首页 > 最新文献

Journal of Pineal Research最新文献

英文 中文
Melatonin Enhances Peanut Productivity by Enriching Root-Associated Nitrogen-Fixing Bacteria 褪黑素通过丰富根相关固氮细菌提高花生产量。
IF 6.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-08 DOI: 10.1111/jpi.70105
Ali Muhammad, Xiangjun Kong, Lijie Li, Muhammad Hafeez Ullah Khan, Peipei Jia, Chen Miao, Zhiyong Zhang

Melatonin, a pleiotropic phytohormone, is widely recognized as a promising bio-stimulant, yet its integrative effects on root development, yield gain, and microbiome assembly in legumes remain underexplored. In this study, we investigated the effects of melatonin seed treatment across three peanut genotypes, focusing on plant productivity and the composition and structure of bacterial communities in root, rhizosphere, and bulk soil compartments. Melatonin treatment substantially improved root biomass, nodulation, nitrogen balance index, and yield-related traits, with the highest response observed in the genotype Xinbaihua 16. Amplicon sequencing revealed that melatonin induced distinct genotype and compartment specific shifts in bacterial community composition, with the root bacteria showing the increased remodeling, including a 45.9% increase in unique amplicon sequence variants (ASVs). Melatonin selectively enriched key Proteobacteria taxa such as Rhizobium, Sphingomonas, and Enterobacter hormaechei, known for their plant-growth promoting and biocontrol capabilities. Notably, melatonin-enriched taxa also included widely recognized nitrogen-fixing symbionts such as Pararhizobium and Ensifer, underscoring a direct link between melatonin-induced microbiome shifts and enhanced nitrogen acquisition capacity. Co-occurrence network analysis indicated that melatonin-treated roots harbored more complex bacterial networks, and Modules 3 and 4, dominated by melatonin-induced Proteobacteria, were strongly correlated with most plant traits. Collectively these findings highlight melatonin dual role as a bio-stimulant and microbiome modulator, promoting a functionally enriched and responsive bacteria that support enhanced plant performance. This study provides novel insights into the melatonin-mediated coordination of plant performance and bacterial assembly, offering a foundation for microbiome-informed crop improvement strategies.

褪黑素是一种多效性植物激素,被广泛认为是一种有前景的生物兴奋剂,但其对豆科植物根系发育、产量增加和微生物群聚集的综合影响尚未得到充分研究。在这项研究中,我们研究了褪黑素种子处理对三种花生基因型的影响,重点研究了植物生产力以及根、根际和散装土壤区室细菌群落的组成和结构。褪黑素处理显著提高了根生物量、结瘤率、氮平衡指数和产量相关性状,其中以新百花16基因型的响应最高。扩增子测序显示,褪黑素诱导了细菌群落组成的不同基因型和室特异性变化,根细菌显示出增加的重塑,包括独特扩增子序列变异(asv)增加45.9%。褪黑素选择性地富集了关键的变形菌群,如根瘤菌、鞘氨单胞菌和霍马切肠杆菌,这些细菌以其促进植物生长和生物防治能力而闻名。值得注意的是,富含褪黑激素的类群还包括广泛认可的固氮共生体,如副根瘤菌和Ensifer,这强调了褪黑激素诱导的微生物群变化与增强的氮获取能力之间的直接联系。共现网络分析表明,褪黑激素处理的根具有更复杂的细菌网络,模块3和模块4以褪黑激素诱导的变形杆菌为主,与大多数植物性状密切相关。总的来说,这些发现强调了褪黑激素作为生物刺激剂和微生物组调节剂的双重作用,促进了功能丰富和反应灵敏的细菌,支持提高植物性能。该研究为褪黑激素介导的植物性能和细菌组装的协调提供了新的见解,为微生物组知情的作物改良策略提供了基础。
{"title":"Melatonin Enhances Peanut Productivity by Enriching Root-Associated Nitrogen-Fixing Bacteria","authors":"Ali Muhammad,&nbsp;Xiangjun Kong,&nbsp;Lijie Li,&nbsp;Muhammad Hafeez Ullah Khan,&nbsp;Peipei Jia,&nbsp;Chen Miao,&nbsp;Zhiyong Zhang","doi":"10.1111/jpi.70105","DOIUrl":"10.1111/jpi.70105","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin, a pleiotropic phytohormone, is widely recognized as a promising bio-stimulant, yet its integrative effects on root development, yield gain, and microbiome assembly in legumes remain underexplored. In this study, we investigated the effects of melatonin seed treatment across three peanut genotypes, focusing on plant productivity and the composition and structure of bacterial communities in root, rhizosphere, and bulk soil compartments. Melatonin treatment substantially improved root biomass, nodulation, nitrogen balance index, and yield-related traits, with the highest response observed in the genotype Xinbaihua 16. Amplicon sequencing revealed that melatonin induced distinct genotype and compartment specific shifts in bacterial community composition, with the root bacteria showing the increased remodeling, including a 45.9% increase in unique amplicon sequence variants (ASVs). Melatonin selectively enriched key Proteobacteria taxa such as <i>Rhizobium</i>, <i>Sphingomonas</i>, and <i>Enterobacter hormaechei</i>, known for their plant-growth promoting and biocontrol capabilities. Notably, melatonin-enriched taxa also included widely recognized nitrogen-fixing symbionts such as <i>Pararhizobium</i> and <i>Ensifer</i>, underscoring a direct link between melatonin-induced microbiome shifts and enhanced nitrogen acquisition capacity. Co-occurrence network analysis indicated that melatonin-treated roots harbored more complex bacterial networks, and Modules 3 and 4, dominated by melatonin-induced Proteobacteria, were strongly correlated with most plant traits. Collectively these findings highlight melatonin dual role as a bio-stimulant and microbiome modulator, promoting a functionally enriched and responsive bacteria that support enhanced plant performance. This study provides novel insights into the melatonin-mediated coordination of plant performance and bacterial assembly, offering a foundation for microbiome-informed crop improvement strategies.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 1","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Melatonin Circadian Phase Timing and Stability: Associations With Mood Symptoms Among a Clinically-Enriched Sample of Young Adults With Mood Disorders 褪黑素昼夜节律期时间和稳定性:与心境障碍青年临床丰富样本中心境症状的关联
IF 6.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-08 DOI: 10.1111/jpi.70104
Rachel F. L. Walsh, Mackenzie A. Maddox, Joshua Klugman, Namni Goel, Lauren B. Alloy

Circadian rhythms regulate many aspects of human health, and disruptions in these rhythms have been implicated in mood disorders. Dim light melatonin onset (DLMO) provides a gold standard measure of circadian timing, yet few studies have examined its stability or relation to mood symptoms in psychiatric populations. This study examined DLMO across three time points over 20 days in a clinically-enriched sample of 124 young adults with and without mood disorders. Participants also reported mood symptom levels three times daily via ecological momentary assessments (EMA). Circadian timing and stability were quantified and their associations with mood symptoms and diurnal mood patterns were assessed. Overall, DLMO demonstrated substantial stability, and did not differ by diagnostic group. The mood disorder group had earlier circadian timing than healthy controls. Hypomanic, but not depressive, symptoms were consistently associated with later DLMO in both cross-sectional and prospective analyses. Moreover, hypomanic symptoms exhibited a diurnal pattern that differed for participants with earlier and later circadian timing. Future work should examine endogenous circadian rhythms in relation to mood disorder subtypes and mood episodes to determine whether circadian timing changes can be used to predict or intervene on psychiatric symptoms.

昼夜节律调节着人类健康的许多方面,这些节律的中断与情绪障碍有关。昏暗光线下褪黑激素的发作(DLMO)提供了衡量昼夜节律的黄金标准,但很少有研究调查其稳定性或与精神病学人群情绪症状的关系。这项研究对124名有或无情绪障碍的年轻人进行了为期20天的临床富集样本,在三个时间点上检查了DLMO。参与者还通过生态瞬间评估(EMA)每天三次报告情绪症状水平。量化昼夜节律时间和稳定性,并评估其与情绪症状和每日情绪模式的关联。总体而言,DLMO表现出相当大的稳定性,并且在诊断组之间没有差异。情绪障碍组的昼夜节律比健康对照组早。在横断面和前瞻性分析中,轻度躁狂症状与晚期DLMO一致相关,而不是抑郁症状。此外,轻躁狂症状表现出不同的昼夜节律时间的参与者的昼夜模式。未来的工作应该检查内源性昼夜节律与情绪障碍亚型和情绪发作的关系,以确定昼夜节律改变是否可用于预测或干预精神症状。
{"title":"Melatonin Circadian Phase Timing and Stability: Associations With Mood Symptoms Among a Clinically-Enriched Sample of Young Adults With Mood Disorders","authors":"Rachel F. L. Walsh,&nbsp;Mackenzie A. Maddox,&nbsp;Joshua Klugman,&nbsp;Namni Goel,&nbsp;Lauren B. Alloy","doi":"10.1111/jpi.70104","DOIUrl":"10.1111/jpi.70104","url":null,"abstract":"<div>\u0000 \u0000 <p>Circadian rhythms regulate many aspects of human health, and disruptions in these rhythms have been implicated in mood disorders. Dim light melatonin onset (DLMO) provides a gold standard measure of circadian timing, yet few studies have examined its stability or relation to mood symptoms in psychiatric populations. This study examined DLMO across three time points over 20 days in a clinically-enriched sample of 124 young adults with and without mood disorders. Participants also reported mood symptom levels three times daily via ecological momentary assessments (EMA). Circadian timing and stability were quantified and their associations with mood symptoms and diurnal mood patterns were assessed. Overall, DLMO demonstrated substantial stability, and did not differ by diagnostic group. The mood disorder group had earlier circadian timing than healthy controls. Hypomanic, but not depressive, symptoms were consistently associated with later DLMO in both cross-sectional and prospective analyses. Moreover, hypomanic symptoms exhibited a diurnal pattern that differed for participants with earlier and later circadian timing. Future work should examine endogenous circadian rhythms in relation to mood disorder subtypes and mood episodes to determine whether circadian timing changes can be used to predict or intervene on psychiatric symptoms.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 1","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic Potential of Melatonin in Gastrointestinal Cancers: Molecular Mechanisms, Preclinical Evidence and Clinical Implications 褪黑素在胃肠道肿瘤中的治疗潜力:分子机制、临床前证据和临床意义。
IF 6.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-04 DOI: 10.1111/jpi.70101
Maciej Gonciarz, Benita Wiatrak, Iga Lombard, Łukasz Konecki, Joanna Sarbinowska

Gastrointestinal (GI) cancers remain a leading cause of global morbidity and mortality, necessitating novel therapeutic strategies. Melatonin (MEL), an indoleamine with pleiotropic biological activities, has emerged as a promising adjuvant in oncology due to its antiproliferative, proapoptotic, and antioxidant properties. This review synthesizes current evidence on MEL's molecular mechanisms in GI carcinogenesis, including modulation of NF-κB, PI3K/AKT, and Wnt/β-catenin pathways, suppression of reactive oxygen species (ROS), and regulation of circadian rhythm-related genes (e.g., CLOCK, BMAL1). Preclinical studies demonstrate that MEL enhances chemoradiotherapy efficacy-reducing tumor volume by 70% in murine colorectal models and decreasing 5-fluorouracil (5-FU) resistance via miR-532-3p/β-catenin axis modulation. Clinical trials report a 23%–41% risk reduction in colorectal cancer among shift workers with MEL supplementation and a 53% decrease in radiotherapy-induced oral mucositis. Despite promising data, limitations persist: fewer than 15% of clinical trials focus on GI cancers, dosing remains unstandardized (10–40 mg/day), and molecular heterogeneity (e.g., KRAS mutations in pancreatic cancer) may limit therapeutic responses. Future research must prioritize phase III trials, chronotherapy optimization, and biomarker-driven approaches, including MT1/MT2 receptor expression and microbiome profiling. Given its low toxicity and putative synergy with immunotherapies, MEL should be regarded as an adjunct under investigation rather than an established option; to date, no GI-specific phase III randomized trials exist, and clinical signals come primarily from small, heterogeneous cohorts. Dosing is unstandardized and limited by low oral bioavailability (first-pass) and possible pharmacogenomic variability.

胃肠道(GI)癌症仍然是全球发病率和死亡率的主要原因,需要新的治疗策略。褪黑素(MEL)是一种具有多效生物活性的吲哚胺,由于其抗增殖、促细胞凋亡和抗氧化的特性,已成为一种很有前途的肿瘤学辅助药物。本文综述了MEL在GI癌变中的分子机制,包括NF-κB、PI3K/AKT和Wnt/β-catenin通路的调节、活性氧(ROS)的抑制以及昼夜节律相关基因(如CLOCK、BMAL1)的调控。临床前研究表明,MEL通过miR-532-3p/β-catenin轴调节提高了放化疗的疗效,使小鼠结直肠模型的肿瘤体积减少了70%,并降低了5-氟尿嘧啶(5-FU)的耐药性。临床试验报告,补充MEL的轮班工人患结直肠癌的风险降低23%-41%,放射治疗引起的口腔黏膜炎降低53%。尽管有很好的数据,但局限性仍然存在:不到15%的临床试验关注胃肠道癌症,剂量仍然不标准化(10-40 mg/天),分子异质性(例如胰腺癌中的KRAS突变)可能限制治疗反应。未来的研究必须优先考虑III期试验、时间疗法优化和生物标志物驱动的方法,包括MT1/MT2受体表达和微生物组分析。鉴于其低毒性和与免疫疗法的协同作用,MEL应被视为一种正在研究的辅助疗法,而不是一种既定的选择;到目前为止,还没有针对gi的III期随机试验存在,临床信号主要来自小的异质队列。由于口服生物利用度低(首次通过)和可能的药物基因组变异性,给药不标准化,受到限制。
{"title":"Therapeutic Potential of Melatonin in Gastrointestinal Cancers: Molecular Mechanisms, Preclinical Evidence and Clinical Implications","authors":"Maciej Gonciarz,&nbsp;Benita Wiatrak,&nbsp;Iga Lombard,&nbsp;Łukasz Konecki,&nbsp;Joanna Sarbinowska","doi":"10.1111/jpi.70101","DOIUrl":"10.1111/jpi.70101","url":null,"abstract":"<p>Gastrointestinal (GI) cancers remain a leading cause of global morbidity and mortality, necessitating novel therapeutic strategies. Melatonin (MEL), an indoleamine with pleiotropic biological activities, has emerged as a promising adjuvant in oncology due to its antiproliferative, proapoptotic, and antioxidant properties. This review synthesizes current evidence on MEL's molecular mechanisms in GI carcinogenesis, including modulation of NF-κB, PI3K/AKT, and Wnt/β-catenin pathways, suppression of reactive oxygen species (ROS), and regulation of circadian rhythm-related genes (e.g., CLOCK, BMAL1). Preclinical studies demonstrate that MEL enhances chemoradiotherapy efficacy-reducing tumor volume by 70% in murine colorectal models and decreasing 5-fluorouracil (5-FU) resistance via miR-532-3p/β-catenin axis modulation. Clinical trials report a 23%–41% risk reduction in colorectal cancer among shift workers with MEL supplementation and a 53% decrease in radiotherapy-induced oral mucositis. Despite promising data, limitations persist: fewer than 15% of clinical trials focus on GI cancers, dosing remains unstandardized (10–40 mg/day), and molecular heterogeneity (e.g., KRAS mutations in pancreatic cancer) may limit therapeutic responses. Future research must prioritize phase III trials, chronotherapy optimization, and biomarker-driven approaches, including MT1/MT2 receptor expression and microbiome profiling. Given its low toxicity and putative synergy with immunotherapies, MEL should be regarded as an adjunct under investigation rather than an established option; to date, no GI-specific phase III randomized trials exist, and clinical signals come primarily from small, heterogeneous cohorts. Dosing is unstandardized and limited by low oral bioavailability (first-pass) and possible pharmacogenomic variability.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 1","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12676935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exogenous Melatonin Enhances Waterlogging Tolerance in Sesame by Modulating Physiological, Biochemical, and Proteomic Responses 外源褪黑素通过调节芝麻的生理、生化和蛋白质组反应增强其耐涝能力
IF 6.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-26 DOI: 10.1111/jpi.70102
Sheng Fang, Yiming Xu, Min Wang

Waterlogging is a major abiotic stress that severely impedes sesame growth and productivity. Melatonin has emerged as a multifaceted regulator in plant stress responses, but its protective mechanisms against waterlogging in sesame, particularly at the proteomic level, remain largely unexplored. A pot experiment was conducted using two sesame genotypes with contrasting waterlogging tolerance (sensitive JHM and tolerant PYH) under well-drained, waterlogging, and waterlogging with melatonin pretreatment conditions. Results showed that waterlogging significantly inhibited plant growth, impaired root architecture, and induced oxidative stress, with more severe impacts on sensitive genotype JHM. Exogenous melatonin application markedly mitigated these adverse effects, reducing the decline in plant height and root growth parameters. Melatonin balanced osmotic pressure by modulating proline and soluble protein content, alleviated oxidative damage by decreasing MDA and H₂O₂ accumulation, and enhanced the activities of SOD, POD, and CAT. It also ameliorated stress signaling by downregulating the accumulation of ABA and ACC, while elevating endogenous melatonin levels. The PYH possessed a superior constitutive antioxidant capacity and hormonal stability, while melatonin was particularly beneficial for JHM. Proteomic analysis identified 1846 differentially expressed proteins (DEPs) in roots of JHM between waterlogged and melatonin-treated plants. These DEPs were predominantly enriched in metabolic pathways, phenylpropanoid biosynthesis, glutathione metabolism, and ROS metabolic processes. MT priming upregulated the expression of superoxide dismutase peroxidase 7, and peroxidase 15-like while downregulated hydrogen peroxide induced protein 1, which were consistent with the results of physiological analysis in JMH. Protein-protein interaction analysis highlighted key proteins like RPL6 and RPL4 as potential hubs within the melatonin-mediated ROS metabolic network. This study provides a comprehensive physiological and molecular elucidation of the multifaceted mechanisms by which melatonin confers waterlogging tolerance, establishing a theoretical foundation for its application in waterlogged regions.

内涝是严重影响芝麻生长和产量的主要非生物胁迫。褪黑素在植物胁迫反应中具有多方面的调节作用,但其对芝麻内涝的保护机制,特别是在蛋白质组学水平上的保护机制仍未得到充分研究。采用两种耐涝性对比基因型(敏感型JHM和耐涝型PYH),在排水、涝渍和褪黑素预处理条件下进行盆栽试验。结果表明,涝渍显著抑制植株生长,破坏根系构型,诱导氧化应激,对敏感基因型JHM的影响更为严重。外源褪黑素的施用显著减轻了这些不利影响,减少了植物高度和根系生长参数的下降。褪黑素通过调节脯氨酸和可溶性蛋白含量平衡渗透压力,通过降低MDA和H₂O₂积累减轻氧化损伤,提高SOD、POD和CAT活性。它还通过下调ABA和ACC的积累来改善应激信号,同时提高内源性褪黑激素水平。PYH具有优越的组成抗氧化能力和激素稳定性,而褪黑素对JHM特别有益。蛋白质组学分析发现,在淹水和褪黑激素处理的JHM植株根系中存在1846个差异表达蛋白(DEPs)。这些DEPs主要富集于代谢途径、苯丙素生物合成、谷胱甘肽代谢和ROS代谢过程中。MT启动上调了超氧化物歧化酶过氧化物酶7和过氧化物酶15样蛋白的表达,下调了过氧化氢诱导蛋白1的表达,这与JMH的生理分析结果一致。蛋白-蛋白相互作用分析强调了RPL6和RPL4等关键蛋白是褪黑激素介导的ROS代谢网络中的潜在枢纽。本研究对褪黑素耐涝的生理和分子机制进行了全面的阐述,为其在涝渍地区的应用奠定了理论基础。
{"title":"Exogenous Melatonin Enhances Waterlogging Tolerance in Sesame by Modulating Physiological, Biochemical, and Proteomic Responses","authors":"Sheng Fang,&nbsp;Yiming Xu,&nbsp;Min Wang","doi":"10.1111/jpi.70102","DOIUrl":"https://doi.org/10.1111/jpi.70102","url":null,"abstract":"<div>\u0000 \u0000 <p>Waterlogging is a major abiotic stress that severely impedes sesame growth and productivity. Melatonin has emerged as a multifaceted regulator in plant stress responses, but its protective mechanisms against waterlogging in sesame, particularly at the proteomic level, remain largely unexplored. A pot experiment was conducted using two sesame genotypes with contrasting waterlogging tolerance (sensitive JHM and tolerant PYH) under well-drained, waterlogging, and waterlogging with melatonin pretreatment conditions. Results showed that waterlogging significantly inhibited plant growth, impaired root architecture, and induced oxidative stress, with more severe impacts on sensitive genotype JHM. Exogenous melatonin application markedly mitigated these adverse effects, reducing the decline in plant height and root growth parameters. Melatonin balanced osmotic pressure by modulating proline and soluble protein content, alleviated oxidative damage by decreasing MDA and H₂O₂ accumulation, and enhanced the activities of SOD, POD, and CAT. It also ameliorated stress signaling by downregulating the accumulation of ABA and ACC, while elevating endogenous melatonin levels. The PYH possessed a superior constitutive antioxidant capacity and hormonal stability, while melatonin was particularly beneficial for JHM. Proteomic analysis identified 1846 differentially expressed proteins (DEPs) in roots of JHM between waterlogged and melatonin-treated plants. These DEPs were predominantly enriched in metabolic pathways, phenylpropanoid biosynthesis, glutathione metabolism, and ROS metabolic processes. MT priming upregulated the expression of superoxide dismutase peroxidase 7, and peroxidase 15-like while downregulated hydrogen peroxide induced protein 1, which were consistent with the results of physiological analysis in JMH. Protein-protein interaction analysis highlighted key proteins like RPL6 and RPL4 as potential hubs within the melatonin-mediated ROS metabolic network. This study provides a comprehensive physiological and molecular elucidation of the multifaceted mechanisms by which melatonin confers waterlogging tolerance, establishing a theoretical foundation for its application in waterlogged regions.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 1","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exogenous Melatonin Enhances the Cold Resistance of Pepper (Capsicum annuum L. var. cerasiforme Bailey) by Promoting the Synthesis of Long-Chain Alkanes in the Epicuticular Wax 外源褪黑素通过促进辣椒表皮蜡长链烷烃的合成而增强辣椒(Capsicum annuum L. var. cerasiformme Bailey)的抗寒性。
IF 6.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-20 DOI: 10.1111/jpi.70097
Bingjie Wu, Ruixin Li, Minghui Ye, Wei Wang, Hengjia Zhang, Kunyang Zhuang, Tengfei Qin, Shangjing Guo, Yun Ling, Chen Zhou, Kexin Ma, Qin Guo, Xiaolin Wang

Pepper (Capsicum annuum L. var. cerasiforme Bailey) is highly sensitive to low temperatures, limiting its cultivation in cooler regions. While melatonin (MT) is known to enhance plant cold tolerance through antioxidant and hormonal pathways, its role in modulating cuticular wax composition remains unclear. In this study, we demonstrate that exogenous MT application significantly improves cold resistance in pepper seedlings by upregulating the biosynthesis of long-chain alkanes in epicuticular wax. Physiological assessments revealed that MT treatment (100 μM) increased photosynthetic rate (Pn) by 65.66%, enhanced antioxidant enzyme activities (CAT, POD, SOD), and reduced malondialdehyde (MDA) content by 20.88% after 8 h at 4°C. Transcriptomic and gas chromatography–mass spectrometry (GC–MS) analyses identified two key alkane biosynthesis genes, CaCER1-like and CaCER1-like1. The expression of CaCER1-like was specifically induced by exogenous melatonin, while CaCER1-like1 was primarily upregulated by low-temperature stress. This coordinated transcriptional activation enhanced the accumulation of C27, C29, and C31 alkanes. Beyond cold-induced alkane biosynthesis, melatonin treatment provided a further 25.5% increase in total alkane content (MT8 vs. CK8), with a marked 27.5% rise in the critical C31 alkane. These compounds constituted over 57.7% of the wax. Scanning electron microscopy (SEM) imaging further showed that MT-induced wax crystallization shifted from lamellar to aggregated structures, with a reduction in epidermal gaps, suggesting a potential reduction in nonstomatal water loss. These findings reveal a novel mechanism by which melatonin enhances cold tolerance via wax modification, providing a potential strategy for improving pepper cultivation in cold climates.

辣椒(Capsicum annuum L. var. cerasiformme Bailey)对低温高度敏感,限制了其在较冷地区的种植。虽然已知褪黑素(MT)通过抗氧化和激素途径增强植物的抗寒性,但其在调节角质层蜡成分中的作用尚不清楚。在本研究中,我们证明了外源MT施用通过上调表皮蜡长链烷烃的生物合成,显著提高了辣椒幼苗的抗寒性。经4℃处理8 h后,100 μM的MT处理可使植株光合速率(Pn)提高65.66%,抗氧化酶(CAT、POD、SOD)活性增强,丙二醛(MDA)含量降低20.88%。转录组学和气相色谱-质谱(GC-MS)分析鉴定了两个关键的烷烃生物合成基因,CaCER1-like和CaCER1-like1。CaCER1-like1的表达主要受外源褪黑素的特异性诱导,而CaCER1-like1的表达主要受低温胁迫的上调。这种协调的转录激活促进了C27、C29和C31烷烃的积累。除了冷诱导的烷烃生物合成外,褪黑素处理进一步增加了总烷烃含量25.5% (MT8 vs. CK8),其中关键烷烃C31显著增加27.5%。这些化合物占蜡的57.7%以上。扫描电镜(SEM)成像进一步显示,mt诱导的蜡结晶从片层结构转变为聚集结构,表皮间隙减少,表明可能减少非气孔水分损失。这些发现揭示了褪黑素通过蜡修饰增强耐寒性的新机制,为改善寒冷气候条件下辣椒种植提供了潜在的策略。
{"title":"Exogenous Melatonin Enhances the Cold Resistance of Pepper (Capsicum annuum L. var. cerasiforme Bailey) by Promoting the Synthesis of Long-Chain Alkanes in the Epicuticular Wax","authors":"Bingjie Wu,&nbsp;Ruixin Li,&nbsp;Minghui Ye,&nbsp;Wei Wang,&nbsp;Hengjia Zhang,&nbsp;Kunyang Zhuang,&nbsp;Tengfei Qin,&nbsp;Shangjing Guo,&nbsp;Yun Ling,&nbsp;Chen Zhou,&nbsp;Kexin Ma,&nbsp;Qin Guo,&nbsp;Xiaolin Wang","doi":"10.1111/jpi.70097","DOIUrl":"10.1111/jpi.70097","url":null,"abstract":"<div>\u0000 \u0000 <p>Pepper (<i>Capsicum annuum</i> L. var. <i>cerasiforme</i> Bailey) is highly sensitive to low temperatures, limiting its cultivation in cooler regions. While melatonin (MT) is known to enhance plant cold tolerance through antioxidant and hormonal pathways, its role in modulating cuticular wax composition remains unclear. In this study, we demonstrate that exogenous MT application significantly improves cold resistance in pepper seedlings by upregulating the biosynthesis of long-chain alkanes in epicuticular wax. Physiological assessments revealed that MT treatment (100 μM) increased photosynthetic rate (<i>P</i><sub>n</sub>) by 65.66%, enhanced antioxidant enzyme activities (CAT, POD, SOD), and reduced malondialdehyde (MDA) content by 20.88% after 8 h at 4°C. Transcriptomic and gas chromatography–mass spectrometry (GC–MS) analyses identified two key alkane biosynthesis genes, <i>CaCER1-like</i> and <i>CaCER1-like1</i>. The expression of <i>CaCER1-like</i> was specifically induced by exogenous melatonin, while <i>CaCER1-like1</i> was primarily upregulated by low-temperature stress. This coordinated transcriptional activation enhanced the accumulation of C27, C29, and C31 alkanes. Beyond cold-induced alkane biosynthesis, melatonin treatment provided a further 25.5% increase in total alkane content (MT8 vs. CK8), with a marked 27.5% rise in the critical C31 alkane. These compounds constituted over 57.7% of the wax. Scanning electron microscopy (SEM) imaging further showed that MT-induced wax crystallization shifted from lamellar to aggregated structures, with a reduction in epidermal gaps, suggesting a potential reduction in nonstomatal water loss. These findings reveal a novel mechanism by which melatonin enhances cold tolerance via wax modification, providing a potential strategy for improving pepper cultivation in cold climates.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Coupling Melatonin and Ultrasound Modulates ROS Production, Antioxidant System, and Biochemical Attributes Linked to Oxidative Browning in Litchi Pericarp 褪黑素和超声耦合调节荔枝果皮氧化褐变相关的ROS生成、抗氧化系统和生化特性。
IF 6.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-18 DOI: 10.1111/jpi.70100
Mohammed Wasim Siddiqui, Fozia Homa, Duniya Ram Singh, Vinayak V. Deshi, Hidayatullah Mir, Sareeta Nahakpam

Litchi (Litchi chinensis Sonn.) is a non-climacteric fruit with a red pericarp that browns after harvest, reducing market value. Pericarp browning is linked to oxidative stress caused by reactive oxygen species (ROS). This study explored the combined effects of ultrasound (US; 37 ± 3 kHz for 10 min) and melatonin (1 and 2 mM) on litchi pericarp browning during ambient storage. On last day of storage, US combined with 1 and 2 mM melatonin exhibited lowest pericarp browning compared to their individual application with a score of 2.54 and 3.64. The results suggest that, combined treatment of ultrasound and melatonin effectively mitigates oxidative stress with lower ROS accumulation and polyphenol oxidase activity. Additionally, higher levels of anthocyanins, polyphenols, antioxidants, and phenylalanine ammonia lyase activity were maintained. It also preserved fruit quality, including weight, soluble solids, and titratable acidity, while reducing decay suggesting combined treatment of ultrasound and melatonin effectively enhances the postharvest quality of litchi fruit with reduced pericarp browning

荔枝(Litchi chinensis Sonn.)是一种非更年期水果,收获后果皮变红,降低了市场价值。果皮褐变与活性氧(ROS)引起的氧化应激有关。本研究探讨了超声(US; 37±3 kHz, 10 min)和褪黑素(1和2 mM)对荔枝贮藏过程中果皮褐变的联合影响。在贮藏的最后一天,US与1和2 mM褪黑素联合使用的果皮褐变分数最低,分别为2.54和3.64。结果表明,超声和褪黑激素联合治疗可有效减轻氧化应激,降低ROS积累和多酚氧化酶活性。此外,花青素、多酚、抗氧化剂和苯丙氨酸解氨酶活性保持较高水平。它还保留了果实的质量,包括重量、可溶性固形物和可滴定的酸度,同时减少了腐烂,这表明超声波和褪黑激素联合处理有效地提高了荔枝果实的采后质量,减少了果皮的褐变。
{"title":"Coupling Melatonin and Ultrasound Modulates ROS Production, Antioxidant System, and Biochemical Attributes Linked to Oxidative Browning in Litchi Pericarp","authors":"Mohammed Wasim Siddiqui,&nbsp;Fozia Homa,&nbsp;Duniya Ram Singh,&nbsp;Vinayak V. Deshi,&nbsp;Hidayatullah Mir,&nbsp;Sareeta Nahakpam","doi":"10.1111/jpi.70100","DOIUrl":"10.1111/jpi.70100","url":null,"abstract":"<div>\u0000 \u0000 <p>Litchi (<i>Litchi chinensis</i> Sonn.) is a non-climacteric fruit with a red pericarp that browns after harvest, reducing market value. Pericarp browning is linked to oxidative stress caused by reactive oxygen species (ROS). This study explored the combined effects of ultrasound (US; 37 ± 3 kHz for 10 min) and melatonin (1 and 2 mM) on litchi pericarp browning during ambient storage. On last day of storage, US combined with 1 and 2 mM melatonin exhibited lowest pericarp browning compared to their individual application with a score of 2.54 and 3.64. The results suggest that, combined treatment of ultrasound and melatonin effectively mitigates oxidative stress with lower ROS accumulation and polyphenol oxidase activity. Additionally, higher levels of anthocyanins, polyphenols, antioxidants, and phenylalanine ammonia lyase activity were maintained. It also preserved fruit quality, including weight, soluble solids, and titratable acidity, while reducing decay suggesting combined treatment of ultrasound and melatonin effectively enhances the postharvest quality of litchi fruit with reduced pericarp browning</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145547387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Discovery Begets Discovery: Special Edition on Melatonin and the Musculoskeletal System 发现引发发现:褪黑素和肌肉骨骼系统特别版。
IF 6.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-13 DOI: 10.1111/jpi.70099
Paula A. Witt-Enderby
{"title":"Discovery Begets Discovery: Special Edition on Melatonin and the Musculoskeletal System","authors":"Paula A. Witt-Enderby","doi":"10.1111/jpi.70099","DOIUrl":"10.1111/jpi.70099","url":null,"abstract":"","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145501260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Melatonin Overcomes Cancer Multidrug Resistance by Downregulating ABCB1 Expression and Modulating Mitochondrial Function 褪黑素通过下调ABCB1表达和调节线粒体功能克服癌症多药耐药。
IF 6.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-04 DOI: 10.1111/jpi.70096
Alba López-Rodríguez, Laura Martinez-Ruiz, Raquel Morales-Gallel, Javier Florido, Fabiola Bermejo-Casares, José Manuel Garcia-Verdugo, María Martín Estebané, Víctor Carriel, Noelia Maldonado-Pérez, Pilar González-García, Seyedeh T. Ahmadpour, Yolanda Ramírez-Casas, Francisco Martín, Jean-Francois Dumas, Christophe Vandier, Yang Yang, Darío Acuña-Castroviejo, Germaine Escames

Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. A critical factor contributing to MDR is overexpression of ATP-binding cassette (ABC) transporters, such as ABCB1. Novel alternative therapeutic strategies are needed to overcome resistance associated with ABC transporters. In the present study, we aimed to elucidate the mechanisms by which melatonin overcomes ABCB1-mediated MDR in cancer cells, with a focus on mitochondrial function. We analyzed the effects of melatonin (1 mM) on head and neck squamous cell carcinoma cell lines (CAL 27 and SCC-9) overexpressing ABCB1 and exhibiting increased resistance to cisplatin (CDDP) compared to their parental cells. To further validate the role of melatonin in reversing ABCB1-mediated MDR, we also evaluated its effects on doxorubicin-resistant MCF-7 breast cancer cells. We further examined the potential of melatonin to overcome MDR in CAL 27 xenografted mice. Here, we report that melatonin treatment specifically triggered reactive oxygen species (ROS) production in mitochondria and weakened chemoresistance. ROS oxidized NADH into NAD+, and limiting the availability of ATP for efflux pump activity. Additionally, melatonin decreased the number of mitochondria localized near the nucleus instead of the cytoplasm and downregulated ABCB1 expression. Intratumoral administration of melatonin effectively overcame CDDP resistance in CAL 27/ABCB1 xenografts, significantly reducing tumor volume and promoting apoptosis. These findings demonstrate that melatonin enhances chemosensitivity in ABCB1-overexpressing cells by modulating mitochondrial metabolism, redox balance, and ABCB1 expression, highlighting its potential as an adjuvant therapy to overcome MDR.

多药耐药(MDR)是癌症化疗面临的主要挑战。导致MDR的一个关键因素是atp结合盒(ABC)转运体(如ABCB1)的过度表达。需要新的替代治疗策略来克服与ABC转运蛋白相关的耐药性。在本研究中,我们旨在阐明褪黑激素克服abcb1介导的癌细胞MDR的机制,重点是线粒体功能。我们分析了褪黑素(1mm)对过度表达ABCB1的头颈部鳞状细胞癌细胞系(CAL 27和SCC-9)的影响,与亲代细胞相比,这些细胞对顺铂(CDDP)的耐药性增加。为了进一步验证褪黑素在逆转abcb1介导的MDR中的作用,我们还评估了褪黑素对阿霉素耐药MCF-7乳腺癌细胞的作用。我们进一步研究了褪黑素在CAL 27异种移植小鼠中克服多药耐药的潜力。在这里,我们报道褪黑激素治疗特异性地触发线粒体中的活性氧(ROS)产生并减弱化疗耐药。ROS将NADH氧化为NAD+,限制了ATP对外排泵活性的可用性。此外,褪黑激素减少了位于细胞核附近的线粒体数量,而不是细胞质,并下调了ABCB1的表达。瘤内给药褪黑素能有效克服CAL 27/ABCB1异种移植物对CDDP的耐药性,显著减少肿瘤体积,促进细胞凋亡。这些发现表明,褪黑激素通过调节线粒体代谢、氧化还原平衡和ABCB1表达,增强ABCB1过表达细胞的化学敏感性,突出了其作为克服耐多药的辅助治疗的潜力。
{"title":"Melatonin Overcomes Cancer Multidrug Resistance by Downregulating ABCB1 Expression and Modulating Mitochondrial Function","authors":"Alba López-Rodríguez,&nbsp;Laura Martinez-Ruiz,&nbsp;Raquel Morales-Gallel,&nbsp;Javier Florido,&nbsp;Fabiola Bermejo-Casares,&nbsp;José Manuel Garcia-Verdugo,&nbsp;María Martín Estebané,&nbsp;Víctor Carriel,&nbsp;Noelia Maldonado-Pérez,&nbsp;Pilar González-García,&nbsp;Seyedeh T. Ahmadpour,&nbsp;Yolanda Ramírez-Casas,&nbsp;Francisco Martín,&nbsp;Jean-Francois Dumas,&nbsp;Christophe Vandier,&nbsp;Yang Yang,&nbsp;Darío Acuña-Castroviejo,&nbsp;Germaine Escames","doi":"10.1111/jpi.70096","DOIUrl":"10.1111/jpi.70096","url":null,"abstract":"<p>Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. A critical factor contributing to MDR is overexpression of ATP-binding cassette (ABC) transporters, such as ABCB1. Novel alternative therapeutic strategies are needed to overcome resistance associated with ABC transporters. In the present study, we aimed to elucidate the mechanisms by which melatonin overcomes ABCB1-mediated MDR in cancer cells, with a focus on mitochondrial function. We analyzed the effects of melatonin (1 mM) on head and neck squamous cell carcinoma cell lines (CAL 27 and SCC-9) overexpressing <i>ABCB1</i> and exhibiting increased resistance to cisplatin (CDDP) compared to their parental cells. To further validate the role of melatonin in reversing ABCB1-mediated MDR, we also evaluated its effects on doxorubicin-resistant MCF-7 breast cancer cells. We further examined the potential of melatonin to overcome MDR in CAL 27 xenografted mice. Here, we report that melatonin treatment specifically triggered reactive oxygen species (ROS) production in mitochondria and weakened chemoresistance. ROS oxidized NADH into NAD<sup>+</sup>, and limiting the availability of ATP for efflux pump activity. Additionally, melatonin decreased the number of mitochondria localized near the nucleus instead of the cytoplasm and downregulated ABCB1 expression. Intratumoral administration of melatonin effectively overcame CDDP resistance in CAL 27/ABCB1 xenografts, significantly reducing tumor volume and promoting apoptosis. These findings demonstrate that melatonin enhances chemosensitivity in ABCB1-overexpressing cells by modulating mitochondrial metabolism, redox balance, and ABCB1 expression, highlighting its potential as an adjuvant therapy to overcome MDR.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12586911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Key Role of the CRE Sequence in the Per1 Promoter in Mediating the Switch Between Unipolar and Bipolar Depression-Like Behaviors Per1启动子中CRE序列在调节单极和双相抑郁样行为转换中的关键作用
IF 6.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-31 DOI: 10.1111/jpi.70095
Xin-Ling Wang, Xuan Tan, Ke Wang, Xiao-Xing Liu, Kai Yuan, Kai-Mo Ding, Ying Han, Yan-Xue Xue, Shi-Qiu Meng, Su-Xia Li

The cAMP response element-binding protein (CREB) and Period1 (Per1) have been implicated in depression, but their interactive mechanisms remain unclear. This study investigated the integrative role of CREB and Per1 in depression and explores a potential strategy for rapid antidepressant treatment. Using a chronic unpredictable stress (CUS) model, we conducted behavioral assessments including the sucrose preference test, forced swimming test, elevated plus maze, and open field test. Gene expression was manipulated via stereotaxic surgery and RNA interference (RNAi), while protein levels and viral injection sites were verified through Western blot analysis and immunofluorescence. Additionally, we generated Per1 CRE knockout rats using CRISPR/Cas9, with genotypes confirmed by Sanger sequencing. CUS significantly reduced phosphorylated CREB (pCREB) and PER1 levels in the CA1 region. Both Per1 knockdown in CA1 and CRE sequence knockout induced depression-like behaviors, whereas Per2 knockdown in CA1 produced mania-like behaviors. Notably, CRE knockout in the Per1 promoter increased pCREB binding to the Per2 promoter, upregulating PER2 expression in the CA1 and resulting in depression-like phenotypes that are partially lithium-responsive. Treatment with the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) elevated pCREB and PER1 levels in the CA1 and elicited rapid antidepressant effects. These effects were present in heterozygotes but absent in homozygotes with a mutated Per1 CRE sequence. These results revealed the pivotal role of the pCREB-CRE-Per1 pathway in CUS-induced depression and its mediation of rapid antidepressant-like effects via adenosine A1 receptor activation. Moreover, the CRE sequence in the Per1 promoter may be a critical molecular link to the pathophysiology of bipolar depression.

cAMP反应元件结合蛋白(CREB)和Period1 (Per1)与抑郁症有关,但它们的相互作用机制尚不清楚。本研究探讨了CREB和Per1在抑郁症中的综合作用,并探索了快速抗抑郁治疗的潜在策略。采用慢性不可预测应激(CUS)模型,对小鼠进行蔗糖偏好测试、强迫游泳测试、高架迷宫测试和野外测试等行为评估。通过立体定向手术和RNA干扰(RNAi)操纵基因表达,通过Western blot分析和免疫荧光验证蛋白水平和病毒注射部位。此外,我们利用CRISPR/Cas9技术培育了Per1 CRE敲除大鼠,并通过Sanger测序确认了基因型。CUS显著降低了CA1区域磷酸化CREB (pCREB)和PER1水平。CA1中Per1敲低和CRE序列敲低均诱导抑郁样行为,而CA1中Per2敲低产生躁狂样行为。值得注意的是,Per1启动子中的CRE敲除增加了pCREB与Per2启动子的结合,上调了CA1中Per2的表达,并导致部分锂响应的抑郁样表型。用腺苷A1受体激动剂2-氯- n6 -环戊基腺苷(CCPA)治疗可提高CA1中的pCREB和PER1水平,并引起快速的抗抑郁作用。这些影响在杂合子中存在,但在Per1 CRE序列突变的纯合子中不存在。这些结果揭示了pCREB-CRE-Per1通路在cu诱导的抑郁症中的关键作用及其通过腺苷A1受体激活介导的快速抗抑郁样作用。此外,Per1启动子中的CRE序列可能是双相抑郁症病理生理的关键分子链接。
{"title":"Key Role of the CRE Sequence in the Per1 Promoter in Mediating the Switch Between Unipolar and Bipolar Depression-Like Behaviors","authors":"Xin-Ling Wang,&nbsp;Xuan Tan,&nbsp;Ke Wang,&nbsp;Xiao-Xing Liu,&nbsp;Kai Yuan,&nbsp;Kai-Mo Ding,&nbsp;Ying Han,&nbsp;Yan-Xue Xue,&nbsp;Shi-Qiu Meng,&nbsp;Su-Xia Li","doi":"10.1111/jpi.70095","DOIUrl":"https://doi.org/10.1111/jpi.70095","url":null,"abstract":"<div>\u0000 \u0000 <p>The cAMP response element-binding protein (CREB) and <i>Period1</i> (<i>Per1</i>) have been implicated in depression, but their interactive mechanisms remain unclear. This study investigated the integrative role of CREB and <i>Per1</i> in depression and explores a potential strategy for rapid antidepressant treatment. Using a chronic unpredictable stress (CUS) model, we conducted behavioral assessments including the sucrose preference test, forced swimming test, elevated plus maze, and open field test. Gene expression was manipulated via stereotaxic surgery and RNA interference (RNAi), while protein levels and viral injection sites were verified through Western blot analysis and immunofluorescence. Additionally, we generated <i>Per1</i> CRE knockout rats using CRISPR/Cas9, with genotypes confirmed by Sanger sequencing. CUS significantly reduced phosphorylated CREB (pCREB) and PER1 levels in the CA1 region. Both <i>Per1</i> knockdown in CA1 and CRE sequence knockout induced depression-like behaviors, whereas <i>Per2</i> knockdown in CA1 produced mania-like behaviors. Notably, CRE knockout in the <i>Per1</i> promoter increased pCREB binding to the <i>Per2</i> promoter, upregulating PER2 expression in the CA1 and resulting in depression-like phenotypes that are partially lithium-responsive. Treatment with the adenosine A<sub>1</sub> receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) elevated pCREB and PER1 levels in the CA1 and elicited rapid antidepressant effects. These effects were present in heterozygotes but absent in homozygotes with a mutated <i>Per1</i> CRE sequence. These results revealed the pivotal role of the pCREB-CRE-<i>Per1</i> pathway in CUS-induced depression and its mediation of rapid antidepressant-like effects via adenosine A<sub>1</sub> receptor activation. Moreover, the CRE sequence in the <i>Per1</i> promoter may be a critical molecular link to the pathophysiology of bipolar depression.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
‌Liquid–Liquid Phase Separation of AR Orchestrated by Melatonin Sensitizes Prostate Cancer to Ferroptosis Via MCM5/NRF2 Axis Collapse 褪黑素介导的AR液-液相分离通过MCM5/NRF2轴塌陷使前列腺癌对铁上落症敏感。
IF 6.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-10-29 DOI: 10.1111/jpi.70094
Xianyanling Yi, Zeyu Han, Yaxiong Tang, Jin Li, Xuanji Li, Hang Xu, Xiaonan Zheng, Dazhou Liao, Hong Li, Qiang Wei, Lu Yang, Jianzhong Ai

The treatment of prostate cancer (PCa) remains challenging, and while melatonin (MEL) has demonstrated therapeutic potential, its precise mechanisms require further elucidation. Through integrated in vitro, in vivo, and bioinformatics analyses, this study demonstrated that MEL functioned as a novel ferroptosis inducer in PCa by disrupting androgen receptor (AR) liquid-liquid phase separation (LLPS). We found that MEL effectively inhibited PCa proliferation, migration, and invasion in vitro while suppressing tumor growth safely in mice models. Mechanistically, MEL impaired AR LLPS dynamics, reducing AR-driven transcription of minichromosome maintenance protein 5 (MCM5). MCM5 was a clinically relevant biomarker associated with aggressive PCa and poor survival. Crucially, downregulated MCM5 attenuated its physical interaction with NRF2, leading to uncontrolled activation of the NRF2/HMOX1 pathway, GPX4 suppression, and accumulation of ferroptosis hallmarks. These findings defined an AR/MCM5/NRF2 axis regulating ferroptosis susceptibility, establishing MEL as the first-reported ferroptosis inducer that expands the mechanistic foundation and therapeutic potential of MEL-based PCa treatment strategies.

前列腺癌(PCa)的治疗仍然具有挑战性,虽然褪黑素(MEL)已经显示出治疗潜力,但其确切机制需要进一步阐明。通过体外、体内和生物信息学综合分析,本研究证明了MEL通过破坏雄激素受体(AR)液-液相分离(LLPS)在PCa中作为一种新的铁ptosis诱导剂。我们发现MEL在小鼠模型中有效抑制PCa的增殖、迁移和侵袭,同时安全抑制肿瘤生长。在机制上,MEL破坏了AR LLPS动力学,减少了AR驱动的小染色体维持蛋白5 (MCM5)的转录。MCM5是与侵袭性PCa和不良生存率相关的临床相关生物标志物。至关重要的是,下调的MCM5减弱了其与NRF2的物理相互作用,导致NRF2/HMOX1途径的不受控制的激活,GPX4的抑制和铁死亡标志的积累。这些发现定义了AR/MCM5/NRF2轴调控铁下垂易感性,确立了MEL作为首个报道的铁下垂诱导剂,扩展了基于MEL的PCa治疗策略的机制基础和治疗潜力。
{"title":"‌Liquid–Liquid Phase Separation of AR Orchestrated by Melatonin Sensitizes Prostate Cancer to Ferroptosis Via MCM5/NRF2 Axis Collapse","authors":"Xianyanling Yi,&nbsp;Zeyu Han,&nbsp;Yaxiong Tang,&nbsp;Jin Li,&nbsp;Xuanji Li,&nbsp;Hang Xu,&nbsp;Xiaonan Zheng,&nbsp;Dazhou Liao,&nbsp;Hong Li,&nbsp;Qiang Wei,&nbsp;Lu Yang,&nbsp;Jianzhong Ai","doi":"10.1111/jpi.70094","DOIUrl":"10.1111/jpi.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>The treatment of prostate cancer (PCa) remains challenging, and while melatonin (MEL) has demonstrated therapeutic potential, its precise mechanisms require further elucidation. Through integrated in vitro, in vivo, and bioinformatics analyses, this study demonstrated that MEL functioned as a novel ferroptosis inducer in PCa by disrupting androgen receptor (AR) liquid-liquid phase separation (LLPS). We found that MEL effectively inhibited PCa proliferation, migration, and invasion in vitro while suppressing tumor growth safely in mice models. Mechanistically, MEL impaired AR LLPS dynamics, reducing AR-driven transcription of minichromosome maintenance protein 5 (MCM5). MCM5 was a clinically relevant biomarker associated with aggressive PCa and poor survival. Crucially, downregulated MCM5 attenuated its physical interaction with NRF2, leading to uncontrolled activation of the NRF2/HMOX1 pathway, GPX4 suppression, and accumulation of ferroptosis hallmarks. These findings defined an AR/MCM5/NRF2 axis regulating ferroptosis susceptibility, establishing MEL as the first-reported ferroptosis inducer that expands the mechanistic foundation and therapeutic potential of MEL-based PCa treatment strategies.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Pineal Research
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1