Molecular Biotechnology最新文献

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Role of microRNA in Diabetic Osteoporosis.
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2024-11-28 DOI: 10.1007/s12033-024-01316-1
Qiong Yuan, Yuhan Wang, Shan Hu, Zhi Cai, Ling Jiang, Yuanshuai Huang
{"title":"Role of microRNA in Diabetic Osteoporosis.","authors":"Qiong Yuan, Yuhan Wang, Shan Hu, Zhi Cai, Ling Jiang, Yuanshuai Huang","doi":"10.1007/s12033-024-01316-1","DOIUrl":"https://doi.org/10.1007/s12033-024-01316-1","url":null,"abstract":"<p><p>Diabetic osteoporosis (DOP), a complication associated with diabetes mellitus (DM), is a metabolic bone disorder characterized by a reduction in bone mass per unit volume, impaired bone tissue microarchitecture, heightened bone fragility, and increased susceptibility to fractures. Individuals with diabetes exhibit a significantly greater incidence of osteoporosis and related fractures than those without diabetes. These fractures present a significant challenge in terms of the healing process and can result in severe consequences, including fatalities. MicroRNAs (miRNAs), a class of noncoding RNAs, play a pivotal role in numerous human diseases and are implicated in the pathogenesis of DOP. This review initially elucidates the essential role of miRNAs in the pathogenesis of DOP. Next, we emphasize the potential significance of miRNAs as valuable biomarkers for diagnosing DOP and predicting DOP-related fractures. Furthermore, we explore the involvement of miRNAs in managing DOP through various pathways, including conventional pharmaceutical interventions and exercise therapy. Importantly, miRNAs exhibit potential as targeted therapeutic agents for effectively treating DOP. Finally, we highlight the use of novel materials and exosomes for miRNA delivery, which has significant advantages in the treatment of DOP and overcomes the limitations associated with miRNA delivery.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751217","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
Mapping the Potential Genes and Associated Pathways Involved in Long COVID-Associated Brain Fog Using Integrative Bioinformatics and Systems Biology Strategy. 利用综合生物信息学和系统生物学策略,绘制与长 COVID 相关脑雾有关的潜在基因和相关途径图谱
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2024-11-27 DOI: 10.1007/s12033-024-01324-1
Chiranjib Chakraborty, Manojit Bhattacharya, Abdulrahman Alshammari, Norah A Albekairi, Sang-Soo Lee
{"title":"Mapping the Potential Genes and Associated Pathways Involved in Long COVID-Associated Brain Fog Using Integrative Bioinformatics and Systems Biology Strategy.","authors":"Chiranjib Chakraborty, Manojit Bhattacharya, Abdulrahman Alshammari, Norah A Albekairi, Sang-Soo Lee","doi":"10.1007/s12033-024-01324-1","DOIUrl":"https://doi.org/10.1007/s12033-024-01324-1","url":null,"abstract":"<p><p>One of the recent emerging global health issues is long COVID. Among long COVID patients, long COVID-associated brain fog is an important area. We noted an immense gap in understanding the genes and associated pathways involved in long COVID-associated brain fog. Therefore, the study has been selected to understand the genes and pathways involved in patients with long COVID-associated brain fog. A GEO dataset, which was developed through the RNA-seq, was used for the analysis. The dataset encompasses 22 human samples of PBMC. The dataset (human samples of PBMC) was grouped into four cohorts for this study: healthy cohort, COVID convalescent, long COVID, and long COVID brain fog. Therefore, the selection criteria for the 22 PBMC samples were based on the individual infection type (COVID convalescent, long COVID, and long COVID brain fog) and the healthy cohort. Using DEG profile evaluation, we revealed 250 top-ranked DEGs with P values, Padj, baseMean, etc. From the top-ranked DEGs, we listed 24 significant DEGs and some significant DEGs are SMAD3 (P value = 6.34e-07), PF4 (P value = 1.88e-05), TNFAIP3 (P value = 3.70e-06), CXCL5 (P value = 1.22e-08), etc. Among the top-ranked DEGs, we found some genes linked with different biological functions, such as inflammatory cytokine secretion, inflammation, microclot formation, and BBB disruption. From our investigation, we found some genes that are associated with this condition, namely PF4, SMAD3, CXCL5, TNFAIP3, etc. From the literature survey and functional pathway enrichment analysis, we noted the function of the genes such as PF4, SMAD3, and CXCL5. We found that PF4 assists in clot formation, and SMAD3 is associated with neuroinflammation. Similarly, CXCL5 is an inflammatory marker associated with neuroinflammation and BBB damage. At the same time, the study with functional pathway enrichment analysis reflects that DEGs of long COVID-related brain fog might be associated with several biological pathways and processes, cell signatures, and gene-disease associations. It reflects that the disease is a highly complex one. Our study will provide an understanding of the genes and associated pathways in long COVID-related brain fog, which will assist in the next-generation biomarker discovery and therapeutics for these patients.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739927","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
Triple-Action Therapy: Combining Machine Learning, Docking, and Dynamics to Combat BRCA1-Mutated Breast Cancer. 三联疗法:结合机器学习、对接和动力学来对抗 BRCA1 基因突变的乳腺癌。
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2024-11-26 DOI: 10.1007/s12033-024-01328-x
Ashiru Aliyu Zainulabidin, Aminu Jibril Sufyan, Muthu Kumar Thirunavukkarasu
{"title":"Triple-Action Therapy: Combining Machine Learning, Docking, and Dynamics to Combat BRCA1-Mutated Breast Cancer.","authors":"Ashiru Aliyu Zainulabidin, Aminu Jibril Sufyan, Muthu Kumar Thirunavukkarasu","doi":"10.1007/s12033-024-01328-x","DOIUrl":"https://doi.org/10.1007/s12033-024-01328-x","url":null,"abstract":"<p><p>Breast cancer dominates women's mortality, and among other factors, mutations in the BRCA1 gene are significant risk factors. Several approaches are followed to treat the BRCA1 affected cancer patients. However, specific BRCA1 inhibitors are not available till date due to its structural complexity. In addition, there are several limitations associated with the existing drugs used to treat BRCA1-related breast cancer and some side effects. The side effects include symptoms such as hot flashes, joint pain, nausea, fatigue, hair loss, diarrhea, chills, fever, and others. Therefore, advanced approaches needed that can overcome all the limitations and side effects of the current inhibitors. In this study, we adopted a multistep approach to identify potential inhibitors for BRCA1-mutated breast cancer. We used our developed machine learning models to screen potential inhibitors. Molecular docking approach was carried out for the screened hit compounds with BRCA1 and its mutated forms. Two ligands, β-amyrin and Narirutin, has shown significant performance in multiple scoring schemes such as molecular docking and RF score calculations. Molecular dynamics simulations demonstrated the stability of the complexes formed by β-amyrin and Narirutin with BRCA1, with lower RMSD values and less RMSF fluctuations at the binding site locations. Principal component analysis (PCA) and free energy landscape (FEL) further confirmed the compactness and favorable binding of β-Amyrin and Narirutin to BRCA1. These findings suggest that β-amyrin and Narirutin have potential as therapeutic agents against BRCA1-mutated breast cancer.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715853","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
Evaluation of Skin Color Supervision Genes in Chickpea Seeds by Multiomics. 通过多组学评估鹰嘴豆种子中的肤色监督基因
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2024-11-26 DOI: 10.1007/s12033-024-01304-5
Yanming Ma, Lin Xu, Hongmei Zhuang, Faten A Abd-Eldaim, Zhonghua Tang, Youssef Dewer, Hao Wang
{"title":"Evaluation of Skin Color Supervision Genes in Chickpea Seeds by Multiomics.","authors":"Yanming Ma, Lin Xu, Hongmei Zhuang, Faten A Abd-Eldaim, Zhonghua Tang, Youssef Dewer, Hao Wang","doi":"10.1007/s12033-024-01304-5","DOIUrl":"https://doi.org/10.1007/s12033-024-01304-5","url":null,"abstract":"<p><p>Seed samples of two types of chickpea (Cicer arietinum Linn.), including variety A (NRCGR-4452) and variety B (local varieties), with different seed colors, were collected every five days for a total of four times during the seed development period. Non-targeted metabolome and transcriptome sequencing were conducted to identify differentially expressed genes and metabolites associated with chickpea seed coat color. The results indicated that the relative quercetin, pelargonidin, luteolin, rutin, myricetin, kaempferol, glycitin, and naringin contents were higher in variety A than in variety B, and that carbohydrate and amino acid metabolites had a greater impact on flavonoid metabolites. Quercetin, luteolin, and kaempferol were most significantly associated with seed color differences, the associated enzyme genes were LOC101491583 (callose synthase 5-like), LOC101503703 (flavonoid 3',5'-hydroxylase), LOC101514158 (callose synthase 5), LOC101497872 (UDP-glycosyltransferase 74F1-like), LOC101500232 (callose synthase 7 isoform X1), LOC101511206 (UDP-glycosyltransferase 73C3-like), LOC101502065 (galactoside 2-alpha-L-fucosyltransferase), LOC101492791 (sulfoquinovosyl transferase SQD2), and LOC101509377 (flavonol synthase). Additionally, the gene transcription factor MYB44 may regulate UDP-glycosyltransferase 73C3 to affect seed color differences.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715837","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 Simple and Cost-Efficient Method for the Production of Recombinant Horseradish Peroxidase in E. coli. 在大肠杆菌中生产重组辣根过氧化物酶的简单而经济的方法。
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2024-11-25 DOI: 10.1007/s12033-024-01314-3
Kimia Abraheh, Maryam Esmaeili, Nazanin Shans, Saba Ghaffari, Marjan Mohammadi
{"title":"A Simple and Cost-Efficient Method for the Production of Recombinant Horseradish Peroxidase in E. coli.","authors":"Kimia Abraheh, Maryam Esmaeili, Nazanin Shans, Saba Ghaffari, Marjan Mohammadi","doi":"10.1007/s12033-024-01314-3","DOIUrl":"https://doi.org/10.1007/s12033-024-01314-3","url":null,"abstract":"<p><p>Horseradish peroxidase (HRP) is a chromogenic glycoenzyme widely used in research, diagnostics, and therapeutics. Due to its high demand, various eukaryotic and prokaryotic expression systems have been employed for the production of recombinant HRP. Eukaryotic systems yield properly folded, fully functional enzymes with the necessary post-translational modifications. However, these systems can be costly, time-consuming, and prone to hyperglycosylation. In contrast, prokaryotic systems are simple, inexpensive, and readily available, but achieving proper folding and subsequent modifications can be challenging. In this study, we employed a simple and cost-effective method to produce recombinant HRP in soluble form, using the E. coli expression system. The produced enzyme demonstrated substantial activity (89.75 ± 3.25 U/mg) and resistance to heat (T<sub>1/2</sub> = 5 min at 50 °C), pH variations (up to 8), and H<sub>2</sub>O<sub>2</sub> concentrations (up to 10 mM). Additionally, we systematically compared our method with those of other researchers, highlighting methodological details and outcomes of HRP production in E. coli.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710528","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
Harnessing Simple Animal Models to Decode Sleep Mysteries. 利用简单的动物模型破解睡眠之谜。
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2024-11-23 DOI: 10.1007/s12033-024-01318-z
Seithikurippu R Pandi-Perumal, Konda Mani Saravanan, Sayan Paul, Saravana Babu Chidambaram
{"title":"Harnessing Simple Animal Models to Decode Sleep Mysteries.","authors":"Seithikurippu R Pandi-Perumal, Konda Mani Saravanan, Sayan Paul, Saravana Babu Chidambaram","doi":"10.1007/s12033-024-01318-z","DOIUrl":"https://doi.org/10.1007/s12033-024-01318-z","url":null,"abstract":"<p><p>Whether it involves human subjects or non-human animals, basic, translational, or clinical sleep research poses significant ethical challenges for researchers and ethical committees alike. Sleep research greatly benefits from using diverse animal models, each offering unique insights into sleep control mechanisms. The fruit fly (Drosophila melanogaster) is a superior genetic model due to its quick generation period, large progenies, and rich genetic tools. Its well-characterized genome and ability to respond to hypnotics and stimulants make it an effective tool for studying sleep genetics and physiological foundations. The nematode (Caenorhabditis elegans) has a simpler neural organization and transparent body, allowing researchers to explore molecular underpinnings of sleep control. Vertebrate models, like zebrafish (Danio rerio), provide insights into circadian rhythm regulation, memory consolidation, and drug effects on sleep. Invertebrate models, like California sea hare (Aplysia californica) and Upside-down jellyfish (Cassiopea xamachana), have simpler nervous systems and behave similarly to humans, allowing for the examination of sleep principles without logistical and ethical challenges. Combining vertebrate and invertebrate animal models offers a comprehensive approach to studying sleep, improving our understanding of sleep regulation and potentially leading to new drug discovery processes for sleep disorders and related illnesses.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695738","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
Inhibition of miR-20a-5p Suppresses Epithelial-Mesenchymal Transition of Colorectal Cancer Cells Through GJA1. 抑制 miR-20a-5p 可通过 GJA1 抑制结直肠癌细胞的上皮-间质转化
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2024-11-22 DOI: 10.1007/s12033-024-01315-2
Lu Zhang, Jun-Bin Wang, Zhen-Yuan Gao, Xiao Wu, Hai-Rong Zhou
{"title":"Inhibition of miR-20a-5p Suppresses Epithelial-Mesenchymal Transition of Colorectal Cancer Cells Through GJA1.","authors":"Lu Zhang, Jun-Bin Wang, Zhen-Yuan Gao, Xiao Wu, Hai-Rong Zhou","doi":"10.1007/s12033-024-01315-2","DOIUrl":"https://doi.org/10.1007/s12033-024-01315-2","url":null,"abstract":"<p><p>This study was designed to clarify the role of GJA1 in colorectal cancer. qPCR was adopted to detect the GJA1 and miR-20a-5p expression levels in tumor tissues and cells; and EdU, Transwell assay, Scratch test to examine the migration, invasion, and proliferation of colorectal cancer cells. The EMT-related protein expression was measured by immunofluorescence and western Blot. The binding relationship between GJA1 and miR-20a-5p was examined using dual luciferase reporting subsystem. In situ hybridization was utilized to examine the miR-20a-5p expression in tumor tissues and metastases. Rescue experiments were performed by simultaneous transfection of sh-GJA1 inhibitor and miR-20a-5p inhibitor. The miR-20a-5p expression was high and the GJA1 expression was low in colorectal cancer tissues and cells. A targeting relationship was found in GJA1 and miR-20a-5p targets. The invasion, migration, and proliferation of colorectal cancer cells can be inhibited by overexpression of GJA1. Meanwhile, overexpression of GJA1 markedly elevated the e-cadherin expression, but reduced the levels of vimentin, α-SMA and n-cadherin expression. miR-20a-5p inhibitor + sh-GJA1 promoted the invasion, migration, and proliferation of colon cancer cells and EMT process. Overall, miR-20a-5p could target GJA1 to down-regulate the GJA1 expression, thereby regulating the EMT response, and ultimately promoting the progression of colorectal cancer.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687093","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
Association Between the Expression of T Helper Type 17 Cell-Related Cytokines and Valve Damage in Rheumatic Heart Disease. 风湿性心脏病中 17 型 T 辅助细胞相关细胞因子的表达与瓣膜损伤之间的关系
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2024-11-22 DOI: 10.1007/s12033-024-01321-4
Caiyun Zhang, Zhenghua Xiao, Dongmei Yang
{"title":"Association Between the Expression of T Helper Type 17 Cell-Related Cytokines and Valve Damage in Rheumatic Heart Disease.","authors":"Caiyun Zhang, Zhenghua Xiao, Dongmei Yang","doi":"10.1007/s12033-024-01321-4","DOIUrl":"https://doi.org/10.1007/s12033-024-01321-4","url":null,"abstract":"<p><p>The study aimed to clarify the association between Th17 cell-related cytokine expressions and valve damage in rheumatic heart disease (RHD). Twenty RHD patients undergoing mitral valve replacement surgery were selected as the observation group (Group O), and 20 non-rheumatic valve disease patients undergoing mitral valve replacement surgery (degenerative mitral valve prolapse) were recruited as the control group (Group C). Histopathological examination with hematoxylin and eosin (H&E) staining was conducted to observe inflammatory cell infiltration, fibrosis, and neovascularization. Immunohistochemical staining was performed to analyze Th17 cell-related cytokines (interleukin (IL)-17, IL-6, IL-23, IL-21) in patients' cardiac valve tissues. Spearman correlation analysis was employed to investigate the correlation between Th17-related cytokines and inflammatory cell infiltration, fibrosis, and neovascularization. compared to the Group C, the Group O exhibited significantly higher proportions of IL-17, IL-21, IL-6, and IL-23 positive cells and immunohistochemical scores in valve tissues (P < 0.05). Additionally, inflammatory cell infiltration scores, tissue fibrosis scores, and neovascularization scores in valve tissues were significantly higher in the Group O compared to the Group C (P < 0.05). The expression of Th17-related cytokines IL-17, IL-21, IL-6, and IL-23 in valve tissues showed a positive correlation with inflammatory cell infiltration, fibrosis, and neovascularization (P < 0.05). Conclusion: The results demonstrate a notable association between Th17 cell-related cytokine expressions in the heart valves of RHD patients and valve damage, providing a potential target for the treatment and prevention of RHD.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687080","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
Network Pharmacology and Molecular Docking-Based Screening of Immunotherapeutic Targets for HuaChanSu Against Breast Cancer. 基于网络药理学和分子对接的华蟾素乳腺癌免疫治疗靶点筛选。
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2024-11-20 DOI: 10.1007/s12033-024-01305-4
Yujun Tang, Jie Luo, Liuqing Qin, Chaoyi Tang, Caixin Qiu, Jiehua Li, Liuqing Qin
{"title":"Network Pharmacology and Molecular Docking-Based Screening of Immunotherapeutic Targets for HuaChanSu Against Breast Cancer.","authors":"Yujun Tang, Jie Luo, Liuqing Qin, Chaoyi Tang, Caixin Qiu, Jiehua Li, Liuqing Qin","doi":"10.1007/s12033-024-01305-4","DOIUrl":"https://doi.org/10.1007/s12033-024-01305-4","url":null,"abstract":"<p><p>Breast cancer has emerged as the primary cause of mortality stemming from malignancies among women. HuaChanSu has demonstrated efficacy in suppressing the progression of various malignancies. However, the specific immune targets and pathways influenced by HuaChanSu within mammary tumors remain elusive. This study is designed to uncover potent monomers and pivotal targets associated with HuaChanSu's anti-breast cancer Immunotherapy. The genes pertinent to HuaChanSu and breast cancer were acquired individually from publicly available databases. Interaction analysis using Cytoscape was conducted on common genes to determine the most suitable targets and crucial constituents of HuaChanSu's Immunotherapy against breast cancer. Following this, molecular docking was employed to validate ligand and receptor binding interactions. Lastly, the identified core genes underwent assessment of immune infiltration. The intersection of HuaChanSu and BC targets yielded a total of 49 differentially expressed genes. Bufalin emerged as the most potent constituent in Immunotherapy. Immunoassay data demonstrated significant correlations (r > 0.03, p < 0.05) between S100B, MMP9, FOS, EGFR, KIT, MME, and immune infiltration within BC. Molecular docking further corroborated the effective binding of Bufalin with immune-related genes. Through network pharmacological validation, we propose the extraction of Bufalin, a monomeric constituent of Huachansu, to exert immunomodulatory effects aimed at inhibiting the progression of breast cancer. Most of the target genes (S100B, BIRC5, MMP9, FOS, EGFR, KIT, and MME) are common targets for immunotherapy.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676193","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
Generation of Ext1 Gene-Edited Mice Model Via Dual sgRNAs/Cas9 System and Phenotypic Analyses. 通过双 sgRNAs/Cas9 系统生成 Ext1 基因编辑小鼠模型并进行表型分析
IF 2.4 4区 生物学
Molecular Biotechnology Pub Date : 2024-11-20 DOI: 10.1007/s12033-024-01325-0
Lan Zhou, Xin Li, Zihan Ji, Can Zhou, Lingling Yang, Yong Li, Can Fu, Lantao Gu, Shun Zhang, JinTao Gao, Pengpeng Yue, Honghao Yu
{"title":"Generation of Ext1 Gene-Edited Mice Model Via Dual sgRNAs/Cas9 System and Phenotypic Analyses.","authors":"Lan Zhou, Xin Li, Zihan Ji, Can Zhou, Lingling Yang, Yong Li, Can Fu, Lantao Gu, Shun Zhang, JinTao Gao, Pengpeng Yue, Honghao Yu","doi":"10.1007/s12033-024-01325-0","DOIUrl":"https://doi.org/10.1007/s12033-024-01325-0","url":null,"abstract":"<p><p>Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disease. Genetic linkage analyses have identified that mutations in the exostosin glycosyltransferase (EXT)1 and EXT2 genes are linked to HME pathogenesis, with EXT1 mutation being the most frequent. The aim of this study was to generate a mice model with Ext1 gene editing to simulate human EXT1 mutation and investigate the genetic pathogenicity of Ext1 through phenotypic analyses. We designed a pair of dual sgRNAs targeting exon 1 of the mice Ext1 gene for precise deletion of a 46 bp DNA fragment, resulting in frameshift mutation of the Ext1 gene. The designed dual sgRNAs and Cas9 proteins were injected into mice zygotes cytoplasm. A total of 14 mice were obtained via embryo transfer, among which two genotypic chimera mice had a deletion of the 46 bp DNA fragment in exon 1 of the Ext1 gene. By hybridization and breeding, we successfully generated heterozygous mice with edited Ext1 gene (Ext<sup>+/-</sup>). Off-target effect analysis did not reveal off-target mutations in Ext<sup>+/-</sup> mice caused by the two sgRNAs used. Compared to wild-type mice, Ext<sup>+/-</sup> mice exhibited lower body weights. X-ray imaging showed hyperplastic bone near caudal vertebrae only in male Ext<sup>+/-</sup> mice, with computed tomography values approximately at 200 HU for hyperplastic bone between ribs and spine regions. Furthermore, immunohistochemical analysis revealed fewer articular chondrocytes expressing EXT1 in edited mice compared to wild-type ones. Pathological section analysis demonstrated no structural or morphological abnormalities in heart, liver, lung, or kidney tissues from Ext<sup>+/-</sup> mice. In conclusion, we successfully generated an accurate DNA deletion model for studying Ext1 using dual sgRNAs/Cas9 systems. In conclusion, we successfully generated precise DNA deletions in the Ext1 mice model using the dual sgRNAs/Cas9 system. In conclusion, we observed significant phenotypic changes in Ext<sup>+/-</sup> mice, particularly bone hyperplasia in male individuals; however, no exostosis was detected in the gene-edited mice. The introduction of a frameshift mutation into the Ext1 gene through CRISPR/Cas9 technology resulted in novel phenotypic alterations, highlighting the genetic pathogenicity of Ext1. Therefore, our Ext<sup>+/-</sup> mice serve as a valuable model for further biomedical investigations related to the Ext1 gene.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676183","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
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