Molecular Biotechnology最新文献

{"title":"Nanotechnology and CRISPR/Cas-Mediated Gene Therapy Strategies: Potential Role for Treating Genetic Disorders.","authors":"Guneet Kaur, Jasnoor Arora, Abhinashi Singh Sodhi, Sonu Bhatia, Navneet Batra","doi":"10.1007/s12033-024-01301-8","DOIUrl":"10.1007/s12033-024-01301-8","url":null,"abstract":"<p><p>Gene therapy has made substantial progress in the treatment of the genetic diseases, focussing on the reduction of characteristics of recessive/dominant disorders, as well as various cancers. Extensive research has been conducted in the past few decades to investigate the application of nanotechnology and CRISPR/Cas technology in gene therapy. Nanotechnology due to attributes such has targeted drug delivery, controlled release, scalability and low toxicity has gained attention of the medical world. CRISPR/Cas9 system is considered as an impactful genome editing tool in the area of next-generation therapeutics and molecular diagnostics. CRISPR technology emphasises on gene editing, gene regulation modulation, and formulation of defined genetic changes. Its applications in treatment of the genetic disorders are extended beyond traditional therapies. These techniques are being explored as treatment of several genetic disorders including Duchenne muscular dystrophy, cystic fibrosis, Alzheimer's disease, Parkinson's disease, and Huntington disease. Despite considerable therapeutic potential of gene therapy, several obstacles must be addressed before it can be widely adopted in clinical practice, particularly in terms of ensuring safety and effectiveness. As research advances in this captivating field, these therapies will become the primary treatments and will have significant beneficial effects on the lives of patients with genetic disorders.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3800-3822"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Temperature Sensitive PNIPAm-g-PEI/Gold Nanotriangle for Gene Delivery Promotion.","authors":"Yan Wang, Senli Wang, Zhenyuan Cheng, Rongqian Dong, Xiangdi Jia, Fan Yang, Wan Sun","doi":"10.1007/s12033-025-01498-2","DOIUrl":"10.1007/s12033-025-01498-2","url":null,"abstract":"","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"4021-4023"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miR-494 Regulates the Biological Behavior of Trophoblasts by Targeting mTOR in Unexplained Recurrent Spontaneous Abortion.","authors":"Yihong Guo, Lujing Chen, Qiulin Ma, Peiyu Liu","doi":"10.1007/s12033-024-01298-0","DOIUrl":"10.1007/s12033-024-01298-0","url":null,"abstract":"<p><p>Recurrent spontaneous abortion (RSA) is a pregnancy disorder, and trophoblasts are involved in its complex pathogenesis. This study aimed to identify the functional role of exosomal miR-494 in promoting the development of unexplained RSA (uRSA). 15 uRSA tissues and 15 healthy controls were collected to compare the exosomal miR-494 expression. The ultracentrifugation method was used for serum exosome isolation, and exosome characteristics were examined using transmission electron microscopy (TEM). The affection of exosomal miR-494 on HTR-8/SVneo cells were determined by CCK-8, EdU, Wound healing, and Transwell assays. Our findings demonstrated that miR-494 levels were markedly lower in placental tissue and plasma exosomes from patients with uRSA than in normal pregnant women. Furthermore, treatment with miR-494-overexpressing exosomes reduced the viability, invasion, and migration of HTR-8/SVneo cells. In terms of regulation, exosomal miR-494 downregulated mTOR levels in HTR-8/SVneo cells. Mechanism research suggested that exosomal miR-494 reduces the viability, invasion, and migration of trophoblasts by targeting mTOR. Exosomal miR-494 and mTOR are potential predicative biomarkers and therapeutic targets for uRSA patients.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3898-3905"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment the Efficacy of the CRISPR System for Inducing Mutations in the AIMP2 Gene to Create a Cell Line Model of HLD17 Disease.","authors":"Shima Farrokhi, Atieh Eslahi, Farzaneh Alizadeh, Mohammad Amin Kerachian, Majid Mojarrad","doi":"10.1007/s12033-024-01257-9","DOIUrl":"10.1007/s12033-024-01257-9","url":null,"abstract":"<p><p>Hypomyelinating leukodystrophy-17 is a neurodevelopmental disorder caused by autosomal recessive mutations in the AIMP2 gene, resulting in a lack of myelin deposition during brain development, leading to variable neurological symptoms. Research on brain function in these disorders is challenging due to the lack of access to brain tissue. To overcome this problem, researchers have utilized different cell and animal models. The CRISPR-Cas9 system is considered the most optimal and effective method for genetic modification and developing cell models. We studied the efficacy of the CRISPR-Cas9 technology in inducing mutations in the AIMP2 gene in HEK293 cell lines. The study involved transfecting HEK293 cells with recombinant PX458 plasmids targeting spCas-9 and AIMP2 sgRNA. The cells were evaluated using fluorescent microscopy and enriched using serial dilution. The CRISPR/Cas9 plasmids were validated through PCR and Sanger sequencing. After serial dilution, AS-PCR, Sanger sequencing, and TIDE program analysis showed the construct successfully induces an indel mutation in HEK cells. Our findings demonstrated the great efficacy of the CRISPR system and produced a construct for inducing mutations in the AIMP2 gene, which can be utilized to edit the AIMP2 gene in nerve cells and create a cellular model of the HLD17 disease.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3922-3929"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Indicator for Distinguishing Multi-drug-Resistant Tuberculosis from Drug Sensitivity Tuberculosis and Potential Medications for Treatment.","authors":"Shulin Song, Donghui Gan, Di Wu, Ting Li, Shiqian Zhang, Yibo Lu, Guanqiao Jin","doi":"10.1007/s12033-024-01299-z","DOIUrl":"10.1007/s12033-024-01299-z","url":null,"abstract":"<p><p>The issue of multi-drug-resistant tuberculosis (MDR-TB) presents a substantial challenge to global public health. Regrettably, the diagnosis of drug-resistant tuberculosis (DR-TB) frequently necessitates an extended period or more extensive laboratory resources. The swift identification of MDR-TB poses a particularly challenging endeavor. To identify the biomarkers indicative of multi-drug resistance, we conducted a screening of the GSE147689 dataset for differentially expressed genes (DEGs) and subsequently conducted a gene enrichment analysis. Our analysis identified a total of 117 DEGs, concentrated in pathways related to the immune response. Three machine learning methods, namely random forest, decision tree, and support vector machine recursive feature elimination (SVM-RFE), were implemented to identify the top 10 genes according to their feature importance scores. A4GALT and S1PR1, which were identified as common genes among the three methods, were selected as potential molecular markers for distinguishing between MDR-TB and drug-susceptible tuberculosis (DS-TB). These markers were subsequently validated using the GSE147690 dataset. The findings suggested that A4GALT exhibited area under the curve (AUC) values of 0.8571 and 0.7121 in the training and test datasets, respectively, for distinguishing between MDR-TB and DS-TB. S1PR1 demonstrated AUC values of 0.8163 and 0.5404 in the training and test datasets, respectively. When A4GALT and S1PR1 were combined, the AUC values in the training and test datasets were 0.881 and 0.7551, respectively. The relationship between hub genes and 28 immune cells infiltrating MDR-TB was investigated using single sample gene enrichment analysis (ssGSEA). The findings indicated that MDR-TB samples exhibited a higher proportion of type 1 T helper cells and a lower proportion of activated dendritic cells in contrast to DS-TB samples. A negative correlation was observed between A4GALT and type 1 T helper cells, whereas a positive correlation was found with activated dendritic cells. S1PR1 exhibited a positive correlation with type 1 T helper cells and a negative correlation with activated dendritic cells. Furthermore, our study utilized connectivity map analysis to identify nine potential medications, including verapamil, for treating MDR-TB. In conclusion, our research identified two molecular indicators for the differentiation between MDR-TB and DS-TB and identified a total of nine potential medications for MDR-TB.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3946-3959"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Large Clostridial Toxins: A Brief Review and Insights into Antigen Design for Veterinary Vaccine Development.","authors":"Rafael Rodrigues Rodrigues, Mariliana Luiza Ferreira Alves, Miguel Andrade Bilhalva, Frederico Schmitt Kremer, Clóvis Moreira Junior, Marcos Roberto Alves Ferreira, Cleideanny Cancela Galvão, Pedro Henrique Dala Nora Quatrin, Fabricio Rochedo Conceição","doi":"10.1007/s12033-024-01352-x","DOIUrl":"10.1007/s12033-024-01352-x","url":null,"abstract":"","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"4012"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking Hope: Paving the Way for a Cutting-Edge Multi-Epitope Dengue Virus Vaccine.","authors":"Amtul Wadood Wajeeha, Mamuna Mukhtar, Najam Us Sahar Sadaf Zaidi","doi":"10.1007/s12033-024-01294-4","DOIUrl":"10.1007/s12033-024-01294-4","url":null,"abstract":"<p><p>Dengue fever is a significant health issue in Pakistan, demanding a vaccine effective against all the viral strains. This study employs reverse vaccinology to develop potential dengue vaccine candidates (DVAX I-III). The study thoroughly examined conserved areas of dengue virus serotypes 1-4's structural and non-structural proteins. Key viral proteins were analyzed to find antigenic peptides, which were incorporated into vaccine candidates and potentiated with adjuvants. Computational methods predicted peptide structures and evaluated their binding to immune receptors TLR 2, TLR 4, HLA *A1101, and DRB*401. A molecular dynamics simulation lasting 100 ns of the DVAX II-TLR4 complex at different time intervals clearly indicated that the ligand is attached to the receptor. Normal mode analysis assessed the stability and flexibility of these interactions. Encouragingly, all three vaccine candidates demonstrated favorable interactions with these immune receptors and the potential to induce a robust immune response. These findings suggest their safety and warrant further in vivo studies to evaluate their efficacy for clinical development.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3874-3897"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioencapsulation of Transgenic Nannochloropsis sp. Using Artemia as a Vaccine Delivery System to Zebrafish as a Fish Model Against Vibriosis.","authors":"Nur Farhah Nabihan Ismail, Aisamuddin Ardi Zainal Abidin, Fatimah Md Yusoff, Murni Marlina Abd Karim, Ina Salwany Md Yasin, Zetty Norhana Balia Yusof","doi":"10.1007/s12033-025-01496-4","DOIUrl":"https://doi.org/10.1007/s12033-025-01496-4","url":null,"abstract":"<p><p>Aquaculture faces decline due to diseases like vibriosis from Vibrio spp. This study aimed to examined the effect of transgenic microalgae Nannochloropsis sp. expressing the antigen OmpK gene originated from Vibrio harveyi and bioencapsulated with Artemia offers any potential as an oral vaccine in zebrafish. Nannochloropsis sp. was transformed using VCP_OMPK_ZA1 vector and successful transformant was incubated with Artemia prior fed to zebrafish. Zebrafish RNA was extracted to investigate immune response activation via gene expression analysis specifically the IgZ, TNF-ɑ, and IL-1β genes. Vaacinated and Unvaccinated fish were then challenged with pathogenic strain to test the efficacy of the oral vaccine. Results showed IgZ and IL-1β expressions increased on Days 7 and 14, while TNF-ɑ upregulated significantly in transgenic-fed zebrafish compared to wild-type. Upon bacterial challenge, transgenic-fed fish exhibited 100% relative percentage survival (RPS) compared to wild-type-fed (RPS = 40%). The histopathological analysis revealed that the fish that were not vaccinated had severe changes such as hemorrhages and necrosis, whereas those that were vaccinated showed only mild changes such as tubular degeneration and muscle regeneration following the bacterial challenge trial. Results indicate transgenic microalgae enhance larval fish immunity against vibriosis, potentially serving as an effective vaccination method.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WGCNA-Based Identification of Hub Genes and Key Pathways Involved in Obesity.","authors":"Yin Yuan, Shujiao Yue, Zixuan Wu, Xuan Sun, Hongwu Wang","doi":"10.1007/s12033-025-01503-8","DOIUrl":"https://doi.org/10.1007/s12033-025-01503-8","url":null,"abstract":"<p><p>The prevalence of obesity is increasing year by year, but its characteristic molecular targets are still unclear, and the available therapeutic approaches are relatively limited. Therefore, it is crucial to elucidate the molecular mechanisms underlying the pathogenesis of obesity and to explore potential molecular targets for obesity drug therapy. The expression dataset (GSE73304) was downloaded from the gene expression omnibus database for between-group differential expression gene analyses (DEGs), genome enrichment analysis (GSEA), and weighted gene co-expression network analysis (WGCNA) in healthy and obese populations. Intersecting genes obtained from DEGs and WGCNA difference modules were analyzed with three machine learning methods (LASSO, RandomForest, SVM-REF) to obtain obesity characteristic Genes. Analysis of ROC curves, intergroup differences, and intergene correlations for Genes characterizing obesity. The results of the study showed that 10 specimens and their Gene expression matrices were collected from each of the normal and obese patient groups, yielding 1937 DEGs. GSEA results showed that DEGs were enriched for 32 significant KEGG pathways. Forty gene co-expression modules of the gene expression matrix were constructed by WGCNA. Forty-five intersecting genes were obtained from DEGs and WGCNA significant difference module, which were associated with cellular differentiation, mitochondria, and a variety of endocrine factors and hormones. Eleven genes, including XLOC_004699, RIMBP2, COX6B2, OR5T1, RXFP2, XLOC_003676, XLOC_013038, VAX1, Q07610, XLOC_011515, and PTPN3, were obtained as the obesity characterization Genes through machine learning analysis of intersecting Genes. Based on WGCNA and machine learning, this study found that 11 genes, including RIMBP2, COX6B2, and OR5T1, differed significantly between healthy and obese populations and were closely associated with multiple molecular mechanisms, and these genes may be potential targets for drug therapy and diagnostic biomarkers.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TFAP2A-mediated Transcriptional Activation of ELMO1 Inhibits Ferroptosis and Promotes Esophageal Squamous Cell Carcinoma Progression.","authors":"Zhensheng Deng, Jinghong Xu, Zhenguo Liu","doi":"10.1007/s12033-025-01511-8","DOIUrl":"https://doi.org/10.1007/s12033-025-01511-8","url":null,"abstract":"<p><p>The role of engulfment and cell motility protein 1 (ELMO1) in esophageal squamous cell carcinoma (ESCC) is still unknown, even though it is critical for cellular behaviors. Our bioinformatics analyses have predicted transcription factor AP-2 alpha (TFAP2A) as a potential upstream regulator of ELMO1, suggesting its involvement in ESCC progression. ELMO1 expression in ESCC cells was analyzed. Lentivirus-mediated gene silencing was conducted, while cell counting kit-8, wound healing, and transwell assays evaluated the effects of ELMO1 on ESCC cell activities. The transcriptional regulatory effect of TFAP2A on ELMO1 was verified using dual-luciferase reporter assays and ChIP-qPCR. Additionally, ferroptosis-related indicators were detected to explore the potential role of TFAP2A/ELMO1 in ESCC. A nude mouse xenograft model was established to analyze tumor growth in vivo. ELMO1 was upregulated in KYSE150 cells. Silencing of ELMO1 suppressed ESCC cell migration and invasion, while sensitizing cells to ferroptosis. TFAP2A transcriptionally activated ELMO1 by binding to its promoter, thereby enhancing ESCC cell invasive potential. In vivo, TFAP2A knockdown activated ferroptosis and inhibited tumor growth, whereas ELMO1 overexpression promoted tumor progression. TFAP2A facilitates ESCC cell proliferation, migration, and invasion by promoting ELMO1 transcription and inhibiting ferroptosis. Both TFAP2A and ELMO1 act as oncogenic drivers in ESCC and may represent potential therapeutic targets.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}