IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-28 DOI: 10.1016/j.gene.2024.149054

Haixia Yu , Liming Xia , Jiawei Zhu , Xiaojie Xie , Ying Wei , Xi Li , Xinhua He , Cong Luo

Mango (Mangifera indica L.) is an important tropical fruit, and timely flowering and fruit setting are very important for mango production. The MADS-box gene family is involved in the regulation of flower induction, floral organ specification, and fruit development in plants. The identification and analysis of the MADS-box gene family can lay a foundation for the study of the molecular mechanism of flowering and fruit development in mango. In this study, 119 MiMADS-box genes were identified on the basis of genome and transcriptome data. Phylogenetic analysis revealed that these genes can be divided into two classes. Forty-one type I proteins were further divided into three subfamilies, and seventy-eight type II proteins were further classified into eleven subfamilies. Several pairs of alternative splicing genes were found, especially in the SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) subfamily. The MiMADS-box genes were distributed on 18 out of the 20 mango chromosomes. Cis-element analysis revealed many light-, stress-, and hormone-responsive elements in the promoter regions of the mango MiMADS-box genes. Expression pattern analysis revealed that these genes were differentially expressed in multiple tissues in mango. The highly expressed MiMADS77 was subsequently transformed into Arabidopsis, resulting in significant early flowering and abnormal floral organs. Yeast two-hybrid (Y2H) assays revealed that MiMADS77 interacts with several MiMADS-box proteins. In addition, we constructed a preliminary flowering regulatory network of MADS-box genes in mango on the basis of related studies. These results suggest that MiMADS77 genes may be involved in flowering regulation of mango.

芒果（Mangifera indica L.）是一种重要的热带水果，适时开花和坐果对芒果生产非常重要。MADS-box 基因家族参与调控植物的花诱导、花器官规格化和果实发育。对 MADS-box 基因家族的鉴定和分析可为研究芒果开花和果实发育的分子机制奠定基础。本研究根据基因组和转录组数据鉴定了 119 个 MiMADS-box 基因。系统进化分析表明，这些基因可分为两类。41 个 I 型蛋白被进一步划分为三个亚家族，78 个 II 型蛋白被进一步划分为 11 个亚家族。发现了几对替代剪接基因，尤其是在 CONSTANS 1（SOC1）亚家族中。MiMADS-box 基因分布在 20 条芒果染色体中的 18 条上。顺式元件分析表明，在芒果 MiMADS-box 基因的启动子区域存在许多光、胁迫和激素响应元件。表达模式分析显示，这些基因在芒果的多个组织中都有不同程度的表达。高表达的 MiMADS77 随后被转化到拟南芥中，结果导致拟南芥明显早花和花器官异常。酵母双杂交（Y2H）试验发现，MiMADS77 与多个 MiMADS-box 蛋白相互作用。此外，我们还在相关研究的基础上初步构建了芒果中 MADS-box 基因的开花调控网络。这些结果表明，MiMADS77基因可能参与了芒果的开花调控。

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引用次数: 0

Apigenin inhibits epithelial mesenchymal transition in renal tubular epithelial cells through PI3K/AKT and NF-κB pathways for treating renal fibrosis 芹菜素通过 PI3K/AKT 和 NF-κB 通路抑制肾小管上皮细胞的上皮间充质转化以治疗肾脏纤维化

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-28 DOI: 10.1016/j.gene.2024.149056

Tao Sun , Baoying Wang , Zhan Wang , Lei Chen , Zhenzhen Li , Ningning Li

Renal fibrosis is a crucial factor in the progression of chronic kidney diseases. Previous studies have suggested that apigenin (API) has potential in ameliorating renal fibrosis, but its therapeutic mechanism remains unclear. This study aims to elucidate the mechanisms by which API treats renal fibrosis using network pharmacology and experimental validation. Initially, we used the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and GeneCards database to identify molecular targets of API and associated genes. Next, we constructed a network of API-renal fibrosis targets, followed by protein–protein interaction (PPI) analysis. Subsequent analyses, such as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We also performed molecular docking studies to explore API’s interactions with key proteins. To validate API’s mechanism in treating renal fibrosis, we used a Human Kidney-2 (HK-2) cell model of epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1). We identified 77 API target genes, 8434 renal fibrosis target genes, and 64 intersection genes, which were primarily enriched in nuclear factor kappa-B (NF-κB) and Phosphatidylinositide 3-kinases/protein kinase B (PI3K-AKT) pathways. API significantly inhibited EMT in TGF-β1-induced HK-2 cells by regulating the expression of α-Smooth muscle actin (α-SMA) and E-cadherin and suppressing the protein expression of p-PI3K, p-AKT, and p-P65, which are related to the PI3K-AKT and NF-κB pathways. However, co-administration of the PI3K agonist 740Y-P counteracted API’s inhibitory effects on these protein expressions. In summary, these findings highlight API’s therapeutic potential in treating renal fibrosis by modulating EMT in renal tubular epithelial cells via the PI3K-AKT and NF-κB pathways.

肾脏纤维化是慢性肾脏疾病进展的关键因素。以往的研究表明，芹菜素（API）具有改善肾脏纤维化的潜力，但其治疗机制仍不清楚。本研究旨在利用网络药理学和实验验证阐明芹菜素治疗肾脏纤维化的机制。首先，我们利用中药系统药理学（TCMSP）数据库和GeneCards数据库确定了API的分子靶点和相关基因。接着，我们构建了API-肾脏纤维化靶点网络，然后进行了蛋白-蛋白相互作用（PPI）分析。随后，我们利用注释、可视化和综合发现数据库（DAVID）进行了基因本体（GO）和京都基因和基因组百科全书（KEGG）通路富集等分析。我们还进行了分子对接研究，以探索 API 与关键蛋白的相互作用。为了验证 API 治疗肾脏纤维化的机制，我们使用了由转化生长因子-β1（TGF-β1）诱导的上皮-间质转化（EMT）人肾-2（HK-2）细胞模型。我们发现了77个API靶基因、8434个肾脏纤维化靶基因和64个交叉基因，它们主要富集于核因子卡巴-B（NF-κB）和磷脂酰肌醇3-激酶/蛋白激酶B（PI3K-AKT）通路。原料药通过调节α-平滑肌肌动蛋白（α-SMA）和E-钙粘蛋白的表达，以及抑制与PI3K-AKT和NF-κB通路相关的p-PI3K、p-AKT和p-P65的蛋白表达，明显抑制了TGF-β1诱导的HK-2细胞的EMT。然而，同时服用 PI3K 激动剂 740Y-P 可以抵消原料药对这些蛋白表达的抑制作用。总之，这些发现突出了API通过PI3K-AKT和NF-κB途径调节肾小管上皮细胞EMT从而治疗肾纤维化的潜力。

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引用次数: 0

Integrated miRNA sequencing and experimental validation Unveil that low-level laser enhances vascular endothelial cell proliferation, migration, and lumen formation via miR-90/VEGFA 综合 miRNA 测序和实验验证揭示了低强度激光可通过 miR-90/VEGFA 增强血管内皮细胞的增殖、迁移和管腔形成。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-28 DOI: 10.1016/j.gene.2024.149049

Lili Wu , Boyuan Zhang , Yue Li , Chao Xiong , Jinhai Yu , Jiancheng Gan , Qihua Xu , Yaohua Wang , Hongfei Liao

The hydroxyapatite orbital implantation is widely used to treat orbital malformation, but delayed postoperative angiogenesis can hinder conjunctival wound healing, potentially leading to implant exposure and prolapse. Low-intensity laser therapy (LLLT) is recognized for its ability to promote tissue regeneration, reduce inflammation, and alleviate pain. This study aims to explore the specific mechanism of miRNAs-VEGFA pathway regulation in early vascularization after orbital implant placement induced by LLLT. A hydroxyapatite orbital implant model was established and treated with LLLT. Vascular tissues surrounding the ocular prosthesis were extracted for high-throughput sequencing to identify differentially expressed miRNAs. miRNAs predicted to bind with VEGFA were selected for validation. GO and KEGG analyses were performed to reveal the functional enrichment of target genes regulated by these miRNAs. Dual luciferase assay, qRT-PCR, and Western blotting were used to verify the targeting relationship between miR-90 and VEGFA. The effects of miR-90 on rabbit microvascular endothelial cell function were assessed through CCK-8 assay, scratch test, and tube formation assay. High-throughput sequencing revealed 32 differentially expressed miRNAs, with 8 upregulated and 24 downregulated. miR-90 was predicted to have a high binding score and expression abundance with VEGFA and was confirmed to regulate VEGFA expression. In vitro functional tests showed that miR-90 inhibited rabbit microvascular endothelial cell proliferation, migration, and tube formation. This study is the first to demonstrate that LLLT regulates ocular prosthesis angiogenesis via the miR-90/VEGFA pathway, providing a new target for treating vascular-dependent diseases.

羟基磷灰石眼眶植入术被广泛用于治疗眼眶畸形，但术后血管生成延迟会阻碍结膜伤口愈合，可能导致植入物外露和脱垂。低强度激光疗法（LLLT）具有促进组织再生、减轻炎症和缓解疼痛的作用。本研究旨在探索 miRNAs-VEGFA 通路在 LLLT 诱导眼眶植入物置入后早期血管形成过程中的具体调控机制。研究人员建立了羟基磷灰石眼眶植入物模型，并用激光照射治疗。提取眼球假体周围的血管组织进行高通量测序，以鉴定差异表达的 miRNA。进行GO和KEGG分析，以揭示这些miRNA调控的靶基因的功能富集。采用双荧光素酶检测、qRT-PCR 和 Western 印迹技术验证了 miR-90 与 VEGFA 的靶向关系。通过CCK-8试验、划痕试验和试管形成试验评估了miR-90对家兔微血管内皮细胞功能的影响。高通量测序发现了 32 个差异表达的 miRNA，其中 8 个上调，24 个下调。预测 miR-90 与 VEGFA 有较高的结合得分和表达丰度，并证实它能调控 VEGFA 的表达。体外功能测试显示，miR-90 可抑制家兔微血管内皮细胞的增殖、迁移和管形成。这项研究首次证明了 LLLT 通过 miR-90/VEGFA 通路调节眼假体血管生成，为治疗血管依赖性疾病提供了一个新靶点。

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引用次数: 0

Effect of epigenetic changes in hypoxia induced factor (HIF) gene across cancer types 不同癌症类型中低氧诱导因子 (HIF) 基因表观遗传变化的影响

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-26 DOI: 10.1016/j.gene.2024.149047

Aditi P. Agarwal, Maushmi S. Kumar

Cancer hypoxia, a crucial characteristic of malignancy, ranging from practically non-hypoxic to severe, impacts gene expression, metabolism and mechanisms associated with tumor formation serves as a key obstacle in cancer therapy. It triggers a complex network of cell signaling pathways, such as the NF-κB, PI3K, mTOR/AKT, MAPK, HIF and their associated genes regulating the effects of the same. The onset and advancement of cancer are attributed to genetic and epigenetic modifications which are intrinsically related. Off late, it has been observed that in disease progression, the epigenetic modifications lead to gene mutations that in turn alter the epigenome, presenting a major hurdle in fabricating treatment strategies. However, the progress in science and technology has led to the emergence of various surfacing omics and multi-view clustering algorithms, which offer unparalleled prospects for further subtyping cancers, enhancing the prognosis and treatment results of these subtypes, and comprehending crucial pathophysiological mechanisms across diverse molecular strata. Multi-omics has allowed scientists to gain a more comprehensive understanding of the various ways that cellular malfunction can lead to cancer. So, it becomes of utmost importance to firstly understand the epigenetic changes taking place in tumor hypoxia at gene level. This review sheds light on the role of HIF gene in hypoxic milieu and its relationship with mechanisms of cancer epigenetics. It further glances as to how omics approach can be used to study the oncogenic cellular changes and how bioinformatic tools aid in identification of complex gene networks involved in disease progression. Lastly, it glimpses through the benefits and shortcomings of the existing epi drug therapy and how it can be used in developing novel treatment options.

癌症缺氧是恶性肿瘤的一个重要特征，从几乎不缺氧到严重缺氧，都会影响基因表达、新陈代谢和与肿瘤形成相关的机制，是癌症治疗的一个关键障碍。它触发了一个复杂的细胞信号通路网络，如 NF-κB、PI3K、mTOR/AKT、MAPK、HIF 及其相关基因的调节作用。癌症的发生和发展归因于基因和表观遗传学的改变，这两者有着内在的联系。近来，人们发现，在疾病进展过程中，表观遗传修饰会导致基因突变，而基因突变又会改变表观基因组，这给制定治疗策略带来了重大障碍。然而，随着科学技术的进步，各种表观组学和多视角聚类算法不断涌现，为进一步细分癌症类型、提高这些亚型的预后和治疗效果以及理解不同分子层的关键病理生理机制提供了无与伦比的前景。多组学使科学家们能够更全面地了解细胞功能失调导致癌症的各种途径。因此，首先了解肿瘤缺氧在基因水平上发生的表观遗传变化就变得至关重要。这篇综述揭示了 HIF 基因在缺氧环境中的作用及其与癌症表观遗传学机制的关系。它还进一步介绍了如何利用全息方法来研究致癌细胞的变化，以及生物信息学工具如何帮助识别参与疾病进展的复杂基因网络。最后，它还介绍了现有表观药物疗法的优势和不足，以及如何将其用于开发新型治疗方案。

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引用次数: 0

BZW2 is a potential regulator of non-small cell lung cancer progression. BZW2 是非小细胞肺癌进展的潜在调控因子。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-26 DOI: 10.1016/j.gene.2024.149055

Yan Mo, Xueyong Feng, Jincheng Su, Guoyong Chen, Lei Xian

Background: Personalized targeted therapy has become an important strategy for cancer treatment owing to its remarkable therapeutic efficacy and safety. However, drug resistance remains the primary cause of treatment failure. Basic leucine zipper and W2 domain 2 (BZW2), which is aberrantly expressed in cancer, has been implicated in tumor progression and may serve as a new therapeutic target. Therefore, the role of BZW2 in non-small cell lung cancer (NSCLC) requires further investigation.

Methods: The expression and genetic alterations of BZW2 in pan-cancers were explored using The Cancer Genome Atlas (TCGA) PanCancer databases. The mRNA and protein levels of BZW2 in patients with NSCLC were verified in our cohort. Functional experiments including CCK8, colony formation, and transwell assays were performed to evaluate the impact of BZW2 on the proliferative, migratory, and invasive capacities of SK-MES-1 cells. Gene Set Enrichment Analysis was used to identify underlying biological processes and pathways. Single-cell RNA (scRNA) sequencing data were employed to investigate the tumor microenvironment of NSCLC and the co-expression of BZW2 and stemness-related genes.

Results: Dysregulated BZW2 expression was observed in various malignant tumors. BZW2 expression was found to be significantly elevated in NSCLC. BZW2 depletion inhibited the growth, mobility, and invasive abilities of lung squamous cell carcinoma SK-MES-1 cells. BZW2 may be related to signaling pathways such as nucleotide excision repair, ubiquitin-mediated proteolysis, and the P53 signaling pathway. Biological processes, including translational initiation, tRNA processing, and RNA methylation, were observed to be enriched in the high-BZW2 group. Furthermore, there was a positive correlation between BZW2 and the m6A- and m5C-related genes. scRNA analysis revealed a co-expression relationship between BZW2 and stemness-related genes such as CD44, SOX9, and CD133.

Conclusions: Elevated BZW2 expression is associated with the proliferation, migration, and invasion of NSCLC, and BZW2 may be a potential therapeutic target for NSCLC.

背景：个性化靶向治疗因其显著的疗效和安全性已成为癌症治疗的重要策略。然而，耐药性仍然是治疗失败的主要原因。在癌症中异常表达的碱性亮氨酸拉链和W2结构域2（BZW2）被认为与肿瘤进展有关，可作为新的治疗靶点。因此，BZW2在非小细胞肺癌（NSCLC）中的作用需要进一步研究：方法：利用癌症基因组图谱（TCGA）泛癌数据库探讨了BZW2在泛癌中的表达和基因改变。在我们的队列中，BZW2在NSCLC患者中的mRNA和蛋白水平得到了验证。为了评估BZW2对SK-MES-1细胞的增殖、迁移和侵袭能力的影响，我们进行了包括CCK8、集落形成和透孔实验在内的功能实验。基因组富集分析（Gene Set Enrichment Analysis）用于确定潜在的生物过程和通路。利用单细胞RNA（scRNA）测序数据研究了NSCLC的肿瘤微环境以及BZW2和干细胞相关基因的共表达：结果：在各种恶性肿瘤中都观察到了BZW2的表达失调。结果：在多种恶性肿瘤中都观察到了BZW2表达失调的现象，发现BZW2在NSCLC中表达明显升高。抑制BZW2可抑制肺鳞癌SK-MES-1细胞的生长、移动和侵袭能力。BZW2 可能与核苷酸切除修复、泛素介导的蛋白水解和 P53 信号通路等信号通路有关。据观察，高BZW2组富集了包括翻译启动、tRNA加工和RNA甲基化在内的生物过程。scRNA分析显示，BZW2与CD44、SOX9和CD133等干性相关基因之间存在共表达关系：结论：BZW2表达升高与NSCLC的增殖、迁移和侵袭有关，BZW2可能是NSCLC的潜在治疗靶点。

{"title":"BZW2 is a potential regulator of non-small cell lung cancer progression.","authors":"Yan Mo, Xueyong Feng, Jincheng Su, Guoyong Chen, Lei Xian","doi":"10.1016/j.gene.2024.149055","DOIUrl":"https://doi.org/10.1016/j.gene.2024.149055","url":null,"abstract":"<p><strong>Background: </strong>Personalized targeted therapy has become an important strategy for cancer treatment owing to its remarkable therapeutic efficacy and safety. However, drug resistance remains the primary cause of treatment failure. Basic leucine zipper and W2 domain 2 (BZW2), which is aberrantly expressed in cancer, has been implicated in tumor progression and may serve as a new therapeutic target. Therefore, the role of BZW2 in non-small cell lung cancer (NSCLC) requires further investigation.</p><p><strong>Methods: </strong>The expression and genetic alterations of BZW2 in pan-cancers were explored using The Cancer Genome Atlas (TCGA) PanCancer databases. The mRNA and protein levels of BZW2 in patients with NSCLC were verified in our cohort. Functional experiments including CCK8, colony formation, and transwell assays were performed to evaluate the impact of BZW2 on the proliferative, migratory, and invasive capacities of SK-MES-1 cells. Gene Set Enrichment Analysis was used to identify underlying biological processes and pathways. Single-cell RNA (scRNA) sequencing data were employed to investigate the tumor microenvironment of NSCLC and the co-expression of BZW2 and stemness-related genes.</p><p><strong>Results: </strong>Dysregulated BZW2 expression was observed in various malignant tumors. BZW2 expression was found to be significantly elevated in NSCLC. BZW2 depletion inhibited the growth, mobility, and invasive abilities of lung squamous cell carcinoma SK-MES-1 cells. BZW2 may be related to signaling pathways such as nucleotide excision repair, ubiquitin-mediated proteolysis, and the P53 signaling pathway. Biological processes, including translational initiation, tRNA processing, and RNA methylation, were observed to be enriched in the high-BZW2 group. Furthermore, there was a positive correlation between BZW2 and the m6A- and m5C-related genes. scRNA analysis revealed a co-expression relationship between BZW2 and stemness-related genes such as CD44, SOX9, and CD133.</p><p><strong>Conclusions: </strong>Elevated BZW2 expression is associated with the proliferation, migration, and invasion of NSCLC, and BZW2 may be a potential therapeutic target for NSCLC.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

C2C12 myoblasts differentiate into myofibroblasts via the TGF-β1 signaling pathway mediated by Fibulin2. C2C12 肌母细胞通过 Fibulin2 介导的 TGF-β1 信号通路分化成肌成纤维细胞。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-26 DOI: 10.1016/j.gene.2024.149048

Yongqiang Yang, Lei Li, Jun Fei, Zhong Li

Myoblast cells play a critical role in the regeneration of skeletal muscle following injury. It has been reported that local elevation of transforming growth factor-β1(TGF-β1) after skeletal muscle injury induces differentiation of myoblast cells into myofibroblasts.However, the mechanisms underlying this differentiation process remain incompletely understood. In this study, we found that Fibulin2 expression significantly increases in myoblast cells in response to TGF-β1 stimulation.Elevated Fibulin2 levels enhance the expression of fibrotic markers, mediated through phosphorylation of Smad2.Conversely, downregulation of Fibulin2 in myoblast cells inhibits the upregulation of fibrotic markers induced by TGF-β1 stimulation.Extracellular secretion of Fibulin2 activates the TGF-β1-Smad2 pathway, thereby promoting the upregulation of fibrotic markers.Hence, Fibulin2 and TGF-β1 form a positive feedback loop that facilitates differentiation of myoblast cells into myofibroblasts.

成肌细胞在骨骼肌损伤后的再生过程中起着至关重要的作用。据报道，骨骼肌损伤后，局部转化生长因子-β1（TGF-β1）的升高可诱导肌母细胞分化为肌成纤维细胞。在这项研究中，我们发现在 TGF-β1 的刺激下，肌母细胞中 Fibulin2 的表达会显著增加。Fibulin2的细胞外分泌激活了TGF-β1-Smad2通路，从而促进了纤维化标志物的上调。因此，Fibulin2和TGF-β1形成了一个正反馈回路，促进了成肌细胞向肌成纤维细胞的分化。

引用次数: 0

Epigenetics of concussion: A systematic review 脑震荡的表观遗传学：系统回顾

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-26 DOI: 10.1016/j.gene.2024.149046

Mark R. Antrobus , Terun Desai , David Young , Lee Machado , William J. Ribbans , Louis Y. El Khoury , Jon Brazier

Background

Concussion is the most common neurological disorder affecting millions of people globally each year. Identifying epigenetic mechanisms influencing concussion incidence, severity and recovery could provide diagnostic and prognostic insight into this injury.

Objectives

This systematic review aims to identify the epigenetic mechanisms underpinning concussion.

Methods

Seven electronic databases; PubMed, MEDLINE, CINAHL, Cochrane library, SPORTDiscus, Scopus and Web of Science were searched for studies that investigated the epigenetic mechanisms of concussion and its underlying neuropathology.

Results

Based on inclusion and exclusion criteria, 772 titles were independently analysed by two of the authors to a final list of 28 studies that totaled 3042 participants. We observed separate associations between sncRNAs, methylation, histone modification and concussion. Overall, 204 small non-coding RNAs were significantly dysregulated between concussed participants and controls or between concussion participants with no post-concussive symptoms and those with post-concussive symptoms. From these, 37 were reported in more than one study and 23 of these were expressed in a consistent direction with at least one further study. Ingenuity pathway analysis identified 10 miRNAs known to regulate 15 genes associated with human neurological pathologies. Two studies found significant changes in global methylation in concussed participants and one study found a decrease in H3K27Me3 in the context of DNA damage and concussion.

Conclusions

The review findings suggest that epigenetic mechanisms may play an important role in the pathophysiological mechanisms that could influence outcome, recovery, and potential long-term consequences of concussion for individuals.

背景脑震荡是最常见的神经系统疾病，每年影响全球数百万人。确定影响脑震荡发病率、严重程度和恢复的表观遗传学机制可以为这种损伤的诊断和预后提供洞察力。方法在 PubMed、MEDLINE、CINAHL、Cochrane library、SPORTDiscus、Scopus 和 Web of Science 七个电子数据库中检索了调查脑震荡表观遗传学机制及其潜在神经病理学的研究。我们观察到 sncRNAs、甲基化、组蛋白修饰和脑震荡之间存在不同的关联。总体而言，有 204 种小非编码 RNA 在脑震荡参与者与对照组之间，或在无脑震荡后症状的脑震荡参与者与有脑震荡后症状的脑震荡参与者之间出现了明显的失调。其中，37 个在不止一项研究中被报道，23 个在至少一项进一步研究中表达方向一致。Ingenuity pathway 分析确定了 10 个 miRNA，这些 miRNA 可调控 15 个与人类神经系统疾病相关的基因。两项研究发现，脑震荡参与者的全局甲基化发生了重大变化，一项研究发现，在 DNA 损伤和脑震荡的背景下，H3K27Me3 发生了下降。结论综述结果表明，表观遗传机制可能在病理生理机制中发挥重要作用，这些机制可能会影响脑震荡对个人造成的结果、恢复和潜在的长期后果。

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引用次数: 0

Analysis of rosmarinic acid synthase (RAS) gene family and functional study of SmRAS1/2/4 in Salvia miltiorrhiza 丹参中的迷迭香酸合成酶（RAS）基因家族分析和 SmRAS1/2/4 的功能研究

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-26 DOI: 10.1016/j.gene.2024.149057

Yujie Xin , Hongbin Zhan , Heng Kang , Qianmo Li , Fan Fu , Limin Han , Wenping Hua , Xiaoyan Cao

Rosmarinic acid synthase is an essential enzyme involved in the biosynthesis of rosmarinic acid (RA), which facilitates the coupling of phenylpropanoid and tyrosine-derived pathway products. Our study identified six SmRAS genes in Salvia miltiorrhiza, with SmRAS1 being the only one functionally characterized to date. Real-time quantitative PCR was employed to analyze the expression profiles of the SmRAS gene family, revealing that SmRAS1/2/4 are predominantly expressed in the roots, which are the medicinal components of S. miltiorrhiza. SmRAS2 and SmRAS4 exhibited significant responses to abscisic acid (ABA), gibberellin (GA₃), and methyl jasmonate (MeJA) stimuli, while SmRAS1 had notable responses to GA₃ and MeJA. β-glucuronidase (GUS) staining in transgenic Arabidopsis thaliana confirmed a spatiotemporal expression pattern of SmRAS1/2/4 that was consistent with the qRT-PCR results. SmRAS1/2/4 are primarily localized to the cytoplasm and plasma membrane. Our findings suggested that the overexpressions of SmRAS1 or SmRAS4 led to increased levels of salvianolic acid B (SalB) and RA, with a concomitant decrease in the Danshensu (DSS) content, which served as a substrate. In contrast, RNA interference lines exhibited a downward trend in the content of these substances. Interestingly, no significant changes were detected in the SalB, RA, or DSS contents due to the overexpression of SmRAS2 or RNA interference lines. Collectively, our study demonstrated that SmRAS1 and SmRAS4 are key regulators of RA and SalB biosynthesis in S. miltiorrhiza, while SmRAS2's role appears less impactful, suggesting a complex regulatory network that influences the medicinal properties of this plant.

迷迭香酸合成酶是参与迷迭香酸（RA）生物合成的一种重要酶，它促进了苯丙氨酸和酪氨酸衍生途径产物的耦合。我们的研究在丹参中发现了六个 SmRAS 基因，其中 SmRAS1 是迄今为止唯一一个具有功能特征的基因。我们采用实时定量 PCR 分析了 SmRAS 基因家族的表达谱，发现 SmRAS1/2/4 主要在根部表达，而根部是丹参的药用成分。SmRAS2 和 SmRAS4 对脱落酸（ABA）、赤霉素（GA3）和茉莉酸甲酯（MeJA）的刺激有明显的反应，而 SmRAS1 对 GA3 和 MeJA 有显著的反应。转基因拟南芥中的β-葡糖醛酸酶（GUS）染色证实了SmRAS1/2/4的时空表达模式与qRT-PCR结果一致。SmRAS1/2/4主要定位于细胞质和质膜。我们的研究结果表明，SmRAS1或SmRAS4的过表达会导致丹参酚酸B（SalB）和RA含量的增加，同时作为底物的丹参素（DSS）含量也会降低。与此相反，RNA 干扰品系中这些物质的含量呈下降趋势。有趣的是，过表达SmRAS2或RNA干扰品系导致的SalB、RA或DSS含量均未发现明显变化。总之，我们的研究表明，SmRAS1 和 SmRAS4 是 S. miltiorrhiza 中 RA 和 SalB 生物合成的关键调控因子，而 SmRAS2 的作用似乎影响较小，这表明有一个复杂的调控网络影响着这种植物的药用特性。

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引用次数: 0

Revolutionizing animal husbandry: Breakthroughs in gene editing delivery systems. 畜牧业的革命：基因编辑传输系统的突破。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-25 DOI: 10.1016/j.gene.2024.149044

Yuan Liu, Xue Bai, Xue Feng, Shuang Liu, Yamei Hu, Hongen Chu, Lingkai Zhang, Bei Cai, Yun Ma

Gene editing technology has become an essential tool for advancing breeding practices, enhancing disease resistance, and boosting productivity in animal husbandry. Despite its potential, the delivery of gene editing reagents into cells faces several challenges, including low targeting efficiency, immunogenicity, and cytotoxicity, which have hindered its wider application in the field. This review discusses the evolution of gene editing technologies and highlights recent advancements in various delivery methods used in animal husbandry. It critically evaluates the strengths and weaknesses of these different delivery approaches while identifying potential directions for future development. The goal is to equip researchers with effective strategies to optimize delivery methods, ultimately facilitating the implementation and progress of gene editing technologies in animal husbandry.

基因编辑技术已成为畜牧业推进育种实践、增强抗病能力和提高生产力的重要工具。尽管基因编辑试剂潜力巨大，但向细胞中传递基因编辑试剂面临着一些挑战，包括低靶向效率、免疫原性和细胞毒性，这些都阻碍了基因编辑试剂在该领域的广泛应用。本综述讨论了基因编辑技术的演变，并重点介绍了动物饲养中使用的各种传递方法的最新进展。它批判性地评估了这些不同传递方法的优缺点，同时确定了未来发展的潜在方向。目的是为研究人员提供优化传递方法的有效策略，最终促进基因编辑技术在畜牧业中的应用和进步。

引用次数: 0

Advances in bacterial artificial chromosome (BAC) transgenic mice for gene analysis and disease research 用于基因分析和疾病研究的细菌人工染色体（BAC）转基因小鼠的研究进展。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-24 DOI: 10.1016/j.gene.2024.149014

Kazumasa Mogi , Hiroyuki Tomita , Masato Yoshihara , Hiroaki Kajiyama , Akira Hara

Transgenic mice, including those created using Bacterial Artificial Chromosomes (BACs), are artificial manipulations that have become critical tools for studying gene function. While conventional transgenic techniques face challenges in achieving precise expression of foreign genes in specific cells and tissues, BAC transgenic mice offer a solution by incorporating large DNA segments that can include entire expression units with tissue-specific enhancers.

This review provides a thorough examination of BAC transgenic mouse technology, encompassing both traditional and humanized models. We explore the benefits and drawbacks of BAC transgenesis compared to other techniques such as knock-in and CRISPR/Cas9 technologies. The review emphasizes the applications of BAC transgenic mice in various disciplines, including neuroscience, immunology, drug metabolism, and disease modeling. Additionally, we address crucial aspects of generating and analyzing BAC transgenic mice, such as position effects, copy number variations, and strategies to mitigate these challenges. Despite certain limitations, humanized BAC transgenic mice have proven to be invaluable tools for studying the pathogenesis of human diseases, drug development, and understanding intricate gene regulatory mechanisms. This review discusses current topics on BAC transgenic mice and their evolving significance in biomedical research.

转基因小鼠，包括使用细菌人工染色体（BAC）创建的转基因小鼠，是一种人工操作方法，已成为研究基因功能的重要工具。传统的转基因技术在实现外来基因在特定细胞和组织中的精确表达方面面临挑战，而 BAC 转基因小鼠则提供了一种解决方案，它通过整合大的 DNA 片段，可以包含具有组织特异性增强子的整个表达单元。这篇综述全面考察了 BAC 转基因小鼠技术，包括传统模型和人源化模型。与基因敲入和 CRISPR/Cas9 技术等其他技术相比，我们探讨了 BAC 转基因技术的优点和缺点。综述强调了 BAC 转基因小鼠在神经科学、免疫学、药物代谢和疾病建模等不同学科中的应用。此外，我们还讨论了生成和分析 BAC 转基因小鼠的关键问题，如位置效应、拷贝数变异以及缓解这些挑战的策略。尽管存在某些局限性，但人源化 BAC 转基因小鼠已被证明是研究人类疾病发病机制、药物开发和了解复杂基因调控机制的宝贵工具。本综述将讨论当前有关 BAC 转基因小鼠的话题及其在生物医学研究中不断发展的意义。

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