Journal of Pineal Research最新文献

{"title":"IAT4, a New Indolamine N-Acetyltransferase in Saccharomyces cerevisiae Involved in Melatonin Biosynthesis","authors":"Andrés Planells-Cárcel,&nbsp;Sandra Sánchez-Martí,&nbsp;Sara Muñiz-Calvo,&nbsp;José Manuel Guillamon","doi":"10.1111/jpi.70053","DOIUrl":"https://doi.org/10.1111/jpi.70053","url":null,"abstract":"<p>Melatonin synthesis by yeast has been described on several occasions, mainly in a fermentative context. However, the genetic determinants involved in its synthesis remain undefined. Understanding melatonin synthesis in yeast is important because it can provide insights into the broader mechanisms of indolamine production, which has implications for both basic biological research and industrial applications. Although two genes with <i>N</i>-acetyltransferase (NAT) activity (<i>PAA1</i> and <i>HPA2</i>) have been identified in <i>Saccharomyces cerevisiae</i>, these genes do not seem to be major contributors to the production of melatonin and other indolamines in yeast in vivo. In this study, we identified the uncharacterized gene YDR391C as the gene encoding a protein with NAT activity, herein named <i>IAT4</i>. By comparing different substrates using the purified Iat4, we found that the <i>K</i>_<i>m</i> values were 353, 356, and 930 µM towards 5-methoxytryptamine, tryptamine, and serotonin, respectively. The substrate affinity of Iat4 towards serotonin was approximately five times higher than that reported for the previous homolog of the melatonin enzyme arylalkylamine <i>N</i>-acetyltransferase (<i>PAA1</i>), suggesting that <i>IAT4</i> could play a more significant role in melatonin biosynthesis. This enhanced affinity could lead to more efficient production of <i>N</i>-acetylserotonin, potentially improving yields in biotechnological applications. Finally, we demonstrate the conversion of serotonin into microbially-produced <i>N</i>-acetylserotonin by overexpressing <i>IAT4</i> in a serotonin-overproducing yeast strain at a titer of 14.5 mg/L. These findings represent the first steps towards the development of yeast strains optimized for the biological production of <i>N</i>-acetylserotonin and related compounds, which might aid in studying the regulatory mechanisms and functions related to melatonin biosynthesis in <i>S. cerevisiae</i> and other yeast species.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925806","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 Supplementation Alleviates Bone Mineral Density Decline and Circulating Oxidative Stress in Iron-Overloaded Thalassemia Patients","authors":"Pokpong Piriyakhuntorn,&nbsp;Adisak Tantiworawit,&nbsp;Mattabhorn Phimphilai,&nbsp;Tawika Kaewchur,&nbsp;Piangrawee Niprapan,&nbsp;Bhumrapee Srivichit,&nbsp;Nattayaporn Apaijai,&nbsp;Krekwit Shinlapawittayatorn,&nbsp;Nipon Chattipakorn,&nbsp;Siriporn C. Chattipakorn","doi":"10.1111/jpi.70055","DOIUrl":"https://doi.org/10.1111/jpi.70055","url":null,"abstract":"<div>\u0000 \u0000 <p>Thalassemia patients often exhibit low bone mineral density (BMD). The iron overload associated with thalassemia elevates oxidative stress levels, leading to reduced BMD. Melatonin improves BMD in postmenopausal osteopenia, however, its effect on BMD in thalassemia patients with iron overload has not been investigated. A randomized controlled study was conducted at Hematology Clinic, Faculty of Medicine, Chiang Mai University. Thalassemia patients with osteopenia and iron overloaded condition, as indicated by BMD Z-score &lt;−2 at <span>l</span>-spine, femoral neck, or total hip, and serum ferritin level &gt; 500 μg/L were recruited in this study. Patients were randomized to receive either melatonin 20 mg/day or placebo at bedtime for 12 months. BMD was re-evaluated 12 months after interventions. Bone turnover markers (BTM), malondialdehyde (MDA as an oxidative stress marker), and pain scores were assessed at baseline, 6, and 12 months. The outcomes, including BMD, BTM, MDA, and pain scores, were evaluated in all patients. Forty-one thalassemia patients (18 males) were enrolled in the study and randomly assigned to either the melatonin group (<i>n</i> = 21) or the placebo group (<i>n</i> = 20). Characteristics of patients were not differences between groups. Mean age was 30.8 ± 6.2 years old. Thirty-three patients (80.4%) were transfusion-dependent patients. At 12 months, mean BMD at <span>l</span>-spine in melatonin group was not significantly different from placebo group (<i>p</i> = 0.069). However, <span>l</span>-spine BMD at 12 months in the melatonin group was significantly greater than baseline (<i>p</i> = 0.029). Serum levels of P1NP and MDA were significantly reduced at 6 months compared to baseline following melatonin treatment. The melatonin group experienced a notable decrease in back pain scores after 12 months compared to the initial measurements. 20 mg daily melatonin supplementation for 12 months alleviated <span>l</span>-spine BMD loss in iron-overloaded thalassemia with low BMD. Melatonin also significantly reduced circulating oxidative stress and mitigated back pain in these patients.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914579","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":"Evaluating Melatonin's Effects on Hepatocyte Lipidome: A Critique of Analytical Methods","authors":"Yoshiyasu Takefuji","doi":"10.1111/jpi.70054","DOIUrl":"https://doi.org/10.1111/jpi.70054","url":null,"abstract":"","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904964","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: Adipocyte Differentiation Is Inhibited by Melatonin Through the Regulation of C/EBPβ Transcriptional Activity","authors":"","doi":"10.1111/jpi.70050","DOIUrl":"https://doi.org/10.1111/jpi.70050","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN</b>: M. I. C. Alonso-Vale, S. B. Peres, C. Vernochet, S. R. Farmer and F. B. Lima, “Adipocyte Differentiation Is Inhibited by Melatonin Through the Regulation of C/EBPβ Transcriptional Activity,” <i>Journal of Pineal Research</i> 47, no. 3 (2009): 221-227, https://doi.org/10.1111/j.1600-079X.2009.00705.x.</p><p>This Expression of Concern is for the above article, published online on 03 September 2009 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. The Expression of Concern has been agreed due to concerns regarding the C/EBPα panel of the western blot shown in Figure 1 and the Perilipin panel in Figure 2. The authors provided an explanation and some data but this was not sufficient to resolve the issue. Therefore, the journal has decided to issue an Expression of Concern to inform and alert the readers about potential data inconsistencies in Figures 1 and 2.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889147","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 and Exercise Restore Myogenesis and Mitochondrial Dynamics Deficits Associated With Sarcopenia in iMS-Bmal1−/− Mice","authors":"Yolanda Ramírez-Casas,&nbsp;José Fernández-Martínez,&nbsp;María Martín-Estebané,&nbsp;Paula Aranda-Martínez,&nbsp;Alba López-Rodríguez,&nbsp;Sergio Esquivel-Ruiz,&nbsp;Yang Yang,&nbsp;Germaine Escames,&nbsp;Darío Acuña-Castroviejo","doi":"10.1111/jpi.70049","DOIUrl":"https://doi.org/10.1111/jpi.70049","url":null,"abstract":"<div>\u0000 \u0000 <p>Sarcopenia, a condition associated with aging, involves progressive loss of muscle mass, strength, and function, leading to impaired mobility, health, and increased mortality. The underlying mechanisms remain unclear, which limits the development of effective therapeutic interventions. Emerging evidence implicates chronodisruption as a key contributor to sarcopenia, emphasizing the role of <i>Bmal1</i>, a circadian clock gene critical for muscle integrity and mitochondrial function. In a skeletal muscle-specific and inducible <i>Bmal1</i> knockout model (iMS-<i>Bmal1</i>^−/−), we observed hallmark features of sarcopenia, including disrupted rhythms, impaired muscle function, and mitochondrial dysfunction. Exercise and melatonin treatment reversed these deficits independently of <i>Bmal1</i>. Building on these findings, the present study elucidates several mechanisms underlying these changes and the pathways by which melatonin and exercise exert their beneficial effects. Our findings indicate that iMS-<i>Bmal1</i>^−/− mice exhibit reduced expression of satellite cell and muscle regulatory factors, indicating impaired muscle regeneration. While mitochondrial respiration remained unchanged, notable alterations in mitochondrial dynamics disrupted mitochondria in skeletal muscle. In addition, these mice showed alterations in muscle energy metabolism, compromised antioxidant defense, and inflammatory response. Remarkably, exercise and/or melatonin successfully mitigated these deficits, restoring muscle health in <i>Bmal1</i>-deficient mice. These findings position exercise and melatonin as promising therapeutic candidates for combating sarcopenia and emphasize the need to elucidate the molecular pathways underlying their protective effects.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840889","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":"Cell-Type-Specific mRNA N6-Methyladenosine Landscape and Regulatory Mechanisms Underlying Immune Dysregulation of Sleep-Deprived","authors":"Yakun Liu,&nbsp;Zhe Wang,&nbsp;Sha Liu,&nbsp;Xinrong Li,&nbsp;Denggao Wang,&nbsp;Dan Wang,&nbsp;Ying Li,&nbsp;Chaojie Liu,&nbsp;Yong Xu","doi":"10.1111/jpi.70046","DOIUrl":"https://doi.org/10.1111/jpi.70046","url":null,"abstract":"<div>\u0000 \u0000 <p>Sleep deprivation impairs daytime cognitive functioning and is a risk factor for various diseases related to immune dysregulation. N⁶-methyladenosine (m⁶A) is a common epigenetic RNA modification with essential roles in regulating neurogenesis and circadian rhythms. m⁶A dysregulation resulting in immune imbalance has received much attention. In this study, we elucidated the landscape and specific mechanisms of m⁶A regulators in the peripheral blood of patients with sleep deprivation through RNA sequencing and single-cell transcriptomics data sets. We observed that m⁶A regulator upregulation aggravated sleep loss and immune disorders. Women were more sensitive to sleep deprivation. Notably, m⁶A regulator <i>ALKBH5</i> was downregulated in peripheral blood mononuclear cells (PBMC) of patients with sleep deprivation at the transcriptome level. However, <i>ALKBH5</i> was cell-type specific upregulated in T cells (TC), B cells (BC), and natural killer (NK) cells, involving the dysregulation of acquired immune mechanisms by aberrant cell–cell communication that mediated ligand–receptor interactions across diverse cell types. Furthermore, the immune dysregulation of sleep loss could be regulated by a potential pathway between ALKBH5 and CD99 in SH-SY5Y and HT22 cells. Sleep deprivation group CD3⁺/CD45⁺ T cells had higher levels of <i>ALKBH5</i> mRNA than the control group. This study demonstrated that abnormal m⁶A modification patterns caused by m⁶A regulators play a key role in the dysregulation of innate and acquired immunity in sleep deprivation.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818640","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":"Circadian Rhythm Disruption in Triple-Negative Breast Cancer: Molecular Insights and Treatment Strategies","authors":"Li-Hua He,&nbsp;Xin-Yi Sui,&nbsp;Yu-Ling Xiao,&nbsp;Peng Ji,&nbsp;Yue Gong","doi":"10.1111/jpi.70042","DOIUrl":"https://doi.org/10.1111/jpi.70042","url":null,"abstract":"<div>\u0000 \u0000 <p>Disruption of the circadian clock has been closely linked to the initiation, development, and progression of cancer. This study aims to explore the impact of circadian rhythm disruption (CRD) on triple-negative breast cancer (TNBC). We analyzed bulk and single-cell RNA sequencing data to assess circadian rhythm status in TNBC using multiple bioinformatic tools, alongside metabolomic profiles and tumor microenvironment evaluations to understand the influence of CRD on metabolic reprogramming and immune evasion. The results indicate that TNBC experiences profound CRD. Patients with a higher CRDscore exhibit significantly poorer relapse-free survival compared to those with a lower CRDscore. Cyclic ordering by periodic structure (CYCLOPS) identified significant changes in rhythmic gene expression patterns between TNBC and normal tissues, with TNBC showing a “rush hour” effect, where peak expression times are concentrated within specific time windows. Transcripts with disrupted circadian rhythms in TNBC were found to be involved in key pathways related to cell cycle regulation, metabolism, and immune response. Metabolomic analysis further revealed that TNBCs with high CRDscore are enriched in carbohydrate and amino acid metabolism pathways, notably showing upregulation of tryptophan metabolism. High CRDscore was also linked to an immunosuppressive tumor microenvironment, characterized by reduced immune cell infiltration, exhausted CD8⁺ T cells, and a diminished response to immune checkpoint blockade therapy. These findings suggest that the disrupted molecular clock in TNBC may activate tryptophan metabolism, thereby promoting immune evasion and potentially reducing the effectiveness of immunotherapy.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787171","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 Repairs the Lipidome of Human Hepatocytes Exposed to Cd and Free Fatty Acid-Induced Lipotoxicity","authors":"Anna Migni,&nbsp;Desirée Bartolini,&nbsp;Giada Marcantonini,&nbsp;Roccaldo Sardella,&nbsp;Mario Rende,&nbsp;Alessia Tognoloni,&nbsp;Maria Rachele Ceccarini,&nbsp;Francesco Galli","doi":"10.1111/jpi.70047","DOIUrl":"https://doi.org/10.1111/jpi.70047","url":null,"abstract":"<p>Hepatocyte lipotoxicity is central to the aetiology of nonalcoholic fatty liver disease (NAFLD), a leading cause of liver failure and transplantation worldwide. Long-lasting toxic pollutants have increasingly been considered as environmental risk factors of NAFLD. These include cadmium (Cd), a metal that synergizes with other cellular toxicants and metabolic stimuli to induce fat build-up and lipotoxicity. Recent studies demonstrated that melatonin (MLT) holds great potential as repairing agent in this form of hepatocyte lipotoxicity. In this study, the molecular hints of this MLT effect were investigated by lipidomics analysis in undifferentiated HepaRG cells, a human pre-hepatocyte cell line, exposed to Cd toxicity either alone or combined with prototypical free fatty acids (FFA), namely the saturated species palmitic acid and the monounsaturated oleic acid (OA and PA, respectively), to simulate the cellular lipotoxicity conditions of fatty liver disease. Cd exposure synergized with FFAs to induce cellular steatosis, and PA produced higher levels of lipotoxicity compared to OA by leading to increased levels of H₂O₂ production and apoptotic death. These effects were associated with changes of the cellular lipidome, which approximate those of NAFLD liver, with differentially expressed lipids in different classes that included triacylglycerols (TG), di- and mono-acylglycerols, phospholipids (PL), sphingolipids, acylcarnitines and FA; characteristic differences were observed in all these classes comparing the combinations of Cd exposure with PA or OA treatments. MLT significantly reduced the effects of either individual or combinatorial treatments of Cd and FFAs on lipotoxicity hallmarks, also repairing most of the alterations of the cellular lipidome, including those of the chain length and number of double bonds of acyl residues esterified to TG and PL classes. These findings and their bioinformatics interpretation suggest a role for the earliest acyl elongase and desaturase steps of FA metabolism in this repairing effect of MLT; biochemistry studies validated such interpretation identifying a specific role for SCD1 activity. This lipidomics study shed light on the cytoprotective mechanism of MLT in Cd and FFA-induced hepatocyte lipotoxicity, highlighting a repairing effect of this molecule on the cellular lipidome, which may hold therapeutic potential in fatty liver diseases.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787168","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":"Identification of a COMT Gene Involved in the Biosynthesis of Melatonin Which Mediates Resistance to Citrus Canker","authors":"Kun Yang,&nbsp;Wenqing Xu,&nbsp;Huanyu Cai,&nbsp;Xiaomei Tang,&nbsp;Xiaoyan An,&nbsp;Chunyang He,&nbsp;Huailong Teng,&nbsp;Qiang Xu,&nbsp;Yuantao Xu","doi":"10.1111/jpi.70043","DOIUrl":"https://doi.org/10.1111/jpi.70043","url":null,"abstract":"<div>\u0000 \u0000 <p>Citrus canker, caused by <i>Xanthomonas citri</i> subsp <i>citri</i> (<i>Xcc</i>), represents a severe threat to the citrus industry. The conventional control measures for citrus canker primarily rely on chemical bactericide. However, overuse of bactericide will cause environmental and food security concerns. To address this problem, efforts are being made to develop environmentally friendly bio-bactericide alternatives. In this study, we identified a caffeic acid O-methyltransferase gene, <i>AbCOMT1</i>, from <i>Atalantia buxifolia</i>, a <i>Citrus</i>-related species exhibiting high resistance to citrus canker. <i>AbCOMT1</i> encodes a key enzyme involved in melatonin biosynthesis, and its overexpression in sweet orange significantly enhances resistance to citrus canker. We found elevated melatonin levels in the <i>AbCOMT1</i> overexpressing sweet orange lines and demonstrated that the <i>AbCOMT1</i> overexpression not only directly inhibited <i>Xcc</i> proliferation but also activated citrus immune responses. To further improve the inhibitory efficacy of melatonin, we tested several melatonin derivatives, achieving a tenfold increase in inhibitory activity. Notably, the melatonin derivative MT-3 exhibited outstanding efficacy in controlling citrus canker under field conditions. Our results revealed <i>AbCOMT1</i> as a promising resistance gene and identified the highly efficient melatonin derivatives for citrus canker disease control.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749450","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":"Human Pinealectomy Syndrome and the Impact of Melatonin Replacement Therapy: 1-Cardiovascular Function","authors":"Claudia Cosentino,&nbsp;Fernanda Gaspar do Amaral,&nbsp;Luciana Aparecida Campos,&nbsp;Fernanda Gentil,&nbsp;Osmar Pinto Neto,&nbsp;Andréa Maria Cappellano,&nbsp;Nasjla Saba da Silva,&nbsp;Ovidiu Constantin Baltatu,&nbsp;José Cipolla-Neto","doi":"10.1111/jpi.70045","DOIUrl":"https://doi.org/10.1111/jpi.70045","url":null,"abstract":"<div>\u0000 \u0000 <p>The purpose of this investigational study was to assess the cardiovascular effects of melatonin replacement therapy in pinealectomized patients. This was a prospective open-label, single-arm proof-of-concept study The study comprised 11 patients aged 16.7 ± 1.7 years, who had undergone pinealectomy, experienced no tumor recurrence, and exhibited undetectable salivary melatonin levels. A 6-month melatonin regimen (0.3 mg daily) was administered. Ambulatory blood pressure monitoring was conducted at baseline, 3-month, and 6-month intervals. First of all, no hypertension was observed in pinealectomized patients. Over the course of the study, diastolic blood pressure progressively decreased, reaching statistical significance at 6 months. Pulse pressure exhibited a gradual increase, reaching statistical significance after 6 months. Short-term blood pressure variability increased significantly for both systolic and diastolic pressures. Morning systolic and diastolic blood pressure levels were significantly decreased by melatonin replacement therapy. Melatonin had no effect on the average heart rate or its variability. Melatonin-deficient pinealectomized patients were normotensive. Melatonin replacement in these patients led to reduced diastolic pressure, increased pulse pressure, and enhanced short-term blood pressure variability. These results are consistent with improved cardiovascular health. Furthermore, melatonin's temporal specificity suggests that it might enhance nighttime recovery, heightening reactivity during wakefulness. While melatonin is used as a dietary supplement for similar effects, caution is advised, and further research is needed to optimize its use in various health and disease contexts. Further, considering the study's limitations, more extensive research would strengthen these findings.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749449","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}