Journal of Pineal Research最新文献

{"title":"Chronic developmental hypoxia alters mitochondrial oxidative capacity and reactive oxygen species production in the fetal rat heart in a sex-dependent manner","authors":"Kerri L. M. Smith,&nbsp;Agnieszka Swiderska,&nbsp;Mitchell C. Lock,&nbsp;Lucia Graham,&nbsp;Wulan Iswari,&nbsp;Tashi Choudhary,&nbsp;Donna Thomas,&nbsp;Hager M. Kowash,&nbsp;Michelle Desforges,&nbsp;Elizabeth C. Cottrell,&nbsp;Andrew W. Trafford,&nbsp;Dino A. Giussani,&nbsp;Gina L. J. Galli","doi":"10.1111/jpi.12821","DOIUrl":"https://doi.org/10.1111/jpi.12821","url":null,"abstract":"<p>Insufficient oxygen supply (hypoxia) during fetal development leads to cardiac remodeling and a predisposition to cardiovascular disease in later life. Previous work has shown hypoxia causes oxidative stress in the fetal heart and alters the activity and expression of mitochondrial proteins in a sex-dependent manner. However, the functional effects of these modifications on mitochondrial respiration remain unknown. Furthermore, while maternal antioxidant treatments are emerging as a promising new strategy to protect the hypoxic fetus, whether these treatments convey similar protection to cardiac mitochondria in the male or female fetus has not been investigated. Therefore, using an established rat model, we measured the sex-dependent effects of gestational hypoxia and maternal melatonin treatment on fetal cardiac mitochondrial respiration, reactive oxygen species (ROS) production, and lipid peroxidation. Pregnant Wistar rats were subjected to normoxia or hypoxia (13% oxygen) during gestational days (GDs) 6–20 (term ~22 days) with or without melatonin treatment (5 µg/ml in maternal drinking water). On GD 20, mitochondrial aerobic respiration and H₂O₂ production were measured in fetal heart tissue, together with lipid peroxidation and citrate synthase (CS) activity. Gestational hypoxia reduced maternal body weight gain (<i>p</i> &lt; .01) and increased placental weight (<i>p</i> &lt; .05) but had no effect on fetal weight or litter size. Cardiac mitochondria from male but not female fetuses of hypoxic pregnancy had reduced respiratory capacity at Complex II (CII) (<i>p</i> &lt; .05), and an increase in H₂O₂ production/O₂ consumption (<i>p</i> &lt; .05) without any changes in lipid peroxidation. CS activity was also unchanged in both sexes. Despite maternal melatonin treatment increasing maternal and fetal plasma melatonin concentration (<i>p</i> &lt; .001), melatonin treatment had no effect on any of the mitochondrial parameters investigated. To conclude, we show that gestational hypoxia leads to ROS generation from the mitochondrial electron transport chain and affects fetal cardiac mitochondrial respiration in a sex-dependent manner. We also show that maternal melatonin treatment had no effect on these relationships, which has implications for the development of future therapies for hypoxic pregnancies.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"73 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6127157","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":"Daytime rest: Association with 24-h rest–activity cycles, circadian timing and cognition in older adults","authors":"Mathilde Reyt,&nbsp;Michele Deantoni,&nbsp;Marion Baillet,&nbsp;Alexia Lesoinne,&nbsp;Sophie Laloux,&nbsp;Eric Lambot,&nbsp;Justine Demeuse,&nbsp;Chiara Calaprice,&nbsp;Caroline LeGoff,&nbsp;Fabienne Collette,&nbsp;Gilles Vandewalle,&nbsp;Pierre Maquet,&nbsp;Vincenzo Muto,&nbsp;Grégory Hammad,&nbsp;Christina Schmidt","doi":"10.1111/jpi.12820","DOIUrl":"https://doi.org/10.1111/jpi.12820","url":null,"abstract":"<p>Growing epidemiological evidence points toward an association between fragmented 24-h rest–activity cycles and cognition in the aged. Alterations in the circadian timing system might at least partially account for these observations. Here, we tested whether daytime rest (DTR) is associated with changes in concomitant 24-h rest probability profiles, circadian timing and neurobehavioural outcomes in healthy older adults. Sixty-three individuals (59–82 years) underwent field actigraphy monitoring, in-lab dim light melatonin onset assessment and an extensive cognitive test battery. Actimetry recordings were used to measure DTR frequency, duration and timing and to extract 24-h rest probability profiles. As expected, increasing DTR frequency was associated not only with higher rest probabilities during the day, but also with lower rest probabilities during the night, suggesting more fragmented night-time rest. Higher DTR frequency was also associated with lower episodic memory performance. Moreover, later DTR timing went along with an advanced circadian phase as well as with an altered phase angle of entrainment between the rest–activity cycle and circadian phase. Our results suggest that different DTR characteristics, as reflective indices of wake fragmentation, are not only underlined by functional consequences on cognition, but also by circadian alteration in the aged.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"73 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5770822","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 alleviates the heat stress-induced impairment of Sertoli cells by reprogramming glucose metabolism","authors":"Cheng-Chen Deng,&nbsp;Ji-Pan Zhang,&nbsp;Yuan-Nan Huo,&nbsp;Hong-Yan Xue,&nbsp;Wenxiu Wang,&nbsp;Jiao-Jiao Zhang,&nbsp;Xian-Zhong Wang","doi":"10.1111/jpi.12819","DOIUrl":"https://doi.org/10.1111/jpi.12819","url":null,"abstract":"<p>Sertoli cells (SCs) provide structural and nutritional support for developing germ cells. Normal glucose metabolism of SCs is necessary for spermatogenesis. Melatonin could alleviate the effects of heat stress on spermatogenesis. However, the influences of heat stress on glucose metabolism in SCs remain unclear, and the potential protective mechanisms of melatonin on SCs need more exploration. In this study, boar SCs were treated at 43°C for 30 min, and different concentrations of melatonin were added to protect SCs from heat stress-induced impairment. These results showed that heat stress-induced oxidative stress caused cell apoptosis, inhibited the pentose phosphate pathway, and decreased the ATP content. Furthermore, heat stress increased the expressions of glucose intake- and glycolytic-related enzymes, which enhanced the glycolysis activity to compensate for the energy deficit. Melatonin relieved heat stress-induced oxidative stress and apoptosis by activating the Kelch-like ECH-associated protein 1 (KEAP1)/NF-E2-related factor 2 signaling pathway to increase the capacity of antioxidants. In addition, melatonin enhanced heat-shock protein 90 (HSP90) expression through melatonin receptor 1B (MTNR1B), thereby stabilizing hypoxia-inducible factor-1α (HIF-1α). Activation of the HIF-1α signaling pathway enhanced glycolysis, promoted the pentose phosphate pathway, and increased cell viability. Our results suggest that melatonin reprograms glucose metabolism in SCs through the MTNR1B–HSP90–HIF-1α axis and provides a theoretical basis for preventing heat stress injury.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"73 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5878688","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":"Human–rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic–ischemic pathway melatonin-sensitive","authors":"Michael D. Weiss,&nbsp;Silvia Carloni,&nbsp;Tania Vanzolini,&nbsp;Sofia Coppari,&nbsp;Walter Balduini,&nbsp;Giuseppe Buonocore,&nbsp;Mariangela Longini,&nbsp;Serafina Perrone,&nbsp;Livia Sura,&nbsp;Atefeh Mohammadi,&nbsp;Marco Bruno Luigi Rocchi,&nbsp;Massimo Negrini,&nbsp;Davide Melandri,&nbsp;Maria Cristina Albertini","doi":"10.1111/jpi.12818","DOIUrl":"https://doi.org/10.1111/jpi.12818","url":null,"abstract":"<p>Neonatal encephalopathy (NE) is a pathological condition affecting long-term neurodevelopmental outcomes. Hypothermia is the only therapeutic option, but does not always improve outcomes; hence, researchers continue to hunt for pharmaceutical compounds. Melatonin treatment has benefitted neonates with hypoxic–ischemic (HI) brain injury. However, unlike animal models that enable the study of the brain and the pathophysiologic cascade, only blood is available from human subjects. Therefore, due to the unavailability of neonatal brain tissue, assumptions about the pathophysiology in pathways and cascades are made in human subjects with NE. We analyzed animal and human specimens to improve our understanding of the pathophysiology in human neonates. A neonate with NE who underwent hypothermia and enrolled in a melatonin pharmacokinetic study was compared to HI rats treated/untreated with melatonin. MicroRNA (miRNA) analyses provided profiles of the neonate's plasma, rat plasma, and rat brain cortexes. We compared these profiles through a bioinformatics tool, identifying Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways common to HI brain injury and melatonin treatment. After evaluating the resulting pathways and the literature, to validate the method, the key proteins expressed in HI brain injury were investigated using cerebral cortexes. The upregulated miRNAs in human neonate and rat plasma helped identify two KEGG pathways, glioma and long-term potentiation, common to HI injury and melatonin treatment. A unified neonatal cerebral melatonin-sensitive HI pathway was designed and validated by assessing the expression of protein kinase Cα (PKCα), phospho (p)-Akt, and p-ERK proteins in rat brain cortexes. PKCα increased in HI-injured rats and further increased with melatonin. p-Akt and p-ERK returned phosphorylated to their basal level with melatonin treatment after HI injury. The bioinformatics analyses validated by key protein expression identified pathways common to HI brain injury and melatonin treatment. This approach helped complete pathways in neonates with NE by integrating information from animal models of HI brain injury.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"73 2","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12818","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5685005","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":"The role of circadian phase in sleep and performance during Antarctic winter expeditions","authors":"Tracey L. Sletten,&nbsp;Jason P. Sullivan,&nbsp;Josephine Arendt,&nbsp;Lawrence A. Palinkas,&nbsp;Laura K. Barger,&nbsp;Lloyd Fletcher,&nbsp;Malcolm Arnold,&nbsp;Jan Wallace,&nbsp;Clive Strauss,&nbsp;Richard J. S. Baker,&nbsp;Kate Kloza,&nbsp;David J. Kennaway,&nbsp;Shantha M. W. Rajaratnam,&nbsp;Jeff Ayton,&nbsp;Steven W. Lockley","doi":"10.1111/jpi.12817","DOIUrl":"https://doi.org/10.1111/jpi.12817","url":null,"abstract":"<p>The Antarctic environment presents an extreme variation in the natural light-dark cycle which can cause variability in the alignment of the circadian pacemaker with the timing of sleep, causing sleep disruption, and impaired mood and performance. This study assessed the incidence of circadian misalignment and the consequences for sleep, cognition, and psychological health in 51 over-wintering Antarctic expeditioners (45.6 ± 11.9 years) who completed daily sleep diaries, and monthly performance tests and psychological health questionnaires for 6 months. Circadian phase was assessed via monthly 48-h urine collections to assess the 6-sulphatoxymelatonin (aMT6s) rhythm. Although the average individual sleep duration was 7.2 ± 0.8 h, there was substantial sleep deficiency with 41.4% of sleep episodes &lt;7 h and 19.1% &lt;6 h. Circadian phase was highly variable and 34/50 expeditioners had sleep episodes that occurred at an abnormal circadian phase (acrophase outside of the sleep episode), accounting for 18.8% (295/1565) of sleep episodes. Expeditioners slept significantly less when misaligned (6.1 ± 1.3 h), compared with when aligned (7.3 ± 1.0 h; <i>p</i> &lt; .0001). Performance and mood were worse when awake closer to the aMT6s peak and with increased time awake (all <i>p</i> &lt; .0005). This research highlights the high incidence of circadian misalignment in Antarctic over-wintering expeditioners. Similar incidence has been observed in long-duration space flight, reinforcing the fidelity of Antarctica as a space analog. Circadian misalignment has considerable safety implications, and potentially longer term health risks for other circadian-controlled physiological systems. This increased risk highlights the need for preventative interventions, such as proactively planned lighting solutions, to ensure circadian alignment during long-duration Antarctic and space missions.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"73 2","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5652673","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":"Recharge of chondrocyte mitochondria by sustained release of melatonin protects cartilage matrix homeostasis in osteoarthritis","authors":"Yijian Zhang,&nbsp;Mingzhuang Hou,&nbsp;Yang Liu,&nbsp;Tao Liu,&nbsp;Xi Chen,&nbsp;Qin Shi,&nbsp;Dechun Geng,&nbsp;Huilin Yang,&nbsp;Fan He,&nbsp;Xuesong Zhu","doi":"10.1111/jpi.12815","DOIUrl":"https://doi.org/10.1111/jpi.12815","url":null,"abstract":"<p>Recent evidence indicates that the mitochondrial functions of chondrocytes are impaired in the pathogenesis of osteoarthritis (OA). Melatonin can attenuate cartilage degradation through its antioxidant functions. This study aims to investigate whether melatonin could rescue the impaired mitochondrial functions of OA chondrocytes and protect cartilage metabolism. OA chondrocytes showed a compromised matrix synthesis capacity associated with mitochondrial dysfunction and aberrant oxidative stress. In vitro treatments with melatonin promoted the expression of cartilage extracellular matrix (ECM) components, improved adenosine triphosphate production, and attenuated mitochondrial oxidative stress. Mechanistically, either silencing of SOD2 or inhibition of SIRT1 abolished the protective effects of melatonin on mitochondrial functions and ECM synthesis. To achieve a sustained release effect, a melatonin-laden drug delivery system (DDS) was developed and intra-articular injection with DDS successfully improved cartilage matrix degeneration in a posttraumatic rat OA model. These findings demonstrate that melatonin-mediated recharge of mitochondria to rescue the mitochondrial functions of chondrocytes represents a promising therapeutic strategy to protect cartilage from OA.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"73 2","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5746241","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":"The role of MEK1/2 and MEK5 in melatonin-mediated actions on osteoblastogenesis, osteoclastogenesis, bone microarchitecture, biomechanics, and bone formation","authors":"Fahima Munmun,&nbsp;Omair A. Mohiuddin,&nbsp;Van T. Hoang,&nbsp;Matthew E. Burow,&nbsp;Bruce A. Bunnell,&nbsp;Veronica M. Sola,&nbsp;Agata R. Carpentieri,&nbsp;Paula A. Witt-Enderby","doi":"10.1111/jpi.12814","DOIUrl":"https://doi.org/10.1111/jpi.12814","url":null,"abstract":"<p>Melatonin, the primary hormone involved in circadian entrainment, plays a significant role in bone physiology. This study aimed to assess the role of MEK1/2 and MEK5 in melatonin-mediated actions in mouse and human mesenchymal stem cells (MSCs) and on bone using small-molecule inhibitors and CRISPR/Cas9 knockout approaches. Consistent with in vitro studies performed in mMSCs and hMSCs, nightly (25 mg/kg, i.p., 45 days) injections with PD184352 (MEK1/2 inhibitor) or Bix02189 (MEK5 inhibitor) or SC-1-151 (MEK1/2/5 inhibitor) demonstrated that MEK1/2 and MEK5 were the primary drivers underlying melatonin's actions on bone density, microarchitecture (i.e., trabecular number, separation, and connectivity density), and bone mechanical properties (i.e., ultimate stress) through increases in osteogenic (RUNX2, BMP-2, FRA-1, OPG) expression and decreases in PPARγ. Furthermore, CRISPR/Cas9 knockout of MEK1 or MEK5 in mMSCs seeded on PLGA scaffolds and placed into critical-size calvarial defects in Balb(c) mice (male and female) revealed that treatment with melatonin (15 mg/L; p.o., nightly, 90 days) mediates sex-specific actions of MEK1 and MEK5 in new bone formation. This study is the first to demonstrate a role for MEK1/2 and MEK5 in modulating melatonin-mediated actions on bone formation in vivo and in a sex-specific manner.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"73 2","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6133271","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 may suppress lung adenocarcinoma progression via regulation of the circular noncoding RNA hsa_circ_0017109/miR-135b-3p/TOX3 axis","authors":"Yuanyong Wang,&nbsp;Zhaoyang Wang,&nbsp;Changjian Shao,&nbsp;Guofang Lu,&nbsp;Mei Xie,&nbsp;Jian Wang,&nbsp;Hongtao Duan,&nbsp;Xiaofei Li,&nbsp;Wanpeng Yu,&nbsp;Weixun Duan,&nbsp;Xiaolong Yan","doi":"10.1111/jpi.12813","DOIUrl":"https://doi.org/10.1111/jpi.12813","url":null,"abstract":"<p>Melatonin is a hormone synthesized in the pineal gland and has widespread physiological and pharmacological functions. Moreover, it can activate protective receptor-dependent processes. These processes can prevent tissue carcinogenesis and inhibit malignant tumor progression and metastasis. Therefore, we investigated the regulatory effects of melatonin on dysregulated circular RNAs in human lung adenocarcinoma (LUAD) cells. In this study, we treated LUAD cells with melatonin and measured the expression of hsa_circ_0017109, miR-135b-3p, and TOX3 by quantitative reverse transcription polymerase chain reaction. Colony formation and cell counting kit-8 assays were used to determine cell proliferation. The wound-healing assay and Transwell experiment were carried out to evaluate the migration potential and invasive capacity of LUAD cells. Also, cell apoptosis was detected using a cell apoptosis kit, and protein production was identified by Western blot. It was suggested that melatonin could inhibit LUAD progression in vivo and in vitro, and the role of TOX3 in this process was explored. Additionally, hsa_circ_0017109 was found to sponge miR-135b-3p, a downstream factor of circ_0017109, which was demonstrated to target TOX3 in LUAD cells and could promote the Hippo pathway and epithelial–mesenchymal transition pathway. To summarize, we demonstrated that melatonin decreases the expression of circ_0017109 and suppresses the non-small-cell lung cancer cell migration, invasion, and proliferation through decreasing TOX3 expression via direct activation of miR-135b-3p.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"73 2","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6076124","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 mitigates aflatoxin B1-induced liver injury via modulation of gut microbiota/intestinal FXR/liver TLR4 signaling axis in mice","authors":"Shuiping Liu,&nbsp;Weili Kang,&nbsp;Xinru Mao,&nbsp;Lei Ge,&nbsp;Heng Du,&nbsp;Jinyan Li,&nbsp;Lili Hou,&nbsp;Dandan Liu,&nbsp;Yulong Yin,&nbsp;Yunhuan Liu,&nbsp;Kehe Huang","doi":"10.1111/jpi.12812","DOIUrl":"https://doi.org/10.1111/jpi.12812","url":null,"abstract":"<p>Aflatoxin B1 (AFB1) is a widespread contaminant in foods and feedstuffs, and its target organ is the liver. Melatonin (MT) has been shown to alleviate inflammation in organs and remodel gut microbiota in animals and humans. However, the underlying mechanism by which MT alleviates AFB1-induced liver injury remains unclear. In the present study, MT pretreatment markedly increased the expression of intestinal tight junction proteins (ZO-1, Occludin, and Claudin-1), decreased intestinal permeability, reduced production of gut-derived Lipopolysaccharide (LPS) and remodeled gut microbiota, ultimately alleviated AFB1-induced liver injury in mice. Interestingly, MT pretreatment failed to exert beneficial effects on the intestine and liver in antibiotic-treated mice. Meanwhile, MT pretreatment significantly increased the farnesoid X receptor (FXR) protein expression of ileum, and decreased the TLR4/NF-κB signaling pathway-related messenger RNA (mRNA) and proteins (TLR4, MyD88, p-p65, and p-IκBα) expression in livers of AFB1-exposed mice. Subsequently, pretreatment by Gly-β-MCA, an intestine-selective FXR inhibitor, blocked the alleviating effect of MT on liver injury through increasing the liver-specific expression of TLR4/NF-κB signaling pathway-related mRNA and proteins (TLR4, MyD88, p-p65, and p-IκBα). In conclusion, MT pretreatment ameliorated AFB1-induced liver injury and the potential mechanism may be related to regulate gut microbiota/intestinal FXR/liver TLR4 signaling axis, which provides a strong evidence for the protection of gut-derived liver inflammation.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"73 2","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6044431","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 use and the risk of 30-day mortality among US veterans with sepsis: A retrospective study","authors":"S. Scott Sutton,&nbsp;Joseph Magagnoli,&nbsp;Tammy H. Cummings,&nbsp;James W. Hardin","doi":"10.1111/jpi.12811","DOIUrl":"https://doi.org/10.1111/jpi.12811","url":null,"abstract":"<p>Prior research suggests melatonin has beneficial effects that could improve survival among sepsis patients. This exploratory analysis sought to compare 30-day survival among melatonin treated and untreated patients with sepsis. A retrospective cohort study was conducted among patients with a primary inpatient admission diagnosis for sepsis utilizing the International Classification of Diseases, versions 9 and 10, Clinical Modification (ICD-9-CM and ICD-10-CM) diagnosis codes between 2000 and 2021. Propensity score weighting was utilized, accounting for demographic, clinical, and laboratory factors. Weighted Cox models were estimated for 30-day in-hospital and 30-day overall survival. A total of 9386 patients were included in the study with 593 exposed to melatonin within the first day of hospitalization. Propensity score weighted Cox models reveal melatonin was associated with a 37.9% decreased risk of 30-day in-hospital mortality (HR = 0.621; 95% CI = [0.415–0.931]) and a 33.5% decreased risk of 30-day overall mortality (HR = 0.665; 95% CI = [0.493–0.897]). Factors associated with higher risk of both in-hospital and overall mortality include male sex, white race, age, higher Charlson comorbidity burden, sodium and potassium levels, intensive care unit stay, invasive ventilation, and vasopressor use. Higher serum albumin levels are associated with lower mortality risks. Among patients diagnosed with sepsis, exposure to melatonin was associated with a lower in-hospital and 30-day mortality. Additional research is warranted to fully understand the role of melatonin in sepsis.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"73 2","pages":""},"PeriodicalIF":10.3,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5669220","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}