Next-generation sequencing (NGS) is a high-throughput technology capable of determining the sequence of nucleotides in the genome. Over the past few years, the advent of NGS-based methods has provided timely and economical approaches for diagnosing and screening genetic conditions throughout an individual’s lifespan, and prenatal period. Prenatal screening for congenital abnormalities has opened the door to reducing the incidence of genetic disorders. Early detection of genetic diseases using NGS-based methods enables better management of these conditions, thereby improving the quality of life for patients. NGS has also played a pivotal role in pharmacogenetics and drug delivery, facilitating a more personalized approach to medicine. NGS-based methods are increasingly being utilized in genome editing to provide essential information that enhances the precision and effectiveness of editing techniques. This review presents information on how various NGS-based methods function from a technical perspective. Furthermore, we will explore the applications and benefits of these methods in the fields of diagnosis, screening, pharmacogenetics, and genome editing.
{"title":"Next-generation sequencing as an applicable method: from technical basis to use in medical diagnosis","authors":"Arman Moradi , Mina Mousavi , Majid Maleki , Seyedeh Zoha Tabatabaei , Mahshid Malakootian","doi":"10.1016/j.gene.2026.150002","DOIUrl":"10.1016/j.gene.2026.150002","url":null,"abstract":"<div><div>Next-generation sequencing (NGS) is a high-throughput technology capable of determining the sequence of nucleotides in the genome. Over the past few years, the advent of NGS-based methods has provided timely and economical approaches for diagnosing and screening genetic conditions throughout an individual’s lifespan, and prenatal period. Prenatal screening for congenital abnormalities has opened the door to reducing the incidence of genetic disorders. Early detection of genetic diseases using NGS-based methods enables better management of these conditions, thereby improving the quality of life for patients. NGS has also played a pivotal role in pharmacogenetics and drug delivery, facilitating a more personalized approach to medicine. NGS-based methods are increasingly being utilized in genome editing to provide essential information that enhances the precision and effectiveness of editing techniques. This review presents information on how various NGS-based methods function from a technical perspective. Furthermore, we will explore the applications and benefits of these methods in the fields of diagnosis, screening, pharmacogenetics, and genome editing.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"986 ","pages":"Article 150002"},"PeriodicalIF":2.4,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948717","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 : 2026-04-10Epub Date: 2026-01-24DOI: 10.1016/j.gene.2026.150029
Yong Yan Tang , Ya Chen Gao , Tao Liu , Jian Wu , Liang Bing Wei , Jia Rong Gao
Background
Chronic glomerulonephritis (CGN) primarily arises from immune-mediated inflammation, but the exact targets driving its initiation and progression remain unclear. This study identified the YTHDC2/RAB20/NLRP3 axis as a potential therapeutic target in CGN.
Methods
RAB20 and YTHDC2 expression was analyzed through bioinformatics. In vitro, lipopolysaccharide (LPS)-stimulated mouse mesangial cells (MMCs) were transfected with siRNA targeting RAB20 and YTHDC2, along with overexpression plasmids. Actinomycin D was utilized to evaluate RAB20 mRNA stability. RNA immunoprecipitation quantitative PCR (RIP-qPCR) was performed to investigate the interaction between RAB20 mRNA and YTHDC2 protein. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) and 5‑Ethynyl ‑2′‑Deoxyuridine (EdU) incorporation assays. NLRP3 inflammasome priming was measured by Enzyme-Linked Immunosorbent Assay (ELISA), immunofluorescence, and Western blot (WB). In vivo, adenine-induced CGN mice were treated with adeno-associated virus 9 (AAV9-YTHDC2). Renal function markers were assessed, and kidney histopathology was analyzed via tissue staining.
Results
Both clinical, cellular, and animal models revealed a significant reduction in RAB20 expression in CGN. RAB20 knockdown facilitated NLRP3 inflammasome priming, while its overexpression suppressed these effects. The YTHDC2 protein specifically binds to RAB20 mRNA. YTHDC2 knockdown increased RAB20 mRNA stability, which inhibited MMC proliferation and NLRP3 inflammasome priming. In CGN mice, AAV9-mediated silencing of YTHDC2 improved renal function, as evidenced by reduced kidney function markers and diminished inflammatory cell infiltration.
Conclusion
This study demonstrates that YTHDC2-mediated degradation of RAB20 mRNA regulates NLRP3 inflammasome priming in glomerular mesangial cells and contributes to CGN pathogenesis.
{"title":"YTHDC2-mediated RAB20 degradation regulates NLRP3 inflammasome priming to improve chronic glomerulonephritis","authors":"Yong Yan Tang , Ya Chen Gao , Tao Liu , Jian Wu , Liang Bing Wei , Jia Rong Gao","doi":"10.1016/j.gene.2026.150029","DOIUrl":"10.1016/j.gene.2026.150029","url":null,"abstract":"<div><h3>Background</h3><div>Chronic glomerulonephritis (CGN) primarily arises from immune-mediated inflammation, but the exact targets driving its initiation and progression remain unclear. This study identified the YTHDC2/RAB20/NLRP3 axis as a potential therapeutic target in CGN.</div></div><div><h3>Methods</h3><div>RAB20 and YTHDC2 expression was analyzed through bioinformatics. <em>In vitro</em>, lipopolysaccharide (LPS)-stimulated mouse mesangial cells (MMCs) were transfected with siRNA targeting RAB20 and YTHDC2, along with overexpression plasmids. Actinomycin D was utilized to evaluate RAB20 mRNA stability. RNA immunoprecipitation quantitative PCR (RIP-qPCR) was performed to investigate the interaction between RAB20 mRNA and YTHDC2 protein. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) and 5‑Ethynyl ‑2′‑Deoxyuridine (EdU) incorporation assays. NLRP3 inflammasome priming was measured by Enzyme-Linked Immunosorbent Assay (ELISA), immunofluorescence, and Western blot (WB). <em>In vivo</em>, adenine-induced CGN mice were treated with adeno-associated virus 9 (AAV9-YTHDC2). Renal function markers were assessed, and kidney histopathology was analyzed <em>via</em> tissue staining.</div></div><div><h3>Results</h3><div>Both clinical, cellular, and animal models revealed a significant reduction in RAB20 expression in CGN. RAB20 knockdown facilitated NLRP3 inflammasome priming, while its overexpression suppressed these effects. The YTHDC2 protein specifically binds to RAB20 mRNA. YTHDC2 knockdown increased RAB20 mRNA stability, which inhibited MMC proliferation and NLRP3 inflammasome priming. In CGN mice, AAV9-mediated silencing of YTHDC2 improved renal function, as evidenced by reduced kidney function markers and diminished inflammatory cell infiltration.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that YTHDC2-mediated degradation of RAB20 mRNA regulates NLRP3 inflammasome priming in glomerular mesangial cells and contributes to CGN pathogenesis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"986 ","pages":"Article 150029"},"PeriodicalIF":2.4,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051302","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 : 2026-04-10Epub Date: 2026-01-23DOI: 10.1016/j.gene.2026.150022
Wei Wei , Yueyuan Liu , Chong Pan , Jiahao Liu , Shaozhuo Xu , Yanfei Shan , Cheng Li , Jiahao Zeng , Cheng Xue , Jun Wu
Basic helix-loop-helix (bHLH) transcription factors play central regulatory roles in plant development and responses to environmental stress. However, the evolutionary dynamics of the bHLH gene family in Rosaceae fruit species remain largely unexplored. In particular, the expression profiles and functional roles of PybHLH genes during stone cell formation in pear fruit are not well understood. In this study, a total of 910 bHLH genes were identified across seven Rosaceae species—Asian pear, European pear, apple, peach, sweet cherry, Japanese apricot, and strawberry—with 198 genes detected in pear (Pyrus spp.). The PybHLH genes were classified into 13 major clusters (A–M) comprising 17 subfamilies. Inter-species collinearity analyses revealed strong macrosyntenic conservation among apple, Asian pear, and European pear. Whole-genome duplication (WGD) and dispersed duplication (DSD) were identified as the main drivers of bHLH gene family expansion. Transcriptome analysis across multiple tissues identified eight PybHLH genes with specific expression in fruit flesh. Integration of differential expression data during stone cell development with a co-expression network of lignin biosynthetic genes further narrowed down four PybHLH candidates associated with lignification. Among them, RT-qPCR and transient expression assays confirmed that PybHLH182 positively regulates stone cell lignification. This study presents the first comprehensive analysis of the bHLH gene family across seven Rosaceae species, clarifying the evolutionary trajectory of bHLHs and the tissue-specific expression patterns of PybHLHs. The Maloideae subfamily maintains gene family stability via WGD and DSD, whereas the genus Prunus drives gene divergence through frequent genomic rearrangements. Meanwhile, PybHLH182 was identified as a core regulator governing stone cell formation in pear fruits. These findings provide a theoretical basis for molecular breeding of Rosaceae fruit trees and elucidating the mechanisms underlying pear fruit quality formation.
{"title":"Genome-wide identification of the rosaceae bHLH gene family and functional characterization of PybHLH182 involved in stone cell formation in pear","authors":"Wei Wei , Yueyuan Liu , Chong Pan , Jiahao Liu , Shaozhuo Xu , Yanfei Shan , Cheng Li , Jiahao Zeng , Cheng Xue , Jun Wu","doi":"10.1016/j.gene.2026.150022","DOIUrl":"10.1016/j.gene.2026.150022","url":null,"abstract":"<div><div>Basic helix-loop-helix (bHLH) transcription factors play central regulatory roles in plant development and responses to environmental stress. However, the evolutionary dynamics of the <em>bHLH</em> gene family in Rosaceae fruit species remain largely unexplored. In particular, the expression profiles and functional roles of <em>PybHLH</em> genes during stone cell formation in pear fruit are not well understood. In this study, a total of 910 <em>bHLH</em> genes were identified across seven Rosaceae species—Asian pear, European pear, apple, peach, sweet cherry, Japanese apricot, and strawberry—with 198 genes detected in pear (<em>Pyrus</em> spp.). The <em>PybHLH</em> genes were classified into 13 major clusters (A–M) comprising 17 subfamilies. Inter-species collinearity analyses revealed strong macrosyntenic conservation among apple, Asian pear, and European pear. Whole-genome duplication (WGD) and dispersed duplication (DSD) were identified as the main drivers of <em>bHLH</em> gene family expansion. Transcriptome analysis across multiple tissues identified eight <em>PybHLH</em> genes with specific expression in fruit flesh. Integration of differential expression data during stone cell development with a co-expression network of lignin biosynthetic genes further narrowed down four <em>PybHLH</em> candidates associated with lignification. Among them, RT-qPCR and transient expression assays confirmed that <em>PybHLH182</em> positively regulates stone cell lignification. This study presents the first comprehensive analysis of the <em>bHLH</em> gene family across seven Rosaceae species, clarifying the evolutionary trajectory of <em>bHLHs</em> and the tissue-specific expression patterns of <em>PybHLHs</em>. The Maloideae subfamily maintains gene family stability via WGD and DSD, whereas the genus <em>Prunus</em> drives gene divergence through frequent genomic rearrangements. Meanwhile, <em>PybHLH182</em> was identified as a core regulator governing stone cell formation in pear fruits. These findings provide a theoretical basis for molecular breeding of Rosaceae fruit trees and elucidating the mechanisms underlying pear fruit quality formation.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"986 ","pages":"Article 150022"},"PeriodicalIF":2.4,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046513","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 : 2026-04-10Epub Date: 2026-01-24DOI: 10.1016/j.gene.2026.150023
Kaifeng Li , Mengran Wang , Yanhong Liu , Ruining Lu , Heng Zhang , Xiaohui Sui , Guiju Zhang , Xuan Li
Objective: Childhood obesity (CO) has become a global epidemic, leading to rising burden of many diseases and premature death. Thus, this study was conducted to screen the mitochondria-associated biomarkers for patients with CO, as well as the involved molecular mechanism.
Methods: After downloading GSE29718 and GSE104815 datasets from GEO database, differential expression analysis was conducted to screen the DEGs. Then the obtained DEGs were intersected with the mitochondrial-associated genes, and mitochondrial-related genes in CO were acquired, followed by key mitochondrial-related genes screening utilizing three machine learning algorithms. The qRT-PCR and western blot were employed to determine the expression of key genes. Gain-of-function experiment was applied to investigate the function of NIPSNAP3B in CO in vitro.
Results: Total 364 DEGs were screened, then 18 mitochondrial-related genes in CO were obtained. These 18 mitochondrial-associated genes in CO enriched in pyruvate metabolism, arginine biosynthesis, and AMPK signaling pathway, etc. ACACB and NIPSNAP3B were considered as the key mitochondrial-related genes. Of note, NIPSNAP3B overexpression markedly reduced the TG level and the protein expression levels of PPARγ and C/EBPα in MDI-induced 3 T3-L1 cells. Also, ATP content, mitochondrial mass, MMP, and protein expression levels of PGC-1α, NRF1, and TFAM were changed after NIPSNAP3B upregulation in MDI-induced 3 T3-L1 cells. However, opposite results were observed after NIPSNAP3B downregulation. Compound C (AMPK inhibitor) or AMPK knockdown administration could reverse the effect of NIPSNAP3B on adipocyte lipid deposition and mitochondrial biogenesis.
Conclusion: NIPSNAP3B enhances mitochondrial biogenesis to attenuate lipid accumulation via AMPK pathway in CO.
{"title":"NIPSNAP3B elevates mitochondrial biogenesis to attenuate lipid accumulation in childhood obesity via AMPK pathway","authors":"Kaifeng Li , Mengran Wang , Yanhong Liu , Ruining Lu , Heng Zhang , Xiaohui Sui , Guiju Zhang , Xuan Li","doi":"10.1016/j.gene.2026.150023","DOIUrl":"10.1016/j.gene.2026.150023","url":null,"abstract":"<div><div><strong>Objective</strong>: Childhood obesity (CO) has become a global epidemic, leading to rising burden of many diseases and premature death. Thus, this study was conducted to screen the mitochondria-associated biomarkers for patients with CO, as well as the involved molecular mechanism.</div><div><strong>Methods</strong>: After downloading GSE29718 and GSE104815 datasets from GEO database, differential expression analysis was conducted to screen the DEGs. Then the obtained DEGs were intersected with the mitochondrial-associated genes, and mitochondrial-related genes in CO were acquired, followed by key mitochondrial-related genes screening utilizing three machine learning algorithms. The qRT-PCR and western blot were employed to determine the expression of key genes. Gain-of-function experiment was applied to investigate the function of NIPSNAP3B in CO <em>in vitro</em>.</div><div><strong>Results</strong>: Total 364 DEGs were screened, then 18 mitochondrial-related genes in CO were obtained. These 18 mitochondrial-associated genes in CO enriched in pyruvate metabolism, arginine biosynthesis, and AMPK signaling pathway, etc. ACACB and NIPSNAP3B were considered as the key mitochondrial-related genes. Of note, NIPSNAP3B overexpression markedly reduced the TG level and the protein expression levels of PPARγ and C/EBPα in MDI-induced 3 T3-L1 cells. Also, ATP content, mitochondrial mass, MMP, and protein expression levels of PGC-1α, NRF1, and TFAM were changed after NIPSNAP3B upregulation in MDI-induced 3 T3-L1 cells. However, opposite results were observed after NIPSNAP3B downregulation. Compound C (AMPK inhibitor) or AMPK knockdown administration could reverse the effect of NIPSNAP3B on adipocyte lipid deposition and mitochondrial biogenesis.</div><div><strong>Conclusion:</strong> NIPSNAP3B enhances mitochondrial biogenesis to attenuate lipid accumulation via AMPK pathway in CO.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"986 ","pages":"Article 150023"},"PeriodicalIF":2.4,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051316","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 : 2026-04-05Epub Date: 2026-01-14DOI: 10.1016/j.gene.2026.150009
Mengdan Ning , Yankun Li , Luhao Yang , Yongtao Li , Yirong Yu , Yu Zhang , Yanpei Zhang , Tao Mu , Maciren Ni , Qiang Qin , Shaowei Li , Junxi Wu , Jianping Yang , Yong Shi
As an important food and feed crop, cultivated rye (Secale cereale L.) exhibits excellent resistance to biotic and abiotic stresses, making it a valuable genetic resource for wheat improvement. However, the functions of phytochromes in rye remain poorly characterized. Here, we cloned and characterized PhyB from the Weining rye variety (ScPhyB). The predicted protein contains conserved phytochrome domains—PAS, GAF, PHY, and HATPase—and phylogenetic analysis revealed that ScPhyB is most closely related to wheat TaPhyB, with both belonging to the monocot clade. Promoter analysis identified multiple cis-acting elements related to hormone response, meristem expression, low temperature responsiveness, light response, and MYB binding. Heterologous expression of ScPhyB in Arabidopsis enhanced photomorphogenesis under white light (WL), red light (R), and blue light (B). Furthermore, ScPhyB attenuated shade avoidance responses to 70 % and 90 % of wildtype seedlings measured by hypocotyl length by perceiving high and low R/FR red to far-red (R/FR) light ratio, respectively. ScPhyB also modulated plant architecture and delayed flowering (6-7d) by repressing FT expression. Yeast two-hybrid (Y2H) assays and split-luciferase (LUC) assay confirmed that ScPhyB interacts with both ScPIF3 and ScCOP1, indicating functional conservation within the PIF signaling pathway and the COP1-SPA1 complex. Our findings provide insight into the role of ScPhyB in light signaling and suggest its potential utility for improving crop traits.
{"title":"The rye photoreceptor ScphyB integrates light signals to control development and architecture in Arabidopsis thaliana","authors":"Mengdan Ning , Yankun Li , Luhao Yang , Yongtao Li , Yirong Yu , Yu Zhang , Yanpei Zhang , Tao Mu , Maciren Ni , Qiang Qin , Shaowei Li , Junxi Wu , Jianping Yang , Yong Shi","doi":"10.1016/j.gene.2026.150009","DOIUrl":"10.1016/j.gene.2026.150009","url":null,"abstract":"<div><div>As an important food and feed crop, cultivated rye (Secale cereale L.) exhibits excellent resistance to biotic and abiotic stresses, making it a valuable genetic resource for wheat improvement. However, the functions of phytochromes in rye remain poorly characterized. Here, we cloned and characterized PhyB from the Weining rye variety (ScPhyB). The predicted protein contains conserved phytochrome domains—PAS, GAF, PHY, and HATPase—and phylogenetic analysis revealed that ScPhyB is most closely related to wheat TaPhyB, with both belonging to the monocot clade. Promoter analysis identified multiple <em>cis</em>-acting elements related to hormone response, meristem expression, low temperature responsiveness, light response, and MYB binding. Heterologous expression of ScPhyB in Arabidopsis enhanced photomorphogenesis under white light (WL), red light (R), and blue light (B). Furthermore, ScPhyB attenuated shade avoidance responses to 70 % and 90 % of wildtype seedlings measured by hypocotyl length by perceiving high and low R/FR red to far-red (R/FR) light ratio, respectively. ScPhyB also modulated plant architecture and delayed flowering (6-7d) by repressing FT expression. Yeast two-hybrid (Y2H) assays and split-luciferase (LUC) assay confirmed that ScPhyB interacts with both ScPIF3 and ScCOP1, indicating functional conservation within the PIF signaling pathway and the COP1-SPA1 complex. Our findings provide insight into the role of ScPhyB in light signaling and suggest its potential utility for improving crop traits.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"985 ","pages":"Article 150009"},"PeriodicalIF":2.4,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988950","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 : 2026-04-05Epub Date: 2026-01-14DOI: 10.1016/j.gene.2026.150012
Liyan Qiu , Caisheng Xu , Renhua Lu , Shaobin Lin , Fang Yang
WNT7B-related pulmonary hypoplasia, diaphragmatic anomalies, anophthalmia/microphthalmia, and cardiac defects (PDAC) syndrome is rarely reported. To date, only two each nonsense and missense variants of WNT7B were identified in five pedigrees affected with a PDAC spectrum from two independent studies. Additionally, the gene-disease association between WNT7B and PDAC syndrome is not yet clarified in OMIM database. Here, the whole exome sequencing was used to identify biallelic novel loss-of-function (LoF) variants c.324C > G (p.Tyr108*) and c.668_669dup (p.Val224Argfs*6) of WNT7B in a fetus affected with a typical PDAC spectrum, including pulmonary hypoplasia/agenesis, bilateral microphthalmia, and absence of pulmonary arteries and veins, from a Chinese family. Subsequent functional analysis revealed that the two LoF variants decreased the RNA and protein expression levels of WNT7B, and significantly impaired the canonical WNT-β-Catenin signaling pathway, which is essential for regulation of human lung development. We broaden the variant spectrum of WNT7B, and provide genetic and experimental evidence to confirm the association between WNT7B pathogenic variants and PDAC spectrum.
wnt7b相关的肺发育不全、膈异常、眼无/小眼和心脏缺陷（PDAC）综合征很少报道。迄今为止，只有两个无义和错义的WNT7B变体被鉴定在5个家谱受影响的PDAC从两个独立的研究。此外，在OMIM数据库中，WNT7B与PDAC综合征之间的基因-疾病关联尚未明确。本研究利用全外显子组测序技术，鉴定了来自一个中国家庭的WNT7B双等位基因新型功能缺失（LoF）变异c.324C > G （p.Tyr108*）和c.668_669dup (p.Val224Argfs*6)，这些变异具有典型的PDAC谱系，包括肺发育不全/发育不全、双侧小眼和肺动脉静脉缺失。随后的功能分析显示，这两个LoF变异降低了WNT7B的RNA和蛋白表达水平，并显著损害了典型的WNT-β-Catenin信号通路，该信号通路是调节人类肺发育所必需的。我们拓宽了WNT7B的变异谱，并提供了遗传和实验证据来证实WNT7B致病变异与PDAC谱之间的关联。
{"title":"Identification and functional analysis of biallelic loss-of-function variants of WNT7B in a Chinese family affected with PDAC syndrome","authors":"Liyan Qiu , Caisheng Xu , Renhua Lu , Shaobin Lin , Fang Yang","doi":"10.1016/j.gene.2026.150012","DOIUrl":"10.1016/j.gene.2026.150012","url":null,"abstract":"<div><div><em>WNT7B</em>-related pulmonary hypoplasia, diaphragmatic anomalies, anophthalmia/microphthalmia, and cardiac defects (PDAC) syndrome is rarely reported. To date, only two each nonsense and missense variants of <em>WNT7B</em> were identified in five pedigrees affected with a PDAC spectrum from two independent studies. Additionally, the gene-disease association between <em>WNT7B</em> and PDAC syndrome is not yet clarified in OMIM database. Here, the whole exome sequencing was used to identify biallelic novel loss-of-function (LoF) variants c.324C > G (p.Tyr108*) and c.668_669dup (p.Val224Argfs*6) of <em>WNT7B</em> in a fetus affected with a typical PDAC spectrum, including pulmonary hypoplasia/agenesis, bilateral microphthalmia, and absence of pulmonary arteries and veins, from a Chinese family. Subsequent functional analysis revealed that the two LoF variants decreased the RNA and protein expression levels of <em>WNT7B</em>, and significantly impaired the canonical WNT-β-Catenin signaling pathway, which is essential for regulation of human lung development. We broaden the variant spectrum of <em>WNT7B</em>, and provide genetic and experimental evidence to confirm the association between <em>WNT7B</em> pathogenic variants and PDAC spectrum.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"985 ","pages":"Article 150012"},"PeriodicalIF":2.4,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975950","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}
Parkinson’s disease (PD) is a progressive degenerative neuronal disorder that involves the selective loss of dopaminergic neurons in the substantia nigra, resulting in severe motor and non-motor impairments. Key pathological hallmarks include the accumulation of misfolded α-synuclein and mitochondrial dysfunction. Emerging evidence indicates that innate immune signalling, particularly the cGAS-STING pathway, contributes to PD pathogenesis. It acts as a cytosolic DNA sensor; cGAS can recognise genomic instability or mitochondrial damage by generating an IFN-I response through STING activation. Persistent stimulation of the cGAS-STING pathway in microglia promotes chronic neuroinflammation and contributes to dopaminergic neuronal loss. Mitochondrial dysfunction, impaired DNA repair, and α-Synuclein aggregation may converge to sustain pathway activation, establishing a self-reinforcing cycle of inflammation and neurodegeneration. Understanding the interaction of cGAS-STING signalling, mitochondrial integrity, and protein aggregation offers important mechanistic insights into PD pathology. It suggests meaningful targets for disease-modifying therapeutic approaches for PD that address neuroinflammation and neuronal survival.
{"title":"cGAS-STING activation in Parkinson’s Disease: From mechanisms to Disease-Modifying therapeutic strategies","authors":"Jemimol Solomon , Snehashis Mandal , Khadga Raj Aran","doi":"10.1016/j.gene.2026.150000","DOIUrl":"10.1016/j.gene.2026.150000","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a progressive degenerative neuronal disorder that involves the selective loss of dopaminergic neurons in the substantia nigra, resulting in severe motor and non-motor impairments. Key pathological hallmarks include the accumulation of misfolded α-synuclein and mitochondrial dysfunction. Emerging evidence indicates that innate immune signalling, particularly the cGAS-STING pathway, contributes to PD pathogenesis. It acts as a cytosolic DNA sensor; cGAS can recognise genomic instability or mitochondrial damage by generating an IFN-I response through STING activation. Persistent stimulation of the cGAS-STING pathway in microglia promotes chronic neuroinflammation and contributes to dopaminergic neuronal loss. Mitochondrial dysfunction, impaired DNA repair, and α-Synuclein aggregation may converge to sustain pathway activation, establishing a self-reinforcing cycle of inflammation and neurodegeneration. Understanding the interaction of cGAS-STING signalling, mitochondrial integrity, and protein aggregation offers important mechanistic insights into PD pathology. It suggests meaningful targets for disease-modifying therapeutic approaches for PD that address neuroinflammation and neuronal survival.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"985 ","pages":"Article 150000"},"PeriodicalIF":2.4,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917539","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}
Long non-coding RNAs (lncRNAs) are increasingly recognized as crucial regulators of gene expression, influencing a wide array of physiological and pathological processes. Among these, Nuclear Enriched Abundant Transcript 1 (NEAT1), an essential component of nuclear paraspeckles, has garnered significant attention for its diverse roles in various diseases, including immune-related disorders and certain cancers. While the involvement of lncRNAs in dermatologic conditions is an expanding field, the specific implications of NEAT1 in the onset and progression of skin diseases remain largely underexplored. This review aims to consolidate current knowledge regarding the multifaceted roles of NEAT1 in skin biology and pathology. Here, we summarize available evidence on NEAT1 in skin disorders, emphasizing its roles in regulating keratinocyte biology, modulating inflammatory pathways, and influencing disease progression. By consolidating current findings, the review provides a framework for understanding the potential role of NEAT1 as a biomarker and therapeutic target in dermatologic conditions.
{"title":"Emerging role of NEAT1 in skin pathology: from molecular regulation to clinical applications","authors":"Wiam Saadi , Ahlam Fatmi , Auda Ameur , Salvatore Spicuglia , Denis Puthier , Mohamed Belhocine","doi":"10.1016/j.gene.2026.150013","DOIUrl":"10.1016/j.gene.2026.150013","url":null,"abstract":"<div><div>Long non-coding RNAs (lncRNAs) are increasingly recognized as crucial regulators of gene expression, influencing a wide array of physiological and pathological processes. Among these, Nuclear Enriched Abundant Transcript 1 (<em>NEAT1</em>), an essential component of nuclear paraspeckles, has garnered significant attention for its diverse roles in various diseases, including immune-related disorders and certain cancers. While the involvement of lncRNAs in dermatologic conditions is an expanding field, the specific implications of <em>NEAT1</em> in the onset and progression of skin diseases remain largely underexplored. This review aims to consolidate current knowledge regarding the multifaceted roles of <em>NEAT1</em> in skin biology and pathology. Here, we summarize available evidence on NEAT1 in skin disorders, emphasizing its roles in regulating keratinocyte biology, modulating inflammatory pathways, and influencing disease progression. By consolidating current findings, the review provides a framework for understanding the potential role of <em>NEAT1</em> as a biomarker and therapeutic target in dermatologic conditions.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"985 ","pages":"Article 150013"},"PeriodicalIF":2.4,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997877","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 : 2026-04-05Epub Date: 2026-01-17DOI: 10.1016/j.gene.2026.150014
Hamit Çelik , Oğuz Çelik , Şeyma Aydın , Sefa Küçükler , Selim Çomaklı , Ahmet Topal , Ramazan Akay , Sinan Gönüllü , Mustafa Onur Yıldız , Bülent Alım , Selçuk Özdemir
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, oxidative stress, and persistent neuroinflammation. Recent studies have increasingly focused on the regulatory role of microRNAs in AD pathogenesis. In this study, we investigated the therapeutic potential of small extracellular vesicles (sEV) enriched with microRNA34 (miRNA34) to target key pathogenic mechanisms of AD. We hypothesized that miRNA34-loaded sEV could alleviate oxidative damage, inhibit neuroinflammatory responses and ferroptosis, reduce mitochondrial impairment, and ultimately improve cognitive function. We evaluated the effects of miRNA34 administration on oxidative stress markers, pro-inflammatory cytokines, synaptic plasticity indicators, and behavioral outcomes in an in vivo Aβ-induced mouse model of AD. The experimental design included five groups, each consisting of seven mice. The findings demonstrated that miRNA34-loaded sEV treatment significantly reduced oxidative stress and neuroinflammation while enhancing memory and learning performance. Overall, our results indicate that miRNA34-enriched sEV represent a promising and minimally invasive therapeutic strategy capable of modulating AD pathogenesis. This research provides a novel perspective on the potential clinical application of miRNA34 and sEVin neurodegenerative disorders.
{"title":"Small extracellular vesicles carrying miRNA34 in Alzheimer’s disease: effects on oxidative stress, neuroinflammation, cognitive function, and mitochondrial/ferroptosis-related protein regulation","authors":"Hamit Çelik , Oğuz Çelik , Şeyma Aydın , Sefa Küçükler , Selim Çomaklı , Ahmet Topal , Ramazan Akay , Sinan Gönüllü , Mustafa Onur Yıldız , Bülent Alım , Selçuk Özdemir","doi":"10.1016/j.gene.2026.150014","DOIUrl":"10.1016/j.gene.2026.150014","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, oxidative stress, and persistent neuroinflammation. Recent studies have increasingly focused on the regulatory role of microRNAs in AD pathogenesis. In this study, we investigated the therapeutic potential of small extracellular vesicles (sEV) enriched with microRNA34 (miRNA34) to target key pathogenic mechanisms of AD. We hypothesized that miRNA34-loaded sEV could alleviate oxidative damage, inhibit neuroinflammatory responses and ferroptosis, reduce mitochondrial impairment, and ultimately improve cognitive function. We evaluated the effects of miRNA34 administration on oxidative stress markers, pro-inflammatory cytokines, synaptic plasticity indicators, and behavioral outcomes in an <em>in vivo</em> Aβ-induced mouse model of AD. The experimental design included five groups, each consisting of seven mice. The findings demonstrated that miRNA34-loaded sEV treatment significantly reduced oxidative stress and neuroinflammation while enhancing memory and learning performance. Overall, our results indicate that miRNA34-enriched sEV represent a promising and minimally invasive therapeutic strategy capable of modulating AD pathogenesis. This research provides a novel perspective on the potential clinical application of miRNA34 and sEVin neurodegenerative disorders.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"985 ","pages":"Article 150014"},"PeriodicalIF":2.4,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003503","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 : 2026-03-21DOI: 10.1016/j.gene.2026.150115
Henrik Christian Bidstrup Leffers, Niels Graudal, Sophine B Krintel, Jesper Lindhardsen, Anne Meldgaard Høy, Bo Baslund
Purpose: Serum angiotensin-converting enzyme (sACE) is widely used as a biomarker in sarcoidosis, yet interpretation is complicated by genetic variability. We investigated whether ACE insertion/deletion (I/D) genotype influences longitudinal sACE activity and its relationship to clinical manifestations and treatment response.
Methods: Forty-six patients with confirmed sarcoidosis and available ACE genotype data were included. sACE activity was measured longitudinally and normalized to the assay-specific upper limit of normal (sACE index). Linear mixed modeling assessed genotype-specific trajectories over time. Organ involvement and treatment response were compared across genotypes.
Results: Genotype distribution was DD (35%), ID (41%), and II (24%). Baseline sACE index showed a descending numerical trend across genotypes but did not differ significantly. Longitudinal modeling demonstrated a significantly steeper decline in sACE index in DD compared with ID and II genotypes (p < 0.001 for interaction). Organ involvement and treatment response did not differ across genotypes.
Conclusion: ACE I/D genotype influences longitudinal serum ACE activity in sarcoidosis. Genotype-informed interpretation may improve biomarker-based monitoring.
{"title":"ACE I/D genotype influences longitudinal serum ACE activity in sarcoidosis.","authors":"Henrik Christian Bidstrup Leffers, Niels Graudal, Sophine B Krintel, Jesper Lindhardsen, Anne Meldgaard Høy, Bo Baslund","doi":"10.1016/j.gene.2026.150115","DOIUrl":"https://doi.org/10.1016/j.gene.2026.150115","url":null,"abstract":"<p><strong>Purpose: </strong>Serum angiotensin-converting enzyme (sACE) is widely used as a biomarker in sarcoidosis, yet interpretation is complicated by genetic variability. We investigated whether ACE insertion/deletion (I/D) genotype influences longitudinal sACE activity and its relationship to clinical manifestations and treatment response.</p><p><strong>Methods: </strong>Forty-six patients with confirmed sarcoidosis and available ACE genotype data were included. sACE activity was measured longitudinally and normalized to the assay-specific upper limit of normal (sACE index). Linear mixed modeling assessed genotype-specific trajectories over time. Organ involvement and treatment response were compared across genotypes.</p><p><strong>Results: </strong>Genotype distribution was DD (35%), ID (41%), and II (24%). Baseline sACE index showed a descending numerical trend across genotypes but did not differ significantly. Longitudinal modeling demonstrated a significantly steeper decline in sACE index in DD compared with ID and II genotypes (p < 0.001 for interaction). Organ involvement and treatment response did not differ across genotypes.</p><p><strong>Conclusion: </strong>ACE I/D genotype influences longitudinal serum ACE activity in sarcoidosis. Genotype-informed interpretation may improve biomarker-based monitoring.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"150115"},"PeriodicalIF":2.4,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503481","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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