{"title":"Comprehensive analysis of the value of angiogenesis and stemness-related genes in the prognosis and immunotherapy of ovarian cancer","authors":"Linsen Zhou, Yu Min, Qiqi Cao, Xun Tan, Yongfen Cui, Jiawei Wang","doi":"10.1002/biof.2155","DOIUrl":"10.1002/biof.2155","url":null,"abstract":"<p>Tumor angiogenesis and the presence of cancer stem cells (CSCs) are critical characteristics of tumors. Previous research has demonstrated that cancer stem cells promote tumor angiogenesis, while increased vascularity, in turn, fosters the growth of cancer stem cells. This creates a detrimental cycle that contributes to tumor progression. However, studies investigating the angiogenesis and stemness characteristics in ovarian cancer (OV) are limited. In this study, we employed cluster analysis and LASSO methods to assess the significance of angiogenesis- and stemness-related genes in the efficacy of OV immunotherapy. Through multivariate Cox regression analysis and Friends analysis, we identified TNFSF11 as the most significant prognostic gene associated with angiogenesis and stemness. Additionally, molecular docking results confirmed that TNFSF11 exhibits a high affinity for sorafenib and sunitinib. In summary, for the first time, we conducted a comprehensive analysis of the roles of angiogenesis and stemness-related genes in the prognosis and immunotherapy of OV patients, revealing TNFSF11 as a novel therapeutic target.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862955","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}
BioFactorsPub Date : 2024-12-09DOI: 10.1002/biof.2148
Cristina Mesas, Javier Moreno, Kevin Doello, Mercedes Peña, Juan M López-Romero, Jose Prados, Consolación Melguizo
{"title":"Cannabidiol effects in stem cells: A systematic review.","authors":"Cristina Mesas, Javier Moreno, Kevin Doello, Mercedes Peña, Juan M López-Romero, Jose Prados, Consolación Melguizo","doi":"10.1002/biof.2148","DOIUrl":"https://doi.org/10.1002/biof.2148","url":null,"abstract":"<p><p>Stem cells play a critical role in human tissue regeneration and repair. In addition, cancer stem cells (CSCs), subpopulations of cancer cells sharing similar characteristics as normal stem cells, are responsible for tumor metastasis and resistance to chemo- and radiotherapy and to tumor relapse. Interestingly, all stem cells have cannabinoid receptors, such as cannabidiol (CBD), that perform biological functions. The aim of this systematic review was to analyze the effect of CBD on both somatic stem cells (SSCs) and CSCs. Of the 276 articles analyzed, 38 were selected according to the inclusion and exclusion criteria. A total of 27 studied the effect of CBD on SSCs, finding that 44% focused on CBD differentiation effect and 56% on its protective activity. On the other hand, 11 articles looked at the effect of CBD on CSCs, including glioblastoma (64%), lung cancer (27%), and breast cancer (only one article). Our results showed that CBD exerted a differentiating and protective effect on SCCs. In addition, this molecule demonstrated an antiproliferative effect on some CSCs, although most of the analyses were performed in vitro. Therefore, although in vivo studies should be necessary to justify its clinical use, CBD and its receptors could be a specific target to act on both SSCs and CSCs.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799350","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}
BioFactorsPub Date : 2024-12-07DOI: 10.1002/biof.2150
Jin-Feng Wang, Jian-She Wang, Yang Liu, Bo Ji, Bei-Chen Ding, Ya-Xuan Wang, Ming-Hua Ren
{"title":"Knockdown of integrin β1 inhibits proliferation and promotes apoptosis in bladder cancer cells.","authors":"Jin-Feng Wang, Jian-She Wang, Yang Liu, Bo Ji, Bei-Chen Ding, Ya-Xuan Wang, Ming-Hua Ren","doi":"10.1002/biof.2150","DOIUrl":"https://doi.org/10.1002/biof.2150","url":null,"abstract":"<p><p>Bladder cancer (BC) is the most common urinary tract malignancy. Identifying biomarkers that predict prognosis and immune function in patients with BC can enhance our understanding of its pathogenesis and provide valuable guidance for diagnosis and treatment. Our findings indicate that increased ITGB1 expression is associated with higher clinical grade and stage, establishing ITGB1 as an independent prognostic risk factor for BC. Enrichment analysis revealed that the function of ITGB1 in BC was linked to the extracellular matrix. The experimental results showed that ITGB1 knockdown in the BC cell lines 5637 and RT112 reduced their proliferation, migration, and invasion. Furthermore, ITGB1 suppression promotes apoptosis in BC cells by inhibiting the PI3K-AKT pathway. A prognostic risk model incorporating CES1, NTNG1, SETBP1, and AIFM3 was developed based on ITGB1, this model can accurately predict patient prognosis based on immunological status. In conclusion, this study shows that knockdown of ITGB1 can restrain the migratory and invasive capabilities of BC cells and accelerate apoptosis, and this role might be associated with PI3K-AKT, highlighting its potential as a diagnostic marker and therapeutic target for BC.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791159","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":"Deciphering potential molecular mechanisms in clear cell renal cell carcinoma based on the ubiquitin-conjugating enzyme E2 related genes: Identifying UBE2C correlates to infiltration of regulatory T cells.","authors":"Xiaoqiang Feng, Zhenwei Wang, Meini Cen, Zongtai Zheng, Bangqi Wang, Zongxiang Zhao, Zhihui Zhong, Yesong Zou, Qian Lv, Shiyu Li, Li Huang, Hai Huang, Xiaofu Qiu","doi":"10.1002/biof.2143","DOIUrl":"https://doi.org/10.1002/biof.2143","url":null,"abstract":"<p><p>Renal clear cell carcinoma (ccRCC) is a highly aggressive and common form of kidney cancer, with limited treatment options for advanced stages. Recent studies have highlighted the importance of the ubiquitin-proteasome system in tumor progression, particularly the role of ubiquitin-conjugating enzyme E2 (UBE2) family members. However, the prognostic significance of UBE2-related genes (UBE2RGs) in ccRCC remains unclear. In this study, bulk RNA-sequencing and single-cell RNA-sequencing data from ccRCC patients were retrieved from the Cancer Genome Atlas and Gene Expression Omnibus databases. Differential expression analysis was performed to identify UBE2RGs associated with ccRCC. A combination of 10 machine learning methods was applied to develop an optimal prognostic model, and its predictive performance was evaluated using area under the curve (AUC) values for 1-, 3-, and 5-year overall survival (OS) in both training and validation cohorts. Functional enrichment analyses of gene ontology and Kyoto Encyclopedia of Genes and Genomes were conducted to explore the biological pathways involved. Correlation analysis was conducted to investigate the association between the risk score and tumor mutational burden (TMB) and immune cell infiltration. Immunotherapy and chemotherapy sensitivity were assessed by immunophenoscore and tumor immune, dysfunction, and exclusion scores to identify potential predictive significance. In vitro, knockdown of the key gene UBE2C in 786-O cells by specific small interfering RNA to validate its impact on apoptosis, migration, cell cycle, migration, invasion of tumor cells, and induction of regulatory T cells (Tregs). Analysis of sc-RNA revealed that UBE2 activity was significantly upregulated in malignant cells, suggesting its role in tumor progression. A three-gene prognostic model comprising UBE2C, UBE2D3, and UBE2T was constructed by Lasoo Cox regression and demonstrated robust predictive accuracy, with AUC values of 0.745, 0.766, and 0.771 for 1-, 3-, and 5-year survival, respectively. The model was validated as an independent prognostic factor in ccRCC. Patients in the high-risk group had a worse prognosis, higher TMB scores, and low responsiveness to immunotherapy. Additionally, immune infiltration and chemotherapy sensitivity analyses revealed that UBE2RGs are associated with various immune cells and drugs, suggesting that UBE2RGs could be a potential therapeutic target for ccRCC. In vitro experiments confirmed that the reduction of UBE2C led to an increase in apoptosis rate, as well as a decrease in tumor cell invasion and metastasis abilities. Additionally, si-UBE2C cells reduced the release of the cytokine Transforming Growth Factor-beta 1 (TGF-β1), leading to a decreased ratio of Tregs in the co-culture system. This study presents a novel three-gene prognostic model based on UBE2RGs that demonstrates significant predictive value for OS, immunotherapy, and chemotherapy in ccRCC patients. The findings undersc","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754497","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}
BioFactorsPub Date : 2024-11-28DOI: 10.1002/biof.2137
Hui-Yen Chuang, Hui-Wen Chan, Kuang-Chung Shih
{"title":"Suppression of colorectal cancer growth: Interplay between curcumin and metformin through DMT1 downregulation and ROS-mediated pathways.","authors":"Hui-Yen Chuang, Hui-Wen Chan, Kuang-Chung Shih","doi":"10.1002/biof.2137","DOIUrl":"https://doi.org/10.1002/biof.2137","url":null,"abstract":"<p><p>The rising incidence of colorectal cancer (CRC) poses significant healthcare challenges. This study explored the therapeutic potential of combined curcumin (CUR) and metformin (MET) treatment in CRC models. Our findings indicate that the combination treatment (COMB) effectively downregulates the expression of divalent metal transporter-1 (DMT-1), leading to a reduction in cell proliferation aligned with suppression of the pAKT/mTOR/Cyclin D1 signaling pathway. The COMB increased reactive oxygen species (ROS) production, triggering activation of the NRF2/KEAP1 pathway. This pathway elicits an antioxidant response to manage oxidative stress in CRC cell lines. Interestingly, the response of NRF2 varied between CT26 and HCT116 cells. Moreover, our study highlights the induction of apoptosis and autophagy, as evidenced by upregulations in Bax/Bcl-2 ratios and autophagy-related protein expressions. Notably, the COMB promoted lipid peroxidation and downregulated xCT levels, suggesting the induction of ferroptosis. Ferroptosis has been shown to activate autophagy, which helps eliminate cells potentially damaged by the increased oxidative stress. Furthermore, the COMB effectively diminished the migratory ability of CRC cells. In vivo experiments using CRC-bearing mouse models, the results confirmed the anti-tumor efficacy of the COMB, leading to substantial inhibition of tumor growth without inducing general toxicity. In conclusion, our study suggests that combining CUR with MET holds promise as a potential option for CRC treatment, with critical mechanisms likely involving ROS elevation, autophagy, and ferroptosis.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738152","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}
BioFactorsPub Date : 2024-11-27DOI: 10.1002/biof.2146
Sachin Kumar, Abhishek Ranga
{"title":"Role of miRNAs in breast cancer development and progression: Current research.","authors":"Sachin Kumar, Abhishek Ranga","doi":"10.1002/biof.2146","DOIUrl":"https://doi.org/10.1002/biof.2146","url":null,"abstract":"<p><p>Breast cancer, a complex and heterogeneous ailment impacting numerous women worldwide, persists as a prominent cause of cancer-related fatalities. MicroRNAs (miRNAs), small non-coding RNAs, have garnered significant attention for their involvement in breast cancer's progression. These molecules post-transcriptionally regulate gene expression, influencing crucial cellular processes including proliferation, differentiation, and apoptosis. This review provides an overview of the current research on the role of miRNAs in breast cancer. It discusses the role of miRNAs in breast cancer, including the different subtypes of breast cancer, their molecular characteristics, and the mechanisms by which miRNAs regulate gene expression in breast cancer cells. Additionally, the review highlights recent studies identifying specific miRNAs that are dysregulated in breast cancer and their potential use as diagnostic and prognostic biomarkers. Furthermore, the review explores the therapeutic potential of miRNAs in breast cancer treatment. Preclinical studies have shown the effectiveness of miRNA-based therapies, such as antagomir and miRNA mimic therapies, in inhibiting tumor growth and metastasis. Emerging areas, including the application of artificial intelligence (AI) to advance miRNA research and the \"One Health\" approach that integrates human and animal cancer insights, are also discussed. However, challenges remain before these therapies can be fully translated into clinical practice. In conclusion, this review emphasizes the significance of miRNAs in breast cancer research and their potential as innovative diagnostic and therapeutic tools. A deeper understanding of miRNA dysregulation in breast cancer is essential for their successful application in clinical settings. With continued research, miRNA-based approaches hold promise for improving patient outcomes in this devastating disease.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725519","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}
BioFactorsPub Date : 2024-11-26DOI: 10.1002/biof.2144
Nicholas Vannuchi, Giovana Jamar, Veridiana Vera de Rosso, Luciana Pellegrini Pisani
{"title":"Dose-dependent effects of anthocyanin-rich extracts on obesity-induced inflammation and gut microbiota modulation.","authors":"Nicholas Vannuchi, Giovana Jamar, Veridiana Vera de Rosso, Luciana Pellegrini Pisani","doi":"10.1002/biof.2144","DOIUrl":"https://doi.org/10.1002/biof.2144","url":null,"abstract":"<p><p>Obesity and its associated inflammatory state pose a significant health burden. Anthocyanins, bioactive compounds found in fruits and vegetables, have garnered interest in their potential to attenuate these conditions. Understanding the dose-dependent response of anthocyanins is essential for optimizing their therapeutic potential in preventing and managing obesity. This comprehensive review explores the current knowledge on the dose-dependent effects of anthocyanins on obesity in both human and animal models, analyzing the structure and mechanism of absorption of these compounds. The article also highlights the diverse mechanisms underlying anthocyanin action, the symbiosis between anthocyanins and gut microbiota impacting metabolite production, influencing diverse health outcomes, modulating cytokines, and activating anti-inflammatory pathways. Additionally, their impact on energy metabolism and lipid regulation is discussed, highlighting potential contributions to weight management through AMPK and PPARγ pathways. Despite promising results, dose-dependent effects are fundamental considerations, with some studies indicating less favorable outcomes at higher doses. Future research should focus on optimizing dosages, accounting for individual responses, and translating findings into effective clinical applications for obesity management.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725516","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}
BioFactorsPub Date : 2024-11-21DOI: 10.1002/biof.2145
Jihyun Kim, Jieun Lee, Eunho Kang, Kyoungmin Lee, Kyungeun Lee, Yeongmi Cheon, Seongsoo Lee, Bokyung Kim, Young Ho Ko, Jin Hae Kim, Su Il In, Chang Hoon Nam
{"title":"Insights into an indolicidin-derived low-toxic anti-microbial peptide's efficacy against bacterial cells while preserving eukaryotic cell viability.","authors":"Jihyun Kim, Jieun Lee, Eunho Kang, Kyoungmin Lee, Kyungeun Lee, Yeongmi Cheon, Seongsoo Lee, Bokyung Kim, Young Ho Ko, Jin Hae Kim, Su Il In, Chang Hoon Nam","doi":"10.1002/biof.2145","DOIUrl":"https://doi.org/10.1002/biof.2145","url":null,"abstract":"<p><p>Antimicrobial peptides (AMPs) are a current solution to combat antibiotic resistance, but they have limitations, including their expensive production process and the induction of cytotoxic effects. We have developed novel AMP candidate (peptide 3.1) based on indolicidin, among the shortest naturally occurring AMP. The antimicrobial activity of this peptide is demonstrated by the minimum inhibitory concentration, while the hemolysis tests and MTT assay indicate its low cytotoxicity. In optical diffraction tomography, red blood cells treated with peptide 3.1 showed no discernible effects, in contrast to indolicidin. However, peptide 3.1 did induce cell lysis in E. coli, leading to a reduced potential for the development of antibiotic resistance. To investigate the mechanism underlying membrane selectivity, the structure of peptide 3.1 was analyzed using nuclear magnetic resonance spectroscopy and molecular dynamics simulations. Peptide 3.1 is structured with an increased distinction between hydrophobic and charged residues and remained in close proximity to the eukaryotic membrane. On the other hand, peptide 3.1 exhibited a disordered conformation when approaching the prokaryotic membrane, similar to indolicidin, leading to its penetration into the membrane. Consequently, it appears that the amphipathicity and structural rigidity of peptide 3.1 contribute to its membrane selectivity. In conclusion, this study may lead to the development of Peptide 3.1, a promising commercial candidate based on its low cost to produce and low cytotoxicity. We have also shed light on the mechanism of action of AMP, which exhibits selective toxicity to bacteria while not damaging eukaryotic cells.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680709","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}
BioFactorsPub Date : 2024-11-07DOI: 10.1002/biof.2138
Yan Li, Zhaolin Zeng
{"title":"Investigating the dysregulation of genes associated with glucose and lipid metabolism in gastric cancer and their influence on immunity and prognosis.","authors":"Yan Li, Zhaolin Zeng","doi":"10.1002/biof.2138","DOIUrl":"https://doi.org/10.1002/biof.2138","url":null,"abstract":"<p><p>Gastric cancer (GC) is one of the most prevalent malignant tumors globally, characterized by a high mortality rate. The disruption of glucose and lipid metabolism plays a critical role in the occurrence and progression of GC. By integrating single-cell and bulk RNA sequencing data, we identified 135 marker genes associated with glucose and lipid metabolism in GC. Building on this, we conducted prognosis and immune-related analyses, followed by cluster analysis that depicted various molecular subtypes, elucidating their distinct molecular mechanisms and treatment strategies. This includes examining how genes related to glucose and lipid metabolism influence GC prognosis through immune pathways. Additionally, we established a clinical prognostic model characterized by THRAP3, KLF5, and ABCA1. Notably, the core target gene ABCA1 may serve as a prognostic and immunotherapy biomarker for GC.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602838","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}