Journal of Pineal Research最新文献

{"title":"The Mechanism by Which Melatonin Improves the Dysregulation of Glucose and Lipid Metabolism in Castrated Female Mice","authors":"Xin Jin,&nbsp;Xuan Liu,&nbsp;Yunjuan Wang,&nbsp;Xiaoqian Li,&nbsp;Tianle Zhang,&nbsp;Jiahui Li,&nbsp;Zili Lei,&nbsp;Yanhong Yang","doi":"10.1111/jpi.70082","DOIUrl":"10.1111/jpi.70082","url":null,"abstract":"<div>\u0000 \u0000 <p>Postmenopausal women have a significantly increased risk of cardiovascular disease and osteoporosis due to the lack of estrogen protection. To explore the effects of melatonin on clock genes and glucose and lipid metabolic disorders of postmenopausal women, the models of ovariectomized (OVX) mice under different dietary conditions were generated and given melatonin gavage for 8 weeks. Biochemical indexes of serum and the morphology and histology of livers of the mice were checked. Transcriptome analysis, qPCR and Western blot were used to detect the expressional levels of genes related to clock and glucose and lipid metabolism in the livers of mice. The intestinal microbiota of the ovariectomized mice under different dietary conditions was further analyzed with 16S rDNA sequences. Melatonin significantly reduced the high concentrations of TC and LDL-C in the serum and lipid accumulation in the livers of the ovariectomized mice, and downregulated the protein expression associated with cholesterol and fatty acid biosynthesis, including HMGCR, FDPS, IDI1, MVK, LSS, FASN, and ACC. Melatonin could also improve the insulin resistance of the ovariectomized mice, upregulate the protein expression levels of p-IRS1, p-AKT, and p-mTOR, and reduce the protein expression level of p-Glycogen Synthase under high-fat diet (HFD) conditions. In addition, melatonin restored the clock genes expression disturbances caused by ovarian removal or high-fat diets, and upregulated the expression of the core circadian clock genes <i>Clock</i> and <i>Bmal1</i>. Melatonin also effectively increased the abundance of beneficial bacteria, improved the structure of microflora, and reduced the harmful bacteria of the ovariectomized mice fed with HFD. These results suggest that melatonin could affect liver clock genes expression and gut microbiota in ovariectomized mice, and improve glucose and lipid metabolic disorders under different dietary conditions.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136154","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":"EXPRESSION OF CONCERN: Melatonin Compensates Silencing of Heat Shock Protein 70 and Suppresses Ultraviolet Radiation-Induced Inflammation in Human Skin Ex Vivo and Cultured Keratinocytes","authors":"","doi":"10.1111/jpi.70084","DOIUrl":"https://doi.org/10.1111/jpi.70084","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN</b>: K. Kleszczyński, S. Zwicker, S. Tukaj, M. Kasperkiewicz, D. Zillikens, R. Wolf, and T. W. Fischer, “Melatonin Compensates Silencing of Heat Shock Protein 70 and Suppresses Ultraviolet Radiation-Induced Inflammation in Human Skin Ex Vivo and Cultured Keratinocytes,” <i>Journal of Pineal Research</i> 58, no. 1 (2015): 117-126, https://doi.org/10.1111/jpi.12197.</p><p>This Expression of Concern is for the above article, published online on 25 November 2014 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Gianluca Tosini; and John Wiley &amp; Sons Ltd. A third party reported that the 24 h 300 mJ/cm² panels for -Melatonin and +Melatonin in Figure 2A shared an overlapping section. The publisher confirmed these concerns, and following the initiation of its investigation, the publisher received further correspondence from University of Münster noting that the university had published a formal statement regarding one of the authors [<span>1</span>]. This statement reported the conclusions from a commission of inquiry which concluded that this author engaged in behavior consistent with scientific misconduct, and that the university had directed the authors to seek corrections with the publications involved in the inquiry. The University of Münster did not provide further details regarding the commission of inquiry with specific reference to this article.</p><p>The authors requested a correction for their article to replace the Hsp70 immunofluorescence 24 h 300 mJ/cm² +Melatonin image and they provided further corroborating evidence regarding their experimental procedures. Following a review of the data, the editors determined that, while the authors had provided evidence to support their claims that the replacement data corresponded to the stated samples and derived from the same experiments, the data provided could not be validated as being qualitatively the same. This Expression of Concern has been agreed to to inform and alert readers to the error in Figure 2A and the results of the publisher's and the university's investigation. All authors disagree with the Expression of Concern. On behalf of all authors, K. Kleszczyński requested correction for the error in Figure 2A. Author D. Zillikens had passed away before the start of the investigation.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111319","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":"EXPRESSION OF CONCERN: Mitochondrial Function Is Controlled by Melatonin and Its Metabolites In Vitro in Human Melanoma Cells","authors":"","doi":"10.1111/jpi.70083","DOIUrl":"https://doi.org/10.1111/jpi.70083","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN</b>: B. Bilska, F. Schedel, A. Piotrowska, J. Stefan, M. Zmijewski, E. Pyza, R. J. Reiter, K. Steinbrink, A. T. Slominski, M. K. Tulic, and K. Kleszczyński, “Mitochondrial Function Is Controlled by Melatonin and Its Metabolites In Vitro in Human Melanoma Cells,” <i>Journal of Pineal Research</i> 70, no. 3 (2021): e12728, https://doi.org/10.1111/jpi.12728.</p><p>This Expression of Concern is for the above article, published online on 02 March 2021 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Gianluca Tosini; and John Wiley &amp; Sons Ltd. A third party reported that the panels in Figure 3B and 3 C shared an overlapping cellular section. The publisher confirmed these concerns, and following the initiation of its investigation, the publisher received further correspondence from University of Münster noting that the university had published a formal statement regarding one of the authors [<span>1</span>]. This statement reported the conclusions from a commission of inquiry which concluded that this author engaged in behavior consistent with scientific misconduct, and that the university had directed the authors to seek corrections with the publications involved in the inquiry. The University of Münster did not provide further details regarding the commission of inquiry with specific reference to this article.</p><p>The authors requested a correction for their article to replace both Figures 3B and 3 C and shared original data as well as further corroborating evidence regarding their experimental procedures. Following a review of the data, the editors determined that, while the authors had provided evidence to support their claims that the new data corresponded to the stated samples, the data provided could not be validated as being qualitatively the same. This Expression of Concern has been agreed to to inform and alert readers to the error in Figure 3 and the results of the publisher's and the university's investigation. All authors disagree with the Expression of Concern. On behalf of all authors, K. Kleszczyński requested correction for the error in Figure 3. Author E. Pyza supported this request.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111320","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-Producing Microorganisms: A Rising Research Interest in Their Melatonin Biosynthesis and Effects on Crops","authors":"Sang-Mo Kang,&nbsp;Ashim Kumar Das,&nbsp;Da-Sol Lee,&nbsp;Byung-Wook Yun,&nbsp;Marino B. Arnao,&nbsp;In-Jung Lee","doi":"10.1111/jpi.70081","DOIUrl":"https://doi.org/10.1111/jpi.70081","url":null,"abstract":"<p>Melatonin is imperative in animals and plants, contributing to multiple physiological roles, and its microbial production could offer an eco-friendly alternative to synthetic melatonin. However, detecting and characterizing it in microorganisms remains ongoing, and the biosynthesis pathways are still poorly explored. We noted that not all microorganisms possess similar enzymes and substrates for melatonin production. Its biosynthesis pathway is well-characterized in yeast, potentiating its importance in agricultural practices in a melatonin-dependent manner. Intercellular melatonin production in algae and fungi boosts their resilience to oxidative cell death by activating the antioxidant defenses. Few studies on the use of <i>Bacillus sp</i>., <i>Pseudomonas sp</i>., and <i>Enterobacter sp</i>. have shown that these bacteria increase their endogenous melatonin contents, which may exchange with their host plants; thereby, mitigating abiotic stresses by modulating cellular damages, ion exchanges, hormonal levels, and related transcript expressions. Though plant-growth-promoting microbes show promise to enhance crop production, melatonin-producing microorganisms (M-PMs) are limited in identification, and their ecological and biological applications are still underutilized in agriculture. With the compounded benefits from M-PMs, it could be an untapped tool for rhizospheric bioengineering. Therefore, this review delivers comprehensive insights into M-PMs for practicing sustainable agriculture under increased climatic changes.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111321","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":"Morten Møller: In Memoriam","authors":"Horst-Werner Korf,&nbsp;Martin Fredensborg Rath","doi":"10.1111/jpi.70074","DOIUrl":"https://doi.org/10.1111/jpi.70074","url":null,"abstract":"&lt;p&gt;Morten Møller, Professor emeritus in Neuroanatomy, Department of Neuroscience, Faculty of Health Sciences, University of Copenhagen passed away on July 16, 2025. This sadly marks the end of a most remarkable scientific career which spanned six decades. Many friends and colleagues worldwide mourn his death (Figure 1).&lt;/p&gt;&lt;p&gt;Morten Møller was born in Odense, Denmark on November 29, 1942. In 1969, Morten got married with Vera Gudjohnsen of Thyborøn, who accompanied and supported Morten for more than 50 years until she passed away on January 24, 2020. As Morten used to say “A secret in a man's life is his wife”. In the same year Morten graduated as MD from the University of Copenhagen and passed the American ECFMG-examination. Thereafter, he worked as a medical intern in in Kansas City. In 1972, he joined the Institute of Medical Anatomy at the University of Copenhagen as research assistant and received tenure as an associate professor in 1976. In 1987, he defended his thesis as Dr. Med. Sci and was promoted full professor in Neuroanatomy in 1994. From 2001 to 2010, Morten served as director of the Graduate School of Neuroscience, University of Copenhagen, and thereafter he was appointed by the University of Copenhagen as Director of the Research Training Programme in Neuroscience and kept this office until 2014. On October 1, 2015, Morten retired and became Professor emeritus, but even after his retirement, Morten was actively engaged in research. On his very last day in the laboratory (May 30, 2024) he worked with the stereotactic frame and discussed recent electron microscopic data and grant applications, before he was hit by a severe stroke from which he unfortunately did not recover.&lt;/p&gt;&lt;p&gt;Morten Møller's research focused on the functional morphology of neuroendocrine systems in the mammalian brain. He loved to work in the laboratory and mastered multiple methods: electron microscopy, immunohistochemistry, tracing techniques, receptor autoradiography, and in-situ hybridization. His initial studies investigated the pineal gland of human fetuses, in which he identified a central innervation establishing a direct connection between the pineal and the brain [&lt;span&gt;1&lt;/span&gt;]. In those days, the concept that the mammalian pineal organ is solely innervated by postganglionic sympathetic nerve fibers had become a dominating dogma, but Morten's work has clearly shown that, in addition, the mammalian pineal organ is innervated by a plethora of axons originating from the brain as well as from parasympathetic and sensory ganglia. This diversified innervation, which also employs several neuropeptides and acetylcholine, has been a major theme of his research [&lt;span&gt;2-6&lt;/span&gt;]. He has also contributed to studies demonstrating immunocytochemical similarities between retinal photoreceptors and pinealocytes that underpinned the concept of multiple types of mammalian pinealocytes [&lt;span&gt;7, 8&lt;/span&gt;] whose functional differences have been further elaborated by R","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111349","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":"Circadian Misalignment as a Determinant of Insomnia Severity: Possible Implications in Sleep Medicine Clinical Practice","authors":"Alessandro Colitta,&nbsp;Ugo Faraguna","doi":"10.1111/jpi.70085","DOIUrl":"https://doi.org/10.1111/jpi.70085","url":null,"abstract":"<div>\u0000 \u0000 <p>In this letter to the editor, we comment on the recently published study from Scott et al. (2025), which highlights circadian misalignment as a possible determinant of insomnia severity. Considering the robust methodology of this study and in light of recent research aiming at optimizing melatonin treatment schedules, our letter explores why these findings may pave the way towards an extension of current recommendations for melatonin administration in insomnia, while encouraging the quantification of circadian misalignment during sleep medicine clinical practice. Finally, possible methodologies to routinely assess circadian misalignment in insomnia patients are discussed.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110913","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":"Relationship Between Urinary 6-Sulfatoxymelatonin Rhythms and the Bone Resorption Marker Amino-Terminal Cross-Linked Telopeptide of Collagen I in Blind Women","authors":"Melissa A. St Hilaire,&nbsp;Erin E. Flynn-Evans,&nbsp;Shadab A. Rahman,&nbsp;Suzanne Higginbotham,&nbsp;Paula Witt-Enderby,&nbsp;Steven W. Lockley","doi":"10.1111/jpi.70079","DOIUrl":"10.1111/jpi.70079","url":null,"abstract":"<div>\u0000 \u0000 <p>Evidence exists for the daily rhythmicity of bone metabolism that may be influenced by melatonin production, reproductive hormones, the light/dark cycle, or all three, but the ability to determine their independent contributions is confounded by the synchrony of the sleep/wake and dark/light cycles with the endogenous circadian system in sighted individuals. Blind participants, who often have no circadian light perception and may exhibit desynchrony between their sleep/wake cycle and circadian system, provide an opportunity to study the independent contribution of melatonin and light on bone metabolism in a field-based setting. In this exploratory study, 35 pre-, peri-, and postmenopausal blind women (<i>N</i> = 13, 8, and 14, respectively) both with (<i>N</i> = 17) and without (<i>N</i> = 18) visual light perception (LP and NPL, respectively) who were either normally entrained (<i>N</i> = 19) or abnormally entrained or non-entrained (<i>N</i> = 16) to the 24-h day were randomly selected from a cohort of 130 visually impaired women. Levels of 6-sulfatoxymelatonin (aMT6s; ng/h) and the bone resorption marker amino-terminal cross-linked telopeptide of collagen I (NTx; BCE nM/h) were assayed from serial urine samples collected over 48 h and fit by a cosinor model to determine the presence of significant 24-h rhythms. Most blind women (<i>N</i> = 32/35, 91%) had a significant 24-h aMT6s rhythm (mean ± SD, 03:44 ± 4:27 hh:mm), but fewer women had a significant 24-h NTx rhythm (<i>N</i> = 20/35, 57%; 21:01 ± 5:50 hh:mm). There was no significant difference in the proportion of women with significant NTx rhythms by visual light perception status (LP: <i>N</i> = 10/17, 59% vs. NPL, N = 10/18, 56%), entrainment status (Entrained: <i>N</i> = 11/19, 58% vs. Abnormal or Not entrained: <i>N</i> = 9/16, 56%) or reproductive status (Premenopausal: <i>N</i> = 7/13, 54% vs. Perimenopausal: 5/8, 63% vs. Postmenopausal: 8/14, 57%). There was no correlation between the peak timings of aMT6s and NTx among the 17 participants with significant rhythms in both metabolites (<i>r</i> = 0.07, <i>p</i> = 0.80). NTx area under the curve was significantly higher among perimenopausal women with LP (<i>p</i> = 0.04). Our results do not support a direct influence of light, melatonin, or reproductive status on NTx rhythms, but the apparent increase of NTx in the perimenopausal period warrants further investigation.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074199","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":"Sequence Symmetry Analysis of the Interrelationships Between Ramelteon and Parkinson's Disease","authors":"Yoshihiro Noguchi,&nbsp;Rikuto Masuda,&nbsp;Tomoaki Yoshimura","doi":"10.1111/jpi.70080","DOIUrl":"https://doi.org/10.1111/jpi.70080","url":null,"abstract":"<div>\u0000 \u0000 <p>Parkinson's disease is the second most frequent neurodegenerative disease after Alzheimer's disease, and the most common neurodegenerative disease that causes movement dysfunction. Without innovations in prevention and treatment, the incidence and prevalence of Parkinson's disease is projected to increase by &gt; 30% by 2030, making the development of new treatments an urgent priority. We previously investigated the association between melatonin receptor agonists and Parkinson's disease using the US Food and Drug Administration's Adverse Event Reporting System (FAERS). The results showed that ramelteon may reduce the incidence of Parkinson's disease. However, since the US FAERS relies on spontaneous reports, which are susceptible to reporting bias, further validation using real-world data is required. This study investigated the association between ramelteon use and risk of developing Parkinson's disease using the DeSC database, a Japanese claims database reported to be representative of the general Japanese population. The association was evaluated using sequence symmetry analysis, with the adjusted sequence ratio (ASR) serving as the evaluation index. Our DeSC database analysis showed a negative association between ramelteon use and Parkinson's disease (ASR: 0.959, 95% confidence interval: 0.955–0.964). Our results support previous reports suggesting that ramelteon may help suppress the onset of Parkinson's disease. However, even though this study used real-world data, these results should be interpreted with caution, as a sequence symmetry analysis cannot be adjusted for covariates. Therefore, additional pharmacoepidemiological studies are needed to further verify the potential risk of Parkinson's disease associated with ramelteon use.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057997","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 Boosts the Phytochemical Profile of Blood Oranges, Enhancing (Poly)phenol and Endogenous Melatonin Content, Through Pre- and Postharvest Treatments","authors":"Fernando Garrido-Auñón,&nbsp;Pedro Antonio Padilla-González,&nbsp;María Serrano,&nbsp;Daniel Valero,&nbsp;Vicente Agulló","doi":"10.1111/jpi.70078","DOIUrl":"https://doi.org/10.1111/jpi.70078","url":null,"abstract":"<p>Nowadays, increasing consumer awareness of the link between diet and health has underscored the value of bioactive compounds in preventing metabolic disorders. In this frame, blood oranges are highly appreciated for their unique phytochemical profile, including anthocyanins along with flavanones with recognised health-promoting benefits. This study explores, for the first time, the combined effect of preharvest and postharvest melatonin treatments, along with cold storage, on the accumulation of endogenous melatonin, phenolic compounds and vitamin C in blood orange (<i>Citrus sinensis</i> L. Osbeck) cv. ‘Sanguinelli’. HPLC-QqQ-MS/MS and HPLC-DAD methodologies were used to analyse the bioactive compounds in leaves, flavedo, albedo and juice. The findings demonstrate that exogenous melatonin is an effective strategy to enhance the functional quality of blood oranges. Preharvest treatments increased endogenous melatonin levels in the leaves, flavedo and albedo, either by positive absorption or enhancement of biosynthetic pathways. However, postharvest melatonin treatments combined with cold storage led to the highest endogenous melatonin accumulation, suggesting a synergistic effect between exogenous supply and stress-induced biosynthesis. Furthermore, melatonin treatments promoted the accumulation of flavanones, anthocyanins and vitamin C, although cold storage remained the key driver of anthocyanin biosynthesis. These findings highlight the potential of melatonin as a natural elicitor to improve the functional quality of blood oranges, identifying preharvest melatonin treatment at 1 mM combined with cold storage as the most effective strategy. Nonetheless, further studies on bioavailability and bioactivity are required to determine whether these enhancements translate into greater health benefits for consumers.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038371","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 Ameliorates Circadian Disruption-Associated Dry Eye via Modulation of BMAL1-REV-ERBα-IL-17 Axis and Ocular Surface Microbiota Homeostasis","authors":"Bowen Wang,&nbsp;Hao Zeng,&nbsp;Xue Yang,&nbsp;Xin Zuo,&nbsp;Lihong Liang,&nbsp;Runze Zhang,&nbsp;Wenrui Deng,&nbsp;Rong Ju,&nbsp;Xiaoran Wang,&nbsp;Jin Yuan","doi":"10.1111/jpi.70076","DOIUrl":"https://doi.org/10.1111/jpi.70076","url":null,"abstract":"<div>\u0000 \u0000 <p>The association between modern lifestyle factors and dry eye disease (DED) pathogenesis has garnered increasing scientific attention. Emerging evidence implicates circadian disruption—a prevalent consequence of contemporary living patterns—as a significant yet not fully clarified pathogenic factor in DED development. To address this knowledge gap, we developed a circadian disruption mouse model using chronic jet lag exposure. Mice subjected to chronic jet lag exhibited conjunctival clock gene dysregulation and upregulated pro-inflammatory mediators, such as TNF-α, IL-6, and IL-17. Transcriptomic profiling demonstrated marked activation of IL-17-mediated inflammatory pathways within the conjunctival tissue. Therapeutic IL-17 neutralization substantially attenuated ocular surface inflammation, improved corneal epithelial integrity, and decreased apoptotic cell density in circadian disruption-induced dry eye mouse model. Moreover, REV-ERBα agonism potently suppressed IL-17 transcription, whereas BMAL1 deficiency exacerbated IL-17-driven inflammatory responses through REV-ERBα downregulation. Chronic jet lag additionally induced ocular surface microbiota dysbiosis, characterized by Firmicutes overproliferation. Melatonin administration effectively suppressed conjunctival IL-17 expression through BMAL1-REV-ERBα pathway activation while reducing the relative abundance of Firmicutes to restore ocular surface microbiota balance. Our study reveals that circadian disruption induces ocular surface inflammation through the BMAL1-REV-ERBα-IL-17 signaling axis and exacerbates dysbiosis of the ocular surface microbiota. Melatonin mitigates these pathological alterations via dual-directional modulation of circadian-immune signaling crosstalk and restoration of microbiota balance. Importantly, this study establishes melatonin as a multifaceted therapeutic agent for combating lifestyle-associated DED, while elucidating the underlying mechanisms governing circadian rhythm-microbiome axis dynamics in ocular surface pathogenesis.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038375","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}