Journal of Pineal Research最新文献

Chronic manganese (Mn) exposure induces severe neurotoxicity, characterized by impaired neurogenesis and disrupted metabolic homeostasis. Although melatonin (MT) possesses established neuroprotective properties, its clinical utility is hindered by poor bioavailability and limited brain delivery. Here, we developed a brain-targeted, rabies virus glycoprotein (RVG)-modified liposomal delivery system encapsulating melatonin (MT@RVG-Lip) to enhance therapeutic efficacy. Multi-omics analyses including brain and intestinal transcriptomics, serum metabolomics, and gut metagenomics were conducted to elucidate the underlying mechanisms. MT@RVG-Lip significantly improved motor deficits and enhanced neurogenesis while reducing neuroinflammation in Mn-exposed mice. Compared with regular MT and CaNa₂-EDTA, MT@RVG-Lip more effectively alleviated Mn-disrupted gene expression in neurogenesis regions, particularly genes involved in amino acid metabolism. Additionally, MT@RVG-Lip demonstrated a regulatory effect on serum amino acid profiles and intestinal transporter gene expression. Gut microbiota analysis further revealed that MT@RVG-Lip partially reversed Mn-associated dysbiosis and promoted the improvement of key amino acid-related microbiota-mediated metabolic pathways. The RVG-modified liposomal formulation conferred sustained release and improved brain-targeting capability, prolonging MT bioavailability and enhancing therapeutic outcomes. These findings provide a new mechanistic framework for MT-based interventions in neurodegenerative diseases and highlight the therapeutic potential of multifunctional delivery strategies.

Melatonin, a signaling molecule secreted by the pineal gland, is closely associated with physiological activities, such as animal growth, development, and reproduction. Multiple studies have indicated that melatonin acts on the adenohypophysis to promote the synthesis and secretion of growth hormone (GH), but the specific mechanism of melatonin remains unclear. We have previously reported that melatonin levels in bovine serum are closely correlated with GH levels. In the present study, transcriptome sequencing was performed on primary bovine adenohypophyseal cells treated with melatonin, which identified FOXO1 as a key transcription factor that is responsive to melatonin and regulates GH synthesis and secretion. Cellular experiments revealed that melatonin binds to the MTNR1A in bovine adenohypophyseal cells, activates the cAMP/PKA signaling pathway, and promotes the expression of FOXO1 protein. Dual-luciferase reporter assays verified the binding of FOXO1 to the GH1 promoter. Treatment with Luzindole, 4P-PDOT, 2',5'-Dideoxyadenosine or H-89 elucidated the molecular mechanism through which melatonin promotes GH synthesis and secretion in adenohypophyseal cells through the cAMP/PKA/CREB/FOXO1 pathway. The present study provides critical evidence for the direct action of melatonin on adenohypophyseal cells and its targeted regulatory sites, and it offers new insights into the conserved and species-specific modes of action of melatonin across different species, providing data and theoretical support for the application of melatonin in promoting animal growth and development.

As a chronobiotic with sleep-promoting properties, melatonin is frequently recommended by sleep medicine practitioners and widely available as an over-the-counter drug. Recently, two publications questioned melatonin safety profile in insomnia patients, with one of these receiving vast media coverage and noticeable resonance among the general public. This letter to the Editor critically evaluates such research, offering a broader contextualization within the existing body of literature about melatonin safety and insomnia-related health outcomes.

Retraction: D. Shi, X. Xiao, J. Wang, L. Liu, W. Chen, L. Fu, F. Xie, W. Huang, and W. Deng, "Melatonin Suppresses Proinflammatory Mediators in Lipopolysaccharide-Stimulated CRL1999 Cells via Targeting MAPK, NF-κB, c/EBPβ, and p300 Signaling," Journal of Pineal Research 53, no. 2 (2012): 154-165, https://doi.org/10.1111/j.1600-079X.2012.00982.x. The above article, published online on 30 January 2012 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Gianluca Tosini; and John Wiley & Sons Ltd. A third party raised concerns that three of the four bands in the IL-1β image in Figure 1D were copied and presented as the COX-2 image in Figure 2B. An investigation by the publisher confirmed this duplication and also confirmed that the GAPDH control bands had been reused in both figures. The authors responded to an inquiry by the publisher, but they could not supply all of the original data for the article to validate the data. The retraction has been agreed to because the evidence of image duplication and manipulation in the article compromises the editors' confidence in the results presented. The authors were informed about the retraction.

Retraction: K. Ganguly and S. Swarnakar, "Induction of Matrix Metalloproteinase-9 and -3 in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Ulcers in Mice: Regulation by Melatonin," Journal of Pineal Research 47, no. 1 (2009): 43-55, https://doi.org/10.1111/j.1600-079X.2009.00687.x. The above article, published online on 01 July 2009 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Gianluca Tosini; and John Wiley & Sons Ltd. The retraction has been agreed due to concerns raised by third parties. Specifically, sharp vertical lines indicative of splicing were identified in Figure 3E. In addition, similarities between bands were observed within Figures 4B, 5A, and 6A. Areas of overlap were also detected between Figures 1F, 1H, and 1J, as well as between Figures 4A(b) and 4A(f). Because of the time elapsed since publication, the authors were unable to provide the original raw data underlying these figures, and the clarification provided did not adequately resolve the concerns raised. Accordingly, the article has been retracted, as the editors determined that the extent of the identified issues invalidates the article's conclusions. The corresponding author, Snehasikta Swarnakar, disagrees with this decision; author Krishnendu Ganguly could not be reached.

As emerging pollutants of global concern, the toxicity of polystyrene nanoplastics (PS-NPs) in plants has received widespread attention, but little is known about how to alleviate their adverse impacts on wood plants. In Paeonia ostii, PS-NPs could be uptood by roots, transported and accumulated in stems and leaves, and induced oxidative stress and negatively affected plant growth. Exogenous melatonin application has for the first time shown to reduce the cell wall porosity to prevent PS-NPs from entering the cells via inhibiting the expression of genes associated with expansins, ultimately decreasd PS-NPs accumulation. And exogenous melatonin also activated the antioxidant system to scavenge reactive oxygen species (ROS) and alleviated the adverse impacts of PS-NPs on plant growth. Moreover, increasing endogenous melatonin by overexpressing N-acetylserotonin-O-methyltransferase gene obtained the similar results as mentioned above. And the transgenic plants uptook and accumulated relatively lower levels of PS-NPs by reducing the cell wall porosity, and induced lower ROS accumulation by activating the antioxidant system. Collectively, these results suggested that melatonin could defend against the oxidative stress caused by PS-NPs via preventing their uptake and activating the antioxidant system in P. ostii, which highlighted that melatonin can be used to protect plants in the nanoplastic-polluted environments.

Spontaneous parturition in both humans and sows occurs predominantly at night. Melatonin is thought to facilitate nocturnal parturition in humans by synergistically enhancing myometrial contractions with oxytocin, but the precise underlying mechanisms remain unclear. In this study, in vivo analyses showed that melatonin levels in both serum and myometrium were significantly increased in laboring sows, accompanied by increased melatonin synthesized in the myometrium. Moreover, exogenous melatonin administration to pregnant sows potentially shifted parturition time. Functional studies demonstrated that melatonin supplementation significantly enhanced spontaneous myometrial contractility and sensitivity to oxytocin. Mechanistic investigations revealed that transcription factors NRF2 and MAFF were involved in the signaling pathway of melatonin, enhancing myometrial contractility. Silencing NRF2 or MAFF in melatonin-treated myometrial cells reduced the expression of contraction-associated proteins (CAPs) and attenuated collagen gel contraction. Dual-luciferase reporter assays indicated that NRF2 and MAFF directly targeted the promoters of key contraction-associated genes, including PTGS2 and OXTR. Additionally, molecular analysis revealed that melatonin enhanced myometrial contraction by binding to the MT2 receptor. Furthermore, our results showed that PKC participated in melatonin-induced myometrial contraction by regulating NRF2 and MAFF expression. Collectively, our data reveal, for the first time, that the MT2-PKC-NRF2/MAFF axis mediates melatonin-enhanced myometrial contraction in sows. These findings advance our understanding of parturition initiation in mammals and may provide a novel theoretical basis for developing therapeutic strategies for preterm or delayed/prolonged labor.

Melatonin (MEL) is a multifunctional bioactive compound known for its antioxidant properties and regulatory roles in both animal and microbial systems. Although MEL has been shown to interact with glycolytic enzymes in yeast, the molecular basis and physiological relevance of these interactions remain unclear. Here, we investigate MEL interactions with key glycolytic proteins in Saccharomyces cerevisiae during alcoholic fermentations, using CRISPR-Cas9-generated gene deletion mutants. Protein interactions in wild type and mutant strains were analysed via co-immunoprecipitation and western blotting. The fermentative behavior of single and double TDH deletion mutants was assessed in both laboratory and wine yeast strains. TDH2 and TDH3 deletions extended the lag phase and reduced GAPDH activity, while TDH1 deletion had minor effects, indicating a differential contribution of glycolytic isoenzymes to fermentation kinetics. Analysis of MEL-bound proteins revealed that Tdh2p is essential for complex formation, as its absence abolished MEL binding to other glycolytic proteins. Molecular docking predicted stable hydrogen bonds between MEL and Tdh2p, supporting a direct interaction. These results demonstrate the formation of a glycolytic protein-MEL complex and identify Tdh2p as a key mediator, providing a foundation for further studies on its physiological relevance and regulatory mechanisms.