analysis, combined with correlated mRNA and protein expression, suggested that Ezh2 and its downstream targets (Opa1, Gsk3a, Wnt3a, Hif1a, and Hspa9) may be involved in O-GlcNAcylation-regulated Mito-ER coupling, ultimately impacting osteoblast differentiation. In conclusion, our findings indicate that O-GlcNAcylation-regulated osteoblast differentiation is linked to morphological changes in mitochondria, cytoskeleton, and ER, with Ezh2 potentially playing a crucial role.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457163","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}