Pub Date : 2024-10-19DOI: 10.1016/j.gene.2024.149018
Yuanxuan Ma , Guixia Li , Ling Li , Jinbao Zong , Wenmiao Liu , Ru Zhang , Shiguo Liu
Recent studies have shown that homozygous and compound heterozygous variants in the 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) gene contribute to a novel early onset neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), a severe neurodevelopmental disorder characterized by impaired psychomotor development in infancy. Using whole-exome sequencing and Sanger sequencing, we identified and verified a novel compound heterozygous variant in HPDL, c.502 T > C (p.Cys278Arg)/c.833G > A (p.Gly278Asp), which may lead to lethal NEDSWMA, with individual differences in severity. We systematically summarized the clinical characteristics of the patients and their family members and analyzed the genetic characteristics such as homozygosity, conservatism, and pathogenicity of the variants by various prediction methods. Further in vitro functional experiments showed that the identified variants inhibited the proliferative capacity but not apoptosis of SH-SY5Y cells by altering HPDL expression at the mRNA and protein levels and negatively affecting endogenous CoQ10 secretion. Our study further contributes to the assessment of genotype-phenotype correlations, and firstly provides new insights for elucidating specific pathogenesis mechanisms and identifying precision-targeted therapies.
最近的研究表明，4-羟基苯基丙酮酸二氧酶样（HPDL）基因中的同源和复合杂合变异导致了一种新型早发性神经发育障碍伴进行性痉挛和脑白质异常（NEDSWMA），这是一种以婴儿期精神运动发育受损为特征的严重神经发育障碍。通过全外显子组测序和桑格测序，我们发现并验证了 HPDL 中的一个新型复合杂合变异，即 c.502 T > C (p.Cys278Arg)/c.833G > A (p.Gly278Asp)，该变异可能导致致命性 NEDSWMA，且严重程度存在个体差异。我们系统地总结了患者及其家庭成员的临床特征，并通过各种预测方法分析了变异体的同源性、保守性和致病性等遗传特征。进一步的体外功能实验表明，所发现的变异体通过改变 HPDL 在 mRNA 和蛋白水平的表达，并对内源性 CoQ10 的分泌产生负面影响，从而抑制了 SH-SY5Y 细胞的增殖能力，但没有抑制其凋亡。我们的研究进一步促进了基因型与表型相关性的评估，并首次为阐明特定发病机制和确定精准靶向疗法提供了新的见解。
{"title":"Two novel heterozygous HPDL variants in a Chinese family with a neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities","authors":"Yuanxuan Ma , Guixia Li , Ling Li , Jinbao Zong , Wenmiao Liu , Ru Zhang , Shiguo Liu","doi":"10.1016/j.gene.2024.149018","DOIUrl":"10.1016/j.gene.2024.149018","url":null,"abstract":"<div><div>Recent studies have shown that homozygous and compound heterozygous variants in the 4-hydroxyphenylpyruvate dioxygenase-like (<em>HPDL</em>) gene contribute to a novel early onset neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), a severe neurodevelopmental disorder characterized by impaired psychomotor development in infancy. Using whole-exome sequencing and Sanger sequencing, we identified and verified a novel compound heterozygous variant in <em>HPDL</em>, c.502 T > C (p.Cys278Arg)/c.833G > A (p.Gly278Asp), which may lead to lethal NEDSWMA, with individual differences in severity. We systematically summarized the clinical characteristics of the patients and their family members and analyzed the genetic characteristics such as homozygosity, conservatism, and pathogenicity of the variants by various prediction methods. Further in vitro functional experiments showed that the identified variants inhibited the proliferative capacity but not apoptosis of SH-SY5Y cells by altering <em>HPDL</em> expression at the mRNA and protein levels and negatively affecting endogenous CoQ10 secretion. Our study further contributes to the assessment of genotype-phenotype correlations, and firstly provides new insights for elucidating specific pathogenesis mechanisms and identifying precision-targeted therapies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462461","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}
Pub Date : 2024-10-19DOI: 10.1016/j.gene.2024.149013
You Wu , Zhicong Zhao , Xia Deng , Jue Jia , Guoyue Yuan
Pregnancy zone protein (PZP) is an antiprotease-resistant immunosuppressant belonging to the α-macroglobulin (αM) protein family. PZP is secreted by the liver and was found to be upregulated in plasma during pregnancy. α-2-macroglobulin (Α2M) shares 71 % serial homology with PZP, but low PZP levels do not lead to increased A2M levels in pregnancy. PZP can interact with several factors such as low-density lipoprotein receptor-associated protein (LRP), transforming growth factor-β (TGF-β), 78 kDa glucose-regulated protein (GRP78), and glycoside A (GdA). PZP is involved in the development of glycolipid metabolism disorders, bronchiectasis, Alzheimer’s disease (AD), rheumatoid arthritis (RA), myocardial infarction (MI) and inflammatory bowel disease (IBD). PZP is also associated with the progression of tumorigenesis such as breast cancer (BC), homologyepatocellular carcinoma (HCC), lung adenocarcinoma (LAC), and colorectal cancer (CRC). Therefore, this review analyzes the role of PZP in pathophysiology of various diseases.
{"title":"Pregnancy zone protein, a potential research target in multiple diseases","authors":"You Wu , Zhicong Zhao , Xia Deng , Jue Jia , Guoyue Yuan","doi":"10.1016/j.gene.2024.149013","DOIUrl":"10.1016/j.gene.2024.149013","url":null,"abstract":"<div><div>Pregnancy zone protein (PZP) is an antiprotease-resistant immunosuppressant belonging to the α-macroglobulin (αM) protein family. PZP is secreted by the liver and was found to be upregulated in plasma during pregnancy. α-2-macroglobulin (Α2M) shares 71 % serial homology with PZP, but low PZP levels do not lead to increased A2M levels in pregnancy. PZP can interact with several factors such as low-density lipoprotein receptor-associated protein (LRP), transforming growth factor-β (TGF-β), 78 kDa glucose-regulated protein (GRP78), and glycoside A (GdA). PZP is involved in the development of glycolipid metabolism disorders, bronchiectasis, Alzheimer’s disease (AD), rheumatoid arthritis (RA), myocardial infarction (MI) and inflammatory bowel disease (IBD). PZP is also associated with the progression of tumorigenesis such as breast cancer (BC), homologyepatocellular carcinoma (HCC), lung adenocarcinoma (LAC), and colorectal cancer (CRC). Therefore, this review analyzes the role of PZP in pathophysiology of various diseases.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462459","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}
Pub Date : 2024-10-18DOI: 10.1016/j.gene.2024.149008
Jiale Hu , Rui Liang , Man Li , Xianglian Zhang , Menglong Li , Huaidong Qu , Zhiqiang Wang
Background
The induction of stem cell differentiation to generate intestinal epithelial cells (IECs) with absorptive functions offers significant therapeutic potential for treating conditions such as Crohn’s disease, ulcerative colitis, radiation enteritis, and other refractory intestinal epithelial injuries. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of differentiating into functional IEC-like cells.
Objective
This study aimed to induce the differentiation of hUC-MSCs into IECs using a conditioned medium co-culture method.
Method
A culture medium derived from human IECs was used as the inductive medium to facilitate the differentiation of hUC-MSCs into IECs. The cellular morphology was assessed using inverted microscopy, and the expression of IEC markers, including Villin, CK20, CK8, and CK18 proteins, was analyzed via immunofluorescence staining. Furthermore, the expression levels of IEC markers, such as KRT18, were quantified using real-time quantitative PCR analysis. The functionality of the differentiated IECs in terms of sucrase secretion was assessed through sucrase activity assays.
Results
By the 14th day of induction, hUC-MSCs exhibited a morphology similar to IECs and exhibited the expression of IEC markers, including the KRT18 gene and Villin, CK20, CK8, and CK18 proteins. Sucrase activity assays further confirmed that the differentiated cells demonstrated significant sucrase activity.
Conclusion
The conditioned medium co-culture method effectively induced the differentiation of hUC-MSCs into functional IECs.
{"title":"Differentiation of human umbilical cord mesenchymal stem cells into functional intestinal epithelial cells via conditioned medium co-culture","authors":"Jiale Hu , Rui Liang , Man Li , Xianglian Zhang , Menglong Li , Huaidong Qu , Zhiqiang Wang","doi":"10.1016/j.gene.2024.149008","DOIUrl":"10.1016/j.gene.2024.149008","url":null,"abstract":"<div><h3>Background</h3><div>The induction of stem cell differentiation to generate intestinal epithelial cells (IECs) with absorptive functions offers significant therapeutic potential for treating conditions such as Crohn’s disease, ulcerative colitis, radiation enteritis, and other refractory intestinal epithelial injuries. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of differentiating into functional IEC-like cells.</div></div><div><h3>Objective</h3><div>This study aimed to induce the differentiation of hUC-MSCs into IECs using a conditioned medium co-culture method.</div></div><div><h3>Method</h3><div>A culture medium derived from human IECs was used as the inductive medium to facilitate the differentiation of hUC-MSCs into IECs. The cellular morphology was assessed using inverted microscopy, and the expression of IEC markers, including Villin, CK20, CK8, and CK18 proteins, was analyzed via immunofluorescence staining. Furthermore, the expression levels of IEC markers, such as KRT18, were quantified using real-time quantitative PCR analysis. The functionality of the differentiated IECs in terms of sucrase secretion was assessed through sucrase activity assays.</div></div><div><h3>Results</h3><div>By the 14th day of induction, hUC-MSCs exhibited a morphology similar to IECs and exhibited the expression of IEC markers, including the <em>KRT18</em> gene and Villin, CK20, CK8, and CK18 proteins. Sucrase activity assays further confirmed that the differentiated cells demonstrated significant sucrase activity.</div></div><div><h3>Conclusion</h3><div>The conditioned medium co-culture method effectively induced the differentiation of hUC-MSCs into functional IECs.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462438","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}
Pub Date : 2024-10-18DOI: 10.1016/j.gene.2024.149011
Bitang Huang , Fengbiao Guo , Jiaxuan Chen , Lu Lu , Shenglan Gao , Chunlong Yang , Han Wu , Wenying Luo , Qingjun Pan
Systemic lupus erythematosus (SLE) is a complex autoimmune disease marked by abnormal B-cell proliferation and increased autoantibodies. miRNAs play a crucial role in regulating B-cell dysfunction and SLE pathology. miRNAs influence DNA methylation, B-cell activation, and gene expression, contributing to SLE pathogenesis. miRNAs impact B cells through key processes like proliferation, differentiation, tolerance, and apoptosis. miRNAs also exacerbate inflammation and immune responses by modulating Interleukin 4 (IL-4), IL-6, and interferon cytokines. Autophagy, a key degradation mechanism, is also regulated by specific miRNAs that impact SLE pathology. This article explores the role of multiple miRNAs in regulating B-cell development, proliferation, survival, and immune responses, influencing SLE pathogenesis. miRNAs like miR-23a, the miR-17 ∼ 92 family, and miR-125b/miR-221 affect B-cell development by regulating transcription factors, signaling pathways, and cell cycle genes. miRNAs such as miR-181a-5p and miR-23a-5p are differentially regulated across developmental stages, emphasizing their complex regulatory roles in B-cell biology. This article synthesizes miRNA-B cell interactions to offer new strategies and directions for SLE diagnosis and treatment.
miRNA 在调节 B 细胞功能障碍和系统性红斑狼疮病理过程中发挥着至关重要的作用。miRNA 影响 DNA 甲基化、B 细胞活化和基因表达，有助于系统性红斑狼疮的发病机制。miRNA 还通过调节白细胞介素 4（IL-4）、IL-6 和干扰素细胞因子，加剧炎症和免疫反应。自噬是一种关键的降解机制，也受特定 miRNA 的调控，对系统性红斑狼疮的病理产生影响。本文探讨了多种 miRNA 在调控 B 细胞发育、增殖、存活和免疫反应方面的作用，这些作用影响着系统性红斑狼疮的发病机制。miRNA 如 miR-23a、miR-17 ∼ 92 家族和 miR-125b/miR-221 通过调控转录因子、信号通路和细胞周期基因来影响 B 细胞的发育。miR-181a-5p和miR-23a-5p等miRNA在不同的发育阶段受到不同的调控，强调了它们在B细胞生物学中复杂的调控作用。本文综述了 miRNA 与 B 细胞的相互作用，为系统性红斑狼疮的诊断和治疗提供了新的策略和方向。
{"title":"Regulation of B-cell function by miRNAs impacting Systemic lupus erythematosus progression","authors":"Bitang Huang , Fengbiao Guo , Jiaxuan Chen , Lu Lu , Shenglan Gao , Chunlong Yang , Han Wu , Wenying Luo , Qingjun Pan","doi":"10.1016/j.gene.2024.149011","DOIUrl":"10.1016/j.gene.2024.149011","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a complex autoimmune disease marked by abnormal B-cell proliferation and increased autoantibodies. miRNAs play a crucial role in regulating B-cell dysfunction and SLE pathology. miRNAs influence DNA methylation, B-cell activation, and gene expression, contributing to SLE pathogenesis. miRNAs impact B cells through key processes like proliferation, differentiation, tolerance, and apoptosis. miRNAs also exacerbate inflammation and immune responses by modulating Interleukin 4 (IL-4), IL-6, and interferon cytokines. Autophagy, a key degradation mechanism, is also regulated by specific miRNAs that impact SLE pathology. This article explores the role of multiple miRNAs in regulating B-cell development, proliferation, survival, and immune responses, influencing SLE pathogenesis. miRNAs like miR-23a, the miR-17 ∼ 92 family, and miR-125b/miR-221 affect B-cell development by regulating transcription factors, signaling pathways, and cell cycle genes. miRNAs such as miR-181a-5p and miR-23a-5p are differentially regulated across developmental stages, emphasizing their complex regulatory roles in B-cell biology. This article synthesizes miRNA-B cell interactions to offer new strategies and directions for SLE diagnosis and treatment.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.gene.2024.149015
Yulin Tao , Minqi Xiong , Yirui Peng , Lili Yao , Haibo Zhu , Qiong Zhou , Jun Ouyang
The early diagnosis of diabetic retinopathy (DR) is challenging, highlighting the urgent need to identify new biomarkers. Immune responses play a crucial role in DR, yet there are currently no reports of machine learning (ML) algorithms being utilized for the development of immune-related molecular markers in DR. Based on the datasets GSE102485 and GSE160306, differentially expressed genes (DEGs) were screened using Weighted Gene Co-expression Network Analysis (WGCNA). Five ML algorithms including Bayesian, Learning Vector Quantization (LVQ), Wrapper (Boruta), Random Forest (RF), and Logistic Regression were employed to select immune-related genes associated with DR (DR.Sig). Seven ML algorithms including Naive Bayes (NB), RF, Support Vector Machine (SVM), AdaBoost Classification Trees (AdaBoost), Boosted Logistic Regressions (LogitBoost), K-Nearest Neighbors (KNN), and Cancerclass were utilized to construct a predictive model for DR. The relationship between DR.Sig genes and immune cells was analyzed using single-sample Gene Set Enrichment Analysis (ssGSEA). Additionally, drug sensitivity prediction of DR.Sig genes and molecular docking were performed. Through the utilization of 5 ML algorithms, 6 immune-related biomarkers closely related to the occurrence of DR were identified, including FCGR2B, CSRP1, EDNRA, SDC2, TEK, and CIITA. The DR predictive model constructed based on these 6 DR.Sig genes using the Cancerclass algorithm demonstrated superior predictive performance compared to 4 previously published DR-related biomarkers. In vivo and in vitro experiments also provided strong validation of the expression of the 6 genes in DR. Positive correlations were observed between these genes and 22 types of immune cells. Molecular docking results revealed that CSRP1, EDNRA, and TEK exhibited the highest affinities with the small molecule compounds etoposide, FR-139317, and camptothecin, respectively. The models constructed based on various ML algorithms can effectively predict the occurrence of DR events and hold potential for targeted drug therapies, providing a basis for the early diagnosis and targeted treatment of DR.
糖尿病视网膜病变（DR）的早期诊断具有挑战性，因此迫切需要确定新的生物标记物。免疫反应在糖尿病视网膜病变中起着至关重要的作用，但目前还没有关于利用机器学习（ML）算法开发糖尿病视网膜病变免疫相关分子标记物的报道。基于 GSE102485 和 GSE160306 数据集，利用加权基因共表达网络分析（WGCNA）筛选了差异表达基因（DEGs）。采用贝叶斯算法、学习矢量量化算法（LVQ）、Wrapper算法（Boruta）、随机森林算法（RF）和逻辑回归算法等五种 ML 算法筛选出与 DR 相关的免疫相关基因（DR.Sig）。利用 Naive Bayes (NB)、RF、支持向量机 (SVM)、AdaBoost 分类树 (AdaBoost)、Boosted Logistic Regressions (LogitBoost)、K-Nearest Neighbors (KNN) 和 Cancerclass 等七种 ML 算法构建了 DR 预测模型。利用单样本基因组富集分析（ssGSEA）分析了 DR.Sig 基因与免疫细胞之间的关系。此外，还对 DR.Sig 基因进行了药物敏感性预测和分子对接。通过使用 5 种 ML 算法，确定了 6 个与 DR 发生密切相关的免疫相关生物标志物，包括 FCGR2B、CSRP1、EDNRA、SDC2、TEK 和 CIITA。基于这6个DR.Sig基因使用Cancerclass算法构建的DR预测模型与之前公布的4个DR相关生物标记物相比，显示出更优越的预测性能。体内和体外实验也有力地验证了这 6 个基因在 DR 中的表达。在这些基因和 22 种免疫细胞之间观察到了正相关性。分子对接结果显示，CSRP1、EDNRA 和 TEK 分别与小分子化合物依托泊苷、FR-139317 和喜树碱具有最高的亲和力。基于多种 ML 算法构建的模型能有效预测 DR 事件的发生，并具有靶向药物治疗的潜力，为 DR 的早期诊断和靶向治疗提供了依据。
{"title":"Machine learning-based identification and validation of immune-related biomarkers for early diagnosis and targeted therapy in diabetic retinopathy","authors":"Yulin Tao , Minqi Xiong , Yirui Peng , Lili Yao , Haibo Zhu , Qiong Zhou , Jun Ouyang","doi":"10.1016/j.gene.2024.149015","DOIUrl":"10.1016/j.gene.2024.149015","url":null,"abstract":"<div><div>The early diagnosis of diabetic retinopathy (DR) is challenging, highlighting the urgent need to identify new biomarkers. Immune responses play a crucial role in DR, yet there are currently no reports of machine learning (ML) algorithms being utilized for the development of immune-related molecular markers in DR. Based on the datasets GSE102485 and GSE160306, differentially expressed genes (DEGs) were screened using Weighted Gene Co-expression Network Analysis (WGCNA). Five ML algorithms including Bayesian, Learning Vector Quantization (LVQ), Wrapper (Boruta), Random Forest (RF), and Logistic Regression were employed to select immune-related genes associated with DR (DR.Sig). Seven ML algorithms including Naive Bayes (NB), RF, Support Vector Machine (SVM), AdaBoost Classification Trees (AdaBoost), Boosted Logistic Regressions (LogitBoost), K-Nearest Neighbors (KNN), and Cancerclass were utilized to construct a predictive model for DR. The relationship between DR.Sig genes and immune cells was analyzed using single-sample Gene Set Enrichment Analysis (ssGSEA). Additionally, drug sensitivity prediction of DR.Sig genes and molecular docking were performed. Through the utilization of 5 ML algorithms, 6 immune-related biomarkers closely related to the occurrence of DR were identified, including FCGR2B, CSRP1, EDNRA, SDC2, TEK, and CIITA. The DR predictive model constructed based on these 6 DR.Sig genes using the Cancerclass algorithm demonstrated superior predictive performance compared to 4 previously published DR-related biomarkers. In vivo and in vitro experiments also provided strong validation of the expression of the 6 genes in DR. Positive correlations were observed between these genes and 22 types of immune cells. Molecular docking results revealed that CSRP1, EDNRA, and TEK exhibited the highest affinities with the small molecule compounds etoposide, FR-139317, and camptothecin, respectively. The models constructed based on various ML algorithms can effectively predict the occurrence of DR events and hold potential for targeted drug therapies, providing a basis for the early diagnosis and targeted treatment of DR.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462458","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}
Pub Date : 2024-10-18DOI: 10.1016/j.gene.2024.149010
Natalia E. Gogoleva , Roman O. Cherezov , Yulia V. Lyupina , Kim I. Adameyko , Alexander S. Balkin , Nikolay G. Gornostaev , Oksana I. Kravchuk
The quick-to-court (qtc) gene is expressed in both males and females but affects only the mating behavior of males, probably due to the different composition of isoforms between the sexes. We tested this hypothesis and examined the sex-specific expression of qtc transcripts in the tissues of male and female Oregon-R flies. It was found that some qtc transcripts, such as qtc-RM and qtc-RN, are testis-specific, while others like qtc-RH are found in ovaries but absent in testes. No sex-specific transcripts were identified in the brain, suggesting further investigation into specific brain structures may be needed. There is likely a complex regulation of qtc gene expression, which is potentially influenced by various factors in different tissues.
{"title":"Differential expression of quick-to-court gene isoforms in Drosophila male and female","authors":"Natalia E. Gogoleva , Roman O. Cherezov , Yulia V. Lyupina , Kim I. Adameyko , Alexander S. Balkin , Nikolay G. Gornostaev , Oksana I. Kravchuk","doi":"10.1016/j.gene.2024.149010","DOIUrl":"10.1016/j.gene.2024.149010","url":null,"abstract":"<div><div>The <em>quick-to-court</em> (<em>qtc</em>) gene is expressed in both males and females but affects only the mating behavior of males, probably due to the different composition of isoforms between the sexes. We tested this hypothesis and examined the sex-specific expression of <em>qtc</em> transcripts in the tissues of male and female <em>Oregon-R</em> flies. It was found that some <em>qtc</em> transcripts, such as qtc-RM and qtc-RN, are testis-specific, while others like qtc-RH are found in ovaries but absent in testes. No sex-specific transcripts were identified in the brain, suggesting further investigation into specific brain structures may be needed. There is likely a complex regulation of <em>qtc</em> gene expression, which is potentially influenced by various factors in different tissues.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462437","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}
Pub Date : 2024-10-18DOI: 10.1016/j.gene.2024.149007
Zhaodi Wang , Yihan Chen , Weidong Li , Chuanyu Gao , Jing Zhang , Xiaobiao Zang , Zhihan Zhao , Hongkun Fan , Yonghui Zhao
Dilated cardiomyopathy (DCM) is characterized by immune cell infiltration and can readily progress to heart failure (HF). In the study, differential expression analysis, enrichment analysis, and protein–protein interaction (PPI) network analysis were performed on DCM with HF-related datasets. The CytoHubba was used to identify hub genes. Diagnostic biomarkers were obtained by validating their expression and diagnostic value in another external dataset, and a diagnostic model was constructed. Finally, single-sample gene set enrichment analysis (ssGSEA) was used to predict immune cell infiltration in cardiac samples. The associations between diagnostic biomarkers and immune cells were investigated. The NetworkAnalyst and miRDB databases were used to predict transcription factors and microRNAs, followed by establishing regulatory networks. The DSigDB database was used to predict drug candidates. Subsequently, a mouse model of DCM with HF was used to validate the expression levels of these genes. The present study revealed that differentially expressed genes were enriched in the extracellular matrix organization, cardiac muscle hypertrophy, and other immune-related biological processes. OMD and THBS4 were finally identified, and the nomogram has satisfactory prediction and strong calibration ability. In addition, the two diagnostic biomarkers exhibited significant associations with multiple immune infiltrating cells. Finally, two TFs, 65 microRNAs, and 10 drug candidates were obtained. In animal experiments, two diagnostic biomarkers showed expression trends consistent with the results of bioinformatic analysis. OMD and THBS4 have been identified as hub immune-related diagnostic biomarkers for DCM with HF. Our research provides novel insights into the diagnosis and treatment of the disease.
{"title":"Identification and validation of diagnostic biomarkers and immune infiltration in dilated cardiomyopathies with heart failure and construction of diagnostic model","authors":"Zhaodi Wang , Yihan Chen , Weidong Li , Chuanyu Gao , Jing Zhang , Xiaobiao Zang , Zhihan Zhao , Hongkun Fan , Yonghui Zhao","doi":"10.1016/j.gene.2024.149007","DOIUrl":"10.1016/j.gene.2024.149007","url":null,"abstract":"<div><div>Dilated cardiomyopathy (DCM) is characterized by immune cell infiltration and can readily progress to heart failure (HF). In the study, differential expression analysis, enrichment analysis, and protein–protein interaction (PPI) network analysis were performed on DCM with HF-related datasets. The CytoHubba was used to identify hub genes. Diagnostic biomarkers were obtained by validating their expression and diagnostic value in another external dataset, and a diagnostic model was constructed. Finally, single-sample gene set enrichment analysis (ssGSEA) was used to predict immune cell infiltration in cardiac samples. The associations between diagnostic biomarkers and immune cells were investigated. The NetworkAnalyst and miRDB databases were used to predict transcription factors and microRNAs, followed by establishing regulatory networks. The DSigDB database was used to predict drug candidates. Subsequently, a mouse model of DCM with HF was used to validate the expression levels of these genes. The present study revealed that differentially expressed genes were enriched in the extracellular matrix organization, cardiac muscle hypertrophy, and other immune-related biological processes. OMD and THBS4 were finally identified, and the nomogram has satisfactory prediction and strong calibration ability. In addition, the two diagnostic biomarkers exhibited significant associations with multiple immune infiltrating cells. Finally, two TFs, 65 microRNAs, and 10 drug candidates were obtained. In animal experiments, two diagnostic biomarkers showed expression trends consistent with the results of bioinformatic analysis. OMD and THBS4 have been identified as hub immune-related diagnostic biomarkers for DCM with HF. Our research provides novel insights into the diagnosis and treatment of the disease.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462440","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}
Pub Date : 2024-10-18DOI: 10.1016/j.gene.2024.149006
Chiron Loubser, Natalya V. Nikitina
The genetic basis of somatic cell identity in avian sex determination is still unknown. FET1, an endogenous retrovirus, has previously been demonstrated to be expressed during gonad development. Here, we report expression of FET1 related transcripts in non-gonadal tissue during chicken development. Both the forward and reverse FET1 related transcripts were seen in various developing muscle tissues. Both the “full-length” and partial FET1 transcripts were expressed; the latter however showed a more ubiquitous expression pattern. Female-specific gonadal expression of both sense and antisense transcripts was also confirmed. An anti-FET1 antibody, however, failed to distinguish between the predicted FET1 protein and other endogenous retroviral proteins expressed at E6.5. Our data suggest a possible role for FET1 related transcripts in sex-specific differences in muscle size and growth rate in the chickens.
{"title":"Expression of FET-1 related transcripts during chicken embryogenesis suggests a role in muscle development","authors":"Chiron Loubser, Natalya V. Nikitina","doi":"10.1016/j.gene.2024.149006","DOIUrl":"10.1016/j.gene.2024.149006","url":null,"abstract":"<div><div>The genetic basis of somatic cell identity in avian sex determination is still unknown. <em>FET1</em>, an endogenous retrovirus, has previously been demonstrated to be expressed during gonad development. Here, we report expression of <em>FET1</em> related transcripts in non-gonadal tissue during chicken development. Both the forward and reverse <em>FET1</em> related transcripts were seen in various developing muscle tissues. Both the “full-length” and partial <em>FET1</em> transcripts were expressed; the latter however showed a more ubiquitous expression pattern. Female-specific gonadal expression of both sense and antisense transcripts was also confirmed. An anti-FET1 antibody, however, failed to distinguish between the predicted FET1 protein and other endogenous retroviral proteins expressed at E6.5. Our data suggest a possible role for <em>FET1</em> related transcripts in sex-specific differences in muscle size and growth rate in the chickens.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.gene.2024.149009
Gong Xiao, Shumei Tang, Yan Zhang, Qiongjing Yuan, Danni Sun, Wei Wang
Background
The role of ferroptosis in lupus nephritis (LN) is unclear. This study aimed to explore the effects of ferroptosis-related genes in LN through bioinformatics prediction and experimental validation.
Methods
Sample data were collected from the GEO dataset and divided into glomeruli and tubulointerstitium. We collected 382 ferroptosis-related genes. The intersection of ferroptosis-related genes with glomeruli and tubulointerstitium data, respectively, was performed. Machine learning methods (including unsupervised cluster typing and random forests) were operated to identify ferroptosis subtyping and ferroptosis important genes in LN. Immune infiltration and functional analysis were performed. The expression of ferroptosis important gene ATF3 was validated in vivo and in vitro.
Results
6 ferroptosis important genes common to glomeruli and tubulointerstitium were screened, including ATF3, CD44, CYBB, JUN, NCF2, and NNMT. ATF3 decreased in the LN group compared to the Control. Silencing ATF3 mitigated LPS/erastin-induced ferroptosis. Functional analysis showed that ATF3 was markedly enriched in the interferon-gamma-mediated signaling pathway, ECM-receptor interaction, and cell adhesion. In glomeruli, T cells regulatory (Tregs) infiltration decreased and Macrophages M1 levels increased with elevated ATF3 expression. Levels of immune cell infiltration were altered in different ferroptosis subtypes of LN glomeruli and tubulointerstitium.
Conclusions
Ferroptosis-related ATF3 levels decreased in LN. Inhibition of ATF3 might alleviate LN development by affecting the macrophage M1 and Treg cell infiltration. These implied that ATF3 might be a potential target for developing LN therapeutic strategies.
{"title":"Downregulation of ferroptosis-related ATF3 alleviates lupus nephritis progression","authors":"Gong Xiao, Shumei Tang, Yan Zhang, Qiongjing Yuan, Danni Sun, Wei Wang","doi":"10.1016/j.gene.2024.149009","DOIUrl":"10.1016/j.gene.2024.149009","url":null,"abstract":"<div><h3>Background</h3><div>The role of ferroptosis in lupus nephritis (LN) is unclear. This study aimed to explore the effects of ferroptosis-related genes in LN through bioinformatics prediction and experimental validation.</div></div><div><h3>Methods</h3><div>Sample data were collected from the GEO dataset and divided into glomeruli and tubulointerstitium. We collected 382 ferroptosis-related genes. The intersection of ferroptosis-related genes with glomeruli and tubulointerstitium data, respectively, was performed. Machine learning methods (including unsupervised cluster typing and random forests) were operated to identify ferroptosis subtyping and ferroptosis important genes in LN. Immune infiltration and functional analysis were performed. The expression of ferroptosis important gene ATF3 was validated <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Results</h3><div>6 ferroptosis important genes common to glomeruli and tubulointerstitium were screened, including ATF3, CD44, CYBB, JUN, NCF2, and NNMT. ATF3 decreased in the LN group compared to the Control. Silencing ATF3 mitigated LPS/erastin-induced ferroptosis. Functional analysis showed that ATF3 was markedly enriched in the interferon-gamma-mediated signaling pathway, ECM-receptor interaction, and cell adhesion. In glomeruli, T cells regulatory (Tregs) infiltration decreased and Macrophages M1 levels increased with elevated ATF3 expression. Levels of immune cell infiltration were altered in different ferroptosis subtypes of LN glomeruli and tubulointerstitium.</div></div><div><h3>Conclusions</h3><div>Ferroptosis-related ATF3 levels decreased in LN. Inhibition of ATF3 might alleviate LN development by affecting the macrophage M1 and Treg cell infiltration. These implied that ATF3 might be a potential target for developing LN therapeutic strategies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462439","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}
Pub Date : 2024-10-16DOI: 10.1016/j.gene.2024.149004
Shiyi Zhang , Shuman Liu , Yantong Zhu , Linyu Geng , Lingyun Sun
Introduction
The etiology of systemic lupus erythematosus (SLE) is complex, involving both environmental and genetic factors. Previous research has indicated a potential link between autoimmune diseases, such as SLE, and variations in the vitamin D receptor gene (VDR). This study intended to explore the relationship between VDR SNPs, susceptibility to SLE, clinical parameters, and prognosis in the Chinese Han SLE population.
Method
Totally, 461 healthy individuals and 503 patients were recuited SLE diagnoses were chosen. Data on clinical symptoms, scores from the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and results from clinical examinations were collected. The study analyzed four variations in the VDR gene (FokI, BsmI, ApaI, TaqI) using MassARRAY® Iplex GOLD SNP genotyping.
Results
The dominant model showed significant correlations between susceptibility to SLE and the FokI (P < 0.001) and ApaI (P < 0.001) SNPs. Additionally, mucosal ulcer was linked to FokI, while hematologic disorder, rash, photosensitivity, and anti-dsDNA positivity were associated with ApaI. Subsequent studies indicated that the FokI SNP was connected to a poorer prognosis in SLE patients.
Conclusions
This research indicates that VDR SNPs could potentially contribute to the susceptibility of SLE, as well as impacting the clinical presentation and outlook for Chinese individuals with SLE. (Protocol No. 2016-027, registered retrospectively).
{"title":"Association of Vitamin D receptor gene polymorphism with susceptibility and prognosis of Systemic Lupus Erythematosus in Chinese patients","authors":"Shiyi Zhang , Shuman Liu , Yantong Zhu , Linyu Geng , Lingyun Sun","doi":"10.1016/j.gene.2024.149004","DOIUrl":"10.1016/j.gene.2024.149004","url":null,"abstract":"<div><h3>Introduction</h3><div>The etiology of systemic lupus erythematosus (SLE) is complex, involving both environmental and genetic factors. Previous research has indicated a potential link between autoimmune diseases, such as SLE, and variations in the vitamin D receptor gene (VDR). This study intended to explore the relationship between VDR SNPs, susceptibility to SLE, clinical parameters, and prognosis in the Chinese Han SLE population.</div></div><div><h3>Method</h3><div>Totally, 461 healthy individuals and 503 patients were recuited SLE diagnoses were chosen. Data on clinical symptoms, scores from the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and results from clinical examinations were collected. The study analyzed four variations in the VDR gene (FokI, BsmI, ApaI, TaqI) using MassARRAY® Iplex GOLD SNP genotyping.</div></div><div><h3>Results</h3><div>The dominant model showed significant correlations between susceptibility to SLE and the FokI (P < 0.001) and ApaI (P < 0.001) SNPs. Additionally, mucosal ulcer was linked to FokI, while hematologic disorder, rash, photosensitivity, and anti-dsDNA positivity were associated with ApaI. Subsequent studies indicated that the FokI SNP was connected to a poorer prognosis in SLE patients.</div></div><div><h3>Conclusions</h3><div>This research indicates that VDR SNPs could potentially contribute to the susceptibility of SLE, as well as impacting the clinical presentation and outlook for Chinese individuals with SLE. (Protocol No. 2016-027, registered retrospectively).</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462463","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}
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