Bioimpacts最新文献

{"title":"Anticancer impacts of the unicellular cyanobacterium <i>Chroococcus turgidus</i> bioactive compounds in colorectal adenocarcinoma.","authors":"Hamieh Goshtasbi, Azam Safary, Ali Movafeghi, Jaleh Barar, Mostafa Akbarzadeh-Khiavi, Yadollah Omidi","doi":"10.34172/bi.30867","DOIUrl":"10.34172/bi.30867","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Microalgae and cyanobacteria are promising sources of bioactive compounds with antioxidant and anticancer properties. The cyanobacterium <i>Chroococcus turgidus</i> has been studied for its potential antioxidant, anti-inflammatory, antibacterial, antiviral, and anticancer effects. This study investigates its anticancer effects on colorectal cancer (CRC) at the cellular and molecular levels.</p><p><strong>Methods: </strong>The metabolites of <i>C. turgidus</i> were screened using the Folin-Ciocalteu reagent and GC-MS. Antioxidant activity was assessed using the DPPH assay. The biological effects of methanolic extract (ME) were evaluated using MTT assay, Annexin V/PI staining, DAPI staining, and western blotting. Cells were treated with ME at concentrations ranging from 5 to 500 µg/mL for 24 and 48 hours, with the IC₅₀ values determined at 373 µg/mL and 291 µg/mL, respectively.</p><p><strong>Results: </strong>ME contained bioactive compounds such as phenols, flavonoids, and anthocyanins. Identified fatty acids included palmitic acid ethyl ester (15.53%), 1-bromo-11-iodoundecane (2.31%), undecanoic acid 2,8-dimethyl methyl ester (6.62%), oleic acid (6.47%), and 7-dehydrocholesterol (7.97%). ME inhibited SW480 cell proliferation in a dose- and time-dependent manner and induced nuclear fragmentation, chromatin remodeling, and apoptosis. Annexin V/PI staining confirmed apoptosis as the dominant mode of cell death. Western blot analysis showed increased Bax and decreased Bcl2 expression, supporting its pro-apoptotic activity.</p><p><strong>Conclusion: </strong><i>C. turgidus</i> may serve as a potential therapeutic agent for gastrointestinal cancers through its ability to modulate the Bax/Bcl2 pathway and promote apoptosis. These findings highlight its novel anticancer effects and support further preclinical investigations.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30867"},"PeriodicalIF":2.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chloroquine inhibits salinomycin-induced autophagy for collaborative anticancer effect in breast cancer.","authors":"Xiaoting Yang, Zhan Jin, Gao Chen, Gaobo Hu","doi":"10.34172/bi.30821","DOIUrl":"10.34172/bi.30821","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Breast cancer (BC) presents significant morbidity and mortality challenges. Autophagy plays a contradictory role in BC. The chemotherapeutic agent salinomycin exhibits anticancer effects, but its effectiveness is limited by over-activation of autophagy. This study aimed to investigate the effects and mechanisms of salinomycin and its combination with chloroquine in BC.</p><p><strong>Methods: </strong>The MCF-7 and MCF-7 tumor spheroids (MCF-7-TS) BC models were treated separately with salinomycin and autophagy inducer/inhibitor (rapamycin/chloroquine). Cell proliferation, apoptosis, and cell cycle progression were measured using cell counting kit-8 (CCK-8), cell colony assay, and flow cytometry. The expression of apoptosis-related, autophagy-related, and phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway-related proteins was measured via Western blot. Light chain 3 (LC3) expression was detected via immunofluorescence.</p><p><strong>Results: </strong>In the MCF-7 and MCF-7-TS cells, salinomycin inhibited cell viability, p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR expression, and increased apoptosis and LC3 expression, with reduced tumor spheroid number and volume of MCF-7-TS cells. Interestingly, rapamycin enhanced LC3 expression but prevented apoptosis in salinomycin-treated cells, with elevated tumor spheroid number and volume of MCF-7-TS cells. Moreover, after screening for a suitable ratio of salinomycin and chloroquine (1:2.5), compared to salinomycin group, salinomycin+chloroquine group exhibited decreased tumor spheroid number and volume of MCF-7-TS cells; reduced B-cell lymphoma-2 (Bcl-2), LC3, LC3II/LC3I, and Beclin-1 expression; and enhanced G0/G1 phase arrest and Bcl-2-associated X protein expression in MCF-7 and MCF-7-TS cells.</p><p><strong>Conclusion: </strong>Chloroquine enhanced the anticancer efficacy of salinomycin by suppressing salinomycin-induced autophagy, providing a solid theoretical basis for its clinical application in BC.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30821"},"PeriodicalIF":2.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosynthesis of sulfur quantum dots and cerium oxide nanoparticles for bioimaging and reactive oxygen species modulation in Y79 retinoblastoma cancer cells.","authors":"Zahra Foroutan, Sadaf Afshari, Sajjad Njafi, Amir R Afshari, Seyed Sajad Ahmadi, Seyedsina Nemati, Seyedeh Mozhdeh Mirzaei, Afsane Bahrami","doi":"10.34172/bi.30954","DOIUrl":"10.34172/bi.30954","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Retinoblastoma is considered a common cancer in early childhood with a poor prognosis, and innovative strategies for early diagnosis and treatment are essential. The use of nanoparticles is one of the most efficient approaches among these strategies.</p><p><strong>Methods: </strong>Sulfur quantum dots (SQDs) and cerium oxide nanoparticles (CeO₂) were synthesized through simple and eco-friendly green synthesis method using Arabic gum and an extract from Okra (<i>Abelmoschus esculentus</i>) fruit, respectively. Then, the nanoparticles were characterized using UV-Vis, PL, FTIR, XRD, FESEM/TEM, and XPS techniques. The cytotoxicity, Annexin V-FITC apoptosis assay, and measurement of reactive oxygen species along with cellular uptake, were evaluated.</p><p><strong>Results: </strong>The results of characterization confirmed the successful synthesis of SQDs and CeO₂ with a crystalline nature and the average size of 4.79 and 27.31 nm, respectively. The findings indicated that SQDs had no significant inhibitory effect on normal and cancer cells. The cell uptake of SQDs demonstrated high internalization into Y79 cells with an exited green light color under a fluorescent microscope. On the other hand, CeO₂ nanoparticles showed the ability to suppress the growth and increase early and late apoptosis of Y79 cells at concentrations of 500 μg/mL after 24 h. The level of reactive oxygen species (ROS) was also increased in Y79 cells after treatment with CeO₂.</p><p><strong>Conclusion: </strong>As the SQDs exhibited green light color and CeO₂ enhanced apoptosis and ROS levels, this study suggested SQDs could be a potential bioimaging and labeling agent, while CeO₂ may be considered for therapeutic applications in retinoblastoma.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30954"},"PeriodicalIF":2.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilization of Hoogsteen H-bonds in G-quartet sheets by coordinated K⁺ ion for enhanced efficiency in guanine-rich DNA nanomotor.","authors":"Abolfazl Barzegar, Nastaran Tohidifar","doi":"10.34172/bi.30596","DOIUrl":"10.34172/bi.30596","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>G-rich DNA nanomotors function as nanoscale devices and nanoswitches powered by the conversion of chemical energy into mechanical motion through transitions between duplex (DU) and tetraplex (TE) conformations. The stability of the TE conformation, crucial for nanomotor function, relies on G-quadruplex structures formed by guanine quartets. However, the detailed factors influencing TE stability remain unclear.</p><p><strong>Methods: </strong>This study investigated the role of coordinated K⁺ ion and Hoogsteen H-bonds in stabilizing the TE structure of a truncated 15-nucleotide G-rich DNA nanomotor with the sequence GGTTGGTGTGGTTGG using atomic-scale computational analysis. Three systems were simulated: TE1K with a crystal K⁺ ion, TE2K with a manually embedded K⁺ ion, and TE3 lacking a K⁺ ion. All systems underwent molecular dynamics simulations using the Amber force field and TIP3P water model.</p><p><strong>Results: </strong>The simulations revealed a clear dependence of G-quadruplex rigidity and TE conformation stability on the presence of coordinated K⁺ ion. TE1K and TE2K, containing K⁺ ions, exhibited significantly lower RMSD values compared to TE3, indicating more excellent structural stability and rigidity. K⁺ ion coordination facilitated the formation of all eight Hoogsteen H-bonds within G-quartets, whereas the K⁺ ion-free system (TE3) displayed distorted G-quadruplexes and a reduction in H-bonds, leading to a less stable \"wobble TE*\" state. The diameter of G-quartets and the radius of gyration (Rg) further supported these observations, with TE1K and TE2K maintaining compact structures compared to the more open and flexible \"wobble TE*\" conformation in TE3.</p><p><strong>Conclusion: </strong>These findings demonstrate that coordinated K⁺ ion play a critical role in stabilizing the TE conformation of G-rich DNA nanomotors by promoting G-quadruplex rigidity and facilitating Hoogsteen H-bond formation. This enhanced stability is essential for efficient DNA nanomotor function in the DU-TE nanoswitching process.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30596"},"PeriodicalIF":2.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The promise of gene therapy in common types of dementia.","authors":"Mojtaba Ghobadi, Mohammad Foad Heidari, Arezoo Farhadi, Ali Shakerimoghaddam, Mahdi Ghorbani, Zahra Hami, Naeim Ehtesham, Javad Behroozi","doi":"10.34172/bi.30795","DOIUrl":"10.34172/bi.30795","url":null,"abstract":"<p><p>Dementia is an umbrella term describing different types of diseases that lead to cognitive impairment and memory dysfunction, predominantly affecting older adults. The most common forms include Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Despite extensive research, there is no definitive cure for dementia, primarily due to its complex and multifactorial nature, particularly the role of genetic abnormalities. Gene therapy, a novel therapeutic approach, aims to correct defective genes or introduce functional gene products by delivering specific DNA sequences to patients, and is often considered for individuals unresponsive to conventional treatments, such as those with dementia. Over the past decade, significant research has explored the potential of gene therapy in dementia, offering new hope for more effective treatments. However, several challenges remain in its practical application. One key challenge is developing safe and efficient gene delivery methods, as the brain's intricate structure and protective barriers present significant obstacles. Furthermore, ensuring the long-term expression and stability of therapeutic genes is crucial for sustained benefit. Future studies should focus on identifying genes implicated in different types of dementia, optimizing gene delivery systems, improving gene-targeting specificity, and conducting comprehensive clinical trials to assess the safety and efficacy of these therapies. Addressing these challenges could pave the way for novel treatment strategies, ultimately improving the quality of life for individuals with dementia.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30795"},"PeriodicalIF":2.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-silico analysis of CEP55/E2F1/hsa-let-7b-5p/TMPO-AS1 axis-based ceRNA network promoting poor prognosis in lung adenocarcinoma smokers.","authors":"Prerna Vats, Sakshi Nirmal, Gurpreet Bamrah, Saurabh Srivastava, Rajeev Nema","doi":"10.34172/bi.30585","DOIUrl":"10.34172/bi.30585","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Smoking causes severe lung adenocarcinoma. High CEP55 expression correlates with clinico-pathological features, suggesting the mRNA/miRNA/lncRNA-ceRNA network's crucial to prognosis.</p><p><strong>Methods: </strong>The study used databases like TIMER 2.0, UALCAN, OncoMX, GEPIA2, OncoDB, ENCORI, KM Plotter, TNMplot, CancerSEA, CellTracer, GENI, Intogen, miRNet, TISIDB, GSCA, the Enrichr, HDOCK, and LigPlot databases to analyze CEP55 and associated ceRNA expression in lung cancer tumors and normal tissues.</p><p><strong>Results: </strong>The CEP55 gene is overexpressed in both lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD). Findings suggested that overexpression of CEP55 has a poor prognosis in terms of overall survival (OS) (HR=1.63, CI=1.44-1.84, <i>P</i>=1.4e-15), first progression (FP) (HR=1.81, CI=1.52-2.15, <i>P</i>=6.4e-12), and post-progression survival (PPS) (HR=1.141, CI=1.14-1.74, <i>P</i>=00012). Particularly, high CEP55 expression is significantly associated with OS+LUAD patients (HR=1.55, CI=1.3-1.84, <i>P</i>=7.2e-07) and those with OS+LUAD smokers (HR=1.49, CI=1.15-1.94, <i>P</i>=0.0026). The study found a strong link between lncRNA-TMPO-AS1 overexpression and poor prognosis in LUAD+smokers, and hsa-let-7b-5p downexpression was associated with poor survival in LUAD. The least binding energy or most favourable interaction score between hsa-let-7b-5p and CEP55 was found to be -124.52 kcal/mol.</p><p><strong>Conclusion: </strong>Smokers with lung adenocarcinoma had worse prognoses due to higher E2F1, CEP55, and TMPO-AS1 levels. Also, TMPO-AS1 sponge formation with hsa-let-7b-5p may be the cause of this feedback loop.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30585"},"PeriodicalIF":2.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering the anticancer effects of Bhallataka Taila in lung cancer: A metabolomic and network pharmacology approach.","authors":"G P Suchitha, Shubham S Upadhyay, Ravishankar Pervaje, T S Keshava Prasad, Shobha Dagamajalu","doi":"10.34172/bi.30568","DOIUrl":"10.34172/bi.30568","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Bhallataka (<i>Semecarpus anacardium</i> Linn.) is used in traditional medicine to treat various ailments. The nut extract of Bhallataka, known as Bhallataka taila, has anticancer properties. Although several studies have explored to verify and evaluate its anticancer properties and efficacy against various cancers, the specific target proteins, mode of action, and associated metabolites have not yet been identified. This study aimed to elucidate the biological mechanisms of Bhallataka taila using an integrated metabolomics and systems pharmacology approach with <i>in vitro</i> validation.</p><p><strong>Methods: </strong>Untargeted metabolomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to evaluate the metabolites in Bhallataka taila, identify key protein targets and link them to cellular pathways through bioinformatics-based network pharmacology. Protein targets were mapped using BindingDB, and pathway enrichment was analyzed using STRINGdb. An <i>in vitro</i> study of A549 cells assessed the impact of Bhallataka taila on cellular viability (MTT assay), apoptosis (AO-EB staining), reactive oxygen species (ROS) production (fluorescent spectroscopy and DCFDA staining), and marker validation (immunoblotting and qRT-PCR). The integration of metabolomics, network pharmacology, and <i>in vitro</i> experiments offers a significant understanding of the anticancer mechanisms and pathways influenced by Bhallataka taila in non-small cell lung cancer (NSCLC) cells. Statistical analysis was performed using GraphPad Prism using one-way ANOVA.</p><p><strong>Results: </strong>Metabolomics combined with network pharmacology detected 2023 unique metabolites at the MS1 level and 216 metabolites at the MS2 level. Bhallataka taila metabolites were found to interact with 180 human target proteins identified through BindingDB analysis. These target proteins were mapped to key cancer regulatory signaling pathways, along with TNF-related apoptosis-inducing ligand (TRAIL), protease-activated receptor-1 (PAR1)-mediated thrombin signaling, Syndecan-1 and Glypican pathways, and vascular endothelial growth factor receptor (VEGFR)1/2 pathways. <i>In vitro</i> validation demonstrated that Bhallataka taila significantly regulated apoptosis (57%) and ROS production (56%) in A549 cells compared to control while modulating other cancer-related regulatory pathways.</p><p><strong>Conclusion: </strong>This data-driven study can help researchers identify promising cancer treatment candidates and validate their efficacy. This approach integrates traditional knowledge with modern scientific techniques to reinforce the anticancer potential of Bhallataka taila and its mechanisms.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30568"},"PeriodicalIF":2.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A hybrid transformer-based approach for early detection of Alzheimer's disease using MRI images.","authors":"Qi Wu, Yannan Wang, Xiaojuan Zhang, Hongqiang Zhang, Kuanyu Che","doi":"10.34172/bi.30849","DOIUrl":"10.34172/bi.30849","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder that poses significant challenges for early detection. Advanced diagnostic methods leveraging machine learning techniques, particularly deep learning, have shown great promise in enhancing early AD diagnosis. This paper proposes a multimodal approach combining transfer learning, Transformer networks, and recurrent neural networks (RNNs) for diagnosing AD, utilizing MRI images from multiple perspectives to capture comprehensive features.</p><p><strong>Methods: </strong>Our methodology integrates MRI images from three distinct perspectives: sagittal, coronal, and axial views, ensuring the capture of rich local and global features. Initially, ResNet50 is employed for local feature extraction using transfer learning, which improves feature quality while reducing model complexity. The extracted features are then processed by a Transformer encoder, which incorporates positional embeddings to maintain spatial relationships. Finally, 2D convolutional layers combined with LSTM networks are used for classification, enabling the model to capture sequential dependencies in the data.</p><p><strong>Results: </strong>The proposed framework was rigorously tested on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Our approach achieved an impressive accuracy of 96.92% on test data and 98.12% on validation data, significantly outperforming existing methods in the field. The integration of Transformer and LSTM models led to enhanced feature representation and improved diagnostic performance.</p><p><strong>Conclusion: </strong>This study demonstrates the effectiveness of combining transfer learning, Transformer networks, and LSTMs for AD diagnosis. The proposed framework provides a comprehensive analysis that improves classification accuracy, offering a valuable tool for early detection and intervention in clinical practice. These findings highlight the potential for advancing neuroimaging analysis and supporting future research in AD diagnostics.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30849"},"PeriodicalIF":2.2,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanobody-functionalized liposomal doxorubicin: A novel strategy for angiogenesis suppression via VEGFR2 targeting.","authors":"Aezam Akbari, Azadeh Ghaffari, Fahimeh Haji-Ahmadi, Vahideh Farzam Rad, Mahdi Behdani, Hamidreza Kheiri-Manjili, Cobra Moradian, Davoud Ahmadvand","doi":"10.34172/bi.30707","DOIUrl":"10.34172/bi.30707","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Doxorubicin (DOX) is a widely used first-line treatment for various cancers but causes toxicity. Targeted drug delivery systems, particularly DOX-encapsulated liposomes, show clinical success and lower toxicity. The abnormal angiogenesis in high-grade tumors, making it crucial to develop strategies that target this process in conjunction with chemotherapy. This study presents an innovative formulation of anti-VEGFR2-functionalized liposomal DOX, designed to reduce systemic drug release, enhance drug release and bioavailability at tumor sites, and reducing adverse effects, representing a promising advancement in targeted cancer therapy.</p><p><strong>Methods: </strong>Liposome formulations including liposome (Lip), DOX loaded liposome (Lip-DOX), anti VEGFR2 Nanobody-conjugated liposome (Lip-Nb), and anti VEGFR2 Nanobody- conjugated DOX-loaded liposome (Lip-DOX-Nb) were prepared by film hydration method and then fully characterized. The cellular uptake of these nanocarriers were assessed by flow cytometry analysis in human umbilical vein endothelial cells (HUVECs). Further, the ability of the different liposomal formulations to suppress angiogenesis were assessed by performing tube formation assay on HUVECs. In addition, the inhibitory impact of low dose consumption of the formulations to inhibit the migratory capacity of glioma cells were assessed by scratch migration assay on U87 cells.</p><p><strong>Results: </strong>The prepared liposomal formulations displayed optimal size range of 120-131 nm, with slightly negative charge about -2.4 mv, spherical morphology and effective encapsulation of about 91% of the total DOX and high conjugation efficiency of about 87% of total anti VEGFR2 Nb that are acceptable for nano sized targeted drug delivery systems. <i>In vitro</i> experiments; flow cytometry results verified cellular uptake of DOX loaded liposomes to HUVEC cell line and more cellular uptake was observed for Lip-DOX-Nb liposomes demonstrated that the anti-VEGFR2-conjugated liposomes enhance cellular uptake. Lip-DOX-Nb liposomes also showed more cytotoxicity effect against VEGFR2-positive HUVEC cells in compare with non-conjugated liposomes; effectively induced apoptosis to HUVEC cells and reduced the migratory capacity on U87 cancer cells. Analysis of the treated cells using DHM revealed that Lip-DOX-Nb enhanced nuclear integrity of U87 cancer cells while inducing cell death.</p><p><strong>Conclusion: </strong>This designed drug delivery system worked as strong anticancer and angiogenesis suppression agent <i>ex-vitro</i> angiogenesis model via VEGFR2 targeting.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30707"},"PeriodicalIF":2.2,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoinformatics design of an mRNA vaccine against classical swine fever virus using conserved E2 protein and NS3 T-lymphocyte epitopes.","authors":"Edward C Banico, Ella Mae Joy S Sira, Lauren Emily Fajardo, Fredmoore L Orosco","doi":"10.34172/bi.30778","DOIUrl":"10.34172/bi.30778","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>The classical swine fever virus (CSFV) causes significant economic losses in the livestock industry. While the existing E2 marker vaccine offers protection against infections, it is characterized by delayed immunity and reduced effectiveness over time. Optimizing the existing vaccine is crucial to better control CSFV outbreaks worldwide. This study aimed to improve the existing E2 marker vaccine for CSFV by integrating NS3 T lymphocyte-inducing epitopes into the conserved E2 protein sequence and using mRNA technology for vaccine delivery.</p><p><strong>Methods: </strong>The design and evaluation of the vaccine were carried out exclusively through <i>in silico</i> methods. T lymphocyte epitopes were identified from the CSFV NS3 protein using multiple epitope prediction tools. A vaccine construct was formed after linking the predicted NS3 epitopes, E2 protein, and an immunogenic adjuvant. Molecular docking and dynamics simulations were performed to analyze the interaction between the adjuvant used and its immune receptor. Signal peptides were incorporated into the design, and mRNA sequences with varying codon usage biases were generated using LinearDesign. The mRNA sequence with minimum free energy (MFE) and codon adaptation index (CAI) closest to the controls was selected as the final design.</p><p><strong>Results: </strong>Twenty epitopes with high binding affinity to major histocompatibility complexes (MHCs) were identified from the CSFV NS3 protein. The vaccine construct with swine CD154 adjuvant demonstrated high antigenicity, making it the optimal choice for the final vaccine design. Molecular docking and dynamics simulations confirmed the adjuvant's strong affinity and stable interaction with its canonical receptor, swine CD40. Moreover, the final vaccine design exhibited higher populations of lymphocytes and antibodies compared to the components of the commercialized E2 marker vaccine in immune simulation. The final mRNA vaccine sequence exhibited a higher MFE and CAI than the two licensed mRNA vaccine controls.</p><p><strong>Conclusion: </strong>The mRNA vaccine designed in this study serves as a potential CSFV vaccine candidate. <i>In vivo</i> and <i>in vitro</i> validation is needed to confirm its efficacy.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30778"},"PeriodicalIF":2.2,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}