Journal of Pineal Research最新文献

Circadian rhythmicity plays a crucial role in regulating sleep timing and continuity, but it may be altered in people with insomnia. This study tested whether dim-light melatonin onset (DLMO) timing is associated with sleep difficulties in insomnia. In total, 128 people diagnosed with insomnia disorder were recruited. Participants completed daily sleep diaries and wore an actigraph for up to 14 days before the laboratory visit to estimate mean sleep continuity (e.g., sleep latency, sleep duration) and sleep timing (sleep onset time and wake time from diaries, bedtime from diaries and actigraphy). After a sleep study, participants underwent salivary melatonin collection to estimate DLMO on the following night. Regressions and analyses of variances on tertile groups tested associations between DLMO (clock times and phase angle differences between DLMO and sleep timing) and sleep continuity and timing. There were associations between DLMO and sleep timing, r_(s) = 0.27–0.37, but not with sleep continuity. The phase angle between sleep onset time and DLMO was associated with sleep latency, sleep duration, and sleep efficiency, r_(s) = −0.32 to 0.41. Participants with a longer phase angle between DLMO and sleep onset time (> 3 h; i.e., greater delays) had longer sleep latencies (Mean diff = 43.21 min, SE = 12.99, p = 0.004) and shorter sleep durations (Mean diff = −65.66 min, SE = 20.75, p = 0.006) than participants with a shorter phase angle (< 2 h). Other phase angles (DLMO and mid-sleep, wake time) were not consistently associated with sleep continuity. Melatonin onset timing is associated with sleep timing in insomnia disorder. Larger phase angle differences between sleep onset and DLMO are linked to poorer sleep continuity. These findings highlight the importance of considering circadian alignment and its impact on sleep in understanding the pathophysiology of insomnia and in developing targeted treatment interventions.

In response to Yoshiyasu Takefuji's critique regarding the use of Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) in the study “Melatonin Repairs the Lipidome of Human Hepatocytes Exposed to Cd and Free Fatty Acid-Induced Lipotoxicity,” we provide a methodological clarification. PCA and PLS-DA are well-established, widely validated tools for exploratory analysis of high-dimensional omics data, including lipidomics data. Although these methods are linear, they are appropriate for capturing systematic and directional variations in complex biological systems, particularly in controlled in vitro models like ours. Our analytical approach integrates PCA and PLS-DA with rigorous statistical testing, data transformations, and biological validation, ensuring robustness and biological relevance of the findings. We reaffirm that these methods represent a standard, reliable practice in lipidomics, and the potential of nonlinear techniques does not diminish the appropriateness or utility of linear multivariate models when applied with scientific rigor.

Rest-activity rhythm and sleep may serve as potential intervention targets for a variety of diseases. However, the underlying biological mechanisms of rest-activity rhythm, sleep, and their proteomic associations with multiple diseases remain largely unexplored. Here, using data from approximately 10 000 participants in the UK Biobank with accelerometer-derived measures and proteomics profiles, we characterized the proteomic signatures of rest-activity and sleep and explored their associations with health outcomes. We found that the proteins associated with rest-activity and sleep were mainly enriched in inflammation, immune response and complement system. Most rest-activity and sleep measures, along with their associated proteomic signatures, were significantly associated with incident diabetes, cardiovascular disease, chronic kidney disease, respiratory diseases, and extended life expectancy. Several proteins, such as ADM and CA14, were observed to mediate multiple associations across distinct rest-activity and sleep measures. The impact of rest-activity and sleep measures on chronic diseases and mortality may be mediated through diverse biological pathways involving multiple proteins. These findings reveal potential mechanisms underlying these complex relationships and provide novel insights for the development of targeted intervention strategies.

Recent evidence highlights the protective role of melatonin in a variety of pathological conditions, including multiple types of cancer. Epidemiological studies increasingly suggest that exposure to light at night suppresses melatonin synthesis in night-shift and rotating-shift workers, potentially elevating their risk of cancer development. Experimental data further indicate that melatonin can inhibit the proliferation of tumor cells, including glioblastoma-like stem cells. In the present study, we investigated the effect of melatonin on the expression of genes involved in regulating the circadian rhythm, cell cycle progression, and angiogenesis in rats exposed to constant light, a model of circadian disruption. Our findings demonstrate that melatonin administration significantly inhibited tumor growth and reduced the vascularization associated with circadian rhythm disturbance. Molecular analysis revealed that melatonin altered the circadian expression of several genes affecting tumor biology, including p53, TNF-α, Per2, VEGF-A, PDGF-C, and Ang, which are involved in circadian rhythms, cell cycle, and angiogenesis regulation. These results strengthen the existing hypothesis that circadian disruption contributes to tumor progression and suggest that melatonin exerts anticancer effects by modulating circadian gene expression and angiogenesis. Our findings provide further insight into the mechanism by which melatonin may exert oncostatic effects and highlight its potential as a therapeutic agent in cancers associated with circadian rhythm disruption.

Light influences human physiology profoundly, affecting the circadian clock and suppressing the endogenous hormone melatonin. Experimental studies often employ either homogenous full-field stimulation, or overhead illumination, which are hard to standardize across studies and laboratories. Here, we present a novel technique to examine nonvisual responses to light using virtual-reality (VR) head-mounted displays (HMDs) for delivering standardized and calibrated light stimuli to observers in a reproducible and controlled manner. We find that VR HMDs are well-suited for delivering standardized stimuli defined in luminance and across time, with excellent properties up to 10 Hz. We examine melatonin suppression to continuous luminance-defined light stimuli in a sample of healthy participants (n = 32, mean ± SD age: 27.2 ± 5.6), and find robust melatonin suppression in 24 out of 32 participants (75% of the sample). Our findings demonstrate that VR HMDs are well-suited for studying the mechanisms underlying human nonvisual photoreception in a reproducible and standardized fashion.

Melatonin is a versatile neurohormone with diverse molecular functions, including sleep regulation, inflammation reduction, antioxidant activity, immune modulation, and anticancer properties. In bone metabolism, it promotes osteoblast formation, inhibits osteoclast activity, and synchronizes skeletal tissue rhythms to support bone health. As melatonin is not yet clinically used for osteoporosis and concerns about the current treatments' side effects remain, this review highlights its role in modulating osteoblast and osteoclast interactions, particularly through regulation of the receptor activator of nuclear factor-κB ligand and osteoprotegerin, to achieve bone-forming and antiresorptive effects. These effects have been demonstrated across various concentrations in diverse cell types and In Vivo models. Furthermore, melatonin safeguards the bone microenvironment by mitigating oxidative stress and inflammation, protecting osteoblasts, preventing bone loss, and maintaining the gut microbiota and brain–gut–bone axis. These attributes underscore melatonin's potential as an effective alternative or complementary therapy for promoting bone health and managing osteoporosis. Future research is needed to determine optimal dosing and timing for maximum efficacy.