Journal of Gene Medicine最新文献

{"title":"Novel co-delivery of oridonin and docetaxel nanoliposome for an enhanced antitumor effect on esophageal cancer","authors":"Xi Chen,&nbsp;Hengyu Mao,&nbsp;Feng Peng,&nbsp;Jiang Fan,&nbsp;Fu Yang","doi":"10.1002/jgm.3725","DOIUrl":"10.1002/jgm.3725","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Esophageal cancer is one of the major cancers in China. Most patients with esophageal cancer are diagnosed at an advanced stage, and the 5 year survival rate is discouraging. Combined chemotherapy is a common method for the treatment of esophageal cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, distearoyl phosphatidyl ethanolamine polyethylene glycol 2000 (DSPE-PEG2000) nanoliposomes (NLPs) encapsulating the anticancer drugs docetaxel (DOX) and oridonin (ORD) were prepared, and their ability to enhance the release of anticancer drugs was determined. The NLP system was characterized by transmission electron microscopy, particle size and encapsulation efficiency. In addition, the release characteristics and pharmacodynamics of these drugs were also studied in detail.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>When the DOX/ORD ratio was 2:1, the higher proportion of DOX led to a stronger synergy effect. DOX/ORD NLPs were prepared by the high-pressure homogenization method and had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 246.4 and 0.163, respectively. The stability results showed that no significant change was observed in particle size, zeta potential, Encapsulation efficiency and dynamic light scattering for DOX/ORD NLPs during the observation period. The results of <i>in vitro</i> release illustrated that the acidic environment of tumor might be beneficial to drug release. The three-dimensional tumorsphere showed that DOX/ORD NLPs can reach the interior of tumor spheres, which destroys the structure of cells, resulting in irregular spherical tumor spheres. The <i>in vivo</i> study results indicated that DOX/ORD NLPs had an obvious targeting effect on subcutaneous tumors and have the potential to actively deliver drugs to tumor tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to detect apoptosis. The results showed that DOX/ORD NLP treatment could significantly induce apoptosis and inhibit tumor growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The DOX/ORD NLPs prepared in this study can enhance the anti-tumor activity, and are expected to be a promising co-delivery platform for the treatment of esophageal cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Long non-coding RNA KCNQ1OT1 Promotes the Progression of Gastric Cancer via the miR-145-5p/ARF6 Axis","authors":"","doi":"10.1002/jgm.3727","DOIUrl":"10.1002/jgm.3727","url":null,"abstract":"<p><b>RETRACTION</b>: X. Zhong, X. Wen, L. Chen, N. Gu, X. Yu, and K. Sui, “Long non-coding RNA KCNQ1OT1 Promotes the Progression of Gastric Cancer via the miR-145-5p/ARF6 Axis,” <i>The Journal of Gene Medicine</i> 23, no. 5 (2021): e3330, https://doi.org/10.1002/jgm.3330.</p><p>The above article, published online on 8 March 2021 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Jiang Fan; and John Wiley &amp; Sons Ltd. The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Several flaws and inconsistencies between results presented and experimental methods described were found. Specifically, multiple image elements were found to have been published elsewhere in a different scientific context. Furthermore, the article presents results from multiple non-verifiable/unknown cell lines: BSG823, BSG803, BGC803, and GSE1. Accordingly, the conclusions of this article are considered invalid by the editors. The authors have been informed of the decision of retraction but unavailable for a final confirmation.</p>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.3727","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDCL3 as a prognostic factor and associated with the VEGF signaling pathway in glioma","authors":"Bo Yang,&nbsp;Guangwei Zheng,&nbsp;Feng Lu","doi":"10.1002/jgm.3724","DOIUrl":"10.1002/jgm.3724","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>New targeted drugs about angiogenesis could develop the treatment of glioma. We aimed to explore the role of phosducin like 3 (PDCL3) in angiogenesis of glioma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>RNA sequencing data and matched clinical data were downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. To screen for the reliable genes with the filtering analyses, survival, multivariate Cox, receiver operating characteristic (ROC) curve filtration, and clinical correlation analyses were performed. The PDCL3 gene was validated by immunohistochemistry as a reliable gene for further analysis. Then we used the combined data of TCGA and Genotype-Tissue Expression from UCSC to detect the differential gene expression of PDCL3. Related signal pathways in glioma were explored by the gene set enrichment analysis and co-expression analysis. Lastly, we performed <i>in vitro</i> experiments to verify the gene functions and related mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The three filtering analyses and immunostaining indicated that the expression of PDCL3 in glioma tissues was higher than the normal tissues. Gene function analysis showed that PDCL3 activated the vascular endothelial growth factor (VEGF) signal pathway, and its mechanism was related to pathways in cancer, like NOD like receptor signaling pathway, the RIG-I like receptor signaling pathway and the P53 signaling pathway by MAPK/AKT in gliomas. This suggested that the proliferation, migration and invasion of glioma cells might be inhibited by the downregulation of PDCL3 <i>in vitro</i>, which may be related to the activation of VEGF signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We demonstrated that PDCL3 could function as an independent adverse prognostic marker in glioma. Its pro-oncogenic mechanism may be related to the VEGF signaling pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of intravitreally delivered AAV2 vector-mediated multi-characteristic opsin genetic construct in wild type beagle dogs","authors":"Samarendra Mohanty,&nbsp;Subrata Batabyal,&nbsp;Ananta Ayyagari,&nbsp;Najam A. Sharif","doi":"10.1002/jgm.3720","DOIUrl":"10.1002/jgm.3720","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A novel adeno-associated virus 2 (AAV2)-carried multi-characteristic opsin (MCO) (MCO-010) is undergoing several clinical trials as a novel therapeutic modality for the treatment of degenerative retinal diseases including retinitis pigmentosa and Stargardt disease. The present study aimed to determine the ocular and systemic safety of MCO-010 and the AAV2 vehicle in adult Beagle dogs following intravitreal (IVT) injection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The current safety/toxicology studies spanning 13 weeks described here utilized well-documented techniques to assess the effects of IVT injection of MCO-010 up to 2.2 × 10¹¹ genome copies (gc) per eye, or the AAV2 capsid (vehicle control) on gross behavioral and immunogenic changes, alterations in body weights, blood biochemistry, hematology, blood coagulation, gross necropsy lesions, organ weight changes and histopathology in the dogs (n = 4 per group; two males and two females per group). Immunohistochemical and functional electroretinogram studies were also conducted to determine MCO expression in the retina and determine any retinal toxicity associated with MCO-010.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were no significant deleterious effects of the MCO-010 (or the AAV2 at the tested doses) on any of the examined parameters, including the absence of any severe ocular or systemic adverse events. However, as expected, inflammation after IVT delivery of AAV2 and MCO-010 was observed in the conjunctivae of all groups of animals, although this self-resolved within 1 week post-injection. Quantitative immunohistochemical analyses of MCO-010-associated mCherry revealed successful delivery of the gene therapy within the inner retina.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In summary, MCO-010 demonstrated a favorable safety profile when administered to the eyes of adult Beagle dogs of both sexes at dose levels up to 2.2 × 10¹¹ gc per eye, with no adverse effects observed. This dose was identified as the No Observed Adverse Effect Level (i.e. NOAEL) and guided selection of safe doses for human clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icariin attenuates asthmatic airway inflammation via modulating alveolar macrophage activation based on network pharmacology and in vivo experiments","authors":"Xiaofei Zhu,&nbsp;Bin Wang,&nbsp;Hang Yu,&nbsp;Congcong Li,&nbsp;Yuhang Zhao,&nbsp;Yuanyuan Zhong,&nbsp;Weifeng Tang,&nbsp;Yaolong Zhou,&nbsp;Xi Huang,&nbsp;Huahe Zhu,&nbsp;Yueren Wu,&nbsp;Kai Yang,&nbsp;Ying Wei,&nbsp;Zhen Gao,&nbsp;Jingcheng Dong","doi":"10.1002/jgm.3718","DOIUrl":"10.1002/jgm.3718","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Icariin (ICA) inhibits inflammatory response in various diseases, but the mechanism underlying ICA treating airway inflammation in asthma needs further understood. We aimed to predict and validate the potential targets of ICA against asthma-associated airway inflammation using network pharmacology and experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The ovalbumin-induced asthma-associated airway inflammation mice model was established. The effects of ICA were evaluated by behavioral, airway hyperresponsiveness, lung pathological changes, inflammatory cell and cytokines counts. Next, the corresponding targets of ICA were mined via the SEA, CTD, HERB, PharmMapper, Symmap database and the literature. Pubmed-Gene and GeneCards databases were used to screen asthma and airway inflammation-related targets. The overlapping targets were used to build an interaction network, analyze gene ontology and enrich pathways. Subsequently, flow cytometry, quantitative real-time PCR and western blotting were employed for validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ICA alleviated the airway inflammation of asthma; 402 targets of ICA, 5136 targets of asthma and 4531 targets of airway inflammation were screened; 216 overlapping targets were matched and predicted ICA possesses the potential to modulate asthmatic airway inflammation by macrophage activation/polarization. Additionally, ICA decreased M1 but elevated M2. Potential targets that were disrupted by asthma inflammation were restored by ICA treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ICA alleviates airway inflammation in asthma by inhibiting the M1 polarization of alveolar macrophages, which is related to metabolic reprogramming. <i>Jun</i>, <i>Jak2</i>, <i>Syk</i>, <i>Tnf</i>, <i>Aldh2</i>, <i>Aldh9a1</i>, <i>Nos1</i>, <i>Nos2</i> and <i>Nos3</i> represent potential targets of therapeutic intervention. The present study enhances understanding of the anti-airway inflammation effects of ICA, especially in asthma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematopoietic stem cell gene therapy for the treatment of SYNGAP1-related non-specific intellectual disability","authors":"Joseph S. Anderson,&nbsp;Alyse L. Lodigiani,&nbsp;Camilla M. Barbaduomo,&nbsp;Julie R. Beegle","doi":"10.1002/jgm.3717","DOIUrl":"10.1002/jgm.3717","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Synaptic Ras GTPase activating protein 1 (SYNGAP1)-related non-specific intellectual disability is a neurodevelopmental disorder caused by an insufficient level of SynGAP1 resulting in a dysfunction of neuronal synapses and presenting with a wide array of clinical phenotypes. Hematopoietic stem cell gene therapy has the potential to deliver therapeutic levels of functional SynGAP1 to affected neurons upon transduction of hematopoietic stem and progenitor cells with a lentiviral vector.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>As a novel approach toward the treatment of SYNGAP1, we have generated a lentiviral vector expressing a modified form of SynGAP1 for transduction of human CD34+ hematopoietic stem and progenitor cells. The gene-modified cells were then transplanted into adult immunodeficient SYNGAP1+/− heterozygous mice and evaluated for improvement of SYNGAP1-related clinical phenotypes. Expression of SynGAP1 was also evaluated in the brain tissue of transplanted mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In our proof-of-concept study, we have demonstrated significant improvement of SYNGAP1-related phenotypes including an improvement in motor abilities observed in mice transplanted with the vector transduced cells because they displayed decreased hyperactivity in an open field assay and an increased latency to fall in a rotarod assay. An increased level of SynGAP1 was also detected in the brains of these mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These early-stage results highlight the potential of this stem cell gene therapy approach as a treatment strategy for SYNGAP1.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.3717","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icariside II in NSCLC and COVID-19: Network pharmacology and molecular docking study","authors":"Qing Kong,&nbsp;Huahe Zhu,&nbsp;Jingcheng Dong,&nbsp;Baojun Liu","doi":"10.1002/jgm.3710","DOIUrl":"10.1002/jgm.3710","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with non-small cell lung cancer (NSCLC) are susceptible to coronavirus disease-2019 (COVID-19), but current treatments are limited. Icariside II (IS), a flavonoid compound derived from the plant epimedin, showed anti-cancer,anti-inflammation and immunoregulation effects. The present study aimed to evaluate the possible effect and underlying mechanisms of IS on NSCLC patients with COVID-19 (NSCLC/COVID-19).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>NSCLC/COVID-19 targets were defined as the common targets of NSCLC (collected from The Cancer Genome Atlas database) and COVID-19 targets (collected from disease database of Genecards, OMIM, and NCBI). The correlations of NSCLC/COVID-19 targets and survival rates in patients with NSCLC were analyzed using the survival R package. Prognostic analyses were performed using univariate and multivariate Cox proportional hazards regression models. Furthermore, the targets in IS treatment of NSCLC/COVID-19 were defined as the overlapping targets of IS (predicted from drug database of TMSCP, HERBs, SwissTarget Prediction) and NSCLC/COVID-19 targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of these treatment targets were performed aiming to understand the biological process, cellular component, molecular function and signaling pathway. The hub targets were analyzed by a protein–protein interaction network and the binding capacity with IS was characterized by molecular docking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The hub targets for IS in the treatment of NSCLC/COVID-19 includes F2, SELE, MMP1, MMP2, AGTR1 and AGTR2, and the molecular docking results showed that the above target proteins had a good binding degree to IS. Network pharmacology showed that IS might affect the leucocytes migration, inflammation response and active oxygen species metabolic process, as well as regulate the interleukin-17, tumor necrosus factor and hypoxia-inducible factor-1 signaling pathway in NSCLC/COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IS may enhance the therapeutic efficacy of current clinical anti-inflammatory and anti-cancer therapy to benefit patients with NSCLC combined with COVID-19.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA expression profiling in lymphoblastoid cell lines from mutated and non-mutated amyotrophic lateral sclerosis patients","authors":"Jessica Garau,&nbsp;Maria Garofalo,&nbsp;Francesca Dragoni,&nbsp;Eveljn Scarian,&nbsp;Rosalinda Di Gerlando,&nbsp;Luca Diamanti,&nbsp;Susanna Zucca,&nbsp;Matteo Bordoni,&nbsp;Orietta Pansarasa,&nbsp;Stella Gagliardi","doi":"10.1002/jgm.3711","DOIUrl":"10.1002/jgm.3711","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of upper and lower motor neurons with an unknown etiology. The difficulty of recovering biological material from patients led to employ lymphoblastoid cell lines (LCLs) as a model for ALS because many pathways, typically located in neurons, are also activated in these cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To investigate the expression of coding and long non-coding RNAs in LCLs, a transcriptomic profiling of sporadic ALS (SALS) and mutated patients (<i>FUS</i>, <i>TARDBP</i>, <i>C9ORF72</i> and <i>SOD1</i>) and matched controls was realized. Thus, differentially expressed genes (DEGs) were investigated among the different subgroups of patients. Peripheral blood mononuclear cells (PBMCs) were isolated and immortalized into LCLs via Epstein–Barr virus infection; RNA was extracted, and RNA-sequencing analysis was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Gene expression profiles of LCLs were genetic-background-specific; indeed, only 12 genes were commonly deregulated in all groups. Nonetheless, pathways enriched by DEGs in each group were also compared, and a total of 89 Kyoto Encyclopedia of Genes and Genomes (KEGG) terms were shared among all patients. Eventually, the similarity of affected pathways was also assessed when our data were matched with a transcriptomic profile realized in the PBMCs of the same patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We conclude that LCLs are a good model for the study of RNA deregulation in ALS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.3711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell analysis of Crohn's disease: Unveiling heterogeneity and evaluating ustekinumab outcomes","authors":"Zheng-Yang Li,&nbsp;Yong-Hong Sun,&nbsp; Qian-Hua,&nbsp;Hai-Yan Wang,&nbsp;Ya-Jie Wang,&nbsp; Miao-Jiang","doi":"10.1002/jgm.3715","DOIUrl":"10.1002/jgm.3715","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The present study aimed to dissect the cellular complexity of Crohn's disease (CD) using single-cell RNA sequencing, focusing on identifying key cell populations and their transcriptional profiles in inflamed tissue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We applied scRNA-sequencing to compare the cellular composition of CD patients with healthy controls, utilizing Seurat for clustering and annotation. Differential gene expression analysis and protein–protein interaction networks were constructed to identify crucial genes and pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study identified eight distinct cell types in CD, highlighting crucial fibroblast and T cell interactions. The analysis revealed key cellular communications and identified significant genes and pathways involved in the disease's pathology. The role of fibroblasts was underscored by elevated expression in diseased samples, offering insights into disease mechanisms and potential therapeutic targets, including responses to ustekinumab treatment, thus enriching our understanding of CD at a molecular level.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings highlight the complex cellular and molecular interplay in CD, suggesting new biomarkers and therapeutic targets, offering insights into disease mechanisms and treatment implications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.3715","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biocompatible hydroxyapatite-based nano vehicle bypasses viral transduction and enables sustained silencing of a pluripotency marker gene, demonstrating desired differentiation in mouse embryonic stem cells","authors":"Pranjita Zantye,&nbsp;Asha Dahiya,&nbsp;Meenal Kowshik,&nbsp;Sutapa Roy Ramanan,&nbsp;Indrani Talukdar","doi":"10.1002/jgm.3716","DOIUrl":"10.1002/jgm.3716","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Differentiation of pluripotent stem cells into desired lineages is the key aspect of regenerative medicine and cell-based therapy. Although RNA interference (RNAi) technology is exploited extensively for this, methods for long term silencing of the target genes leading to differentiation remain a challenge. Sustained knockdown of the target gene by RNAi is often inefficient as a result of low delivery efficiencies, protocol induced toxicity and safety concerns related to viral vectors. Earlier, we established octa-arginine functionalized hydroxyapatite nano vehicles (R8HNPs) for delivery of small interfering RNA (siRNA) against a pluripotency marker gene in mouse embryonic stem cells. Although we demonstrated excellent knockdown efficiency of the target gene, sustained gene silencing leading to differentiation was yet to be achieved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To establish a sustained non-viral gene silencing protocol using R8HNP, we investigated various methods of siRNA delivery: double delivery of adherent cells (Adh-D), suspension delivery followed by adherent delivery (Susp + Adh), single delivery in suspension (Susp-S) and multiple deliveries in suspension (Susp-R). Sustained knockdown of a pluripotent marker gene followed by differentiation was analysed by reverse transcriptase-PCR, fluoresence-activated cell sorting and immunofluorescence techniques. Impact on cell viability as a result of repeated exposure of the R8HNP was also tested.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Amongst the protocols tested, the most efficient knockdown of the target gene for a prolonged period of time was obtained by repeated suspension delivery of the R8HNP-siRNA conjugate. The long-term silencing of a pluripotency marker gene resulted in differentiation of R1 ESCs predominantly towards the extra embryonic and ectodermal lineages. Cells displayed excellent tolerance to repeated exposures of R8HNPs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results demonstrate that R8HNPs are promising, biocompatible, non-viral alternatives for prolonged gene silencing and obtaining differentiated cells for therapeutics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"26 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.3716","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}