Biochimica et biophysica acta. General subjects最新文献

{"title":"A potent candicidal peptide designed based on an encrypted peptide from a proteinase inhibitor","authors":"Luís Henrique de Oliveira Almeida ,&nbsp;Suellen Rodrigues Ramalho ,&nbsp;Claudiane Vilharroel Almeida ,&nbsp;Camila de Oliveira Gutierrez ,&nbsp;Janaína de Cassia Orlandi Sardi ,&nbsp;Antonio de Miranda ,&nbsp;Ricardo Abreu de Oliveira ,&nbsp;Samilla Beatriz de Rezende ,&nbsp;Edson Crusca ,&nbsp;Octávio Luiz Franco ,&nbsp;Caio Fernando Ramalho de Oliveira ,&nbsp;Marlon Henrique Cardoso ,&nbsp;Maria Lígia Rodrigues Macedo","doi":"10.1016/j.bbagen.2024.130583","DOIUrl":"10.1016/j.bbagen.2024.130583","url":null,"abstract":"<div><p>Antimicrobial peptides (AMP) represent an alternative in the treatment of fungal infections associated with countless deaths. Here, we report a new AMP, named KWI-19, which was designed based on a peptide encrypted in the sequence of an <em>Inga laurina</em> Kunitz-type inhibitor (ILTI). KWI-19 inhibited the growth of <em>Candida</em> species and acted as a fungicidal agent from 2.5 to 20 μmol L⁻¹, also showing synergistic activity with amphotericin B. Kinetic assays showed that KWI-19 killed <em>Candida tropicalis</em> cells within 60 min. We also report the membrane-associated mechanisms of action of KWI-19 and its interaction with ergosterol. KWI-19 was also characterized as a potent antibiofilm peptide, with activity against <em>C. tropicalis</em>. Finally, non-toxicity was reported against <em>Galleria mellonella</em> larvae, thus strengthening the interest in all the bioactivities mentioned above. This study extends our knowledge on how AMPs can be engineered from peptides encrypted in larger proteins and their potential as candicidal agents.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740257","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":"Evaluation of molecular mechanisms of riboflavin anti-COVID-19 action reveals anti-inflammatory efficacy rather than antiviral activity","authors":"Roman A. Akasov ,&nbsp;Olga E. Chepikova ,&nbsp;Tatiana N. Pallaeva ,&nbsp;Neonila V. Gorokhovets ,&nbsp;Andrei E. Siniavin ,&nbsp;Vladimir A. Gushchin ,&nbsp;Lyudmila V. Savvateeva ,&nbsp;Ivan A. Vinokurov ,&nbsp;Dmitry A. Khochenkov ,&nbsp;Andrey A. Zamyatnin Jr ,&nbsp;Evgeny V. Khaydukov","doi":"10.1016/j.bbagen.2024.130582","DOIUrl":"10.1016/j.bbagen.2024.130582","url":null,"abstract":"<div><h3>Background</h3><p>Riboflavin (vitamin B2) is one of the most important water-soluble vitamins and a coenzyme involved in many biochemical processes. It has previously been shown that adjuvant therapy with flavin mononucleotide (a water-soluble form of riboflavin) correlates with normalization of clinically relevant immune markers in patients with COVID-19, but the mechanism of this effect remains unclear. Here, the antiviral and anti-inflammatory effects of riboflavin were investigated to elucidate the molecular mechanisms underlying the riboflavin-induced effects.</p></div><div><h3>Methods</h3><p>Riboflavin was evaluated for recombinant SARS-CoV-2 PLpro inhibition in an enzyme kinetic assay and for direct inhibition of SARS-CoV-2 replication in Vero E6 cells, as well as for anti-inflammatory activity in polysaccharide-induced inflammation models, including endothelial cells <em>in vitro</em> and acute lung inflammation <em>in vivo</em>.</p></div><div><h3>Results</h3><p>For the first time, the ability of riboflavin at high concentrations (above 50 μM) to inhibit SARS-CoV-2 PLpro protease <em>in vitro</em> was demonstrated; however, no inhibition of viral replication in Vero E6 cells <em>in vitro</em> was found. At the same time, riboflavin exerted a pronounced anti-inflammatory effect in the polysaccharide-induced inflammation model, both <em>in vitro</em>, preventing polysaccharide-induced cell death, and <em>in vivo</em>, reducing inflammatory markers (IL-1β, IL-6, and TNF-α) and normalizing lung histology.</p></div><div><h3>Conclusions</h3><p>It is concluded that riboflavin reveals anti-inflammatory rather than antiviral activity for SARS-CoV-2 infection.</p></div><div><h3>General significance</h3><p>Riboflavin could be suggested as a promising compound for the therapy of inflammatory diseases of broad origin.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139715690","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":"Methoxychalcones as potential anticancer agents for colon cancer: Is membrane perturbing potency relevant?","authors":"Anna Palko-Łabuz ,&nbsp;Olga Wesołowska ,&nbsp;Maria Błaszczyk ,&nbsp;Anna Uryga ,&nbsp;Beata Sobieszczańska ,&nbsp;Magdalena Skonieczna ,&nbsp;Edyta Kostrzewa-Susłow ,&nbsp;Tomasz Janeczko ,&nbsp;Kamila Środa-Pomianek","doi":"10.1016/j.bbagen.2024.130581","DOIUrl":"10.1016/j.bbagen.2024.130581","url":null,"abstract":"<div><p>Chalcones are naturally produced by many plants, and constitute precursors for the synthesis of flavons and flavanons. They were shown to possess antibacterial, antifungal, anti-cancer, and anti- inflammatory properties. The goal of the study was to assess the suitability of three synthetic methoxychalcones as potential anticancer agents. In a panel of colon cancer cell lines they were demonstrated to be cytotoxic, proapoptotic, causing cell cycle arrest, and increasing intracellular level of reactive oxygen species. Anticancer activity of the compounds was not diminished in the presence of stool extract containing microbial enzymes that could change the structure of chalcones. Moreover, methoxychalcones interacted strongly with model phosphatidylcholine membranes as detected by differential scanning calorimetry. Metohoxychalcones particularly affected the properties of lipid domains in giant unilamellar liposomes formed from raft-mimicking lipid composition. This may be of importance since many molecular targets for therapy of metastatic colon cancer are raft-associated receptors (<em>e.g.</em>, receptor tyrosine kinases). The importance of membrane perturbing potency of methoxychalcones for their biological activity was additionally corroborated by the results obtained by molecular modelling.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139711391","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":"Epigenetic regulation influenced by soil microbiota and nutrients: Paving road to epigenome editing in plants","authors":"Bhavya Doddavarapu ,&nbsp;Charu Lata ,&nbsp;Jasmine M. Shah","doi":"10.1016/j.bbagen.2024.130580","DOIUrl":"10.1016/j.bbagen.2024.130580","url":null,"abstract":"<div><p>Soil is a complex ecosystem that houses microbes and nutrients that are necessary for plant development. Edaphic properties of the soil and environmental conditions influence microbial growth and nutrient accessibility. Various environmental stimuli largely affect the soil microbes and ionic balance, in turn influencing plants. Soil microflora helps decompose organic matter and is involved in mineral uptake. The combination of soil microbes and mineral nutrients notably affects plant growth. Recent advancements have enabled a deeper understanding of plant genetic/molecular regulators. Deficiencies/sufficiencies of soil minerals and microbes also alter plant gene regulation. Gene regulation mediated by epigenetic mechanisms comprises conformational alterations in chromatin structure, DNA/histone modifications, or involvement of small RNAs. Epigenetic regulation is unique due to its potential to inherit without involving alteration of the DNA sequence. Thus, the compilation study of heritable epigenetic changes driven by nutrient imbalances and soil microbes would facilitate understanding this molecular phenomenon in plants. This information can aid in epigenome editing, which has recently emerged as a promising technology for plant non-transgenic/non-mutagenic modification. Potential epigenetic marks induced by biotic and abiotic stresses in plants could be explored as target sites for epigenome editing. This review discusses novel ways of epigenome editing to create epigenome edited plants with desirable and heritable phenotypes. As plants are sessile and in constant exposure to the soil microbiome and nutrients, epigenetic changes induced by these factors could provide more effective, stable and a sustainable molecular solution for crop improvement.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139701650","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":"Understanding the structural and functional changes and biochemical pathomechanism of the cardiomyopathy-associated p.R123W mutation in human αB-crystallin","authors":"Leila Rezaei Somee ,&nbsp;Anis Barati ,&nbsp;Mohammad Bagher Shahsavani ,&nbsp;Masaru Hoshino ,&nbsp;Jun Hong ,&nbsp;Ashutosh Kumar ,&nbsp;Ali Akbar Moosavi-Movahedi ,&nbsp;Massoud Amanlou ,&nbsp;Reza Yousefi","doi":"10.1016/j.bbagen.2024.130579","DOIUrl":"10.1016/j.bbagen.2024.130579","url":null,"abstract":"<div><p>αB-crystallin, a member of the small heat shock protein (sHSP) family, is expressed in diverse tissues, including the eyes, brain, muscles, and heart. This protein plays a crucial role in maintaining eye lens transparency and exhibits holdase chaperone and anti-apoptotic activities. Therefore, structural and functional changes caused by genetic mutations in this protein may contribute to the development of disorders like cataract and cardiomyopathy. Recently, the substitution of arginine 123 with tryptophan (p.R123W mutation) in human αB-crystallin has been reported to trigger cardiomyopathy. In this study, human αB-crystallin was expressed in <em>Escherichia coli</em> (<em>E. coli</em>), and the missense mutation p.R123W was created using site-directed mutagenesis. Following purification <em>via</em> anion exchange chromatography, the structural and functional properties of both proteins were investigated and compared using a wide range of spectroscopic and microscopic methods. The p.R123W mutation induced significant alterations in the secondary, tertiary, and quaternary structures of human αB-crystallin. This pathogenic mutation resulted in an increased β-sheet structure and formation of protein oligomers with larger sizes compared to the wild-type protein. The mutant protein also exhibited reduced chaperone activity and lower thermal stability. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) demonstrated that the p.R123W mutant protein is more prone to forming amyloid aggregates. The structural and functional changes observed in the p.R123W mutant protein, along with its increased propensity for aggregation, could impact its proper functional interaction with the target proteins in the cardiac muscle, such as calcineurin. Our results provide an explanation for the pathogenic intervention of p.R123W mutant protein in the occurrence of hypertrophic cardiomyopathy (HCM).</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139661369","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":"FBXO8 is a novel prognostic biomarker in different molecular subtypes of breast cancer and suppresses breast cancer progression by targeting c-MYC","authors":"Abdul Jamil Khan ,&nbsp;Shad Man ,&nbsp;Manzar Abbas ,&nbsp;Shihao Liu ,&nbsp;Feng Zhang","doi":"10.1016/j.bbagen.2024.130577","DOIUrl":"10.1016/j.bbagen.2024.130577","url":null,"abstract":"<div><p>F-box only protein 8 (FBXO8) is a recently identified member of the F-box proteins, showcasing its novelty in this protein family. Extensive research has established FBXO8's role as a tumor suppressor in various cancers, including hepatocellular carcinoma, and colorectal cancer, Nevertheless, its functional, mechanistic, and prognostic roles in primary and metastatic breast cancer, particularly in different molecular subtypes of breast cancer, various stages, as well as its potential implications in immunotherapy, tumor microenvironment, and prognostic survival among breast cancer patients, remain unexplored. In this article, we employed a multi-dimensional investigation leveraging TCGA, TIMER, TISIDB, STRING, MEXPRESS, UALCAN, and cBioPortal databases to explore the underlying suppression mechanism of FBXO8 in breast cancer. FBXO8 negatively correlates with MYC, NOTCH, WNT and inflammatory signaling pathways in breast tumor microenvironment. Furthermore we conducted RT-PCR, western blot, cell proliferation, cell migration, and mRNA target gene RT-PCR analyses to elucidate the role of FBXO8 in breast cancer progression. Mechanistically, PTEN and FBXW7 expression were down-regulated and MYC, IL10, IL6, NOTCH1, WNT6 mRNA expressions were up-regulated in FBXO8 knockdown cell lines. c-MYC silenced cells showed an increase in FBXO8 protein level, which suggests a negative feedback loop between FBXO8 and c-MYC to control breast cancer metastasis. These findings illuminate the novel role of FBXO8 as a prognostic and therapeutic target across different molecular subtypes of breast cancer. Finally, through the utilization of virtual screening and Molecular Dynamics simulations, we successfully identified two FDA-approved medications, Ledipasvir and Paritaprevir, that demonstrated robust binding capabilities and interactions with FBXO8</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139646230","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":"Charge manipulation of the human insulin B chain C-terminal to shed light on the complex mechanism of insulin fibrillation","authors":"Mohammad Bagher Shahsavani ,&nbsp;Masaru Hoshino ,&nbsp;Ashutosh Kumar ,&nbsp;Reza Yousefi","doi":"10.1016/j.bbagen.2024.130578","DOIUrl":"10.1016/j.bbagen.2024.130578","url":null,"abstract":"<div><p><span><span>Insulin fibrillation poses a significant challenge in the development and treatment of diabetes. Current efforts to unravel its mechanisms have thus far remained incomplete. To shed light on the intricate processes behind insulin fibrillation, we employed mutagenesis techniques to introduce additional positive charge residues into the C-terminal region of the insulin B chain which plays an important role in insulin </span>dimerization<span><span><span>. We employed our investigation with various spectroscopic methods, </span>electron microscopy, and molecular dynamics simulations. These methods allowed us to explore the structure and fibrillation behavior of the engineered B chains following their expression in a bacterial host and successful </span>purification. This manipulation had a pronounced impact on the </span></span>oligomerization<span><span> behavior of the insulin B chain. It appears that these mutations delay the formation of the dimeric state in the process of transitioning to larger oligomers, consequently, leading to an alteration in the kinetics of fibrillation. Our findings also indicated that the mutant insulin B chains (Di-R, Di-K, and Di-H) displayed resistance to the initiation of fibrillation. This resistance can be attributed to the repulsive forces generated by the introduced positive charges, which disrupt the attractive interactions favoring nucleation. Notably, the mutant B chains formed shorter and less abundant oligomers and fibrils, which can be ascribed to the alterations induced by repulsion. Our engineered mutant B chains exhibited enhanced stability against stress-induced fibrillation, hinting at their potential utility in the development of new insulin analogs. This study underscores the significance of the C-terminal region in the initial stages of insulin B chain fibrillation, providing valuable insights into the intricate mechanisms involved and their potential </span>pharmaceutical applications.</span></p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559132","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":"Selenomethionine modulates the JAK2 / STAT3 / A20 pathway through oxidative stress to alleviate LPS-induced pyroptosis and inflammation in chicken hearts","authors":"Yutian Lei ,&nbsp;Wenying Sun ,&nbsp;Tong Xu ,&nbsp;Jianhua Shan ,&nbsp;Meichen Gao ,&nbsp;Hongjin Lin","doi":"10.1016/j.bbagen.2024.130564","DOIUrl":"10.1016/j.bbagen.2024.130564","url":null,"abstract":"<div><p>Selenium (Se) is involved in many physiopathologic processes in humans and animals and is strongly associated with the development of heart disease. Lipopolysaccharides<span> (LPS) are cell wall components of gram-negative bacteria that are present in large quantities during environmental pollution. To investigate the mechanism of LPS-induced cardiac injury and the efficacy of the therapeutic effect of SeMet<span><span><span> on LPS, a chicken model supplemented with selenomethionine (SeMet) and/or LPS treatment, as well as a primary chicken embryo cardiomyocyte model with the combined effect of SeMet / JAK2 inhibitor (INCB018424) and/or LPS were established in this experiment. CCK8 kit, Trypan blue staining, DCFH-DA staining, </span>oxidative stress<span><span> kits, immunofluorescence staining, LDH kit, real-time fluorescence quantitative PCR, and </span>western blot<span> were used. The results proved that LPS exposure led to ROS explosion, hindered the antioxidant system, promoted the expression of the JAK2 pathway, and increased the expression of genes involved in the pyroptosis<span> pathway, inflammatory factors, and heat shock proteins (HSPs). Upon co-treatment with SeMet and LPS, SeMet reduced LPS-induced pyroptosis and inflammation and restored the expression of HSPs by inhibiting the ROS burst and modulating the antioxidant capacity. Co-treatment with INCB018424 and LPS resulted in inhibited of the JAK2 pathway, attenuating pyroptosis, inflammation, and high expression of HSPs. Thus, LPS induced pyroptosis, inflammation, and changes in HSPs activity by activating of the JAK2 / </span></span></span></span>STAT3 / A20 signaling axis in chicken hearts. Moreover, SeMet has a positive effect on LPS-induced injury. This work further provides a theoretical basis for treating cardiac injury by SeMet.</span></span></p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559323","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":"Gastric cancer patient-derived organoids model for the therapeutic drug screening","authors":"Jiao Xu ,&nbsp;Jin Gong ,&nbsp;Mengyang Li ,&nbsp;Ye Kang ,&nbsp;Jinrong Ma ,&nbsp;Xi Wang ,&nbsp;Xiao Liang ,&nbsp;Xin Qi ,&nbsp;Bixin Yu ,&nbsp;Jin Yang","doi":"10.1016/j.bbagen.2024.130566","DOIUrl":"10.1016/j.bbagen.2024.130566","url":null,"abstract":"<div><h3>Background</h3><p>Gastric cancer (GC) is a highly heterogeneous disease featuring many various histological and molecular subtypes. Therefore, it is imperative to have well-characterized in vitro models for personalized treatment development. Gastric cancer patient-derived organoids (PDOs), re-capitulating in vivo conditions, exhibit high clinical efficacy in predicting drug sensitivity to facilitate the development of cancer precision medicine.</p></div><div><h3>Methods</h3><p>PDOs were established from surgically resected GC tumor tissues. Histological and molecular characterization of PDOs and primary tissues were performed via IHC and sequencing analysis. We also conducted drug sensitivity tests using PDO cultures with five chemotherapeutic drugs and twenty-two targeted drugs.</p></div><div><h3>Results</h3><p>We have successfully constructed a PDOs biobank that included EBV+, intestinal/CIN, diffuse/GS, mixed and Her2+ GC subtypes, and these PDOs captured the pathological and genetic characteristics of corresponding tumors and exhibited different sensitivities to the tested agents. In a clinical case study, we performed an additional drug sensitivity test for a patient who reached an advanced progressive stage after surgery. We discovered that the combination of napabucasin and COTI-2 exhibited a stronger synergistic effect than either drug alone.</p></div><div><h3>Conclusion</h3><p>PDOs maintained the histological and genetic characteristics of original cancer tissues. PDOs biobank opens up new perspectives for studying cancer cell biology and personalized medicine as a preclinical study platform.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139508682","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":"Insights into the roles of non-coding RNAs and angiogenesis in glioblastoma: An overview of current research and future perspectives","authors":"Zhengfei Song ,&nbsp;Zhaoliang Xue ,&nbsp;Yirong Wang ,&nbsp;Muhammad Imran ,&nbsp;Mohammed Assiri ,&nbsp;Shah Fahad","doi":"10.1016/j.bbagen.2024.130567","DOIUrl":"10.1016/j.bbagen.2024.130567","url":null,"abstract":"<div><p><span><span>Glioblastoma (GBM) is a highly aggressive type of primary brain cancer with a poor prognosis, and despite intensive research, survival rates have not significantly improved. Non-coding RNAs (ncRNAs) are emerging as critical regulators of GBM pathogenesis, including angiogenesis, which is essential for tumor growth and invasion. </span>MicroRNAs<span> (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs<span> (circRNAs) have been identified as regulators of angiogenesis in GBM. miRNAs such as miR-21, miR-10b, and miR-26a promote angiogenesis by targeting anti-angiogenic factors, while lncRNAs such as H19 and MALAT1 inhibit angiogenesis by regulating pro-angiogenic factors. CircRNAs, such as circSMARCA5 and circBACH2, also regulate angiogenesis through various mechanisms. Similarly, </span></span></span>signaling pathways such as the vascular endothelial growth factor (VEGF) pathway play critical roles in angiogenesis and have been targeted for GBM therapy. However, resistance to anti-angiogenic therapies is a significant obstacle in clinical practice. Developing novel therapeutic strategies targeting ncRNAs and angiogenesis is a promising approach for GBM. Potential targets include miRNAs, lncRNAs, circRNAs, and downstream signaling pathways that regulate angiogenesis. This review highlights the critical roles of ncRNAs and angiogenesis in GBM pathogenesis and the potential for new therapeutic strategies targeting these pathways to improve the prognosis and quality of life for GBM patients.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139495015","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}