Journal of Pineal Research最新文献

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 3","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148096544","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}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 3","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148080439","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}

{"title":"Melatonin Facts: Musing With the Concept “Melatonin Travels Freely Through Biological Membranes”","authors":"Jean A. Boutin,&nbsp;Jérôme Leprince,&nbsp;Ralf Jockers","doi":"10.1111/jpi.70142","DOIUrl":"10.1111/jpi.70142","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin has been shown to travel freely through biological membranes. The consequences of this demonstration have been largely underestimated these past years. In particular, the behavior of melatonin during the preparation of samples from organs (ex vivo), from cells (in cellulo), or subcellular compartment(s) has been experimentally ignored. Melatonin is not retained in samples but can diffuse immediately outside those samples. Similarly, melatonin cannot be “trapped” in membrane-based organelles like mitochondria, nucleus, ER/Golgi, or lipid droplets of any sort. Consequently, existing data should be carefully reinterpreted, and future experiments should take the fact of melatonin diffusion into account, in particular when trying to provide convincing experimental evidence for local production of melatonin in cells and organelles outside of the pineal gland and the retina.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 3","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643444","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}

{"title":"Melatonin Receptor–Mediated Signaling and PGPR-Induced Secondary Metabolic Defense Dome Confer Cadmium Tolerance in Brassica juncea: Transcriptomic and Docking Insights","authors":"Tamanna Bhardwaj,&nbsp;Renu Bhardwaj,&nbsp;Nancy Sharma,&nbsp;Atamjit Singh,&nbsp;Harpreet Singh,&nbsp;Preet Mohinder Singh Bedi,&nbsp;Sumit G. Gandhi,&nbsp;Parvaiz Ahmad","doi":"10.1111/jpi.70138","DOIUrl":"10.1111/jpi.70138","url":null,"abstract":"<div>\u0000 \u0000 <p>Anthropogenic activities have increased cadmium (Cd) accumulation in agricultural soils, severely affecting crop productivity. This study investigated the role of melatonin (Mlt) and a <i>Pseudomonas</i> consortium (PGPR) in modulating secondary metabolism in <i>Brassica juncea</i> L. seedlings under Cd stress. Combined Mlt–PGPR treatment significantly reduced Cd accumulation and regulated the expression of genes involved in Cd transport and detoxification. Enhanced levels of osmolytes and organic acids were observed, along with upregulation of genes associated with osmoprotection and metal chelation. Antioxidant defense was experimentally assessed through enzymatic and non-enzymatic analyses, confirming improved redox homeostasis. FTIR spectroscopy supported treatment-induced biochemical alterations. Transcriptomic profiling revealed activation of melatonin biosynthesis genes and secondary metabolism-related pathways. A structural model of BjCand2, a putative melatonin receptor, and docking analysis suggested its involvement in signaling regulation. Overall, Mlt–PGPR application mitigates Cd toxicity through coordinated receptor-mediated signaling and metabolic reprogramming.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 3","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626772","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}

{"title":"Melatonin Promotes the Synthesis and Secretion of Growth Hormone in the Adenohypophysis by Activating the cAMP/FOXO1 Pathway","authors":"Yi Zheng,&nbsp;Qing-qing Chen,&nbsp;Hai-xiang Guo,&nbsp;Yu-xin Zhang,&nbsp;Ling-ling Qiu,&nbsp;Bing-bing Wang,&nbsp;Song Yu,&nbsp;Jia-rui Gao,&nbsp;Zhe Zhang,&nbsp;Jia-bao Zhang,&nbsp;Guo-shi Liu,&nbsp;Bao Yuan","doi":"10.1111/jpi.70139","DOIUrl":"10.1111/jpi.70139","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin, a signaling molecule secreted by the pineal gland, is closely associated with physiological activities, such as animal growth, development, and reproduction. Multiple studies have indicated that melatonin acts on the adenohypophysis to promote the synthesis and secretion of growth hormone (GH), but the specific mechanism of melatonin remains unclear. We have previously reported that melatonin levels in bovine serum are closely correlated with GH levels. In the present study, transcriptome sequencing was performed on primary bovine adenohypophyseal cells treated with melatonin, which identified <i>FOXO1</i> as a key transcription factor that is responsive to melatonin and regulates GH synthesis and secretion. Cellular experiments revealed that melatonin binds to the MTNR1A in bovine adenohypophyseal cells, activates the cAMP/PKA signaling pathway, and promotes the expression of FOXO1 protein. Dual-luciferase reporter assays verified the binding of FOXO1 to the <i>GH1</i> promoter. Treatment with Luzindole, 4P-PDOT, 2′,5′-Dideoxyadenosine or H-89 elucidated the molecular mechanism through which melatonin promotes GH synthesis and secretion in adenohypophyseal cells through the cAMP/PKA/CREB/FOXO1 pathway. The present study provides critical evidence for the direct action of melatonin on adenohypophyseal cells and its targeted regulatory sites, and it offers new insights into the conserved and species-specific modes of action of melatonin across different species, providing data and theoretical support for the application of melatonin in promoting animal growth and development.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497102","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}

{"title":"Melatonin Enhances the Myometrial Contraction Through MT2-PKC-NRF2/MAFF Signaling Pathway in Sows","authors":"Tongjuan Niu,&nbsp;Yewen Zhou,&nbsp;Guobin Qiu,&nbsp;Jinglin Zhang,&nbsp;Jiangpeng Liao,&nbsp;Qing Zhang,&nbsp;Shuai Yu,&nbsp;Kemian Gou,&nbsp;Sheng Cui,&nbsp;Di Zhang","doi":"10.1111/jpi.70135","DOIUrl":"10.1111/jpi.70135","url":null,"abstract":"<div>\u0000 \u0000 <p>Spontaneous parturition in both humans and sows occurs predominantly at night. Melatonin is thought to facilitate nocturnal parturition in humans by synergistically enhancing myometrial contractions with oxytocin, but the precise underlying mechanisms remain unclear. In this study, <i>in vivo</i> analyses showed that melatonin levels in both serum and myometrium were significantly increased in laboring sows, accompanied by increased melatonin synthesized in the myometrium. Moreover, exogenous melatonin administration to pregnant sows potentially shifted parturition time. Functional studies demonstrated that melatonin supplementation significantly enhanced spontaneous myometrial contractility and sensitivity to oxytocin. Mechanistic investigations revealed that transcription factors NRF2 and MAFF were involved in the signaling pathway of melatonin, enhancing myometrial contractility. Silencing NRF2 or MAFF in melatonin-treated myometrial cells reduced the expression of contraction-associated proteins (CAPs) and attenuated collagen gel contraction. Dual-luciferase reporter assays indicated that NRF2 and MAFF directly targeted the promoters of key contraction-associated genes, including <i>PTGS2</i> and <i>OXTR</i>. Additionally, molecular analysis revealed that melatonin enhanced myometrial contraction by binding to the MT2 receptor. Furthermore, our results showed that PKC participated in melatonin-induced myometrial contraction by regulating NRF2 and MAFF expression. Collectively, our data reveal, for the first time, that the MT2-PKC-NRF2/MAFF axis mediates melatonin-enhanced myometrial contraction in sows. These findings advance our understanding of parturition initiation in mammals and may provide a novel theoretical basis for developing therapeutic strategies for preterm or delayed/prolonged labor.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483927","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}

{"title":"Early-Life Melatonin Supplementation Reduces the Long-Term Behavioral, Morphological, and Molecular Alterations in a Rat Model of Autism Spectrum Disorder","authors":"Luis J. Hernández-Sierra,&nbsp;Roberto C. Salgado-Delgado,&nbsp;Osvaldo Ibáñez-Sandoval,&nbsp;Nadia Saderi","doi":"10.1111/jpi.70136","DOIUrl":"10.1111/jpi.70136","url":null,"abstract":"<div>\u0000 \u0000 <p>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by significant challenges in social interactions and repetitive behaviors. Its prevalence is high, with males affected at a rate four times higher than females. Among various comorbidities associated with ASD, sleep disorders and abnormal melatonin levels have emerged as critical areas of concern. Melatonin, a potent endogenous hormone, plays essential roles as a circadian regulator, anti-inflammatory, and antioxidant agent through the release of pro- and anti-inflammatory cytokines and stimulation of endogenous antioxidant enzymes. This study sets out to examine the effects of melatonin administration during gestation and lactation on ASD-related behaviors, focusing on sex-specific differences in a well-established ASD model. Pregnant rats received an intraperitoneal injection of valproic acid (VPA) or saline at gestational day 12.5 (E12.5) and were treated with melatonin or vehicle from E13 until weaning. Our results indicated that chronic melatonin supplementation effectively reversed behavioral, circadian, and morphological abnormalities in male offspring. In females, melatonin prevented the inflammatory responses induced by VPA. Furthermore, chronic melatonin treatment restored the altered profile of serum melatonin observed in VPA animals and also restored the circadian expression of enzymes critical for its synthesis. These findings highlight sex-specific alterations prevalent in this model and strongly suggest that melatonin represents a promising therapeutic approach for mitigating ASD-related behaviors in the VPA model, warranting further investigation to assess its clinical relevance.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483981","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}

{"title":"Brain-Targeted RVG-Liposomal Melatonin Ameliorates Manganese Neurotoxicity by Enhancing Neurogenesis and Modulating Systemic Amino Acid Profiles","authors":"Xueting Wang,&nbsp;Junge Chen,&nbsp;Jiao Xia,&nbsp;Teng Ma,&nbsp;Weitong Yang,&nbsp;Tianzi Shan,&nbsp;Weifeng He,&nbsp;Gaoman Zhang,&nbsp;Zhuoran Xia,&nbsp;Weiwei Wang,&nbsp;Zhusheng Liu,&nbsp;Yanyan Zheng,&nbsp;Kang Nong,&nbsp;Piye Niu,&nbsp;Tian Chen","doi":"10.1111/jpi.70137","DOIUrl":"10.1111/jpi.70137","url":null,"abstract":"<div>\u0000 \u0000 <p>Chronic manganese (Mn) exposure induces severe neurotoxicity, characterized by impaired neurogenesis and disrupted metabolic homeostasis. Although melatonin (MT) possesses established neuroprotective properties, its clinical utility is hindered by poor bioavailability and limited brain delivery. Here, we developed a brain-targeted, rabies virus glycoprotein (RVG)-modified liposomal delivery system encapsulating melatonin (MT@RVG-Lip) to enhance therapeutic efficacy. Multi-omics analyses including brain and intestinal transcriptomics, serum metabolomics, and gut metagenomics were conducted to elucidate the underlying mechanisms. MT@RVG-Lip significantly improved motor deficits and enhanced neurogenesis while reducing neuroinflammation in Mn-exposed mice. Compared with regular MT and CaNa₂-EDTA, MT@RVG-Lip more effectively alleviated Mn-disrupted gene expression in neurogenesis regions, particularly genes involved in amino acid metabolism. Additionally, MT@RVG-Lip demonstrated a regulatory effect on serum amino acid profiles and intestinal transporter gene expression. Gut microbiota analysis further revealed that MT@RVG-Lip partially reversed Mn-associated dysbiosis and promoted the improvement of key amino acid-related microbiota-mediated metabolic pathways. The RVG-modified liposomal formulation conferred sustained release and improved brain-targeting capability, prolonging MT bioavailability and enhancing therapeutic outcomes. These findings provide a new mechanistic framework for MT-based interventions in neurodegenerative diseases and highlight the therapeutic potential of multifunctional delivery strategies.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472109","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}

{"title":"Low-Dose Melatonin, Climacteric Symptoms and Sleep in Female Shift Workers: A Randomized Controlled Trial","authors":"Susy P. Saraiva,&nbsp;Carolina V. R. D'Aurea,&nbsp;Cristina S. S. Luz,&nbsp;Fernanda G. Amaral,&nbsp;Jose Cipolla-Neto,&nbsp;Elaine C. Marqueze,&nbsp;Claudia R. C. Moreno","doi":"10.1111/jpi.70140","DOIUrl":"10.1111/jpi.70140","url":null,"abstract":"<p>Sleep disturbances and mood changes are common during the climacteric, often linked to hormonal fluctuations caused by reduced ovarian function. Evidence suggests that long-term melatonin administration may improve the quality of life in climacteric women. This study aimed to evaluate the effects of exogenous melatonin on climacteric symptoms, sleep quality, and reproductive hormones in women working fixed shifts. A randomized clinical trial was conducted with 46 nurses working fixed shifts at a hospital in São Paulo: morning (7:00–13:00, <i>n</i> = 16; intervention = 7, placebo = 9), afternoon (13:00–19:00, <i>n</i> = 15; intervention = 8, placebo = 7), and night (19:00–7:00, <i>n</i> = 15; intervention = 7, placebo = 8). Participants were randomly assigned to receive either 0.3 mg of melatonin or placebo. For night shift workers, melatonin was administered only on nights off, when they were sleeping at home; the same procedure was applied to morning and afternoon workers. Data collection included sociodemographic information, self-reported sleep quality, and menopausal symptoms. Blood samples were collected at home to measure luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone before and after the intervention. A significant main effect of melatonin was observed, with a 15.8% reduction in climacteric symptoms compared with placebo (<i>p</i> = 0.01), independent of age or sleep duration, while no significant interaction with work shift was detected. Sleep quality improved by 35.33% on days off in the intervention group (<i>p</i> &lt; 0.001), with morning shift workers showing a 32.46% improvement (<i>p</i> &lt; 0.05). No significant changes were observed in reproductive hormone levels or total sleep duration. Exogenous melatonin effectively alleviates climacteric symptoms and improves sleep quality on days off, particularly among day-shift workers, without affecting reproductive hormone concentrations or total sleep duration.</p><p><b>Trial Registration:</b> RBR-10whktxm (UTN: U1111-1305-6221). Registered on 13 August 2025, retrospectively registered.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12993913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472111","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}

{"title":"Melatonin Protects Mouse Oocytes From the Environmental Toxicant 6PPD-Quinone by Preserving Mitochondrial and Endomembrane Homeostasis","authors":"Bei Chen,&nbsp;Jiaqi Wang,&nbsp;Qianrong Qi,&nbsp;Xiaoyan Shi,&nbsp;Yi Zhang,&nbsp;Mengneng Xiong,&nbsp;Jinxin Xiao,&nbsp;Xueli Liu,&nbsp;Jin Luo,&nbsp;Qingzhen Xie","doi":"10.1111/jpi.70133","DOIUrl":"10.1111/jpi.70133","url":null,"abstract":"<div>\u0000 \u0000 <p>N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q) is a ubiquitous tire-derived transformation product with emerging reproductive toxicity; however, its impact on mammalian oocytes and the potential protective role of melatonin (MT) remain unclear. Here, we evaluate 6PPD-Q–induced impairment of mouse oocyte competence and assess the protective efficacy of MT. 6PPD-Q exposure significantly decreases polar body extrusion, fertilization, and 2-cell embryo formation, whereas MT co-treatment markedly restores these developmental outcomes. Mechanistically, MT alleviates 6PPD-Q–induced meiotic spindle defects and cortical F-actin disorganization, reduces DNA damage, and suppresses early apoptotic signaling. Smart-seq. 2 transcriptomic profiling further reveals that 6PPD-Q triggers extensive transcriptional reprogramming, with prominent disruption of mitochondrial metabolism, oxidative phosphorylation, and organelle homeostasis, whereas MT mitigates these pathway perturbations. Consistently, functional assays demonstrate that MT reduces excessive cellular and mitochondrial reactive oxygen species, restores mitochondrial membrane potential and adenosine triphosphate levels, and mitigates global organellar disorganization. Collectively, these findings identify MT as a cytoprotective modulator of 6PPD-Q–induced oocyte dysfunction by preserving mitochondrial and endomembrane homeostasis, thereby supporting oocyte maturation and fertilization.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 2","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442095","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}