Journal of Pineal Research最新文献

{"title":"Protective Effects of Melatonin on Kidney Function Against Contrast Media-Induced Kidney Damage in Patients With Chronic Kidney Disease: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial","authors":"Prit Kusirisin,&nbsp;Nattayaporn Apaijai,&nbsp;Kajohnsak Noppakun,&nbsp;Srun Kuanprasert,&nbsp;Siriporn C. Chattipakorn,&nbsp;Nipon Chattipakorn","doi":"10.1111/jpi.70031","DOIUrl":"10.1111/jpi.70031","url":null,"abstract":"<div>\u0000 \u0000 <p>Patients with chronic kidney disease (CKD) are at increased risk of acute kidney injury following exposure to contrast media. We evaluated the effect of melatonin, a potent antioxidant, as a protective strategy against contrast-induced acute kidney injury (CI-AKI), with a focus on molecular mechanisms. We randomized patients with an eGFR &lt; 60 mL/min/1.73 m² undergoing coronary angiography (CAG) into melatonin (10 mg twice daily) or placebo groups. Treatment started 48 h before CAG and continued for a total of 6 days. Peripheral blood mononuclear cells (PBMCs) were collected at baseline, at the time of CAG, and at 6, 24, 48, 72 h, and Day 30 post-procedure. The primary outcome was the incidence of CI-AKI; secondary outcomes included kidney function, oxidative stress, mitochondrial function, and cell death pathways. Forty patients were randomized into either the treatment or placebo group. All subsequent analyses were conducted on an as-treat basis. The incidence of CI-AKI was significantly lower in the melatonin group compared to the placebo group (25% vs. 60%, <i>p</i> = 0.025). The melatonin group showed a significantly smaller percentage change in plasma neutrophil gelatinase-associated lipocalin (NGAL) at all time points. In the PBMC study, cellular oxidative stress was significantly reduced in the melatonin group at each time point, and mitochondrial oxidative stress was lower at 48–72 h. Mitochondrial respiration improved significantly, and both necrosis and necroptosis were reduced at 24 h. Melatonin administration effectively reduced the incidence of CI-AKI in CKD patients undergoing CAG. This protective effect was associated with decreased oxidative stress, enhanced mitochondrial function, and reduced cell death, suggesting melatonin as a promising preventive strategy for CI-AKI.</p>\u0000 <p><b>Trial Registration:</b> TCTR20210123004</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997050","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":"Resetting of the Human Circadian Melatonin Rhythm by Ambient Hypoxia","authors":"Titiaan E. Post,&nbsp;Riccardo De Gioannis,&nbsp;Jan Schmitz,&nbsp;Martin Wittkowski,&nbsp;Tina Martin Schäper,&nbsp;Anna Wrobeln,&nbsp;Joachim Fandrey,&nbsp;Marie-Therese Schmitz,&nbsp;Joseph S. Takahashi,&nbsp;Jens Jordan,&nbsp;Eva-Maria Elmenhorst,&nbsp;Daniel Aeschbach","doi":"10.1111/jpi.70029","DOIUrl":"10.1111/jpi.70029","url":null,"abstract":"<p>Circadian clocks in the body drive daily cycles in physiology and behavior. A master clock in the brain maintains synchrony with the environmental day–night cycle and uses internal signals to keep clocks in other tissues aligned. Work in cell cultures uncovered cyclic changes in tissue oxygenation that may serve to reset and synchronize circadian clocks. Here we show in healthy humans, following a randomized controlled single-blind counterbalanced crossover study design, that one-time exposure to moderate ambient hypoxia (FiO₂ ~15%, normobaric) for ~6.5 h during the early night advances the dim-light onset of melatonin secretion by 9 min (95% CI: 1–16 min). Exposure to moderate hypoxia may thus be strong enough to entrain circadian clocks to a 24-h cycle in the absence of other entraining cues. Together, the results provide direct evidence for an interaction between the body's hypoxia-sensing pathway and circadian clocks. The finding offers a mechanism through which behaviors that change tissue oxygenation (e.g., exercise and fasting/eating) can affect circadian timing and through which hypoxia-related diseases (e.g., obstructive sleep apnea and chronic obstructive pulmonary disease) can result in circadian misalignment and associated pathologies.</p><p><b>Trial Registration:</b> Registration number: DRKS00023387; German Clinical Trials Register: http://www.drks.de</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997053","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":"GATA3-COMT1-Melatonin as Upstream Signaling of ABA Participated in Se-Enhanced Cold Tolerance by Regulate Iron Uptake and Distribution in Cucumis sativus L","authors":"Dan Wen,&nbsp;Ning Yang,&nbsp;Wenjun Zhang,&nbsp;Xiao Wang,&nbsp;Jibo Zhang,&nbsp;Wenjing Nie,&nbsp;Hualu Song,&nbsp;Shasha Sun,&nbsp;Haijuan Zhang,&nbsp;Yujuan Han,&nbsp;Mingfang Qi","doi":"10.1111/jpi.70028","DOIUrl":"10.1111/jpi.70028","url":null,"abstract":"<div>\u0000 \u0000 <p>Selenium has the function of bio-stimulating hormone. However, the underlying physiological and molecular mechanisms of melatonin and abscisic acid as secondary messengers in improving cold tolerance by selenium are limited. This study investigated the effects of selenite on the cold stress of cucumber seedlings. The results showed that the content of endogenesis abscisic acid significantly changed with exogenous application of selenite under cold stress. Interestingly, we found that the content of iron significantly changed in this process. Iron uptake and distribution may be the important reason of selenium alleviates cold injury of cucumber seedlings. Whole genes transcriptome was used for screening key genes on leaf and root of cucumber seedlings. To determine the interrelation between abscisic acid and melatonin in selenite alleviating cold stress, abscisic acid inhibitor fluridone and melatonin synthesis inhibitor <i>p</i>-chlorophenylalanine were used for in-depth study. The results indicate that melatonin as upstream signal of ABA involved in selenium enhanced cucumber cold tolerance. The results of yeast single hybridization, EMSA, LUC, and overexpression transgenic showed that the transcription factor <i>CsGATA3</i> regulates the expression of <i>CsCOMT1</i> in vitro and in vivo and affects melatonin content. This study provides a theoretical basis for cucumber cultivation and breeding.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055771","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":"Relating Photoperiod and Outdoor Temperature With Sleep Architecture in Patients With Neuropsychiatric Sleep Disorders","authors":"Katy Sarah Weihrich,&nbsp;Frederik Bes,&nbsp;Jan de Zeeuw,&nbsp;Martin Haberecht,&nbsp;Dieter Kunz","doi":"10.1111/jpi.70030","DOIUrl":"10.1111/jpi.70030","url":null,"abstract":"<p>While artificial light in urban environments was previously thought to override seasonality in humans, recent studies have challenged this assumption. We aimed to explore the relationship between seasonally varying environmental factors and changes in sleep architecture in patients with neuropsychiatric sleep disorders by comparing two consecutive years. In 770 patients, three-night polysomnography was performed at the Clinic for Sleep &amp; Chronomedicine (St. Hedwig Hospital, Berlin, Germany) in 2018/2019. Sleep times were adjusted to patients' preferred schedules, patients slept in, and were unaware of day-night indicators. Digital devices and clocks were not allowed. Days were spent outside the lab with work or naps not allowed. After exclusions (mostly due to psychotropic medication), analysis was conducted on the second PSG-night in 377 patients (49.1 ± 16.8 year; 54% female). Sleep parameters were plotted as 90-day moving-averages (MvA) across date-of-record. Periodicity and seasonal windows in the MvA were identified by utilizing autocorrelations. Linear mixed-effect models were applied to seasonal windows. Sleep parameters were correlated with same-day photoperiod, temperature, and sunshine duration. The MvA of total sleep time (TST) and REM sleep began a 5-month-long decline shortly after the last occurrence of freezing 24-h mean temperatures (correlation of TST between 2018 and 2019 at 2-month lag: <i>rs</i>₃₆₁ = 0.87, <i>p</i> &lt; 0.001; maximum peak-to-nadir amplitude: <i>ΔTST</i> ~ 62 min, <i>ΔREM</i> ~ 24 min). The MvA nadirs of slow wave sleep (SWS) occurred approximately at the autumnal equinox (correlation between 2018 and 2019: <i>rs</i>₃₆₁ = 0.83, <i>p</i> &lt; 0.001). Post hoc testing following significant linear mixed-effect model indicate that TST and REM sleep were longer around November till February than May till August (<i>ΔTST</i> = 36 min; <i>ΔREM</i> = 14 min), while SWS was 23 min longer around February till May than August till November. Proportional seasonal variation of SWS and of REM sleep as percentages of TST differed profoundly (SWS = 31.6%; REM = 8.4%). In patients with neuropsychiatric sleep disorders living in an urban environment, data collected in 2018 show similar patterns and magnitudes in seasonal variation of sleep architecture as the 2019 data. Interestingly, whereas SWS patterns were consistent between years with possible links to photoperiod, annual variations of TST and REM sleep seem to be related to times of outside freezing temperature. For generalization, the data need to be confirmed in a healthy population. No clinical trial was registered.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941978","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 Alleviates Circadian Rhythm Disruption-Induced Enhanced Luteinizing Hormone Pulse Frequency and Ovarian Dysfunction","authors":"Yujing Li,&nbsp;Tianjiao Pei,&nbsp;Huili Zhu,&nbsp;Ruiying Wang,&nbsp;Lukanxuan Wu,&nbsp;Xin Huang,&nbsp;Fangyuan Li,&nbsp;Xinyu Qiao,&nbsp;Yuchan Zhong,&nbsp;Wei Huang","doi":"10.1111/jpi.70026","DOIUrl":"10.1111/jpi.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Circadian rhythm disruption (CRD), stemming from sleep disorders and/or shift work, is a risk factor for reproductive dysfunction. CRD has been reported to disturb nocturnal melatonin signaling, which plays a crucial role in female reproduction as a circadian regulator and an antioxidant. The hypothalamic-pituitary-ovarian (HPO) axis regulates female reproduction, with luteinizing hormone (LH) pulse pattern playing a pivotal role in folliculogenesis and steroidogenesis. However, the effect of CRD on the HPO axis and the involvement of melatonin remains unclear. Female CBA/CaJ mice underwent CRD modeling, which involves alternating between standard light conditions and an 8-h advance schedule every 3 days for 8 weeks, whereas control mice were maintained under a standard 12:12-h light/dark (LD) cycle. Subsequent measurements of diurnal melatonin levels, LH pulse patterns assessments via serial tail-tip blood sampling and evaluations of ovarian function were conducted. CRD altered the circadian rhythms of wheel-running activity and melatonin secretion in mice and led to an augmented LH pulse pattern, evidenced by increased LH pulse frequency, mean LH levels, and pituitary <i>LH beta-subunit (LHβ)</i> expression, irregular estrous cycles, abnormal luteal function, altered endocrine function, and ovarian oxidative stress. Melatonin treatment (10 mg/kg/day for 4 weeks) significantly improved the HPO axis disorder in CRD mice, decreasing the enhanced LH pulse frequency and pituitary <i>LHβ</i> expression. These findings were further validated using an in vitro LβT2 cell perfusion model. Furthermore, melatonin restored ovarian function and scavenged reactive oxygen species, thereby preventing apoptosis and preserving ovarian function. This study offers new insights into the impact of CRD on the HPO axis and emphasizes the potential of melatonin supplementation in mitigating its effects on female reproduction.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930127","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, an Antitumor Necrosis Factor Therapy","authors":"Ana Isabel Álvarez-López,&nbsp;Ivan Cruz-Chamorro,&nbsp;Patricia Judith Lardone,&nbsp;Ignacio Bejarano,&nbsp;Karla Aspiazu-Hinostroza,&nbsp;Eduardo Ponce-España,&nbsp;Guillermo Santos-Sánchez,&nbsp;Nuria Álvarez-Sánchez,&nbsp;Antonio Carrillo-Vico","doi":"10.1111/jpi.70025","DOIUrl":"10.1111/jpi.70025","url":null,"abstract":"<p>Tumor necrosis factor (TNF) is a biomarker of inflammation whose levels are elevated in patients with several diseases associated with dysregulation of the immune response. The main limitations of currently used anti-TNF therapies are the induction of immunodepression, which in many cases leads to serious adverse effects such as infection and cancer, and the inability to cross the blood-brain barrier in neuroinflammatory conditions. Melatonin, in addition to being a chronobiotic compound, is widely known for its antioxidant and immunomodulatory capacity to control inflammatory processes in different pathological contexts. The aim of the present review is to address human-based studies that describe the effect of melatonin on TNF production. The review includes all the articles published in PubMed databases until April 15, 2024. After depuration, 45 studies were finally included in the review, 23 related to the in vitro action of melatonin in human cells and 22 in vivo studies in humans. Most of the data reviewed support the idea that melatonin has an immunosuppressive effect on TNF levels, which, together with its low toxicity profile, low cost, and ability to cross the blood-brain barrier, points to melatonin as a potential anti-TNF therapy. Therefore, improving our knowledge of the action of melatonin in regulating TNF through appropriate clinical trials would reveal the true potential of this molecule as a possible anti-TNF therapy.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908736","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":"Light Environment of Arctic Solstices is Coupled With Melatonin Phase-Amplitude Changes and Decline of Metabolic Health","authors":"Denis Gubin,&nbsp;Konstantin Danilenko,&nbsp;Oliver Stefani,&nbsp;Sergey Kolomeichuk,&nbsp;Alexander Markov,&nbsp;Ivan Petrov,&nbsp;Kirill Voronin,&nbsp;Marina Mezhakova,&nbsp;Mikhail Borisenkov,&nbsp;Aislu Shigabaeva,&nbsp;Natalya Yuzhakova,&nbsp;Svetlana Lobkina,&nbsp;Julianna Petrova,&nbsp;Olga Malyugina,&nbsp;Dietmar Weinert,&nbsp;Germaine Cornelissen","doi":"10.1111/jpi.70023","DOIUrl":"10.1111/jpi.70023","url":null,"abstract":"<div>\u0000 \u0000 <p>Light environment in the Arctic differs widely with the seasons. Studies of relationships between objectively measured circadian phase and amplitude of light exposure and melatonin in community-dwelling Arctic residents are lacking. This investigation combines cross-sectional (<i>n</i> = 24–62) and longitudinal (<i>n</i> = 13–27) data from week-long actigraphy (with light sensor), 24-h salivary melatonin profiles, and proxies of metabolic health. Data were collected within the same week bracketing spring equinox (SE), and winter/summer solstices (WS/SS). Drastic seasonal differences in blue light exposure (BLE) corresponded to seasonal changes in the 24-h pattern of melatonin, which was phase delayed and reduced in normalized amplitude (NA) during WS/SS compared to SE. The extent of individual melatonin's acrophase and Dim Light Melatonin Onset (DLMO) change from SE to WS correlated with that from SE to SS. Although similar in extent and direction, melatonin phase changes versus SE were linked to morning BLE deficit in WS, contrasting to evening BLE excess in SS. Seasonal changes in sleep characteristics were closely associated with changes in the phases of BLE and melatonin. Proxies of metabolic health included triglycerides (TG), high-density lipoprotein cholesterol (HDL), TG/HDL ratio, and cortisol. Adverse seasonal changes in these proxies were associated with delayed acrophases of BLE and melatonin during WS and SS. TG and TG/HDL were higher in WS and SS than in SE, and cross-sectionally correlated with later melatonin and BLE acrophases, while lower HDL was associated with later BLE onset and later melatonin acrophase. Overall, this study shows that optimal 24-h patterns of light exposure during SE is associated with an earlier acrophase and a larger 24-h amplitude of melatonin, and that both features are linked to better metabolic health. Improving light hygiene, in particular correcting winter morning light deficit and summer evening light excess may help maintain metabolic health at high latitudes. Novel solutions for introducing proper circadian light hygiene such as human-centric light technologies should be investigated to address these issues in future studies.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891086","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":"Correction to “The Role of MEK1/2 and MEK5 in Melatonin-Mediated Actions on Osteoblastogenesis, Osteoclastogenesis, Bone Microarchitecture, Biomechanics, and Bone Formation”","authors":"","doi":"10.1111/jpi.70024","DOIUrl":"10.1111/jpi.70024","url":null,"abstract":"<p>F. Munmun, O. A. Mohiuddin, V. T. Hoang, et al., “The Role of MEK1/2 and MEK5 in Melatonin-Mediated Actions on Osteoblastogenesis, Osteoclastogenesis, Bone Microarchitecture, Biomechanics, and Bone Formation,” <i>Journal</i> of <i>Pineal Research</i> 73 (2022): e12814, https://doi.org/10.1111/jpi.12814.</p><p>The BSO + GLUT image in Figure 5F was the same as the BSO + GLUT image in Figure 5H. The corrected image for Figure 5F is displayed here:</p><p>We apologize for this error.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891083","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 Affects Peucedanum praeruptorum Vegetative Growth and Coumarin Synthesis by Modulating the Antioxidant System, Photosynthesis, and Endogenous Hormones","authors":"Xiaoting Wan,&nbsp;Yingyu Zhang,&nbsp;Guoyu Wang,&nbsp;Ranran Liao,&nbsp;Haoyu Pan,&nbsp;Cunwu Chen,&nbsp;Bangxing Han,&nbsp;Hui Deng,&nbsp;Cheng Song","doi":"10.1111/jpi.70018","DOIUrl":"10.1111/jpi.70018","url":null,"abstract":"<div>\u0000 \u0000 <p>The dried root of <i>Peucedanum praeruptorum</i> is often used medicinally and has high pyran- and furanocoumarin content. Although exogenous melatonin (MT) impacts the regulation of plant growth, stress responses, secondary metabolism, etc., it remains unclear whether MT regulates the vegetative growth and development of <i>P. praeruptorum</i>. Thus, the aim of the current study is to characterize the effects of different exogenous MT concentrations on the physiological functions, photosynthesis, antioxidant systems, hormone induction, and coumarin synthesis of <i>P. praeruptorum</i>. Different MT concentrations exert distinct regulatory effects on <i>P. praeruptorum</i> growth and the expression of genes related to coumarin synthesis. Treatment of <i>P. praeruptorum</i> with low concentrations of MT increases photosynthesis and leaf growth compared to the control, while high concentrations reduce root vitality and elongation and decrease the expression of photosynthetic system genes. Low concentrations of MT also significantly increase antioxidant enzyme activity and photosynthetic pigment content and modulate the levels of IAA, gibberellic acid, salicylic acid, jasmonic acid, abscisic acid, and endogenous MT. Moreover, MT increases the activity of the MT synthesis enzymes tryptophan decarboxylase, tryptophan hydroxylase, tryptamine-5-hydroxylase, serotonin <i>N</i>-acetyltransferase, acetylserotonin <i>O</i>-methyltransferase, and caffeic acid <i>O</i>-methyltransferase, and promotes the accumulation of isoscopoletin, scopoletin, peucedanocoumarin II, praeruptorin A, praeruptorin B, and praeruptorin E. MT also upregulates most genes associated with coumarin synthesis, including <i>PAL1</i>, <i>C4H</i>, <i>4CL-3</i>, <i>C3H-1</i>, <i>F6H-1</i>, <i>CCoAMT</i>, <i>OMT-1</i>, <i>CYP71AJ1</i>, <i>CYP84A1-1</i>, <i>S8H-1</i>, <i>PT-1</i>, and <i>COSY-1</i>. These findings demonstrate that MT may improve <i>P. praeruptorum</i> growth and development while promoting the synthesis of coumarin components.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875879","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 Endometriosis Growth via Specific Binding and Inhibition of EGFR Phosphorylation","authors":"Yiran Li,&nbsp;Sze-Wan Hung,&nbsp;Xu Zheng,&nbsp;Yang Ding,&nbsp;Tao Zhang,&nbsp;Zhouyurong Tan,&nbsp;Ruizhe Zhang,&nbsp;Yuezhen Lin,&nbsp;Yi Song,&nbsp;Yao Wang,&nbsp;Chi-Chiu Wang","doi":"10.1111/jpi.70022","DOIUrl":"10.1111/jpi.70022","url":null,"abstract":"<p>As a chronic gynecological disease, endometriosis is defined as the implantation of endometrial glands as well as stroma outside the uterine cavity. Proliferation is a major pathophysiology in endometriosis. Previous studies demonstrated a hormone named melatonin, which is mainly produced by the pineal gland, exerts a therapeutic impact on endometriosis. Despite that, the direct binding targets and underlying molecular mechanism have remained unknown. Our study revealed that melatonin treatment might be effective in inhibiting the growth of lesions in endometriotic mouse model as well as in human endometriotic cell lines. Additionally, the drug–disease protein–protein interaction (PPI) network was built, and epidermal growth factor receptor (EGFR) was identified as a new binding target of melatonin treatment in endometriosis. Computational simulation together with BioLayer interferometry was further applied to confirm the binding affinity. Our result also showed melatonin inhibited the phosphorylation level of EGFR not only in endometriotic cell lines but also in mouse models. Furthermore, melatonin inhibited the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)—protein kinase B (Akt) pathway and arrested the cell cycle via inhibiting CyclinD1 (CCND1). In vitro and in vivo knockdown/restore assays further demonstrated the involvement of the binding target and signaling pathway that we found. Thus, melatonin can be applied as a novel therapy for the management of endometriosis.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875933","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}