Journal of Pineal Research最新文献

Reaching term gestation requires a complex interplay between the uterus and hormonal signals regulating its contractile profile. Most pregnancy-associated hormones vary in their overall level of release throughout pregnancy, but also have a circadian release pattern, including progesterone, oxytocin, and melatonin. It remains poorly understood how the circadian release of hormones impacts uterine function. To determine how time-of-day, mouse strain, and melatonin proficiency were associated with the uterotonic efficacy of oxytocin, the primary hormone promoting uterine contractions, we used melatonin-deficient C57BL/6 and melatonin-proficient CBA/C57BL/6 (CBA/B6) female mice on gestation day 18. Through RNAscope, we found that oxytocin receptor (Oxtr) mRNA exhibited a time-of-day variation that differed between the uterine endometrium and myometrium. This uterine layer-specific, time-of-day difference in Oxtr was associated with a shift in phase of the molecular clock reporter PER2::Luciferase. A strain-specific effect of PER2::Luciferase rhythms were observed in the uterus, where CBA/B6 had a shorter PER2::Luciferase period than C57BL/6. In addition, CBA/B6 uteri had lower spontaneous uterine contraction force compared to C57BL/6. Despite the difference in spontaneous contractions and circadian period, the capacity of oxytocin to induce contractions varied by time-of-day, independent of mouse strain. Together, these findings reveal that uterine responsiveness to oxytocin is gated by circadian time, with Oxtr expression and uterine contractions showing diurnal variation. At the same time, mouse strain was associated with PER2::Luciferase period and baseline uterine contractility. These results underscore the relevance of circadian timing in uterine physiology and that strain differences impact basal uterine function.

Circadian rhythm alignment depends on environmental light detection via opsins. Pinopsin, originally identified in the pineal organ of birds and later in amphibian pineal complex and eyes, may play a role in this process, though its function has not been genetically tested. Evolutionary analysis suggests pinopsin was independently lost in several vertebrate lineages, including mammals (Synapsida), some reptiles (e.g. snakes and crocodiles), and teleost fish, but retained in birds, turtles, lizards, and non-teleost Actinopterygii. We conducted a detailed genomic search of the pinopsin gene across 95 amphibian species and assessed its function in Xenopus laevis tadpoles using CRISPR/Cas9-mediated knockout. Our survey indicates that pinopsin is highly conserved in salamanders and most anurans, but absent in many caecilians (Gymnophiona), which have a fossorial lifestyle with limited light exposure. To investigate its biological role, we generated X. laevis F0 pinopsin knockout tadpoles and evaluated two light-sensitive responses: (1) day/night melatonin fluctuations inferred from skin pigmentation changes, and (2) locomotor activity over a 24-h photoperiod. We show these responses depend only on pineal light sensitivity and are independent of eye sensitivity at developmental stage 46/47. Our findings reveal: (1) Pinopsin is co-expressed with Aanat, a key enzyme in melatonin synthesis; (2) knockout tadpoles show paler skin during the light phase, suggesting pinopsin suppresses melatonin production in daylight; and (3) reduced daytime locomotor activity in F0 mutants, consistent with melatonin-induced lethargy. Overall, pinopsin emerges as a critical opsin for light-regulated circadian-associated behavior in Xenopus, with likely conserved roles across amphibians (anurans and salamanders in general) and other non-mammalian vertebrates, including birds, turtles, and lizards.

Exogenous melatonin has emerged as a pivotal multifunctional signaling molecule, recognized for its critical role in enhancing stress tolerance and improving crop productivity. N6-methyladenosine (m6A) is the most prevalent internal modification found in eukaryotic mRNA and plays a crucial role in regulating plant growth, development, and stress responses. Despite its importance, the regulatory mechanisms of the m6A pathway in rice exposed to exogenous melatonin remain inadequately investigated. This study investigates systematic analysis of m6A-regulatory gene families in rice. We identified a total of 124 genes, which include 7 writers, 22 readers, and 95 erasers. The distribution of these genes is uneven across the 11 chromosomes of the rice genome. Analysis of conserved domains revealed structural signatures that are specific to each gene family. Phylogenetic relationships with dicot and monocot species offered insights into evolutionary trajectories. Notably, gene structure and motif analyses revealed functional divergence within and between gene families. Cis-element analysis identified abundance motifs associated with stress adaptation, hormonal signaling, and TFs, including ABRE, DRE, and MYB. Furthermore, synteny analysis unveiled both conserved regions and lineage-specific expansions, particularly within the YTH and ALKBH families. The protein interaction network revealed robust connections among subgroups and identified 10 hub genes. GO and KEGG analyses indicated significant enrichment in stress-related pathways, including secondary metabolite biosynthesis, flavonoid biosynthesis, and cysteine and methionine metabolism. RT-qPCR validates that melatonin Osm6As significantly influences the expression of targeted genes, with melatonin upregulations exhibiting a time-dependent pattern. Furthermore, GFP tagging of OsECT2 revealed that protoplasts are evenly distributed, suggesting robust nuclear enrichment of fluorescence. This study offers new insights into the epitranscriptomic regulatory responses of the m6A-modifier.

Ali, T., Badshah, H., Kim, T.H., & Kim, M.O. (2015). Melatonin attenuates d-galactose-induced memory impairment, neuroinflammation and neurodegeneration via RAGE/NF-KB/JNK signaling pathway in aging mouse model. Journal of Pineal Research, 58 (1), 71-85.

In Figure 3B the results of the 8-oxoG hippocampal CA1 region of the control group was unfortunately overlapped with the CA1 region of d-Gal+M. The corrected image of both the control and d-Gal+M are included in corrected figure below.

We apologize for the error.

Gastrointestinal (GI) cancers remain a leading cause of global morbidity and mortality, necessitating novel therapeutic strategies. Melatonin (MEL), an indoleamine with pleiotropic biological activities, has emerged as a promising adjuvant in oncology due to its antiproliferative, proapoptotic, and antioxidant properties. This review synthesizes current evidence on MEL's molecular mechanisms in GI carcinogenesis, including modulation of NF-κB, PI3K/AKT, and Wnt/β-catenin pathways, suppression of reactive oxygen species (ROS), and regulation of circadian rhythm-related genes (e.g., CLOCK, BMAL1). Preclinical studies demonstrate that MEL enhances chemoradiotherapy efficacy-reducing tumor volume by 70% in murine colorectal models and decreasing 5-fluorouracil (5-FU) resistance via miR-532-3p/β-catenin axis modulation. Clinical trials report a 23%–41% risk reduction in colorectal cancer among shift workers with MEL supplementation and a 53% decrease in radiotherapy-induced oral mucositis. Despite promising data, limitations persist: fewer than 15% of clinical trials focus on GI cancers, dosing remains unstandardized (10–40 mg/day), and molecular heterogeneity (e.g., KRAS mutations in pancreatic cancer) may limit therapeutic responses. Future research must prioritize phase III trials, chronotherapy optimization, and biomarker-driven approaches, including MT1/MT2 receptor expression and microbiome profiling. Given its low toxicity and putative synergy with immunotherapies, MEL should be regarded as an adjunct under investigation rather than an established option; to date, no GI-specific phase III randomized trials exist, and clinical signals come primarily from small, heterogeneous cohorts. Dosing is unstandardized and limited by low oral bioavailability (first-pass) and possible pharmacogenomic variability.