Journal of Pineal Research最新文献

{"title":"Exogenous Melatonin Regulates Hormone Signalling and Photosynthesis-Related Genes to Enhance Brassica napus. Yield: A Transcriptomic Perspective","authors":"Sana Basharat,&nbsp;Wajid Saeed,&nbsp;Samavia Mubeen,&nbsp;Latif Ullah Khan,&nbsp;Shanshan Zhang,&nbsp;Pingwu Liu,&nbsp;Muhammad Waseem","doi":"10.1111/jpi.70077","DOIUrl":"https://doi.org/10.1111/jpi.70077","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin, a multifunctional signalling molecule in plants, has been increasingly recognized for its role in improving stress tolerance, regulating hormone signalling, and enhancing crop productivity. Exogenous melatonin application represents a promising strategy to enhance crop productivity under global agricultural challenges. This study aimed to investigate the physiological and molecular mechanisms by which melatonin improves yield in <i>Brassica napus</i>. under optimal conditions. Two-week old plants were treated with 10 μM melatonin for 7 days and phenotype was observed. The plants exhibited significant increases in plant height, leaf number, pods per plant, seeds per pod, and 100-seed weight compared to controls. Transcriptomic analysis revealed 2924 differentially expressed genes (DEGs; 1655 upregulated, 1269 downregulated) from 66 258 genes in response to exogenously applied melatonin. Functional enrichment highlighted profound upregulation of photosynthesis-related pathways, including photosystem I/II components (PsbO, PsaH), electron transport genes (PetE, PetH), and F-type ATPase subunits. Melatonin also reconfigured phytohormone signaling, upregulating auxin (AUX1; <i>BnaA10g27610D</i>), ABA (ABF; <i>BnaA06g04750D</i>), cytokinin (CRF1; <i>BnaA06g34500D</i>, A-ARR; <i>BnaC03g48210D, Bna08g14280D, Bna09g36380D, BnaCnng49490D, BnaA06g16900D</i>, and <i>BnaA06g06240D</i>), and gibberellin-associated genes while downregulating ABA repressors (PYR/PYL; <i>BnaA06g40360D</i>, <i>BnaC07g19450</i>, PP2C; <i>BnaA06g23040D,</i> and <i>BnaA01g37370D</i>). Transcription factor profiling showed activation of growth-promoting families (NAC, TCP, bHLH) and suppression of stress-responsive TFs (MYB, AP2/ERF, WRKY). Validation via RT-qPCR confirmed RNA-seq reliability (R² = 0.96). Our study demonstrated that low-dose melatonin enhances <i>B. napus</i> yield by coordinately boost photosynthetic efficiency, optimizing hormone signaling, and activating growth-promoting transcription factors to prioritize reproductive development.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012543","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":"Transcriptomic and Metabolomic Signatures of Acute Circadian Misalignment in Mice","authors":"Baoyin Ren,&nbsp;Yingzhi Huang,&nbsp;Hui Wang,&nbsp;Haonan Li,&nbsp;Changxiao Ma,&nbsp;Meina Guo,&nbsp;Jiaxin Liu,&nbsp;Hongmei Tan,&nbsp;Jiayang Zhang,&nbsp;Huiwen Zheng,&nbsp;Bingyi Shen,&nbsp;Jiazhi Li,&nbsp;Zhaiyi Liu,&nbsp;Jingwen Zhu,&nbsp;Lejia Qiu,&nbsp;Xiaoyan Zhang,&nbsp;Youfei Guan,&nbsp;Guangrui Yang,&nbsp;Lihong Chen","doi":"10.1111/jpi.70075","DOIUrl":"https://doi.org/10.1111/jpi.70075","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute circadian misalignment, such as that induced by a single episode of jet lag, can leave molecular traces even after behavioral rhythms appear to recover. Here, we applied an integrated multi-omics approach—combining liver transcriptomics and plasma metabolomics—to characterize residual signatures on the 7th day after a single 6-h phase advance in male mice. Our data revealed significant alterations, particularly in the core clock genes <i>Bmal1</i> and <i>Cry1</i>, and the metabolites <span>l</span>-arginine and SM(d18:1/18:1(11Z)), with notable differences at Zeitgeber Time 0 (ZT0). Additionally, we identified <span>l</span>-Serine as a potential biomarker for circadian misalignment, independent of sampling time. These findings provide new insights into potential biomarkers for detecting acute circadian misalignment.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998730","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":"Modeling Genetic Risk of β-Cell Dysfunction in Human Induced Pluripotent Stem Cells From Patients Carrying the MTNR1B Risk Variant","authors":"Tania Singh,&nbsp;Sebastian Kalamajski,&nbsp;Joãp. P. M. C. M. Cunha,&nbsp;Siarhei Hladkou,&nbsp;Fiona Roberts,&nbsp;Sevda Gheibi,&nbsp;Anahita Soltanian,&nbsp;Kaveh Yektay Farahmand,&nbsp;Ola Ekström,&nbsp;Anant Mamidi,&nbsp;Paul. W. Franks,&nbsp;Anders Rosengren,&nbsp;Henrik Semb,&nbsp;Hindrik Mulder,&nbsp;Malin Fex","doi":"10.1111/jpi.70073","DOIUrl":"https://doi.org/10.1111/jpi.70073","url":null,"abstract":"<p>Disruptions in circadian rhythm, partly controlled by the hormone melatonin, increase the risk of type 2 diabetes (T2D). Accordingly, a variant of the gene encoding the melatonin receptor 1B (<i>MTNR1B</i>) is robustly associated with increased risk of T2D. This single-nucleotide polymorphism (SNP; rs10830963; G-allele) is an expression quantitative trait locus (eQTL) in human pancreatic islets, conferring increased expression of <i>MTNR1B</i>, which is thought to perturb pancreatic β-cell function. To understand this pathogenic mechanism in detail, we utilized human induced pluripotent stem cells (hiPSC), derived from individuals with T2D carrying the <i>MTNR1B</i> G-allele. Patient-derived fibroblasts were reprogrammed to hiPSC and single-base genome editing by CRISPR/Cas9 was employed to create isogenic lines of either the C/C or G/G genotypes (nonrisk and risk, respectively). In addition, the human embryonic stem cell (hESC) line (HUES4) was subjected to genome editing to create isogenic lines of either the C/C or G/G genotypes. hiPSC and hESC were differentiated into β-like cells, using a 50-day 2D protocol. Single-base genome editing generated cells with the desired genotype at a success rate of &gt; 90%. Expression of stage-specific markers confirmed differentiation of both hiPSC and hESC into β-cells. <i>MTNR1B</i> mRNA levels were consistently low in differentiated β-cells, precluding quantitative analysis of gene expression. Western blot analyses indicated slightly higher levels of the MTNR1B protein in differentiated β-cells carrying the risk allele, which is in accord with the notion that rs10830963 (G-allele) functions as an eQTL in β-cells. Insulin secretion in response to the combination of high glucose and IBMX was comparable between genotypes, whereas the addition of melatonin appeared to reduce insulin secretion more efficiently in cells carrying the G-allele. While our data suggest elevated MTNR1B protein levels in stem cell-derived β-like cells carrying the risk allele, these cells do not appear to be sufficiently mature to establish rs10830963 as an eQTL at the mRNA level. The observed nominal increase in melatonin sensitivity in G-allele–carrying cells is suggestive of a functional contribution of rs10830963 to β-cell dysfunction; however, this interpretation remains tentative and will require further validation in more mature β-cell models.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929846","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 Induces PERK-ATF4 Unfolded Protein Response and Apoptosis in Human Choriocarcinoma Cells","authors":"Josianne Bienvenue-Pariseault,&nbsp;Lucas Sagrillo-Fagundes,&nbsp;Philippe Wong-Yen,&nbsp;Darius Stakamatos,&nbsp;Marie Cohen,&nbsp;Cathy Vaillancourt","doi":"10.1111/jpi.70072","DOIUrl":"https://doi.org/10.1111/jpi.70072","url":null,"abstract":"<p>Melatonin, an indolamine primarily recognized for regulating circadian rhythms, has also demonstrated notable antitumoral properties. Melatonin induces endoplasmic reticulum (ER) stress, modulates autophagy, and promotes apoptosis in various tumors, including gastric, ovarian, cervical, oral tongue, colorectal, renal, hepatic, and bladder cancer. In placental choriocarcinoma, melatonin reduces cell viability and induces apoptosis by inhibiting autophagy and disrupting the mitochondrial membrane potential. However, its effects on ER stress and the unfolded protein response (UPR) pathway remain unexplored. It is hypothesized here that the proapoptotic effects of melatonin in choriocarcinoma cells occur through the activation of the UPR pathway. The factors implicated in the UPR (PERK, IRE1ɑ, ATF6, GRP78, ATF4, CHOP, P-eIF2α) pathways were evaluated by Western blot, RT-qPCR, and flow cytometry in BeWo (human choriocarcinoma) cells treated with or without melatonin (1 mM). Melatonin significantly increased protein levels of GRP78 (<i>p</i> = 0.0329), IRE1α (<i>p</i> = 0.0394), p-eIF2α (<i>p</i> = 0.0439), ATF4 (<i>p</i> = 0.0267), CHOP (<i>p</i> = 0.0379), Bax and cleaved PARP but did not affect TRAF2 and NFkB protein levels nor XBP1 mRNA splicing. PERK knockdown, via siRNA, prevented the rise in GRP78, p-eIF2α/eIF2α, and ATF4 levels by melatonin. Additionally, melatonin increased early apoptosis in BeWo cells (<i>p</i> = 0.0371) and PERK knockdown increased the susceptibility of BeWo cells to apoptosis when treated with tunicamycin (<i>p</i> = 0.0359), suggesting that ER stress plays a role in BeWo cell survival. This study demonstrates that melatonin activates the PERK-ATF4-P-eIF2α-CHOP pathway and induces early apoptosis in BeWo cells, while PERK deficiency compromises cell survival under ER stress. Our findings suggest that modulating PERK-UPR signaling with melatonin could present a promising therapeutic strategy for cancer, including placental choriocarcinoma.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910428","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":"NPAS2 Deficiency Leads to Antidepressant-Like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation","authors":"Yiyuan Tian,&nbsp;Jiao Mu,&nbsp;Jiali Ye,&nbsp;Jingyi Wei,&nbsp;Longquan Hu,&nbsp;Menghui Yuan,&nbsp;Wen Huang,&nbsp;Le Yang,&nbsp;Peng Yuan","doi":"10.1111/jpi.70070","DOIUrl":"https://doi.org/10.1111/jpi.70070","url":null,"abstract":"<div>\u0000 \u0000 <p>Major Depressive Disorder (MDD) is closely associated with neuroinflammation, but the underlying mechanisms remain to be fully elucidated. This study investigates the role of NPAS2 in mediating neuroinflammation-induced depressive-like behaviors using <i>NPAS2</i> knockout (KO) mice and lipopolysaccharide (LPS) treatment. We confirmed that NPAS2 protein expression in the hippocampus was significantly increased in mice exposed to LPS or chronic unpredictable mild stress (CUMS). Moreover, in the hippocampus, NPAS2 in astrocytes is more sensitive to inflammatory stimuli than that in neurons. <i>NPAS2</i> KO mice demonstrated attenuated astrocyte activation, reduced neuroinflammation associated with the inhibition of NF-κB and JAK2/STAT3 signaling pathways, and resilience to depressive- and anxiety-like behaviors. Mechanistically, the antidepressant effects in <i>NPAS2</i> KO mice were mediated through the BDNF/TrkB signaling pathway, which is regulated by inflammatory factors and controls synaptic plasticity. This conclusion was supported by the reversal of these effects using the BDNF receptor antagonist k252a. These findings highlight the critical role of astrocytic NPAS2 in mediating neuroinflammation-induced depressive-like behaviors and suggest that targeting NPAS2 may represent a novel therapeutic strategy for MDD.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861851","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 CD4+T Cell Apoptosis via the Bcl-2/BAX Pathway and Improves Survival Rates in Mice With Sepsis","authors":"Zhenggong Li,&nbsp;Huifang Wang,&nbsp;Qiuping Zhou,&nbsp;Qian Li,&nbsp;Nan Liu,&nbsp;Shuqi Jiang,&nbsp;Yiyu Deng","doi":"10.1111/jpi.70071","DOIUrl":"https://doi.org/10.1111/jpi.70071","url":null,"abstract":"<div>\u0000 \u0000 <p>This study examined whether melatonin could decrease CD4 + T cell apoptosis and reduce mortality rates in sepsis-induced mice. Fifty-one male C57BL/6 mice were randomly classified into three groups: Sham, cecal ligation and puncture (CLP), and CLP plus melatonin (CLP + MLT). Mice in the CLP + MLT group were intraperitoneally administered melatonin at 30 mg/kg 10 min before and 30 min after CLP and then once daily for 6 days. Lymphocyte counts, cytokine levels, and apoptosis rates in CD4+ and CD8 + T cells in the spleen and peripheral blood were examined using automatic blood cell analysis, enzyme-linked immunosorbent assay, or flow cytometry. The results demonstrated that melatonin improved the survival of mice following CLP, decreased the levels of IFN-γ, IL-1β, and IL-2 in the serum, and significantly upregulated lymphocyte counts. In addition, melatonin increased the percentage of CD4 + T cells and inhibited the apoptosis of these cells in the spleen and peripheral blood of mice following CLP. Melatonin protected against sepsis-induced organ damage. Melatonin inhibited CD4 + T cell apoptosis in vitro, possibly via the Bcl-2/BAX but not through the PD-1 pathway. Our results suggest that melatonin could mitigate Pro-inflammatory responses, attenuate organ injury, and suppress CD4 + T cell apoptosis via the Bcl-2/BAX pathway, thereby improving survival rates in a mouse model of sepsis. Targeted therapy to protect CD4 + T cells against apoptosis could represent a new approach for sepsis treatment in the future.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832808","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 Timing and Associations With Sleep Symptoms in People With Insomnia","authors":"Hannah Scott,&nbsp;Nicole Lovato,&nbsp;Maria Comas,&nbsp;Delwyn Bartlett,&nbsp;Ronald R. Grunstein,&nbsp;Leon Lack,&nbsp;Christopher J. Gordon","doi":"10.1111/jpi.70069","DOIUrl":"https://doi.org/10.1111/jpi.70069","url":null,"abstract":"<p>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, <i>r</i>_<i>(s)</i> = 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, <i>r</i>_<i>(s)</i> = −0.32 to 0.41. Participants with a longer phase angle between DLMO and sleep onset time (&gt; 3 h; i.e., greater delays) had longer sleep latencies (<i>Mean diff</i> = 43.21 min, <i>SE</i> = 12.99, <i>p</i> = 0.004) and shorter sleep durations (<i>Mean diff</i> = −65.66 min, <i>SE</i> = 20.75, <i>p</i> = 0.006) than participants with a shorter phase angle (&lt; 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.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 5","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773802","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":"Multivariate Data Analysis Methods and Their Application in Lipidomics: A Gentle Comment on Appropriateness and Reliability Criteria","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.70068","DOIUrl":"https://doi.org/10.1111/jpi.70068","url":null,"abstract":"<p>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.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672721","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":"Proteomic Signatures Underlying Sleep, Circadian Activity Patterns, and Major Chronic Diseases","authors":"Jiahe Wei,&nbsp;Hanzhang Wu,&nbsp;Ying Zheng,&nbsp;Bingtao Weng,&nbsp;Yao Xiao,&nbsp;Christian Benedict,&nbsp;Ningjian Wang,&nbsp;Xiang-Hang Luo,&nbsp;Xiao Tan","doi":"10.1111/jpi.70067","DOIUrl":"https://doi.org/10.1111/jpi.70067","url":null,"abstract":"<p>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.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666260","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":"Direct Peritoneal Resuscitation and Melatonin in the Treatment of Abdominal Sepsis-Induced Lung Injury via Macrophage Metabolic Reprogramming","authors":"Zhirong Zhao,&nbsp;Jiamin Ji,&nbsp;Lan Ming,&nbsp;Zhaofeng Luo,&nbsp;Mingyi Li,&nbsp;Yuan Chen,&nbsp;Ran Sun,&nbsp;Weiting Lu,&nbsp;Weiliang Tian,&nbsp;Fan Yang,&nbsp;Qian Huang","doi":"10.1111/jpi.70066","DOIUrl":"https://doi.org/10.1111/jpi.70066","url":null,"abstract":"<div>\u0000 \u0000 <p>Abdominal sepsis and the resultant lung injury lead to high mortality rates, with macrophage metabolic dysfunction and subsequent immune dysregulation being key contributing factors. The clarification of the therapeutic value of direct peritoneal resuscitation (DPR) combined with melatonin in regulating macrophage metabolic reprogramming is crucial for the development of potential treatment strategies. Lipopolysaccharide exposure led to a decrease in mitochondrial membrane potential (MMP) of macrophage, morphological changes in mitochondria, and a substantial accumulation of reactive oxygen species (ROS) within the cells. Melatonin protects the stability of the mitochondrial electron transport chain (ETC) by enhancing the synthesis of Uqcrc1, thereby restoring macrophage function. Silencing Uqcrc1 effectively blocked this protective effect. In the rat sepsis model, DPR combined with melatonin enhanced the survival of alveolar macrophages (AMs) and reduced lung tissue damage. Importantly, in the DPR combined with melatonin treated group, the macrophage metabolic reprogramming was evident through enhanced oxidative phosphorylation and increased adenosine triphosphate (ATP) synthesis, both of which contributed to improved immune function and reduced inflammation. It is found that melatonin promotes the synthesis of Uqcrc1, stabilizing the ETC in macrophages. The combination of DPR and melatonin alleviated sepsis-induced lung injury in rats by modulating macrophage metabolic reprogramming.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624382","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}