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Exploring the Effects of Opioid-Related Drugs on the Clinical Outcome of Prostate Cancer Patients Via Integrated Bioinformatics Analysis. 通过综合生物信息学分析探讨阿片类药物对前列腺癌患者临床预后的影响。
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2025-01-20 DOI: 10.1007/s12033-024-01353-w
Yunxuan Zhang, Yuenan Liu, Kailei Chen, Qi Miao, Qi Cao, Xiaoping Zhang
{"title":"Exploring the Effects of Opioid-Related Drugs on the Clinical Outcome of Prostate Cancer Patients Via Integrated Bioinformatics Analysis.","authors":"Yunxuan Zhang, Yuenan Liu, Kailei Chen, Qi Miao, Qi Cao, Xiaoping Zhang","doi":"10.1007/s12033-024-01353-w","DOIUrl":"https://doi.org/10.1007/s12033-024-01353-w","url":null,"abstract":"<p><p>Opioids are the primary regimens for perioperative analgesia with controversial effects on oncological survival. The underlying mechanism remains unexplored. This study developed survival-related gene co-expression networks based on RNA-seq and clinical characteristics from TCGA cohort. Two survival-related networks were identified, and drug-induced transcriptional profiles were predicted. Immune cell infiltration algorithm, least absolute shrinkage and selection operator (LASSO) regression, and cox proportional models were executed to explore the correlation between opioid-related drugs and prostate cancer patient prognosis. The opioid receptor agonists, represented by tramadol, were evidenced for anti-survival effects on prostate cancer by facilitating the DNA replication and cell cycle, and immune cell infiltration. Conversely, opioid receptor antagonists showed pro-survival effects. A novel prognostic model containing CNIH2, MCCC1, and Gleason scores was established and validated in two independent cohorts. This study revealed opioids' effect on prostate cancer progression, and provided a novel model to predict these regulations in clinical outcomes.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008595","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}
引用次数: 0
Exploration of the Biological Function of Ferroptosis in Bone Nonunion: An Analysis of Bioinformatics Combined Mendelian Randomization. 探讨骨不连中铁下垂的生物学功能:结合孟德尔随机化的生物信息学分析。
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2025-01-19 DOI: 10.1007/s12033-025-01370-3
Jun Yu, Kai Feng, Ming Yang, Kaijie Yang, Yun Jin, Zhanhu Mi
{"title":"Exploration of the Biological Function of Ferroptosis in Bone Nonunion: An Analysis of Bioinformatics Combined Mendelian Randomization.","authors":"Jun Yu, Kai Feng, Ming Yang, Kaijie Yang, Yun Jin, Zhanhu Mi","doi":"10.1007/s12033-025-01370-3","DOIUrl":"https://doi.org/10.1007/s12033-025-01370-3","url":null,"abstract":"<p><p>To deeply investigate the mechanism of ferroptosis-related genes in the process of bone nonunion based on the GEO database. And using Mendelian randomization to explore the causal association of 15 trace elements with the occurrence of bone nonunion. Bone nonunion RNA-seq data were retrieved and downloaded from the GEO database. The differentially expressed genes in bone nonunion were identified using two differential expression analysis methods, \"limma\" and \"WGCNA\". Random Forest Tree, Support Vector Machine, and Lasso-cox were used to analyze and screen the genes related to ferroptosis in bone nonunion; A risk model of bone nonunion was constructed based on the screened ferroptosis-related genes; based on this, the pathway mechanism of ferroptosis-related genes involved in the occurrence and development of bone nonunion was further investigated. Mendelian randomization analysis was performed using inverse variance weighting as the main analysis method, and weighted median, Weighted mode, Mr-Egger, and Simple mode were used as complementary methods. Heterogeneity was detected using Cochran's Q test and funnel plot analysis, horizontal pleiotropy was detected using Mr-Egger intercept, and sensitivity analyses were performed using the \"leave-one-out\" method. PTGS2/PRKCA/MAPK14 all showed excellent diagnostic efficacy for bone nonunion. The risk prediction model based on PTGS2, PRKCA, and MAPK14 showed good predictive efficacy and clinical benefit rate for bone nonunion. Ferroptosis core gene PRKCA may be involved in the VEGF signaling pathway to affect the cell cycle and inhibit fracture healing. MR analysis suggests that Potassium and Vitamin E are protective factors for the development of bone nonunion. Ferroptosis genes PTGS2/PRKCA/MAPK14 are potential diagnostic targets for bone nonunion. The down-regulation of PRKCA expression may inhibit fracture healing through the VEGF signaling pathway during the growth of blood vessels at fracture breaks. The results of MR suggested that Potassium and Vitamin E have a promoting effect on fracture healing.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008591","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}
引用次数: 0
Nucleolin a Central Player in Host Virus Interactions and its Role in Viral Progeny Production. 核蛋白:宿主病毒相互作用的核心参与者及其在病毒子代产生中的作用。
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2025-01-17 DOI: 10.1007/s12033-025-01372-1
Ahsan Naveed, Rumaisa Umer, Ayzal Fatemah, Rabia Naveed
{"title":"Nucleolin a Central Player in Host Virus Interactions and its Role in Viral Progeny Production.","authors":"Ahsan Naveed, Rumaisa Umer, Ayzal Fatemah, Rabia Naveed","doi":"10.1007/s12033-025-01372-1","DOIUrl":"https://doi.org/10.1007/s12033-025-01372-1","url":null,"abstract":"<p><p>Nucleolin (NCL) is a prevalent and widely distributed nucleolar protein in cells. While primarily located in the nucleolus, NCL is also found within the nucleoplasm, cytoplasm, and even on the cell surface. NCL's unique nature arises from its multifaceted roles and extensive interactions with various proteins. The structural stability of NCL is reliant on protease inhibitors, particularly in proliferating cells, indicating its essential role in cellular maintenance. This review is centered on elucidating the structure of NCL, its significance in host-viral interactions, and its various contributions to viral progeny production. This work is to enhance the scientific community's understanding of NCL functionality and its implications for viral infection processes. NCL is highlighted as a crucial host protein that viruses frequently target, exploiting it to support their own life cycles and establish infections. Understanding these interactions is key to identifying NCL's role in viral pathogenesis and its potential as a therapeutic target. Our current knowledge, alongside extensive scientific literature, underscores the critical role of host proteins like NCL in both viral infections and other diseases. As a target for viral exploitation, NCL supports viral replication and survival, making it a promising candidate for therapeutic intervention. By delving deeper into the intricacies of NCL-viral protein interactions, researchers may uncover effective antiviral mechanisms. This review aspires to inspire further research into NCL's role in viral infections and promote advancements in antiviral therapeutic development.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008617","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}
引用次数: 0
Biological Effects of Calceolarioside A as a Natural Compound: Anti-Ovarian Cancer, Anti-Tyrosinase, and Anti-HMG-CoA Reductase Potentials with Molecular Docking and Dynamics Simulation Studies. 天然化合物钙根皂苷A的生物学效应:抗卵巢癌、抗酪氨酸酶和抗hmg - coa还原酶潜能的分子对接和动力学模拟研究
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2025-01-17 DOI: 10.1007/s12033-025-01369-w
Liqin Chen, Dan Han, ChunYan Gu, Wei Huang
{"title":"Biological Effects of Calceolarioside A as a Natural Compound: Anti-Ovarian Cancer, Anti-Tyrosinase, and Anti-HMG-CoA Reductase Potentials with Molecular Docking and Dynamics Simulation Studies.","authors":"Liqin Chen, Dan Han, ChunYan Gu, Wei Huang","doi":"10.1007/s12033-025-01369-w","DOIUrl":"https://doi.org/10.1007/s12033-025-01369-w","url":null,"abstract":"<p><p>One kind of hydroxycinnamic acid is calceolarioside A. Plantago coronopus, Cassinopsis madagascariensis, and other organisms for whom data are available are known to have this naturally occurring compound. IC50 values of Calceolarioside A for ovarian cell lines (NIH-OVCAR-3, ES-2, UACC-1598, Hs832.Tc, TOV-21G, UWB1.289) were 24.42, 13.50, 9.31, 14.90, 20.07, and 16.18 µM, respectively. IC50 values were 19.83 and 73.48 µM for tyrosinase and HMG-CoA reductase enzymes. The chemical activities of Calceolarioside A against HMG-CoA reductase and tyrosinase were assessed by conducting the molecular docking study, MM/GBSA calculation, and molecular dynamics (MD) simulation. The anticancer activities of this compound were evaluated against some ovarian cancer cells, such as NIH-OVCAR-3, ES-2, UACC-1598, Hs832.Tc, TOV-21G, and UWB1.289 cell lines. The chemical activities of Calceolarioside A against some of the expressed surface receptor proteins (folate receptor, CD44, EGFR, Formyl Peptide Receptor-Like 1, M2 muscarinic receptor, and estrogen receptors) were investigated using computational methods. The results exhibited the interplay among atoms. The compound formed robust associations with both the enzymes and receptors. Calceolarioside A can hinder the functioning of these enzymes and the proliferation of malignant cells.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008581","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}
引用次数: 0
Panax Notoginseng Saponins Inhibit Apoptosis and Alleviate Renal Ischemia-Reperfusion Injury Through the ROCK2/NF-κB Pathway. 三七总皂苷通过ROCK2/NF-κB途径抑制细胞凋亡,减轻肾缺血再灌注损伤。
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2025-01-17 DOI: 10.1007/s12033-025-01366-z
Liu Xin, Ning Kanghao, Li Jiacheng, Yan Xiaodong, Yan Juhan, Zhao Xinyang, Li Xiangdong
{"title":"Panax Notoginseng Saponins Inhibit Apoptosis and Alleviate Renal Ischemia-Reperfusion Injury Through the ROCK2/NF-κB Pathway.","authors":"Liu Xin, Ning Kanghao, Li Jiacheng, Yan Xiaodong, Yan Juhan, Zhao Xinyang, Li Xiangdong","doi":"10.1007/s12033-025-01366-z","DOIUrl":"https://doi.org/10.1007/s12033-025-01366-z","url":null,"abstract":"<p><p>Renal ischemia-reperfusion injury (RIRI) is a primary cause of acute kidney injury (AKI), frequently resulting in high mortality rates and progression to chronic kidney disease (CKD). This study aimed to investigate the therapeutic potential of total saponins from Panax notoginseng (PNS) in the context of RIRI. Utilizing a murine RIRI model, the efficacy of PNS was evaluated, demonstrating a significant reduction in renal inflammation and cellular pyroptosis. Furthermore, PNS was found to modulate the ROCK2/NF-κB signaling pathway, thereby attenuating the inflammatory response. Importantly, in vitro experiments with hypoxia/reoxygenation cell models corroborated these findings, showing that PNS inhibited pyroptosis and regulated the ROCK2/NF-κB pathway. This research underscores the therapeutic potential of PNS in the treatment of RIRI, providing a robust scientific basis for its consideration as a prospective clinical therapy.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008597","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}
引用次数: 0
A Rapid PCR-LAMP Assay for the Early Detection of Lasiodiplodia theobromae from Basal Stem Rot-Infected Passion Fruit Plants. 百香果基茎腐病的快速PCR-LAMP早期检测方法。
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2025-01-17 DOI: 10.1007/s12033-024-01363-8
Ying Liu, Usman Rasheed, Bin Shan, Qinyu Lu, Shimiao Chen, Kaikai Meng, Aiying Qin, Ganhui Mo
{"title":"A Rapid PCR-LAMP Assay for the Early Detection of Lasiodiplodia theobromae from Basal Stem Rot-Infected Passion Fruit Plants.","authors":"Ying Liu, Usman Rasheed, Bin Shan, Qinyu Lu, Shimiao Chen, Kaikai Meng, Aiying Qin, Ganhui Mo","doi":"10.1007/s12033-024-01363-8","DOIUrl":"https://doi.org/10.1007/s12033-024-01363-8","url":null,"abstract":"<p><p>Lasiodiplodia theobromae is an emerging threat and the main pathogenic fungi associated with basal stem rot of passion fruit in Guangxi Zhuang Autonomous Region, China. Current pathogen identification protocols are labor-intensive and time-consuming, emphasizing the need for more efficient methods to enable precise surveillance of L. theobromae for early detection and warning. The present study sought to develop a rapid colorimetric LAMP assay for early detection and surveillance of L. theobromae in passion fruit plants. For that, amplifications of ITS locus were performed on fungal genomic DNA using conventional PCR, with the specific primer pair ITS1 and ITS4. The hydroxy naphthol blue (HNB)-dependent colorimetric LAMP assay was then optimized by varying primer sets, inner primers concentration, reaction temperatures and incubation time. A microbial lysis buffer was employed to extract genomic DNA from stems infected with L. theobromae. The prime LAMP primer set targeting the ITS region of L. theobromae was designed and an HNB based colorimetric LAMP assay was optimized. Various optimization parameters were evaluated, with the optimal conditions determined as 1.6 μM of each FIB and BIP, 0.2 μM of each F3 and B3, and incubation at 65 °C for 40 min. This ITS-based LAMP assay could effectively distinguish L. theobromae from less dominant pathogens in passion fruits with a detection limit of 3 pg for ITS locus amplicons. Our proposed method utilizing a microbial lysis buffer enables rapid and cost-effective detection of L. theobromae DNA in early-infected passion fruit plants, eliminating the need for microbial cultivation and DNA purification.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008577","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}
引用次数: 0
Cancer-Specific Activation of the Vesicular Stomatitis Virus Matrix by Survivin Promoter in Breast Cancer Cells. 乳腺癌细胞中Survivin启动子对水泡性口炎病毒基质的癌症特异性激活
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2025-01-17 DOI: 10.1007/s12033-024-01359-4
Atefeh Valouzi, Majid Shahbazi, Vahid Erfani-Moghadam, Mahboobeh Ramezani, Fatemeh T Shamsabadi
{"title":"Cancer-Specific Activation of the Vesicular Stomatitis Virus Matrix by Survivin Promoter in Breast Cancer Cells.","authors":"Atefeh Valouzi, Majid Shahbazi, Vahid Erfani-Moghadam, Mahboobeh Ramezani, Fatemeh T Shamsabadi","doi":"10.1007/s12033-024-01359-4","DOIUrl":"https://doi.org/10.1007/s12033-024-01359-4","url":null,"abstract":"<p><p>Oncolytic viral-based therapy and specific gene expression by promoters are modern targeted oncotherapy approaches that have gained significant attention in recent years. In this study, both strategies were combined by designing cancer-specific activation of vesicular stomatitis virus matrix expression under the survivin promoter. The matrix sequence was cloned downstream of the survivin promoter (pM). After transfecting MCF-7 cells with pM, cell proliferation and apoptosis induction were assessed. Additionally, the transcript levels of matrix and apoptosis-related genes in response to pM was assessed. The proliferation of MCF-7 cells was significantly reduced by the constructed matrix-expressing plasmid at 48 and 72 h post-transfection (p < 0.05). Enhanced matrix expression resulted in the down-regulation of MMP-9, TP53, and NF-kB, while simultaneously up-regulating Bax transcripts. Evaluating the effect of pM vector on apoptosis induction revealed a significant increase in the MCF-7 cells compared to untreated cells (p < 0.05). The absence of significant matrix gene expression in HDF cells, relative to MCF-7 cells, further underscores the specific function of the Survivin promoter in cancer cells. These findings suggest that the matrix may have various biological functions in a diverse set of non-apoptotic pathways. Further research on the association of the matrix with other genes could provide insights into the biomedical significance and future perspectives of the matrix in cancer gene therapy.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008587","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}
引用次数: 0
In Silico Structural Insights into a Glucanase from Clostridium perfringens and Prediction of Structural Stability Improvement Through Hydrophobic Interaction Network and Aromatic Interaction. 对产气荚膜梭菌葡聚糖酶的硅学结构洞察,以及通过疏水相互作用网络和芳香族相互作用改善结构稳定性的预测。
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2025-01-15 DOI: 10.1007/s12033-025-01371-2
Nima Ghahremani Nezhad, Azadeh Eskandari, Oluwaloni Folusho Omotayo, Samah Hashim Albayati, Sunusi Bataiya Buhari, Thean Chor Leow
{"title":"In Silico Structural Insights into a Glucanase from Clostridium perfringens and Prediction of Structural Stability Improvement Through Hydrophobic Interaction Network and Aromatic Interaction.","authors":"Nima Ghahremani Nezhad, Azadeh Eskandari, Oluwaloni Folusho Omotayo, Samah Hashim Albayati, Sunusi Bataiya Buhari, Thean Chor Leow","doi":"10.1007/s12033-025-01371-2","DOIUrl":"https://doi.org/10.1007/s12033-025-01371-2","url":null,"abstract":"<p><p>Glucanases are widely applied in industrial applications such as brewing, biomass conversion, food, and animal feed. Glucanases catalyze the hydrolysis of glucan to produce the sugar hemiacetal through hydrolytic cleavage of glycosidic bonds. Current study aimed to investigate structural insights of a glucanase from Clostridium perfringens through blind molecular docking, site-specific molecular docking, molecular dynamics (MD) simulation, and binding energy calculation. Furthermore, we aimed to enhance structural stabilization through formation of hydrophobic interaction network. The molecular docking results illustrated that residues Glu222 and Asp187 may act as nucleophile acid/base catalyst. Moreover, the MM/PBSA results illustrated a high binding affinity of 108.71 ± 8.5 kJ/mol between glucanase and barely glucan during 100 ns simulation. The RMSF analysis illustrated a high flexible surface loop with the highest mobility at position D130. Therefore, the structural engineering was carried out through introducing a double-mutant S125Y/D130P, and the structural stability was improved by forming the hydrophobic interaction network and one π-π aromatic interaction. The spatial distance between the mutation sites and the catalytic pocket attenuates their direct impact on binding interactions within the catalytic pocket.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984297","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}
引用次数: 0
Metal-Coordinated Histidine-Functionalized Redox-Responsive Polyethyleneimine as a Smart Gene Delivery Vector. 金属配位组氨酸功能化氧化还原反应型聚乙烯亚胺作为智能基因传递载体。
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2025-01-13 DOI: 10.1007/s12033-024-01360-x
Makkieh Jahanpeimay Sabet, Akbar Hasanzadeh, Amirhossein Vahabi, Elaheh Sadat Hosseini, Sara Saeedi, Beheshteh Khodadadi Chegeni, Jafar Kiani, Behjat Kheiri Yeghaneh Azar, Zahra Asghari Molabashi, Mehdi Shamsara, Michael R Hamblin, Mahdi Karimi, Abazar Roustazadeh
{"title":"Metal-Coordinated Histidine-Functionalized Redox-Responsive Polyethyleneimine as a Smart Gene Delivery Vector.","authors":"Makkieh Jahanpeimay Sabet, Akbar Hasanzadeh, Amirhossein Vahabi, Elaheh Sadat Hosseini, Sara Saeedi, Beheshteh Khodadadi Chegeni, Jafar Kiani, Behjat Kheiri Yeghaneh Azar, Zahra Asghari Molabashi, Mehdi Shamsara, Michael R Hamblin, Mahdi Karimi, Abazar Roustazadeh","doi":"10.1007/s12033-024-01360-x","DOIUrl":"https://doi.org/10.1007/s12033-024-01360-x","url":null,"abstract":"<p><p>Despite significant advancements in gene delivery and CRISPR technology, several challenges remain. Chief among these are overcoming serum inhibition and achieving high transfection efficiency with minimal cytotoxicity. To address these issues, there is a need for novel vectors that exhibit lower toxicity, maintain stability in serum-rich environments, and effectively deliver plasmids of various sizes across diverse cell types. In this study, to convert common polyethylenimine (PEI<sub>1.8k</sub>) into high-performance DNA delivery vectors, an innovative multifunctional vector was constructed based on histidine linked to PEI<sub>1.8k</sub> by redox-responsive disulfide bonds. Apart from highly efficient transfection of both small and large plasmids into HEK 293T (Human Embryonic Kidney 293T cells) with negligible cytotoxicity, PEI<sub>1.8k</sub>-S-S-His showed great transfection potential even at low plasmid doses (0.5 µg), as well as at serum concentrations ranging from 5 to 30% into HEK 293T cells, and achieved excellent plasmid transfection into NIH/3T3 (Mouse Embryonic Fibroblast cells), and MCF7 (Human Breast Cancer cells). Additionally, several metals were tested (Co, Cu, Cd, Ni, Zn, and Mn) to promote the plasmid packaging functionality and improve transfection efficiency. We observed that, in comparison to PEI<sub>1.8k</sub>-S-S-His, the manganese-functionalized nanocarrier (PEI<sub>1.8k</sub>-S-S-His-Mn) could transfect a large plasmid with equal efficiency (~ 30%) into MSCs (Mesenchymal Stem Cells). Interestingly, PEI<sub>1.8k</sub>-S-S-His-Mn showed higher transfection efficiency with the small plasmid (~ 90%) and the large one (~ 80%) into HEK 293T cells, even better than its backbone. We propose that the presence of metal-coordinated His ligand, redox-responsive S-S bonds, and the cationic polymer can synergistically provide robust DNA binding, efficient endosomal disruption, tolerance of serum protein adsorption, and low cytotoxicity. These new vectors could be promising for gene delivery and may be therapeutically relevant.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979227","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}
引用次数: 0
CRISPR/Cas9 System as a Promising Therapy in Thalassemia and Sickle Cell Disease: A Systematic Review of Clinical Trials. CRISPR/Cas9系统有望治疗地中海贫血和镰状细胞病:临床试验的系统综述
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2025-01-10 DOI: 10.1007/s12033-025-01368-x
Rehab Ahmed, Wafa N Alghamdi, Fetun R Alharbi, Huda D Alatawi, Kawthar M Alenezi, Turki F Alanazi, Nehal M Elsherbiny
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