Frontiers in Molecular Biosciences最新文献

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Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-05 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1455415
Isaac Micallef, Kimberly Fenech, Byron Baron
{"title":"Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance.","authors":"Isaac Micallef, Kimberly Fenech, Byron Baron","doi":"10.3389/fmolb.2024.1455415","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1455415","url":null,"abstract":"<p><p>Cancer treatments have continued to improve tremendously over the past decade, but therapy resistance is still a common, major factor encountered by patients diagnosed with cancer. Chemoresistance arises due to various circumstances and among these causes, increasing evidence has shown that enzymes referred to as protein methyltransferases (PMTs) play a significant role in the development of chemoresistance in various cancers. These enzymes are responsible for the methylation of different amino acids, particularly lysine and arginine, via protein lysine methyltransferases (PKMTs) and protein arginine methyltransferases (PRMTs), respectively. Various PMTs have been identified to be dysregulated in the development of cancer and chemoresistance. Nonetheless, the functional role of these PMTs in the development of chemoresistance is poorly characterised. This advocates the need for innovative approaches and technologies suitable for better characterisation of these PMTs and their potential clinical inhibitors. In the case of a handful of PMTs, inhibitory small molecules which can function as anticancer drugs have been developed and have also entered clinical trials. Considering all this, PMTs have become a promising and valuable target in cancer chemoresistance related research. This review will give a small introduction on the different PKMTs and PRMTs families which are dysregulated in different cancers and the known proteins targeted by the respective enzymes. The focus will then shift towards PMTs known to be involved in chemoresistance development and the inhibitors developed against these, together with their mode of action. Lastly, the current obstacles and future perspectives of PMT inhibitors in cancer chemoresistance will be discussed.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1455415"},"PeriodicalIF":3.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863905","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}
引用次数: 0
NUF2 is associated with cancer stem cell characteristics and a potential drug target for prostate cancer.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-05 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1481375
Dongxu Zhang, Pu Liang, Qi Wang, Bowen Xia, Liqian Yu, Xiaopeng Hu
{"title":"NUF2 is associated with cancer stem cell characteristics and a potential drug target for prostate cancer.","authors":"Dongxu Zhang, Pu Liang, Qi Wang, Bowen Xia, Liqian Yu, Xiaopeng Hu","doi":"10.3389/fmolb.2024.1481375","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1481375","url":null,"abstract":"<p><strong>Background: </strong>Cancer stem cells are characterized by self-renewal, clonal tumor initiation capacity, and treatment resistance, which play essential roles in the tumor progression of prostate cancer (PCa). In this study, we aim to explore the features of cancer stemness and characterize the expression of stem cell-related genes for PCa.</p><p><strong>Methods: </strong>We downloaded RNA-seq data and related clinical information from The Cancer Genome Atlas (TCGA) database. The mRNA stemness index (mRNAsi) was analyzed for various clinical features, overall survival (OS), and disease-free survival (DFS), and a weighted gene co-expression network analysis (WGCNA) was performed to identify crucial gene modules and key genes, which may play a role in CSCs. The key gene functions were verified using multiple databases, including the TCGA and Gene Expression Omnibus database (GEO). Next, we explored the potential function of the modules and genes obtained using WGCNA using an enrichment analysis. Finally, we performed <i>in vitro</i> experiments for further verification.</p><p><strong>Results: </strong>We found that mRNAsi were higher in PCa tissues than in normal tissues, and the mRNAsi were closely related to the clinical characteristics of PCa. A total of 16 key genes associated with the mRNAsi scores were identified by WGCNA analysis, including NCAPG, NEK2, DLGAP5, CENPA, CENPF, TPX2, GTSE1, KIF4A, NEIL3, CDC25C, UBE2C, CDCA5, MELK, SKA3, NUF2, and BIRC5. These genes were explicitly highly expressed in PCa across TCGA cancers and were validated in 3 independent GEO PCa datasets. The functional annotations of the key genes were linked with the cell proliferation processes. NUF2 may be a potential biomarker for PCa. <i>In vitro</i> experiments showed that knockdown NUF2 reduced the proliferation and migration of PCa cells.</p><p><strong>Conclusion: </strong>The 16 key genes identified in this study significantly correlate with PCa stem cell characteristics and showed prognosis-oriented effects in PCa patients. Further, the NUF2 gene may be used as a drug target for treating PCa.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1481375"},"PeriodicalIF":3.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863904","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}
引用次数: 0
Deciphering the evolving niche interactome of human hematopoietic stem cells from ontogeny to aging.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-04 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1479605
Cong Feng, Haoyan Fan, Ruxiu Tie, Saige Xin, Ming Chen
{"title":"Deciphering the evolving niche interactome of human hematopoietic stem cells from ontogeny to aging.","authors":"Cong Feng, Haoyan Fan, Ruxiu Tie, Saige Xin, Ming Chen","doi":"10.3389/fmolb.2024.1479605","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1479605","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSC) reside within specialized microenvironments that undergo dynamic changes throughout development and aging to support HSC function. However, the evolving cell-cell communication networks within these niches remain largely unexplored. This study integrates single-cell RNA sequencing datasets to systematically characterize the HSC niche interactome from ontogeny to aging. We reconstructed single-cell atlases of HSC niches at different developmental stages, revealing stage-specific cellular compositions and interactions targeting HSC. During HSC maturation, our analysis identified distinct patterns of ligand-receptor interactions and signaling pathways that govern HSC emergence, expansion, and maintenance. HSC aging was accompanied by a decrease in supportive niche interactions, followed by an adaptive increase in interaction strength in old adult bone marrow. This complex aging process involved the emergence of interactions associated with inflammation, altered stem cell function, and a decline in the efficacy of key signaling pathways. Our findings provide a comprehensive understanding of the dynamic remodeling of the HSC niche interactome throughout life, paving the way for targeted interventions to maintain HSC function and promote healthy aging. This study offers valuable insights into the intricate cell-cell communication networks that govern HSC behavior and fate, with implications for hematological disorders and regenerative medicine.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1479605"},"PeriodicalIF":3.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853644","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}
引用次数: 0
Editorial: LncRNA and their role on epigenome in cancer.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-04 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1533057
Qi Su, Francesca Maria Orlandella, Giovanni Smaldone, Yitao Qi
{"title":"Editorial: LncRNA and their role on epigenome in cancer.","authors":"Qi Su, Francesca Maria Orlandella, Giovanni Smaldone, Yitao Qi","doi":"10.3389/fmolb.2024.1533057","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1533057","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1533057"},"PeriodicalIF":3.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853649","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}
引用次数: 0
CircMIB1 inhibits glioma development and progression through a competing endogenous RNA interaction network.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-04 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1513919
Simin Chen, Longping Li, Wei Xu, Nanjiao Xie, Huiting Xu, Yongjun Zhou, Ying Zou, Kai Yi, Yi Liu
{"title":"CircMIB1 inhibits glioma development and progression through a competing endogenous RNA interaction network.","authors":"Simin Chen, Longping Li, Wei Xu, Nanjiao Xie, Huiting Xu, Yongjun Zhou, Ying Zou, Kai Yi, Yi Liu","doi":"10.3389/fmolb.2024.1513919","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1513919","url":null,"abstract":"<p><strong>Introduction: </strong>The critical role of circular RNAs as non-coding RNAs in glioma has been extensively investigated. Therefore, we aimed to explore the role and potential molecular mechanisms of circRNA-mind bomb homolog 1 (circMIB1) in gliomas.</p><p><strong>Methods: </strong>RNA sequencing was used to analyze the expression profiles of circRNAs in glioma tissues and normal brain tissues. Quantitative real-time polymerase chain reaction was implemented to examine the levels of circMIB1 in glioma cells and tissues. The circMIB1 was identified as a cyclic RNA molecule by DNA nucleic acid electrophoresis and ribonuclease R assay. The relationship between circMIB1 expression and the prognosis of glioma patients and its potential as a biomarker were analysed using Kaplan-Meier, Receiver operating characteristic curves, and Principal component analysis. Bioinformatics analysis predicted the miRNAs that bind to circMIB1 and their downstream targets, and analysed the functions of these genes.</p><p><strong>Results: </strong>Firstly, a novel circRNA molecule termed circMIB1 was identified and validated by RNA sequencing. The expression of circMIB1 was significantly downregulated in glioma cells and tissues, and was closely associated with the tumor grade and survival prognosis of patients with glioma. Hence, it may be useful as a biomarker for glioma. Secondly, it was predicted that circMIB1 binds to hsa-miR-1290 based on bioinformatics analysis, which was significantly upregulated in glioma cells and tissues, and correlated with the tumor grade and overall survival of patients. Thirdly, through a series of bioinformatics analyses identified six genes downstream of hsa-miR-1290 that were significantly associated with glioma expression and prognosis, these genes are associated with cell cycle, cell necrosis and cell circadian rhythms.</p><p><strong>Discussion: </strong>CircMIB1 may play a role in inhibiting glioma development through the hsa-miR-1290 competitive endogenous RNA interaction network, these findings provide new ideas and directions for the diagnosis and treatment of glioma.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1513919"},"PeriodicalIF":3.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853639","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}
引用次数: 0
Investigation of the correlation between AGRN expression and perineural invasion in colon cancer.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-03 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1510478
Lei Chen, Haijia Zhang, Kaiyue Gao, Fanqi Meng, Funing Yang, Jiannan Li, Lijie Wang, Jiandong Tai
{"title":"Investigation of the correlation between AGRN expression and perineural invasion in colon cancer.","authors":"Lei Chen, Haijia Zhang, Kaiyue Gao, Fanqi Meng, Funing Yang, Jiannan Li, Lijie Wang, Jiandong Tai","doi":"10.3389/fmolb.2024.1510478","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1510478","url":null,"abstract":"<p><strong>Background and purpose: </strong>Colon cancer is one of the most common gastrointestinal malignancies. According to the traditional view, the primary modes of transmission include direct dissemination, hematogenous metastasis, and lymph node metastasis. In recent years, the role of perineural invasion (PNI) in the spread and metastasis of tumors has received immense attention. However, there are still relatively few reports on the potential mechanisms and biomarkers of PNI occurrence and development in colon cancer.</p><p><strong>Method: </strong>We identified genes linked to the onset and progression of PNI in colon cancer using bioinformatics tools and extensive databases. Gene function enrichment analysis was used to explore the potential roles of these genes in tumor proliferation, invasion, and PNI. A collection of postoperative pathological specimens from colon cancer patients who underwent surgery, related clinicopathological data, and immunohistochemistry were used to validate AGRN expression in PNI tissues.</p><p><strong>Results: </strong>Bioinformatics analysis revealed that AGRN is overexpressed in colon cancer tissues and correlates with poor patient prognosis. The findings from gene association and enrichment studies indicate that AGRN and its associated genes may play a role in PNI development and progression in colon cancer by simultaneously enhancing tumor cell invasion and neural cell growth. Immunohistochemical analysis of clinical samples confirmed that AGRN expression is elevated in colon cancer tissues with PNI.</p><p><strong>Conclusion: </strong>We found that AGRN is significantly overexpressed in colon cancer tissues exhibiting PNI and is linked to poor patient survival. AGRN and its related genes may contribute to PNI by promoting tumor cell invasion and neural cell growth. Hence, AGRN may play a crucial role in the initiation and progression of PNI in colon cancer.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1510478"},"PeriodicalIF":3.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845959","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}
引用次数: 0
The conformation of the nSrc specificity-determining loop in the Src SH3 domain is modulated by a WX conserved sequence motif found in SH3 domains.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-03 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1487276
Frederick Longshore-Neate, Caroline Ceravolo, Cole Masuga, Elise F Tahti, Jadon M Blount, Sarah N Smith, Jeanine F Amacher
{"title":"The conformation of the nSrc specificity-determining loop in the Src SH3 domain is modulated by a WX conserved sequence motif found in SH3 domains.","authors":"Frederick Longshore-Neate, Caroline Ceravolo, Cole Masuga, Elise F Tahti, Jadon M Blount, Sarah N Smith, Jeanine F Amacher","doi":"10.3389/fmolb.2024.1487276","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1487276","url":null,"abstract":"<p><p>Cellular signaling networks are modulated by multiple protein-protein interaction domains that coordinate extracellular inputs and processes to regulate cellular processes. Several of these domains recognize short linear motifs, or SLiMs, which are often highly conserved and are closely regulated. One such domain, the Src homology 3 (SH3) domain, typically recognizes proline-rich SLiMs and is one of the most abundant SLiM-binding domains in the human proteome. These domains are often described as quite <i>versatile</i>, and indeed, SH3 domains can bind ligands in opposite orientations dependent on target sequence. Furthermore, recent work has identified diverse modes of binding for SH3 domains and a wide variety of sequence motifs that are recognized by various domains. Specificity is often attributed to the RT and nSrc loops near the peptide-binding cleft in this domain family, particularly for Class I binding, which is defined as RT and nSrc loop interactions with the N-terminus of the ligand. Here, we used the Src and Abl SH3 domains as a model to further investigate the role of the RT and nSrc loops in SH3 specificity. We created chimeric domains with both the RT and nSrc loop sequences swapped between these SH3 domains, and used fluorescence anisotropy assays to test how relative binding affinities were affected for Src SH3- and Abl SH3-specific ligands. We also used Alphafold-Multimer to model our SH3:peptide complexes in combination with molecular dynamics simulations. We identified a position that contributes to the nSrc loop conformation in Src SH3, the amino acid immediately following a highly conserved Trp that creates a hydrophobic pocket critical for SH3 ligand recognition. We defined this as the WX motif, where X = Trp for Src and Cys for Abl. A broad importance of this position for modulating nSrc loop conformation in SH3 domains is suggested by analyses of previously deposited SH3 structures, multiple sequence alignment of SH3 domains in the human proteome, and our biochemical and computational data of mutant Src and Abl SH3 domains. Overall, our work uses experimental approaches and structural modeling to better understand specificity determinants in SH3 domains.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1487276"},"PeriodicalIF":3.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853653","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}
引用次数: 0
Exploring TAS2R46 biomechanics through molecular dynamics and network analysis.
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-02 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1473675
Marco Cannariato, Riccardo Fanunza, Eric A Zizzi, Marcello Miceli, Giacomo Di Benedetto, Marco A Deriu, Lorenzo Pallante
{"title":"Exploring TAS2R46 biomechanics through molecular dynamics and network analysis.","authors":"Marco Cannariato, Riccardo Fanunza, Eric A Zizzi, Marcello Miceli, Giacomo Di Benedetto, Marco A Deriu, Lorenzo Pallante","doi":"10.3389/fmolb.2024.1473675","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1473675","url":null,"abstract":"<p><p>Understanding the intricate interplay between structural features and signal-processing events is crucial for unravelling the mechanisms of biomolecular systems. G protein-coupled receptors (GPCRs), a pervasive protein family in humans, serve a wide spectrum of vital functions. TAS2Rs, a subfamily of GPCRs, play a primary role in recognizing bitter molecules and triggering events leading to the perception of bitterness, a crucial defence mechanism against spoiled or poisonous food. Beyond taste, TAS2Rs function is associated with many diseases as they are expressed in several extra-oral tissues. Given that the precise functioning mechanisms of TAS2R remain poorly understood, this study employed molecular dynamics simulations combined with network-based analysis to investigate local conformational changes and global structural correlations in different states of the receptor. The focus was on the human TAS2R46 bitter taste receptor, recently resolved experimentally, both in the presence and absence of strychnine, a known bitter agonist. The results showed that the ligand-bound state of the receptor exhibited more correlated dynamics compared to the apo state, and the presence of the agonist mediated the allosteric network between two helices (TM3 and TM6) which mainly convey the signal transferring from the extracellular to the intracellular region. By elucidating the hallmarks of the conformational changes and allosteric network of TAS2R46 under varying conditions, this study has enabled the identification of the unique structural and dynamics features of this receptor, thereby establishing a foundation for a more profound characterisation of this intriguing class of receptors.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1473675"},"PeriodicalIF":3.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835087","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}
引用次数: 0
Avenanthramide-C ameliorate doxorubicin-induced hepatotoxicity via modulating Akt/GSK-3β and Wnt-4/β-Catenin pathways in male rats. 金刚烷胺-C通过调节雄性大鼠的Akt/GSK-3β和Wnt-4/β-Catenin通路改善多柔比星诱导的肝毒性
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-02 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1507786
Maha Abdullah Alwaili, Amal S Abu-Almakarem, Salwa Aljohani, Sahar Abdulrahman Alkhodair, Maha M Al-Bazi, Thamir M Eid, Jehan Alamri, Maysa A Mobasher, Norah K Algarza, Arwa Ishaq A Khayyat, Luluah Saleh Alshaygy, Karim Samy El-Said
{"title":"Avenanthramide-C ameliorate doxorubicin-induced hepatotoxicity via modulating Akt/GSK-3β and Wnt-4/β-Catenin pathways in male rats.","authors":"Maha Abdullah Alwaili, Amal S Abu-Almakarem, Salwa Aljohani, Sahar Abdulrahman Alkhodair, Maha M Al-Bazi, Thamir M Eid, Jehan Alamri, Maysa A Mobasher, Norah K Algarza, Arwa Ishaq A Khayyat, Luluah Saleh Alshaygy, Karim Samy El-Said","doi":"10.3389/fmolb.2024.1507786","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1507786","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) drugs used in cancer treatment can cause various adverse effects, including hepatotoxicity. Natural-derived constituents have shown promising effects in alleviating chemotherapy-induced toxicities. This study addressed the effect of Avenanthramides-C (AVN-C) treatment in rats with DOX-indued hepatotoxicity.</p><p><strong>Methods: </strong>AutoDock Vina was used for the molecular docking investigations. <i>In silico</i> toxicity prediction for AVN-C and DOX was performed using the Pro Tox-III server. Four groups of ten male Sprague-Dawley rats were created: Group 1 (Gp1) served as a negative control, Gp2 received an intraperitoneal (i.p.) injection of AVN-C (10 mg/kg), Gp3 received an i.p. dose of DOX (4 mg/kg) weekly for a month, and Gp4 received the same dose of DOX as G3 and AVN-C as G2. Histopathological, molecular, and biochemical analyses were conducted 1 month later.</p><p><strong>Results: </strong>The study showed that treatment with AVN-C significantly ameliorated DOX-induced hepatotoxicity in rats by restoring biochemical alterations, boosting antioxidant activity, reducing inflammation, and modulating the Akt/GSK-3β and Wnt-4/β-Catenin signaling pathways in male rats.</p><p><strong>Conclusion: </strong>This study is the first to demonstrate the therapeutic effects of AVN-C therapy on DOX-induced liver damage in male rats. Therefore, AVN-C could have a pronounced palliative effect on the hepatotoxicity caused by DOX treatment. These findings suggest that AVN-C could potentially alleviate the hepatotoxicity associated with DOX-based chemotherapy.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1507786"},"PeriodicalIF":3.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835086","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}
引用次数: 0
Editorial: Diving deeper with metabolomics into animal physiology. 社论:利用代谢组学深入研究动物生理学。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-11-29 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1503412
Dagnachew Hailemariam, Elda Dervishi
{"title":"Editorial: Diving deeper with metabolomics into animal physiology.","authors":"Dagnachew Hailemariam, Elda Dervishi","doi":"10.3389/fmolb.2024.1503412","DOIUrl":"10.3389/fmolb.2024.1503412","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1503412"},"PeriodicalIF":3.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828039","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}
引用次数: 0
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