Journal of Pineal Research最新文献

{"title":"Melatonin Suppresses Colorectal Cancer Alongside Coordinated Changes in H3K4me3Q5ser and m6A Modifications","authors":"Wanlu Zhang,&nbsp;Lin Yuan,&nbsp;Dawei Yu,&nbsp;Shihong Qi,&nbsp;Chang Liu,&nbsp;Dongxu Wang,&nbsp;Wenna Wang,&nbsp;Yi Zhang,&nbsp;Sihui Zhang,&nbsp;Liting Lu,&nbsp;Min Wu,&nbsp;Yongye Huang","doi":"10.1111/jpi.70192","DOIUrl":"10.1111/jpi.70192","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin has demonstrated antitumor activity in various cancer models, but its effects may depend on the therapeutic dose and cellular environment. We found that melatonin at millimolar concentrations significantly downregulated transglutaminase 2 (TGM2), histone serotonylation (H3K4me3Q5ser), and YTHDF1/m⁶A (N6-methyladenosine) in a colorectal cancer model. Cross-interference between TGM2 and YTHDF1 supports a link between these regulatory processes, while molecular docking, pharmacological interventions, and co-immunoprecipitation experiments suggest the existence of a signaling pathway involving melatonin and the HTR2B receptor. A combined analysis of CHIP-seq and meRIP-seq identified salt-induced kinase 1 (SIK1) as a potential downstream target, and SIK1 interference affected the proliferation and migration of colorectal cancer. Collectively, these findings support a working model in which melatonin-induced tumor suppression is associated with coordinated changes in TGM2/H3K4me3Q5ser and YTHDF1-associated m⁶A regulation, with SIK1 emerging as a potential convergent downstream effector.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 6","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163652","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 Coordinates Root Cell-Wall Zinc Remobilization and Shoot Transport via Nitric Oxide Signaling Under Zinc Deficiency in Rice","authors":"Jing Huang,&nbsp;Qi Cheng Lu,&nbsp;Wei Huang,&nbsp;Hao Yu Wang,&nbsp;Dao Bo Wang,&nbsp;Ren Fang Shen,&nbsp;Lu Zheng,&nbsp;Xiao Fang Zhu","doi":"10.1111/jpi.70191","DOIUrl":"10.1111/jpi.70191","url":null,"abstract":"<div>\u0000 \u0000 <p>Although zinc (Zn) deficiency severely inhibits rice growth, it remains unclear how melatonin (MT) promotes adaptation under conditions of insufficient Zn supply. To address this issue, rice seedlings were treated with MT, the NO donor sodium nitroprusside (SNP), or the NO scavenger c-PTIO, alone or in combination, under Zn-deficient conditions. Zn starvation rapidly promoted endogenous MT accumulation in rice roots, together with a 90.2%–179.5% rise in the transcript levels of MT biosynthetic genes. Exposure to Zn deprivation reduced root/shoot length and root/shoot biomass, by 46.2%/31.3% and 27.5%/39.6%, respectively. Among the tested concentrations, 10 μM MT produced the strongest protective effect, increasing root length, shoot height, root biomass, and shoot biomass by 59.9%, 34.2%, 21.7%, and 51.8%, respectively, relative to plants that were merely deficient in Zn. In Zn-deficient plants, MT raised Zn concentration in root and shoot both by 16.2% and xylem sap Zn concentration by 15.6%. MT also increased root cell-wall Zn content, pectin abundance, and pectin-associated Zn by 20.0%, 39.3%, and 31.9%, respectively. At the expression level, MT moderated the induction of <i>OsZIP4</i>, <i>OsZIP5</i>, <i>OsZIP8</i>, <i>OsZIP9</i>, <i>OsZIP10</i>, and <i>OsHMA3</i> by Zn deficiency and further repressed <i>OsZIP1</i>, implying feedback regulation of the Zn-homeostasis network instead of direct activation of Zn-transporter transcription. Root NO content rose by 29.8% after MT treatment, and SNP elicited increases in root and shoot Zn concentrations comparable to those associated with MT. Overall, the data suggest that an NO-associated response contributes to MT-mediated Zn-deficiency tolerance by restoring Zn homeostasis, promoting apoplastic Zn remobilization and root-to-shoot transport, and limiting oxidative damage.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 6","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134447","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":"MRI Visualization of Melatonin-Promoted Oligodendrogenesis and Its Neuroprotective Effects in Preterm White Matter Injury Rat Model","authors":"Xiaozu Zhang,&nbsp;Peilun Xiao,&nbsp;Xiaotian Gao,&nbsp;Haimo Zhang,&nbsp;Zhigang Yang,&nbsp;Youcheng Qin,&nbsp;Chunlei Zhang,&nbsp;Yinuo Li,&nbsp;Xin Wang,&nbsp;Jing Sui,&nbsp;Xiaoli Wang","doi":"10.1111/jpi.70190","DOIUrl":"10.1111/jpi.70190","url":null,"abstract":"<div>\u0000 \u0000 <p>Preterm white matter injury (PWMI) is a serious neurologic condition that threatens neonatal survival and severely impairs the cognitive and motor development of affected children. Melatonin (Mel), a neuroendocrine hormone with anti-inflammatory and antioxidant properties, has shown neuroprotective potential in neonatal brain injury, although the mechanisms underlying its effects in PWMI remain incompletely understood. In this study, we established a neonatal rat model of PWMI and combined multimodal magnetic resonance imaging (MRI) with histological analyses to investigate the effects of Mel on oligodendrocyte precursor cells (OPCs) proliferation, differentiation, and subsequent white matter development. We discovered that Mel administration increased cerebral oxygenation and blood flow, thereby altering the cerebral metabolic microenvironment and mitigating white matter damage caused by hypoxic–ischemic injury. Moreover, Mel promoted the proliferation of OPCs and exerted neuroprotective effects by activating the protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK-3β)/β-catenin signaling pathway. In addition, Mel treatment facilitated neural fiber formation in distant white matter regions of PWMI models, ultimately alleviating cognitive and motor impairments in affected rats. Collectively, these findings suggest that Mel facilitates oligodendrogenesis and white matter repair after PWMI, at least in part through modulation of the AKT/GSK-3β/β-catenin pathway. Multimodal MRI can provide a useful noninvasive approach for monitoring treatment-related changes in white matter injury and development, supporting further investigation of Mel as a potential therapeutic strategy for PWMI.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 6","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101749","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":"Influence of Intravenous Norepinephrine Administration on Melatonin Plasma Concentration in Awake and Anaesthetised Healthy Adult Volunteers","authors":"Marko MIrza Sahinovic,&nbsp;Ilonka Nadia de Keijzer,&nbsp;Manon Stern,&nbsp;Karin Marianne Vermeulen,&nbsp;Michel Maria Roger Fernand Struys,&nbsp;Anthony Ray Absalom,&nbsp;Johannes Pieter van den Berg,&nbsp;Jaap Jan Vos","doi":"10.1111/jpi.70188","DOIUrl":"https://doi.org/10.1111/jpi.70188","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Melatonin (MEL) is an endogenous hormone that regulates circadian rhythm, immune function and oxidative stress responses. Norepinephrine (NE), an endogenous catecholamine, increases blood pressure through the sympathetic nervous system and is commonly administered intraoperatively or in the clinically ill patient for hemodynamic support. Although endogenous NE is known to stimulate MEL synthesis, the effects of exogenous intravenous NE on plasma MEL concentration, particularly under general anaesthesia (GA), remain poorly characterised. This study examined the influence of intravenous NE on plasma MEL concentrations in healthy volunteers, both awake and under general anaesthesia. A secondary analysis was conducted using data from a prospective, single-centre, cross-over study involving volunteers who received stepwise NE infusions while awake and under total intravenous general anaesthesia. Arterial blood samples were collected to determine plasma MEL and NE concentrations. Linear mixed-effects modelling was used to assess the relationship between NE and MEL concentrations. A total of 36 healthy volunteers were enroled, yielding 417 MEL-NE samples. Intravenous NE administration was significantly associated with higher plasma MEL concentration, corresponding to an estimated 26% increase in MEL per 1 standard-deviation increase in NE concentration (Estimate = 0.230, <i>p</i> &lt; 0.001). MEL concentrations were approximately 43% higher in the awake phase compared to GA (Estimate = 0.356, <i>p</i> &lt; 0.001). GA did not significantly modify the NE-MEL association (Estimate = −0.02877, <i>p</i> = 0.528). Substantial positive correlation was observed between baseline MEL concentrations and the magnitude of the response to NE administration (<i>r</i> = 0.74). In conclusion, intravenous NE increases plasma MEL concentrations in both awake and anaesthetised individuals. Substantial interindividual variation in MEL response suggests underlying physiological differences. Future studies should explore the long-term effects of NE administration on MEL concentrations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 <p><b>Trial Registration:</b> The study is registered in the Dutch Trial Register (NL9312).</p>\u0000 </section>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 6","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072580","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":"OsCSA Acts as an Upstream Activator of OsCOMT12 to Positively Regulate Copper Stress Tolerance in Rice","authors":"Wenli Lian,&nbsp;Huimin Han,&nbsp;Anjing Geng,&nbsp;Qixin Yang,&nbsp;Shaolong Liu,&nbsp;Chunfeng Cai,&nbsp;Xiaojie Zhao,&nbsp;Xu Wang,&nbsp;Guang Chen","doi":"10.1111/jpi.70187","DOIUrl":"https://doi.org/10.1111/jpi.70187","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin (MT) is a secondary metabolite that plays a role in environmental stress response in plants. However, the physiological and molecular mechanisms by which MT alleviates excessive copper (Cu) toxicity in rice (<i>Oryza sativa</i>) remain unknown. Herein, exogenous MT application increased root and shoot biomass and inhibited the expression of Cu uptake-associated genes, thereby reducing the Cu uptake capacity of the root and Cu concentration <i>in vivo</i> and effectively enhancing Cu stress tolerance compared with Cu treatment. Transcriptome analysis revealed the essential transcription factor <i>CARBON STARVED ANTHER</i> (<i>OsCSA</i>) as responsive to Cu stress. Compared with the wild type, <i>OsCSA</i> overexpression lines exhibited significantly enhanced Cu tolerance, which was manifested by increased MT content, up-regulated expression of the reactive oxygen species (ROS) scavenging genes <i>CATALASE C</i> and <i>ASCORBATE PEROXIDASE</i>, elevated activities of catalase, superoxide dismutase, and ascorbate peroxidase, and decreased hydrogen peroxide and malondialdehyde content. <i>OsCSA</i>-knockout plants showed the opposite results, and exogenous MT rescued its excessive Cu-sensitive phenotype. Further experiments established that OsCSA directly binds to the GTTA/TAAC element of <i>CAFFEIC ACID O-METHYLTRANSFERASE 12</i> (<i>OsCOMT12</i>) promoter, up-regulating its expression. Under Cu stress, significant increases in Cu concentration and ROS accumulation were also observed in loss-of-function <i>oscomt12</i> mutants, consistent with the results observed in <i>OsCSA</i>-knockout lines. Additionally, knockout of <i>OsCOMT12</i> in the <i>OsCSA</i>-overexpression background abolished the positive effect of <i>OsCSA</i> on Cu stress tolerance. These findings establish the OsCSA–OsCOMT12 regulatory module as a new mechanism for MT-mediated Cu stress response in rice, providing a target for genetic improvement of Cu-tolerant crops.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 6","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072579","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":"RETRACTION: Inhibitory Effect of Melatonin on Necroptosis via Repressing the Ripk3-PGAM5-CypD-mPTP Pathway Attenuates Cardiac Microvascular Ischemia–Reperfusion Injury","authors":"","doi":"10.1111/jpi.70186","DOIUrl":"10.1111/jpi.70186","url":null,"abstract":"<p><b>RETRACTION</b>: H. Zhou, D. Li, P. Zhu, Q. Ma, S. Toan, J. Wang, S. Hu, Y. Chen, and Y. Zhang, “Inhibitory Effect of Melatonin on Necroptosis via Repressing the Ripk3-PGAM5-CypD-mPTP Pathway Attenuates Cardiac Microvascular Ischemia–Reperfusion Injury,” <i>Journal of Pineal Research</i> 65, no. 3 (2018): e12503, https://doi.org/10.1111/jpi.12503.</p><p>The above article, published online on 28 May 2018, in Wiley Online Library (https://onlinelibrary.wiley.com/) has been retracted by agreement between the journal Editor-in-Chief, Gianluca Tosini; and John Wiley and Sons Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate duplications of image panels of Figures 2A, 4A and 7A between this and other articles that were published either around the same time or later by different author groups, depicting different experimental conditions. Further review identified additional issues, including undisclosed splicing in Figure 1J, 4B and 5I, as well as image section insertions in Figure 4A and E. As a result, the editors have lost confidence in the integrity of the data and consider the conclusions of the manuscript to be substantially compromised. The authors and their institution were informed of these concerns and the retraction decision, but remained unresponsive.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 5","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007633","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":"Multi-Omics Analysis Provides Insights Into the Molecular Mechanism of Melatonin-Mediated Cadmium Tolerance in Populus tomentosa","authors":"Li Sun,&nbsp;Jiaqi An,&nbsp;Tengyue Yan,&nbsp;Tao Wang,&nbsp;Xiaochun Shu,&nbsp;Zhong Wang,&nbsp;Hui Li,&nbsp;Weibing Zhuang","doi":"10.1111/jpi.70184","DOIUrl":"10.1111/jpi.70184","url":null,"abstract":"<div>\u0000 \u0000 <p>Cadmium (Cd) contamination, a major constraint on plant growth, causes a serious threat to ecological safety. <i>Populus tomentosa</i> is a promising woody species for Cd phytoremediation, but the mechanism of Cd phytoremediation by melatonin (MT) in this species remains unclear. To elucidate how MT confers Cd tolerance in <i>P. tomentosa</i>, four treatments (control, MT: 100 μmol·L⁻¹ melatonin, Cd: 100 μmol·L⁻¹ CdCl₂, and MT + Cd, CM: 100 μmol·L⁻¹ CdCl₂ + 100 μmol·L⁻¹ melatonin) on seedlings were conducted, and integrated analyses of physiological traits, noninvasive micro-test (NMT) data, transcriptomes, and metabolomes were further performed. Cd stress significantly inhibited seedling growth, reduced chlorophyll content, promoted excessive Cd accumulation, and triggered a burst of reactive oxygen species (ROS). Exogenous MT application reversed Cd-induced growth suppression by promoting root Cd²⁺ efflux while reducing Cd influx, decreasing Cd deposition in leaves, and activating superoxide dismutase and peroxidase to scavenge ROS under Cd treatment. Transcriptomic and metabolomic profiling suggested that metabolic pathways, including hormone signaling, glutathione metabolism, and phenylpropanoid biosynthesis, might be participated in the MT-mediated Cd response. Furthermore, three transcription factors, ERF098, bHLH041, and MYB308, were also identified as candidate regulators of MT-mediated Cd detoxification. Heterologous expression in yeast revealed that <i>MYB308</i> not only enhanced Cd tolerance but also reduced Cd accumulation under Cd stress. These findings elucidate the multilayered regulatory network underlying MT-enhanced Cd tolerance in <i>P. tomentosa</i>, and provide genetic resources for breeding Cd-resistant tree varieties and theoretical guidance for remediating Cd-contaminated soils.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 5","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987335","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 Alleviates Diabetic Cardiomyopathy by Inhibiting Cellular Senescence via Activation of the MT2/SIRT1/Nrf2 Signaling Pathway","authors":"Fang Liu,&nbsp;Ailing Zhong,&nbsp;Jinyu Li,&nbsp;Qiang Sun,&nbsp;Xue Fan,&nbsp;Wenjun Fan,&nbsp;Xin Tong,&nbsp;Yuchen Liang,&nbsp;Xiaoshan Wang,&nbsp;Danmei Huang,&nbsp;Yanmei Zhang,&nbsp;Fenfei Gao,&nbsp;Binger Lu,&nbsp;Bin Wang","doi":"10.1111/jpi.70185","DOIUrl":"10.1111/jpi.70185","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetic cardiomyopathy (DCM) is one of the most severe cardiovascular complications of diabetes mellitus (DM), yet effective treatment strategies remain lacking. Cellular senescence is a principal risk factor for multiple cardiovascular diseases, contributing significantly to cardiac dysfunction and disease progression. Melatonin, an endogenous hormone primarily secreted by the pineal gland, exerts cardioprotective effects against DCM. However, the underlying molecular mechanism remains incompletely understood, particularly whether melatonin ameliorates DCM by suppressing cardiomyocyte senescence. In this study, a streptozotocin (STZ)‑induced diabetic mouse model in vivo and an in vitro model of high‑glucose (HG)‑treated primary neonatal rat cardiomyocytes (NRCMs) were established. Melatonin ameliorated cardiac dysfunction in diabetic mice and alleviated the senescence phenotype in cardiomyocytes. Suppressing oxidative stress with the ROS scavenger N-acetylcysteine (NAC) effectively attenuated cardiomyocyte senescence, confirming the causal role of oxidative stress in senescence progression under HG conditions. Mechanistically, melatonin effectively upregulated the expression of melatonin receptor 1B (MT2), thereby activating the SIRT1/Nrf2 signaling pathway and promoting Nrf2 nuclear translocation. Notably, genetic ablation of <i>Nrf2</i> in diabetic mice, as well as pharmacological inhibition of MT2, SIRT1, or Nrf2 in NRCMs, substantially abolished the protective effects of melatonin. Collectively, melatonin alleviates DCM by attenuating oxidative stress-induced cellular senescence through activation of the MT2/SIRT1/Nrf2 signaling pathway. These findings uncover a novel mechanism underlying the cardioprotective action of melatonin against DCM.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 5","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975470","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 Inhibits Metastasis of Sunitinib-Resistant Renal Cell Carcinoma Cells Via the GRP78/p38/CTSD Expression","authors":"Po-Yu Huang,&nbsp;Yi-Hsien Hsieh,&nbsp;Yong-Syuan Chen,&nbsp;Tung-Wei Hung,&nbsp;Hui-Ling Chiou,&nbsp;Pei-Ni Chen,&nbsp;Chun-Wen Cheng,&nbsp;Jen-Pi Tsai","doi":"10.1111/jpi.70183","DOIUrl":"10.1111/jpi.70183","url":null,"abstract":"<div>\u0000 \u0000 <p>Sunitinib resistance contributes to poor outcomes in advanced renal cell carcinoma (RCC). This study investigated the anti-metastatic effects and underlying mechanisms of melatonin in sunitinib-resistant (SR)-RCC. Melatonin significantly inhibited the migration and invasion of A498-SR and Caki-1-SR cells. SR-RCC cells exhibited elevated CTSD expression, impaired endoplasmic reticulum (ER) stress signaling with reduced GRP78 and IRE1α, and enhanced p38 MAPK activation, all of which were reversed by melatonin. Silencing p38 MAPK further potentiated the inhibitory effects of melatonin on cell migration and invasion. Mechanistically, CTSD expression was regulated through both GRP78/p38 MAPK-mediated ER stress. <i>In vivo</i>, melatonin markedly reduced lung metastasis of Caki-1-SR cells without causing significant toxicity to major organs. Collectively, these findings demonstrate that melatonin inhibited the metastatic potential of SR-RCC by decreasing CTSD expression, restoring ER stress response, and decreasing p38 MAPK expression, supporting its potential as an anti-metastatic therapeutic agent for SR-RCC</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 5","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917618","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":"ENLIGHTENme: Translating the Benefits of Self-Administered Daytime Light Supplementation to Older Adults in the Real World","authors":"Débora B. Constantino,&nbsp;Flavia Baccari,&nbsp;Leonardo Caporali,&nbsp;Valerio Carelli,&nbsp;Giulia Amore,&nbsp;Marijke Gordijn,&nbsp;Toomas Haller,&nbsp;Chiara La Morgia,&nbsp;Anne Landvreugd,&nbsp;Marina Marinelli,&nbsp;David McDaid,&nbsp;Monika Nõmm,&nbsp;Francesco Nonino,&nbsp;Martina Romagnoli,&nbsp;Martino Schettino,&nbsp;Corrado Zenesini,&nbsp;Meike Bartels,&nbsp;Debra J. Skene,&nbsp;Daan R. van der Veen","doi":"10.1111/jpi.70174","DOIUrl":"10.1111/jpi.70174","url":null,"abstract":"<p>Controlled studies have demonstrated that light supplementation benefits circadian entrainment, sleep and mood. Translating these findings into effective, real-world usage of light supplementation is, however, challenging because naturalistic and supplemental light exposure are shaped by personal habits and environmental light conditions. Bridging this translation gap is especially critical for older adults, given the reduced ocular light sensitivity associated with natural ageing, which exacerbates low daytime indoor light exposure in urban housing. We therefore set out to investigate the determinants of self-directed light supplementation in this population, and what the real-world feasibility and efficacy of daytime light supplementation is. We recruited 202 participants (63–92 years; 139 females) to our interventional, prospective, randomised study in three major EU cities at different latitudes (Amsterdam, Bologna, Tartu). Participants underwent a 2-week baseline assessment of light exposure, rest–activity patterns and sleep through wearables and daily diaries. Participants were then randomised to either 12 weeks of self-implemented indoor light supplementation using a lamp placed in their most frequently used room (&gt; 8000 melanopic EDI, <i>N</i> = 98) or a no-intervention group. A subsequent 2-week reassessment showed that greater naturalistic light exposure was associated with increased daytime activity, consolidated wakefulness, better subjective sleep quality, and reduced metabolic disorder incidence. Individuals with lower naturalistic light exposure self-initiated earlier and longer indoor light supplementation across seasons, in which supplementation onset before 10:00 was associated with greater daytime activity and lower rest–activity fragmentation. These results confirm that this simple, non-pharmacological, and low-cost intervention has broad potential to support healthy ageing in urban settings.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"78 5","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878670","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}