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Retraction notice to “Correlation between TGF-β1-509 C>T polymorphism and risk of digestive tract cancer in a meta-analysis for 21,196 participants” [Gene 505 (2012) 66-74] 撤回“一项21,196名参与者的meta分析中TGF-β1-509 C>T多态性与消化道癌风险的相关性”[Gene 505(2012) 66-74]。
IF 2.4 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2025-12-17 DOI: 10.1016/j.gene.2025.149948
Jian Min Zhang , Xi Jun Cui , Yun Qiang Xia , Sen Guo
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引用次数: 0
A novel tRNA-derived fragment tRF-Val-CAC-008 as a diagnostic biomarker and pyroptosis regulator in LSCC 一种新的trna衍生片段tRF-Val-CAC-008作为LSCC的诊断生物标志物和焦亡调节剂。
IF 2.4 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2025-12-17 DOI: 10.1016/j.gene.2025.149967
Hongxia Deng , Dong Ye , Shijie Qiu , Shuang Ye , Chongchang Zhou , Shuai Fang , Yuna Zhang , Shanshan Gu

Objective

Laryngeal cancer is one of the most common malignant tumors of the head and neck, with laryngeal squamous cell carcinoma (LSCC) being the most significant pathological type. Transfer RNA-derived fragments (tRFs) fragments have been implicated in tumor progression through diverse regulatory mechanisms. This study examined the diagnostic value and role of tRF-Val-CAC-008 in LSCC.

Methods

Levels of tRF-Val-CAC-008 were quantified in LSCC tissues, plasma, saliva, and cells using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic value of tRF-Val-CAC-008 was then assessed using the receiver operating characteristic (ROC) curve. LSCC cells were transfected with mimics or inhibitors of tRF-Val-CAC-008, which increased or decreased its level accordingly. Cell proliferation was evaluated using EdU and the cell counting kit-8 (CCK-8) assays. The level of lactate dehydrogenase (LDH) in LSCC cells was measured using an LDH release assay. Pyroptosis-associated proteins were analyzed by Western blotting (WB).

Results

tRF-Val-CAC-008 exhibited significantly higher expression levels in LSCC tissues, plasma and saliva. This higher expression correlated with its pro-proliferative effects and suppression of pyroptosis observed in vitro. In LSCC cells, tRF-Val-CAC-008 mimics promoted cell proliferation and reduced LDH secretion. The expression of gasdermin E (GSDME) and caspase-3 proteins was also decreased by tRF-Val-CAC-008 mimics, which in turn regulated pyroptosis. The ROC curves suggest that combined plasma and saliva tRF-Val-CAC-008 can serve as a diagnostic marker to distinguish LSCC patients from healthy participants.

Conclusions

The study concluded that tRF-Val-CAC-008 could act as a diagnostic marker for LSCC; it promotes tumor growth by suppressing pyroptosis and promoting cell proliferation.
目的:喉癌是头颈部最常见的恶性肿瘤之一,喉鳞癌(喉鳞癌)是最重要的病理类型。转移rna衍生片段(tRFs)片段通过多种调节机制与肿瘤进展有关。本研究探讨了tRF-Val-CAC-008在LSCC中的诊断价值和作用。方法:采用实时定量逆转录聚合酶链反应(qRT-PCR)技术,定量检测LSCC组织、血浆、唾液和细胞中tRF-Val-CAC-008的水平。然后用受试者工作特征(ROC)曲线评估tRF-Val-CAC-008的诊断价值。用tRF-Val-CAC-008的模拟物或抑制剂转染LSCC细胞,可相应提高或降低其水平。用EdU和细胞计数试剂盒-8 (CCK-8)测定细胞增殖情况。乳酸脱氢酶(LDH)释放法测定LSCC细胞乳酸脱氢酶(LDH)水平。Western blotting (WB)分析热释热相关蛋白。结果:tRF-Val-CAC-008在LSCC组织、血浆和唾液中的表达水平明显升高。这种高表达与体外观察到的促增殖作用和抑制焦亡有关。在LSCC细胞中,tRF-Val-CAC-008模拟促进细胞增殖并减少LDH分泌。tRF-Val-CAC-008模拟物也降低了gasdermin E (GSDME)和caspase-3蛋白的表达,从而调节焦亡。ROC曲线提示血浆和唾液tRF-Val-CAC-008可作为区分LSCC患者和健康受试者的诊断指标。结论:tRF-Val-CAC-008可作为LSCC的诊断标志物;它通过抑制焦亡和促进细胞增殖来促进肿瘤生长。
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引用次数: 0
Navigating the winding road toward precision prostate cancer care 在通往精确前列腺癌治疗的曲折道路上航行。
IF 2.4 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2025-12-17 DOI: 10.1016/j.gene.2025.149966
Syed Rahman , Adith S. Arun , Isaac Yi Kim , William K. Oh , Joseph W. Kim , William J. Kim
Prostate cancer (PCa) remains the second leading cause of cancer-related mortality among U.S. men, driven in large part by metastatic castration-resistant prostate cancer (mCRPC) despite initial responses to androgen-receptor (AR)–targeted therapies. Over the last two decades, treatment options for mCRPC have significantly expanded to include novel therapeutic modalities that integrate biomarker-guided patient selection. These biomarker-driven therapies have ushered us into the era of “precision oncology” in prostate cancer care, and we highlight key developments. In light of these promising early results, we also review key opportunities and challenges ahead. Additionally, we share a conceptual roadmap to leverage multi-omics molecular data in the era of Artificial Intelligence/Machine Learning (AI/ML) to accelerate progress in prostate cancer precision medicine. Specifically, we discuss how these tools may help facilitate the development of near-patient preclinical models for prostate cancer to better capture key aspects of prostate cancer tumor biology. We also discuss a potential path toward accelerating translation of laboratory discoveries into clinical practice for PCa patients.
前列腺癌(PCa)仍然是美国男性癌症相关死亡的第二大原因,尽管对雄激素受体(AR)靶向治疗有初步反应,但转移性去势抵抗性前列腺癌(mCRPC)在很大程度上是由其驱动的。在过去的二十年中,mCRPC的治疗选择已经显著扩大,包括整合生物标志物引导的患者选择的新型治疗模式。这些生物标志物驱动的疗法将我们带入了前列腺癌治疗的“精确肿瘤学”时代,我们将重点介绍其中的关键进展。鉴于这些有希望的初步结果,我们还审查了未来的主要机遇和挑战。此外,我们还分享了在人工智能/机器学习(AI/ML)时代利用多组学分子数据加速前列腺癌精准医学进展的概念路线图。具体来说,我们讨论了这些工具如何帮助更好地促进前列腺癌近患者临床前模型的发展,以捕获前列腺癌肿瘤生物学的关键方面,以及加速将实验室发现转化为mCPRC患者临床实践的潜在途径。
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引用次数: 0
Trolline attenuates diabetic vascular injury by regulating SLC7A11-mediated ferroptosis and mitochondrial dysfunction troline通过调节slc7a11介导的铁下垂和线粒体功能障碍减轻糖尿病血管损伤。
IF 2.4 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2025-12-17 DOI: 10.1016/j.gene.2025.149968
Wenbo Liu , Cuifang Lu , Bin Yang , Ying Liu , Jie Yan , Tingyu Song , Xiaofei Wang

Aims

This study investigated the therapeutic potential of Trolline, a natural compound, for alleviating high-glucose (HG)-induced vascular endothelial ferroptosis and mitochondrial dysfunction via the cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) pathway.

Materials and methods

In db/db mice, inflammatory damage; glucose tolerance; and the expression of SLC7A11, glutathione peroxidase 4 (GPX4), and long-chain acyl-CoA synthetase family member 4 (ACSL4) were detected after treatment with Trolline. An HG-induced human microvascular endothelial cell (HMEC-1) injury model was established in vitro. Fe2+ deposition and GSH levels serve as important indicators of ferroptosis. The mitochondrial membrane potential and the cytoskeleton were determined by JC-1 and F-actin staining, respectively. The levels of apoptosis, cell cycle and reactive oxygen species (ROS) were determined by flow cytometry. Oxidative stress levels were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Ferroptosis- and inflammation-related protein expression in HMEC-1 cells was verified by Western blotting.

Results

In vivo experiments revealed that Trolline can lower blood sugar levels, alleviate inflammatory damage, and regulate the expression of ferroptosis-related proteins in db/db mice. In vitro experiments demonstrated that Trolline can alleviate various effects induced by HG. Under HG conditions, Trolline can inhibit apoptosis, reverse the cell cycle arrest in the SubG1 phase, reduce oxidative stress levels and Fe2+ overload, restore mitochondrial function, promote cytoskeletal remodelling, and regulate the expression of ferroptosis-related proteins. Mechanistically, ferroptosis inhibitors (Ferrostatin-1) and Trolline have the same protective effect on HMEC-1 cells in an HG environment. However, overexpression of SLC7A11 led to loss of the inhibitory effect of Trolline on ferroptosis, which confirms that the effect of Trolline is dependent on the SLC7A11-ferroptosis axis.

Conclusion

Trolline can alleviate diabetic vascular damage through SLC7A11-mediated inhibition of ferroptosis, improved mitochondrial function, and reduced oxidative inflammatory damage, providing a basis for the treatment of diabetic vascular complications.
目的:本研究探讨天然化合物Trolline通过胱氨酸/谷氨酸反转运蛋白溶质载体家族7成员11 (SLC7A11)途径缓解高糖(HG)诱导的血管内皮铁垂症和线粒体功能障碍的治疗潜力。材料与方法:db/db小鼠,炎性损伤;葡萄糖耐量;经Trolline处理后检测SLC7A11、谷胱甘肽过氧化物酶4 (GPX4)、长链酰基辅酶a合成酶家族成员4 (ACSL4)的表达。建立hg诱导的人微血管内皮细胞(HMEC-1)体外损伤模型。Fe2+沉积和GSH水平是铁下垂的重要指标。JC-1染色测定线粒体膜电位,F-actin染色测定细胞骨架。流式细胞术检测细胞凋亡、细胞周期及活性氧(ROS)水平。通过测量丙二醛(MDA)水平和超氧化物歧化酶(SOD)活性来评估氧化应激水平。Western blotting证实HMEC-1细胞中铁下垂和炎症相关蛋白的表达。结果:体内实验显示,巨魔碱能降低db/db小鼠的血糖水平,减轻炎症损伤,调节铁中毒相关蛋白的表达。体外实验表明,Trolline可以缓解HG诱导的多种作用,在HG条件下,Trolline可以抑制细胞凋亡,逆转细胞周期停滞在SubG1期,降低氧化应激水平和Fe2+超载,恢复线粒体功能,促进细胞骨架重塑,调节铁中毒相关蛋白的表达。在机制上,铁下垂抑制剂(Ferrostatin-1)和Trolline对HG环境中的HMEC-1细胞具有相同的保护作用。然而,SLC7A11的过表达导致Trolline对铁下垂的抑制作用丧失,这证实了Trolline的作用依赖于SLC7A11-铁下垂轴。结论:巨罗林可通过slc7a11介导的抑制上铁,改善线粒体功能,减轻氧化性炎症损伤,为糖尿病血管并发症的治疗提供依据。
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引用次数: 0
Innovative minicircle DNA vector encoding pri-miR-375 silences E6 and E7 oncoproteins in HPV16-positive CaSki cells 创新的微环DNA载体编码pri-miR-375沉默hpv16阳性CaSki细胞中的E6和E7癌蛋白。
IF 2.4 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2025-12-17 DOI: 10.1016/j.gene.2025.149964
D. Pereira , A.M. Almeida , J.A. Queiroz , F. Sousa , N. Alves , J.F.A. Valente , A. Sousa

Background

The infection by Human Papillomaviruses (HPV) has long been established as one of the main causes of cervical cancer, with HPV16/HPV18 high-risk types expressing E6/E7 oncoproteins that inhibit p53/pRB tumor suppressor proteins. Therefore, this work focuses on gene therapy, using the innovative minicircle DNA (mcDNA) vector to protect and express the pri-miR-375 in the cancer cell nucleus, ultimately originating the microRNA-375 (miR-375) in the cytoplasm. This miR-375, initially downregulated in cervical cancer cells, can silence HPV E6/E7 transcripts, thereby negatively regulating the expression of these oncoproteins.

Methods

The mcDNA-pri-miR-375 vector was successfully constructed, biosynthesized in the host cell, extracted, and purified, followed by several in vitro transfection studies in CaSKi cells (HPV16-infected cervical cancer model) to evaluate the mcDNA-pri-miR-375 effect.

Results

FITC-stained-mcDNA-pri-miR-375 was present in cancer cell nucleus, confirmed by confocal microscopy. RT-PCR analysis showed a more intense band of miR-375 transcripts, and RT-PCR/ RT-qPCR confirmed that E6/ E7 transcript levels were nearly 80 % diminished 24 h after CaSki cells transfection. Also, western-blot showed a decreased band intensity for E6/ E7 proteins on transfected cells. Proliferation and cell invasion studies demonstrated growth and migration arrest for CaSki cells throughout 72 h. Cell viability study of these cells also revealed a gradual decrease for the same period, while the NHDF cell viability was not affected, indicating specificity towards CaSki. The consequent effect of silencing the E6/ E7 transcripts was also observed through an increase in p53 protein levels (determined by western blot and ELISA) and caspase-3 activity, after 48 h of CaSki cell transfection.

Conclusions

These results suggest that mcDNA-pri-miR-375 vector has the potential to be further explored in gene therapy for the treatment of HPV-caused cervical cancer.
背景:人乳头瘤病毒(Human papillomavirus, HPV)感染早已被确定为宫颈癌的主要病因之一,HPV16/HPV18高危型表达抑制p53/pRB抑癌蛋白的E6/E7癌蛋白。因此,本工作的重点是基因治疗,利用创新的微环DNA (microiccircle DNA, mcDNA)载体在癌细胞细胞核中保护和表达pri-miR-375,最终在细胞质中产生microRNA-375 (miR-375)。这种最初在宫颈癌细胞中下调的miR-375可以沉默HPV E6/E7转录本,从而负向调节这些癌蛋白的表达。方法:构建mcDNA-pri-miR-375载体,在宿主细胞中进行生物合成、提取、纯化,并在CaSKi细胞(hpv16感染宫颈癌模型)中进行多次体外转染研究,评价mcDNA-pri-miR-375的作用。结果:经共聚焦显微镜证实,癌细胞细胞核中存在fitc染色的mcdna -pri- mir -375。RT-PCR分析显示miR-375转录物的条带更强,RT-PCR/ RT-qPCR证实,CaSki细胞转染后24 h, E6/ E7转录物水平降低了近80% %。western-blot也显示转染细胞上E6/ E7蛋白的条带强度降低。增殖和细胞侵袭研究表明,CaSki细胞在72 h内生长和迁移停滞。这些细胞的细胞活力研究也显示在同一时期逐渐下降,而NHDF细胞活力不受影响,表明对CaSki具有特异性。在CaSki细胞转染48 h后,通过p53蛋白水平(通过western blot和ELISA测定)和caspase-3活性的增加,也观察到E6/ E7转录物沉默的后续效果。结论:这些结果提示mcDNA-pri-miR-375载体在hpv致宫颈癌的基因治疗中具有进一步探索的潜力。
{"title":"Innovative minicircle DNA vector encoding pri-miR-375 silences E6 and E7 oncoproteins in HPV16-positive CaSki cells","authors":"D. Pereira ,&nbsp;A.M. Almeida ,&nbsp;J.A. Queiroz ,&nbsp;F. Sousa ,&nbsp;N. Alves ,&nbsp;J.F.A. Valente ,&nbsp;A. Sousa","doi":"10.1016/j.gene.2025.149964","DOIUrl":"10.1016/j.gene.2025.149964","url":null,"abstract":"<div><h3>Background</h3><div>The infection by Human Papillomaviruses (HPV) has long been established as one of the main causes of cervical cancer, with HPV16/HPV18 high-risk types expressing E6/E7 oncoproteins that inhibit p53/pRB tumor suppressor proteins. Therefore, this work focuses on gene therapy, using the innovative minicircle DNA (mcDNA) vector to protect and express the pri-miR-375 in the cancer cell nucleus, ultimately originating the microRNA-375 (miR-375) in the cytoplasm. This miR-375, initially downregulated in cervical cancer cells, can silence HPV E6/E7 transcripts, thereby negatively regulating the expression of these oncoproteins.</div></div><div><h3>Methods</h3><div>The mcDNA-pri-miR-375 vector was successfully constructed, biosynthesized in the host cell, extracted, and purified, followed by several <em>in vitro</em> transfection studies in CaSKi cells (HPV16-infected cervical cancer model) to evaluate the mcDNA-pri-miR-375 effect.</div></div><div><h3>Results</h3><div>FITC-stained-mcDNA-pri-miR-375 was present in cancer cell nucleus, confirmed by confocal microscopy. RT-PCR analysis showed a more intense band of miR-375 transcripts, and RT-PCR/ RT-qPCR confirmed that E6/ E7 transcript levels were nearly 80 % diminished 24 h after CaSki cells transfection. Also, western-blot showed a decreased band intensity for E6/ E7 proteins on transfected cells. Proliferation and cell invasion studies demonstrated growth and migration arrest for CaSki cells throughout 72 h. Cell viability study of these cells also revealed a gradual decrease for the same period, while the NHDF cell viability was not affected, indicating specificity towards CaSki. The consequent effect of silencing the E6/ E7 transcripts was also observed through an increase in p53 protein levels (determined by western blot and ELISA) and caspase-3 activity, after 48 h of CaSki cell transfection.</div></div><div><h3>Conclusions</h3><div>These results suggest that mcDNA-pri-miR-375 vector has the potential to be further explored in gene therapy for the treatment of HPV-caused cervical cancer.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149964"},"PeriodicalIF":2.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793765","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
In vitro expression and seroreactivity of Toxoplasma gondii GRA1 protein encoded by unmodified and nucleoside-modified mRNA constructs 未修饰和核苷修饰的刚地弓形虫gr1蛋白的体外表达及血清反应性。
IF 2.4 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2025-12-16 DOI: 10.1016/j.gene.2025.149965
Mehmet Nadir Şahinci , Mert Döşkaya , Muhammet Karakavuk , Seren Kaplan , Gizem Mutlu , Tuğçe Gizem Perçin , Sedef Erkunt Alak , Özlem Günay-Esiyok , Aytül Gül Mete , Aysu Değirmenci Döşkaya , Ayşe Gülten Kantarcı , Adnan Yüksel Gürüz , Hüseyin Can
Toxoplasmosis is an infectious parasitic disease caused by Toxoplasma gondii, with a global seroprevalence estimated to affect more than one-third of the human population. T. gondii can be a serious health concern for pregnant women and immunocompromised patients. Currently, there is no effective and safe vaccine for humans. However, mRNA technology is a promising platform to develop efficient and safe vaccines against toxoplasmosis. Therefore, we designed nucleoside-modified and unmodified mRNA vaccine transcripts expressing T. gondii recombinant GRA1 protein and analyzed their in vitro protein expression profile as well as potential immunogenicity using IFAT, Western blot, and ELISA. Moreover, to compare translational efficiency, poly-A tail was extended with an extra ∼150 bp in addition to the existing ∼120 bp poly-A tail in two distinct mRNA designs. The results showed that all four mRNA constructs expressed rGRA1 protein in HEK293T cells. However, mRNA constructs with extended poly-A tails exhibited reduced expression level of rGRA1 protein compared to other mRNA vaccine transcripts. Additionally, unmodified mRNA construct with or without extended poly-A tail yielded significantly higher protein expression compared to nucleoside-modified mRNA constructs through ELISA using anti-polyhis antibody (P<0.05). Western blot showed that rGRA1 protein expressed by all four mRNA constructs reacted strongly with T. gondii IgG seropositive mice sera. Furthermore, ELISA revealed that rGRA1 proteins derived from unmodified and nucleoside-modified mRNA constructs formed significantly stronger immune complexes with T. gondii IgG antibodies compared to negative controls (P<0.05). These data suggest that both unmodified and nucleosidemodified mRNA constructs expressing rGRA1 protein have potential as vaccine candidates and warrant further investigation for development of an mRNA-based vaccine against toxoplasmosis. However, encapsulation of the produced mRNA constructs in LNPs and in vivo studies are required to validate these preliminary results.
弓形虫病是由刚地弓形虫引起的一种传染性寄生虫病,其全球血清患病率估计影响到三分之一以上的人口。弓形虫对孕妇和免疫功能低下的人来说可能是一个严重的健康问题。目前,还没有针对人类的有效疫苗。然而,mRNA技术是开发高效、安全的弓形虫病疫苗的一个有前途的平台。因此,我们设计了核苷修饰和未修饰的编码密码子优化的弓形虫gr1蛋白的mRNA疫苗转录本,并利用IFAT、Western blot和ELISA分析了它们的体外蛋白表达谱和表达蛋白的潜在免疫原性。此外,为了比较翻译效率,在两种mRNA设计中,除了现有的~ 120 bp poly-A尾外,还将聚腺苷化(poly -A)尾长度额外延长了~ 150 bp。结果表明,所有mRNA构建体在HEK293T细胞中均表达重组GRA1蛋白。然而,与其他mRNA疫苗转录物相比,具有延伸poly-A尾部的mRNA构建物表现出rGRA1蛋白表达水平降低。此外,与核苷修饰的mRNA结构相比,未修饰的mRNA结构产生了显著更高的蛋白质表达(P
{"title":"In vitro expression and seroreactivity of Toxoplasma gondii GRA1 protein encoded by unmodified and nucleoside-modified mRNA constructs","authors":"Mehmet Nadir Şahinci ,&nbsp;Mert Döşkaya ,&nbsp;Muhammet Karakavuk ,&nbsp;Seren Kaplan ,&nbsp;Gizem Mutlu ,&nbsp;Tuğçe Gizem Perçin ,&nbsp;Sedef Erkunt Alak ,&nbsp;Özlem Günay-Esiyok ,&nbsp;Aytül Gül Mete ,&nbsp;Aysu Değirmenci Döşkaya ,&nbsp;Ayşe Gülten Kantarcı ,&nbsp;Adnan Yüksel Gürüz ,&nbsp;Hüseyin Can","doi":"10.1016/j.gene.2025.149965","DOIUrl":"10.1016/j.gene.2025.149965","url":null,"abstract":"<div><div>Toxoplasmosis is an infectious parasitic disease caused by <em>Toxoplasma gondii</em>, with a global seroprevalence estimated to affect more than one-third of the human population. <em>T. gondii</em> can be a serious health concern for pregnant women and immunocompromised patients. Currently, there is no effective and safe vaccine for humans. However, mRNA technology is a promising platform to develop efficient and safe vaccines against toxoplasmosis. Therefore, we designed nucleoside-modified and unmodified mRNA vaccine transcripts expressing <em>T. gondii</em> recombinant GRA1 protein and analyzed their <em>in vitro</em> protein expression profile as well as potential immunogenicity using IFAT, Western blot, and ELISA. Moreover, to compare translational efficiency, poly-A tail was extended with an extra ∼150 bp in addition to the existing ∼120 bp poly-A tail in two distinct mRNA designs. The results showed that all four mRNA constructs expressed rGRA1 protein in HEK293T cells. However, mRNA constructs with extended poly-A tails exhibited reduced expression level of rGRA1 protein compared to other mRNA vaccine transcripts. Additionally, unmodified mRNA construct with or without extended poly-A tail yielded significantly higher protein expression compared to nucleoside-modified mRNA constructs through ELISA using anti-polyhis antibody (P&lt;0.05). Western blot showed that rGRA1 protein expressed by all four mRNA constructs reacted strongly with <em>T. gondii</em> IgG seropositive mice sera. Furthermore, ELISA revealed that rGRA1 proteins derived from unmodified and nucleoside-modified mRNA constructs formed significantly stronger immune complexes with <em>T. gondii</em> IgG antibodies compared to negative controls (P&lt;0.05). These data suggest that both unmodified and nucleosidemodified mRNA constructs expressing rGRA1 protein have potential as vaccine candidates and warrant further investigation for development of an mRNA-based vaccine against toxoplasmosis. However, encapsulation of the produced mRNA constructs in LNPs and <em>in vivo</em> studies are required to validate these preliminary results.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149965"},"PeriodicalIF":2.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780138","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
Under the dual hit: genetic and phenotypic analysis of a Han family with severe adolescent cirrhosis from the convergence of Wilson’s disease and favism 双重打击下:一个汉族家族由Wilson病和favism合并的严重青少年肝硬化的遗传和表型分析。
IF 2.4 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2025-12-16 DOI: 10.1016/j.gene.2025.149953
Yu-qin Xie , Zi-yan Xu , Hong Lin , Li-jun Xie , Jie-wei Luo , Li-jun Zhang , Zhi-hai Zheng
Hepatolenticular degeneration (HLD, MIM:277900) is an autosomal recessive disorder characterized by excessive copper accumulation in hepatocytes, leading to hepatic and neurological abnormalities, hepatocellular injury, neurodegeneration, and copper deposition in the cornea. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common genetic cause of hemolytic anemia, which can be triggered by chronic conditions, drugs, food, or infections, and exhibits highly variable severity. In some cases, multiple genetic factors may collectively influence disease presentation and progression. This study reports a proband who developed abnormal liver function at age 20. Four years later, she exhibited severe jaundice, liver dysfunction, serous effusions, anemia, and Kayser–Fleischer rings, leading to diagnoses including decompensated cirrhosis, splenomegaly, suspected HLD, hemolytic anemia, portal hypertension, hypoproteinemia, low T3 syndrome, primary peritonitis, and gallstones with cholecystitis. Genetic screening identified two pathogenic heterozygous variants in ATP7B (NM_000053.4): c.2128G > A (p.G710S) in exon 8 and c.525dupA (p.V176Sfs*28) in exon 2, together forming a compound heterozygous mutation. Additionally, a heterozygous mutation in G6PD (NM_001360016.2), c.1388G > A (p.R463H) in exon 12, was found. Family members carrying the G6PD variant showed recurrent benign jaundice or remained asymptomatic. A heterozygous missense variant of uncertain significance, c.205C > T (p.R69C), was also detected in exon 3 of STEAP3 (NM_182915.3), a gene linked to hypochromic microcytic anemia with iron overload type 2 (MIM#615234). This rare variant was predicted to be deleterious by in silico tools, suggesting possible genetic cosegregation.
SWISS-MODEL analysis indicated that these variants may alter the three-dimensional structures of the copper-transporting ATPase and G6PD proteins, potentially impairing function—particularly the frameshift mutation p.V176Sfs*28. We hypothesize that the accumulation of multiple pathogenic genetic factors resulted in a “double-hit” effect, leading to the patient’s severe phenotypes, including advanced liver cirrhosis and hemolytic anemia. Elucidating such multi-gene “double-hit” mechanisms may enhance the understanding of gene–gene interactions in complex diseases.
肝豆状核变性(HLD, MIM:277900)是一种常染色体隐性遗传病,其特征是肝细胞内铜积聚过多,导致肝脏和神经异常、肝细胞损伤、神经变性和角膜内铜沉积。葡萄糖-6-磷酸脱氢酶(G6PD)缺乏是溶血性贫血最常见的遗传原因,可由慢性疾病、药物、食物或感染引发,并且表现出高度可变的严重程度。在某些情况下,多种遗传因素可能共同影响疾病的表现和进展。本研究报告了一个先证者在20岁时出现肝功能异常。4年后,患者出现严重黄疸、肝功能障碍、浆液积液、贫血、Kayser-Fleischer环,诊断为失代偿性肝硬化、脾肿大、疑似HLD、溶血性贫血、门脉高压、低蛋白血症、低T3综合征、原发性腹膜炎、胆结石合并胆囊炎。遗传筛选在ATP7B (NM_000053.4)中发现两个致病杂合变异体:位于第8外显子的c.2128G > A (p.G710S)和位于第2外显子的c.525dupA (p.V176Sfs*28),共同形成一个复合杂合突变。此外,在G6PD (NM_001360016.2)的第12外显子中发现了c.1388G > a (p.R463H)的杂合突变。携带G6PD变异的家庭成员表现为复发性良性黄疸或无症状。在STEAP3 (NM_182915.3)的外显子3中也检测到一种不确定意义的杂合错义变异c.205C > T (p.R69C),这是一种与低色素小细胞贫血伴铁过载型2 (mim# 615234)相关的基因。这种罕见的变异被计算机工具预测为有害的,表明可能存在遗传共分离。SWISS-MODEL分析表明,这些变异可能改变铜转运ATPase和G6PD蛋白的三维结构,潜在地损害功能,特别是移码突变p.V176Sfs*28。我们假设多种致病遗传因素的积累导致“双重打击”效应,导致患者出现严重的表型,包括晚期肝硬化和溶血性贫血。阐明这种多基因“双重打击”机制可能会增强对复杂疾病中基因-基因相互作用的理解。
{"title":"Under the dual hit: genetic and phenotypic analysis of a Han family with severe adolescent cirrhosis from the convergence of Wilson’s disease and favism","authors":"Yu-qin Xie ,&nbsp;Zi-yan Xu ,&nbsp;Hong Lin ,&nbsp;Li-jun Xie ,&nbsp;Jie-wei Luo ,&nbsp;Li-jun Zhang ,&nbsp;Zhi-hai Zheng","doi":"10.1016/j.gene.2025.149953","DOIUrl":"10.1016/j.gene.2025.149953","url":null,"abstract":"<div><div>Hepatolenticular degeneration (HLD, MIM:277900) is an autosomal recessive disorder characterized by excessive copper accumulation in hepatocytes, leading to hepatic and neurological abnormalities, hepatocellular injury, neurodegeneration, and copper deposition in the cornea. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common genetic cause of hemolytic anemia, which can be triggered by chronic conditions, drugs, food, or infections, and exhibits highly variable severity. In some cases, multiple genetic factors may collectively influence disease presentation and progression. This study reports a proband who developed abnormal liver function at age 20. Four years later, she exhibited severe jaundice, liver dysfunction, serous effusions, anemia, and Kayser–Fleischer rings, leading to diagnoses including decompensated cirrhosis, splenomegaly, suspected HLD, hemolytic anemia, portal hypertension, hypoproteinemia, low T3 syndrome, primary peritonitis, and gallstones with cholecystitis. Genetic screening identified two pathogenic heterozygous variants in ATP7B (NM_000053.4): c.2128G &gt; A (p.G710S) in exon 8 and c.525dupA (p.V176Sfs*28) in exon 2, together forming a compound heterozygous mutation. Additionally, a heterozygous mutation in G6PD (NM_001360016.2), c.1388G &gt; A (p.R463H) in exon 12, was found. Family members carrying the G6PD variant showed recurrent benign jaundice or remained asymptomatic. A heterozygous missense variant of uncertain significance, c.205C &gt; T (p.R69C), was also detected in exon 3 of STEAP3 (NM_182915.3), a gene linked to hypochromic microcytic anemia with iron overload type 2 (MIM#615234). This rare variant was predicted to be deleterious by in silico tools, suggesting possible genetic cosegregation.</div><div>SWISS-MODEL analysis indicated that these variants may alter the three-dimensional structures of the copper-transporting ATPase and G6PD proteins, potentially impairing function—particularly the frameshift mutation p.V176Sfs*28. We hypothesize that the accumulation of multiple pathogenic genetic factors resulted in a “double-hit” effect, leading to the patient’s severe phenotypes, including advanced liver cirrhosis and hemolytic anemia. Elucidating such multi-gene “double-hit” mechanisms may enhance the understanding of gene–gene interactions in complex diseases.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149953"},"PeriodicalIF":2.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780827","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
Age-induced gene expression in Thoroughbred horse skeletal muscle highlights genes that enhance muscle architecture and function 纯种马骨骼肌中年龄诱导的基因表达突出了增强肌肉结构和功能的基因。
IF 2.4 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2025-12-15 DOI: 10.1016/j.gene.2025.149951
Mian Feng , Thomas J. Hall , David E. MacHugh , Lisa M. Katz , Emmeline W. Hill
Early skeletal muscle development is critical for young racehorses, yet research on the transcriptional changes during this period is limited. Additionally, the impact of age on the transcriptional response to exercise training in equine athletes is not well understood. A transcriptome-wide analysis of differential gene expression in skeletal muscle was performed for five untrained Thoroughbred horses sampled at rest at two years old (UR2) and three years old (UR3). A total of 136 differentially expressed genes (DEGs) were identified, with 95 increased and 41 decreased in expression. GO enrichment analysis revealed that the DEGs were primarily associated with terms related to muscle assembly and system development, including Developmental process (GO:0032502), Anatomical structure development (GO:0048856), Actin cytoskeleton (GO:0015629), and Growth factor binding (GO:0019838). KEGG pathway analysis indicated that ECM-receptor interaction, Protein digestion and absorption, Focal adhesion, and PI3K-Akt signalling pathway were the significant functional pathways. Protein-protein interaction network and hub gene analyses identified seven key regulatory genes: COL1A1, COL1A2, COL3A1, S100A4, NOTCH1, THY1 and MT-ND2. In addition, the MSTN, COL4A1, COL4A2, SPEN, S100A4, NOTCH1, NOTCH3, and THY1 genes were found to play key roles in the functional development of skeletal muscle. This study provides insight into the transcriptional landscape of skeletal muscle development in young Thoroughbred horses. The period between two and three years of age represents a crucial stage in skeletal muscle adaptation in the juvenile horse, with a particular emphasis on muscle structural and functional integrity.
早期骨骼肌发育对年轻赛马至关重要,但在这一时期对转录变化的研究有限。此外,年龄对马运动员运动训练转录反应的影响尚不清楚。研究人员对5匹未经训练的纯种马在2岁(UR2)和3岁(UR3)休息时进行了骨骼肌差异基因表达的转录组分析。共鉴定出136个差异表达基因(DEGs),其中95个表达增加,41个表达减少。氧化石墨烯富集分析显示,deg主要与肌肉组装和系统发育相关,包括发育过程(GO:0032502)、解剖结构发育(GO:0048856)、肌动蛋白细胞骨架(GO:0015629)和生长因子结合(GO:0019838)。KEGG通路分析表明,ecm受体相互作用、蛋白质消化吸收、局灶黏附和PI3K-Akt信号通路是重要的功能通路。蛋白-蛋白相互作用网络和枢纽基因分析鉴定出7个关键调控基因:COL1A1、COL1A2、COL3A1、S100A4、NOTCH1、THY1和MT-ND2。此外,还发现MSTN、COL4A1、COL4A2、SPEN、S100A4、NOTCH1、NOTCH3和THY1基因在骨骼肌功能发育中起关键作用。这项研究提供了对年轻纯种马骨骼肌发育的转录景观的见解。2 - 3岁是马幼马骨骼肌适应的关键阶段,特别强调肌肉结构和功能的完整性。
{"title":"Age-induced gene expression in Thoroughbred horse skeletal muscle highlights genes that enhance muscle architecture and function","authors":"Mian Feng ,&nbsp;Thomas J. Hall ,&nbsp;David E. MacHugh ,&nbsp;Lisa M. Katz ,&nbsp;Emmeline W. Hill","doi":"10.1016/j.gene.2025.149951","DOIUrl":"10.1016/j.gene.2025.149951","url":null,"abstract":"<div><div>Early skeletal muscle development is critical for young racehorses, yet research on the transcriptional changes during this period is limited. Additionally, the impact of age on the transcriptional response to exercise training in equine athletes is not well understood. A transcriptome-wide analysis of differential gene expression in skeletal muscle was performed for five untrained Thoroughbred horses sampled at rest at two years old (UR2) and three years old (UR3). A total of 136 differentially expressed genes (DEGs) were identified, with 95 increased and 41 decreased in expression. GO enrichment analysis revealed that the DEGs were primarily associated with terms related to muscle assembly and system development, including <em>Developmental process (GO:0032502</em>)<em>, Anatomical structure development (GO:0048856</em>)<em>, Actin cytoskeleton (GO:0015629</em>)<em>, and Growth factor binding (GO:0019838</em>)<em>.</em> KEGG pathway analysis indicated that <em>ECM-receptor interaction</em>, <em>Protein digestion and absorption</em>, <em>Focal adhesion</em>, and <em>PI3K-Akt signalling pathway</em> were the significant functional pathways. Protein-protein interaction network and hub gene analyses identified seven key regulatory genes: <em>COL1A1, COL1A2, COL3A1, S100A4, NOTCH1, THY1</em> and <em>MT-ND2.</em> In addition, the <em>MSTN, COL4A1, COL4A2, SPEN, S100A4, NOTCH1, NOTCH3, and THY1</em> genes were found to play key roles in the functional development of skeletal muscle. This study provides insight into the transcriptional landscape of skeletal muscle development in young Thoroughbred horses. The period between two and three years of age represents a crucial stage in skeletal muscle adaptation in the juvenile horse, with a particular emphasis on muscle structural and functional integrity.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"980 ","pages":"Article 149951"},"PeriodicalIF":2.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774290","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
Genetic and epigenetic determinants of injury risk and recovery in elite athletes: toward precision sports medicine 精英运动员损伤风险和恢复的遗传和表观遗传决定因素:走向精确运动医学。
IF 2.4 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2025-12-12 DOI: 10.1016/j.gene.2025.149957
Hao Ding , Qilu Deng , Zhenhua Guo
Musculoskeletal injuries and interindividual variability in recovery remain critical challenges for sustaining elite athletic performance. Despite advances in diagnostics, training, and rehabilitation, unexplained differences in injury risk and recovery efficiency persist. Growing evidence implicates genetic and epigenetic mechanisms in these disparities, influencing collagen integrity, inflammatory regulation, oxidative stress, and muscle regeneration. Key contributors include single-nucleotide polymorphisms (SNPs) in COL1A1, COL5A1, ACTN3, and IL6, as well as novel loci identified by genome-wide association studies (GWAS). Polygenic risk scores (PRS), which integrate the effects of multiple low-impact variants, enhance prediction compared to single-gene markers. Epigenetic regulators, including DNA methylation and exercise-responsive microRNAs (e.g., miR-206, miR-133a, miR-486), provide a dynamic interface linking genetic predisposition with environmental factors such as training load and nutrition. Integration of genomic data with wearable technologies and artificial intelligence enables real-time monitoring, adaptive recovery, and precision load management. Yet, clinical translation faces challenges including limited population diversity, interpretative complexity, and ethical concerns over data privacy and potential misuse. Advancing precision sports medicine will require multidisciplinary, systems-level strategies that unite molecular insights with practical implementation, ultimately enabling individualized injury prevention, optimized rehabilitation, and the preservation of long-term athlete health and performance.
肌肉骨骼损伤和恢复中的个体差异仍然是维持精英运动表现的关键挑战。尽管在诊断、训练和康复方面取得了进步,但无法解释的损伤风险和恢复效率差异仍然存在。越来越多的证据暗示这些差异的遗传和表观遗传机制,影响胶原完整性,炎症调节,氧化应激和肌肉再生。关键因素包括COL1A1、COL5A1、ACTN3和IL6的单核苷酸多态性(snp),以及全基因组关联研究(GWAS)发现的新位点。与单基因标记相比,多基因风险评分(PRS)整合了多个低影响变异的影响,提高了预测能力。表观遗传调控因子,包括DNA甲基化和运动反应性microrna(如miR-206, miR-133a, miR-486),提供了一个动态接口,将遗传易感性与环境因素(如训练负荷和营养)联系起来。基因组数据与可穿戴技术和人工智能的集成实现了实时监测、自适应恢复和精确负载管理。然而,临床翻译面临的挑战包括有限的人群多样性,解释的复杂性,以及对数据隐私和潜在滥用的伦理担忧。推进精准运动医学将需要多学科、系统级的策略,将分子见解与实际实施结合起来,最终实现个性化的损伤预防、优化的康复,并保持运动员的长期健康和表现。
{"title":"Genetic and epigenetic determinants of injury risk and recovery in elite athletes: toward precision sports medicine","authors":"Hao Ding ,&nbsp;Qilu Deng ,&nbsp;Zhenhua Guo","doi":"10.1016/j.gene.2025.149957","DOIUrl":"10.1016/j.gene.2025.149957","url":null,"abstract":"<div><div>Musculoskeletal injuries and interindividual variability in recovery remain critical challenges for sustaining elite athletic performance. Despite advances in diagnostics, training, and rehabilitation, unexplained differences in injury risk and recovery efficiency persist. Growing evidence implicates genetic and epigenetic mechanisms in these disparities, influencing collagen integrity, inflammatory regulation, oxidative stress, and muscle regeneration. Key contributors include single-nucleotide polymorphisms (SNPs) in COL1A1, COL5A1, ACTN3, and IL6, as well as novel loci identified by genome-wide association studies (GWAS). Polygenic risk scores (PRS), which integrate the effects of multiple low-impact variants, enhance prediction compared to single-gene markers. Epigenetic regulators, including DNA methylation and exercise-responsive microRNAs (e.g., miR-206, miR-133a, miR-486), provide a dynamic interface linking genetic predisposition with environmental factors such as training load and nutrition. Integration of genomic data with wearable technologies and artificial intelligence enables real-time monitoring, adaptive recovery, and precision load management. Yet, clinical translation faces challenges including limited population diversity, interpretative complexity, and ethical concerns over data privacy and potential misuse. Advancing precision sports medicine will require multidisciplinary, systems-level strategies that unite molecular insights with practical implementation, ultimately enabling individualized injury prevention, optimized rehabilitation, and the preservation of long-term athlete health and performance.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"980 ","pages":"Article 149957"},"PeriodicalIF":2.4,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755941","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
SR protein kinase FoSrk1 integrates RNA splicing, carbon metabolism, and virulence in Fusarium oxysporum f. sp. cubense SR蛋白激酶FoSrk1整合了尖孢镰刀菌的RNA剪接、碳代谢和毒力。
IF 2.4 3区 生物学 Q2 GENETICS & HEREDITY Pub Date : 2025-12-12 DOI: 10.1016/j.gene.2025.149954
Han Ouyang , Jiayi Peng , Zhouqi Huang , Yicong Huang , Yinglan Wen , Yuan Xu , Yu Long , Huijiao Lin , Qiyan Fu , Zhaojian Ding
Fusarium oxysporum f. sp. cubense (Foc), the causal agent of banana Fusarium wilt, is one of the most destructive plant pathogens worldwide. However, the molecular mechanisms that integrate fungal growth, metabolism, and virulence remain poorly understood. This study identifies and functionally characterizes FoSrk1, a serine/arginine-rich protein kinase (SRPK), in Foc. Deletion of FoSrk1 markedly impaired vegetative growth, reduced aerial mycelium formation and conidiation, and significantly attenuated virulence toward banana plantlets. The mutant also exhibited compromised utilization of diverse carbon sources, accompanied by altered expression of 32 genes involved in carbon metabolism. Complementation with the wild-type FoSrk1 allele restored normal growth and pathogenicity, confirming the gene’s essential role. Transcriptomic analyses revealed that loss of FoSrk1 altered the expression of 2,500 genes and was associated with changes in 37 alternative splicing events, predominantly intron retention, affecting transcripts linked to protein metabolism, ribosome biogenesis, and redox processes. Moreover, several virulence-associated genes encoding ABC transporters, cytochrome P450 enzymes, and hydrophobins were downregulated in the FoSrk1-deficient strain. These findings suggest that FoSrk1 acts as an important regulator that couples RNA processing with metabolic and pathogenic pathways and is required for normal fungal development and virulence. This study provides new insight into the molecular basis of pathogenic adaptation and identifies FoSrk1 as a potential target for antifungal intervention strategies.
香蕉枯萎病病原菌Fusarium oxysporum f. sp. cubense (Foc)是世界上最具破坏性的植物病原体之一。然而,整合真菌生长、代谢和毒力的分子机制仍然知之甚少。本研究鉴定并功能表征了FoSrk1,一种在Foc中富含丝氨酸/精氨酸的蛋白激酶(SRPK)。缺失FoSrk1显著损害香蕉植株的营养生长,减少气生菌丝的形成和分生,并显著降低对香蕉植株的毒力。该突变体还表现出对不同碳源的利用受损,并伴有涉及碳代谢的32个基因的表达改变。与野生型FoSrk1等位基因的互补恢复了正常的生长和致病性,证实了该基因的重要作用。转录组学分析显示,FoSrk1的缺失改变了2500个基因的表达,并与37个可变剪接事件的变化有关,主要是内含子保留,影响与蛋白质代谢、核糖体生物发生和氧化还原过程相关的转录本。此外,编码ABC转运蛋白、细胞色素P450酶和疏水蛋白的几个毒力相关基因在fosrk1缺陷菌株中下调。这些发现表明,FoSrk1是一个重要的调节因子,将RNA加工与代谢和致病途径结合起来,是正常真菌发育和毒力所必需的。该研究为致病适应的分子基础提供了新的见解,并确定了FoSrk1作为抗真菌干预策略的潜在靶点。
{"title":"SR protein kinase FoSrk1 integrates RNA splicing, carbon metabolism, and virulence in Fusarium oxysporum f. sp. cubense","authors":"Han Ouyang ,&nbsp;Jiayi Peng ,&nbsp;Zhouqi Huang ,&nbsp;Yicong Huang ,&nbsp;Yinglan Wen ,&nbsp;Yuan Xu ,&nbsp;Yu Long ,&nbsp;Huijiao Lin ,&nbsp;Qiyan Fu ,&nbsp;Zhaojian Ding","doi":"10.1016/j.gene.2025.149954","DOIUrl":"10.1016/j.gene.2025.149954","url":null,"abstract":"<div><div><em>Fusarium oxysporum</em> f. sp. <em>cubense</em> (Foc), the causal agent of banana Fusarium wilt, is one of the most destructive plant pathogens worldwide. However, the molecular mechanisms that integrate fungal growth, metabolism, and virulence remain poorly understood. This study identifies and functionally characterizes FoSrk1, a serine/arginine-rich protein kinase (SRPK), in Foc. Deletion of <em>FoSrk1</em> markedly impaired vegetative growth, reduced aerial mycelium formation and conidiation, and significantly attenuated virulence toward banana plantlets. The mutant also exhibited compromised utilization of diverse carbon sources, accompanied by altered expression of 32 genes involved in carbon metabolism. Complementation with the wild-type <em>FoSrk1</em> allele restored normal growth and pathogenicity, confirming the gene’s essential role. Transcriptomic analyses revealed that loss of <em>FoSrk1</em> altered the expression of 2,500 genes and was associated with changes in 37 alternative splicing events, predominantly intron retention, affecting transcripts linked to protein metabolism, ribosome biogenesis, and redox processes. Moreover, several virulence-associated genes encoding ABC transporters, cytochrome P450 enzymes, and hydrophobins were downregulated in the <em>FoSrk1</em>-deficient strain. These findings suggest that FoSrk1 acts as an important regulator that couples RNA processing with metabolic and pathogenic pathways and is required for normal fungal development and virulence. This study provides new insight into the molecular basis of pathogenic adaptation and identifies FoSrk1 as a potential target for antifungal intervention strategies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"983 ","pages":"Article 149954"},"PeriodicalIF":2.4,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755939","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
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