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RETRACTION: Melatonin Prevents Oxidative Stress and Changes in Antioxidant Enzyme Expression and Activity in the Liver of Aging Rats 回放:褪黑素可防止氧化应激以及衰老大鼠肝脏中抗氧化酶表达和活性的变化。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-06-17 DOI: 10.1111/jpi.12973

RETRACTION: Mauriz JL, Molpeceres V, García-Mediavilla MV, González P, Barrio JP, González-Gallego J. Melatonin prevents oxidative stress and changes in antioxidant enzyme expression and activity in the liver of aging rats. J Pineal Res 2007;42:222-230. https://doi.org/10.1111/j.1600-079X.2006.00409.x

The above article, published online on 12 December 2006 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Gianluca Tosini, and John Wiley and Sons Ltd. Following publication, concerns were raised by third parties regarding Figure 4A. The authors could not provide the original data for this figure, and were unable to provide a satisfactory explanation to resolve the concerns. The retraction has been agreed because of concerns that portions of the figure were duplicated, affecting the interpretation of the data and results presented. The authors disagree with this decision.

撤回:Mauriz JL, Molpeceres V, García-Mediavilla MV, González P, Barrio JP, González-Gallego J. 褪黑激素可防止氧化应激以及衰老大鼠肝脏中抗氧化酶表达和活性的变化。J Pineal Res 2007; 42:222-230。https://doi.org/10.1111/j.1600-079X.2006.00409.x 上述文章于 2006 年 12 月 12 日在线发表于 Wiley Online Library (wileyonlinelibrary.com),经杂志主编 Gianluca Tosini 和 John Wiley and Sons Ltd.协商,该文章已被撤回。文章发表后,第三方对图 4A 提出了质疑。作者无法提供该图的原始数据,也无法提供令人满意的解释来消除疑虑。由于该图部分内容重复,影响了对数据和结果的解释,因此作者同意撤稿。作者不同意这一决定。
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引用次数: 0
RETRACTION: Melatonin Inhibits the Sphingosine Kinase 1/Sphingosine-1-Phosphate Signaling Pathway in Rabbits With Fulminant Hepatitis of Viral Origin 回放:褪黑素抑制病毒性暴发性肝炎家兔的鞘磷脂激酶 1/鞘磷脂-1-磷酸信号通路。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-06-17 DOI: 10.1111/jpi.12979

RETRACTION: Crespo I, San-Miguel B, Sánchez DI, González-Fernández B, Álvarez M, González-Gallego J, Tuñón MJ. Melatonin inhibits the sphingosine kinase 1/sphingosine-1-phosphate signaling pathway in rabbits with fulminant hepatitis of viral origin. J Pineal Res 2016;61: 168-176. https://doi.org/10.1111/jpi.12335

The above article, published online on 22 April 2016 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Gianluca Tosini, and John Wiley and Sons Ltd. Following publication, concerns were raised by third parties regarding Figure 2A. The authors could not provide the original data for this figure. The authors provided an updated image, but this was not sufficient to resolve the concerns, and the authors were unable to provide a satisfactory explanation for the concerns. The retraction has been agreed because of concerns that portions of the figure were duplicated, affecting the interpretation of the data and results presented. The authors disagree with this decision.

撤回:Crespo I, San-Miguel B, Sánchez DI, González-Fernández B, Álvarez M, González-Gallego J, Tuñón MJ.褪黑激素抑制病毒性暴发性肝炎家兔的鞘磷脂激酶1/鞘磷脂-1-磷酸信号通路。J Pineal Res 2016;61: 168-176. https://doi.org/10.1111/jpi.12335 上述文章于2016年4月22日在线发表于《威利在线图书馆》(wileyonlinelibrary.com),经期刊主编Gianluca Tosini和John Wiley and Sons Ltd.协议,该文章已被撤回。文章发表后,第三方对图 2A 提出了质疑。作者无法提供该图的原始数据。作者提供了一张更新后的图片,但这不足以消除疑虑,作者也无法对疑虑做出令人满意的解释。同意撤稿的原因是担心该图的部分内容重复,影响了对所提供数据和结果的解释。作者不同意这一决定。
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引用次数: 0
Zygotic Exposure to Venlafaxine Disrupts the Circadian Locomotor Activity Behaviour in Zebrafish Larvae 斑马鱼幼体的昼夜节律运动行为受到文拉法辛的影响
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-06-14 DOI: 10.1111/jpi.12984
W. Andrew Thompson, Mathilakath M. Vijayan

The antidepressant venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is commonly prescribed to treat major depressive disorder and is found at high concentrations in the aquatic environment. Concerns have been raised related to the health of aquatic organisms in response to this nontargeted pharmaceutical exposure. For instance, we previously demonstrated that exposure to venlafaxine perturbs neurodevelopment, leading to behavioural alterations in zebrafish (Danio rerio). We also observed disruption in serotonin expression in the pineal and raphe, regions critical in regulating circadian rhythms, leading us to hypothesize that zygotic exposure to venlafaxine disrupts the circadian locomotor rhythm in larval zebrafish. To test this, we microinjected zebrafish embryos with venlafaxine (1 or 10 ng) and recorded the locomotor activity in 5-day-old larvae over a 24-h period. Venlafaxine deposition reduced larval locomotor activity during the light phase, but not during the dark phase of the diurnal cycle. The melatonin levels were higher in the dark compared to during the light photoperiod and this was not affected by embryonic venlafaxine deposition. Venlafaxine exposure also did not affect the transcript abundance of clock genes, including clock1a, bmal2, cry1a and per2, which showed a clear day/night rhythmicity. A notable finding was that exposure to luzindole, a melatonin receptor antagonist, decreased the locomotor activity in the control group in light, whereas the activity was higher in larvae raised from the venlafaxine-deposited embryos. Overall, zygotic exposure to venlafaxine disrupts the locomotor activity of larval zebrafish fish during the day, demonstrating the capacity of antidepressants to disrupt the circadian rhythms in behaviour. Our results suggest that disruption in melatonin signalling may be playing a role in the venlafaxine impact on circadian behaviour, but further investigation is required to elucidate the possible mechanisms in larval zebrafish.

抗抑郁药文拉法辛(一种选择性血清素和去甲肾上腺素再摄取抑制剂)是治疗重度抑郁症的常用处方药,在水生环境中的浓度很高。这种非靶向药物接触引起了人们对水生生物健康的关注。例如,我们曾证实,暴露于文拉法辛会扰乱斑马鱼(Danio rerio)的神经发育,导致行为改变。我们还观察到松果体和剑突中的血清素表达受到干扰,而松果体和剑突是调节昼夜节律的关键区域,因此我们推测暴露于文拉法辛的子代会干扰幼体斑马鱼的昼夜节律。为了验证这一假设,我们给斑马鱼胚胎注射了文拉法辛(1 或 10 纳克),并记录了 5 天大幼体在 24 小时内的运动活动。在昼夜周期的光照阶段,文拉法辛的沉积降低了幼体的运动活动,但在黑暗阶段却没有降低。黑暗期的褪黑激素水平高于光照期,但这并不受胚胎期文拉法辛沉积的影响。暴露于文拉法辛也不会影响时钟基因的转录本丰度,包括clock1a、bmal2、cry1a和per2,这些基因表现出明显的昼夜节律性。一个值得注意的发现是,暴露于褪黑激素受体拮抗剂卢吲哚会降低对照组在光照下的运动活性,而文拉法辛沉积胚胎培育的幼虫的运动活性更高。总之,卵子期暴露于文拉法辛会扰乱斑马鱼幼鱼在白天的运动活动,这表明抗抑郁药有能力扰乱行为的昼夜节律。我们的研究结果表明,褪黑激素信号的中断可能是文拉法辛影响昼夜节律行为的原因之一,但要阐明斑马鱼幼体的可能机制还需要进一步的研究。
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引用次数: 0
Melatonin decreases human adipose tissue insulin sensitivity 褪黑素会降低人体脂肪组织对胰岛素的敏感性。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-06-11 DOI: 10.1111/jpi.12965
Carolina Zambrano, Mireia Tena Garitaonaindia, Diego Salmerón, Fernando Pérez-Sanz, Cynthia Tchio, María Cecilia Picinato, Fermín Sánchez de Medina, Juan Luján, Frank A. J. L. Scheer, Richa Saxena, Olga Martínez-Augustin, Marta Garaulet

Melatonin is a pineal hormone that modulates the circadian system and exerts soporific and phase-shifting effects. It is also involved in many other physiological processes, such as those implicated in cardiovascular, endocrine, immune, and metabolic functions. However, the role of melatonin in glucose metabolism remains contradictory, and its action on human adipose tissue (AT) explants has not been demonstrated. We aimed to assess whether melatonin (a pharmacological dose) influences insulin sensitivity in human AT. This will help better understand melatonin administration's effect on glucose metabolism. Abdominal AT (subcutaneous and visceral) biopsies were obtained from 19 participants with severe obesity (age: 42.84 ± 12.48 years; body mass index: 43.14 ± 8.26 kg/m2) who underwent a laparoscopic gastric bypass. AT biopsies were exposed to four different treatments: control (C), insulin alone (I) (10 nM), melatonin alone (M) (5000 pg/mL), and insulin plus melatonin combined (I + M). All four conditions were repeated in both subcutaneous and visceral AT, and all were performed in the morning at 8 a.m. (n = 19) and the evening at 8 p.m. (in a subsample of n = 12). We used western blot analysis to determine insulin signaling (using the pAKT/tAKT ratio). Furthermore, RNAseq analyses were performed to better understand the metabolic pathways involved in the effect of melatonin on insulin signaling. As expected, insulin treatment (I) increased the pAKT/tAKT ratio compared with control (p < .0001). Furthermore, the addition of melatonin (I + M) resulted in a decrease in insulin signaling as compared with insulin alone (I); this effect was significant only during the evening time (not in the morning time). Further, RNAseq analyses in visceral AT during the evening condition (at 8 p.m.) showed that melatonin resulted in a prompt transcriptome response (around 1 h after melatonin addition), particularly by downregulating the insulin signaling pathway. Our results show that melatonin reduces insulin sensitivity in human AT during the evening. These results may partly explain the previous studies showing a decrease in glucose tolerance after oral melatonin administration in the evening or when eating late when endogenous melatonin is present.

褪黑素是一种松果体激素,它能调节昼夜节律系统,并具有催眠和移相作用。它还参与许多其他生理过程,例如与心血管、内分泌、免疫和新陈代谢功能有关的过程。然而,褪黑激素在葡萄糖代谢中的作用仍然存在矛盾,而且它对人体脂肪组织(AT)外植体的作用尚未得到证实。我们的目的是评估褪黑素(药理剂量)是否会影响人体脂肪组织的胰岛素敏感性。这将有助于更好地了解褪黑素对糖代谢的影响。我们从19名接受腹腔镜胃旁路手术的重度肥胖症患者(年龄:42.84 ± 12.48岁;体重指数:43.14 ± 8.26 kg/m2)身上采集了腹部AT(皮下和内脏)活检组织。腹腔镜胃旁路术活检组织接受了四种不同的治疗:对照组(C)、单用胰岛素组(I)(10 nM)、单用褪黑素组(M)(5000 pg/mL)和胰岛素加褪黑素组(I + M)。所有四种情况都在皮下和内脏 AT 中重复进行,并且都在早上 8 点(n = 19)和晚上 8 点(n = 12 的子样本)进行。我们使用 Western 印迹分析来确定胰岛素信号转导(使用 pAKT/tAKT 比值)。此外,我们还进行了 RNAseq 分析,以更好地了解褪黑激素对胰岛素信号转导的影响所涉及的代谢途径。不出所料,与对照组相比,胰岛素处理(I)增加了 pAKT/tAKT 比率(p
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引用次数: 0
Novel melatonin-producing Bacillus safensis EH143 mitigates salt and cadmium stress in soybean 新型褪黑素芽孢杆菌 EH143 可减轻大豆的盐和镉胁迫。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-27 DOI: 10.1111/jpi.12957
Eun-Hae Kwon, Arjun Adhikari, Muhammad Imran, Adil Hussain, Ho-Jun Gam, Ji-In Woo, Jin Ryeol Jeon, Da-Sol Lee, Chung-Yeol Lee, Liny Lay, Sang-Mo Kang, Won-Chan Kim, Byung-Wook Yun, In-Jung Lee

Recently, microorganism and exogenous melatonin application has been recognized as an efficient biological tool for enhancing salt tolerance and heavy metal detoxification in agriculture crops. Thus, the goal of this study was to isolate and evaluate a novel melatonin-producing plant growth promoting bacterium. With high-throughput whole genome sequencing, phytohormone measurements, expression profiling, and biochemical analysis, we can identify a novel PGPB that produces melatonin and unravel how it promotes soybean growth and development and protects against salt and Cd stress. We identify the melatonin synthesis pathway (tryptophan→tryptamine→serotonin melatonin) of the halotolerant (NaCl > 800 mM) and heavy metal-resistant (Cd >3 mM) rhizobacterium Bacillus safensis EH143 and use it to treat soybean plants subjected to Cd and NaCl stresses. Results show that EH143 will highly bioaccumulate heavy metals and significantly improve P and Ca2+ uptake and the K+/Na+ (93%↑under salt stress) ratio while reducing Cd uptake (49% under Cd stress) in shoots. This activity was supported by the expression of the ion regulator HKT1, MYPB67, and the calcium sensors CDPK5 and CaMK1 which ultimately led to increased plant growth. EH143 significantly decreased ABA content in shoots by 13%, 20%, and 34% and increased SA biosynthesis in shoots by 14.8%, 31%, and 48.2% in control, salt, and Cd-treated plants, upregulating CYP707A1 and CYP707A2 and PAL1 and ICS, respectively. The melatonin content significantly decreased along with a reduced expression of ASMT3 following treatment with EH143; moreover, reduced expression of peroxidase (POD) and superoxide dismutase (SOD) by 134.5% and 39% under salt+Cd stress, respectively and increased level of total amino acids were observed. Whole-genome sequencing and annotation of EH143 revealed the presence of the melatonin precursor tryptophan synthase (trpA, trpB, trpS), metal and other ion regulators (Cd: cadA, potassium: KtrA and KtrB, phosphate: glpT, calcium: yloB, the sodium/glucose cotransporter: sgIT, and the magnesium transporter: mgtE), and enzyme activators (including the siderophore transport proteins yfiZ and yfhA, the SOD sodA, the catalase katA1, and the glutathione regulator KefG) that may be involved in programming the plant metabolic system. As a consequence, EH143 treatment significantly reduced the contents of lipid peroxidation (O2-, MDA, and H2O2) up to 69%, 46%, and 29% in plants under salt+Cd stress, respectively. These findings suggest that EH143 could be a potent biofertilizer to alleviate NaCl and Cd toxicity in crops and serve as an alternative substitute for exogenous melatonin application.

最近,微生物和外源褪黑激素的应用被认为是提高农作物耐盐性和重金属解毒能力的有效生物工具。因此,本研究的目标是分离和评估一种新型褪黑激素生产植物生长促进菌。通过高通量全基因组测序、植物激素测定、表达谱分析和生化分析,我们可以鉴定出一种能产生褪黑激素的新型 PGPB,并揭示它是如何促进大豆生长发育并抵御盐和镉胁迫的。我们确定了耐盐(NaCl > 800 mM)和抗重金属(Cd > 3 mM)根瘤菌 Bacillus safensis EH143 的褪黑激素合成途径(色氨酸→色胺→serotonin 褪黑激素),并用它来处理受到 Cd 和 NaCl 胁迫的大豆植株。结果表明,EH143 对重金属有很高的生物积累能力,能显著提高大豆对 P、Ca2+ 的吸收和 K+/Na+(在盐胁迫下为 93%↑)的比率,同时降低大豆嫩芽对 Cd 的吸收(在 Cd 胁迫下为 49%)。离子调节因子 HKT1、MYPB67 以及钙传感器 CDPK5 和 CaMK1 的表达支持了这种活性,最终导致植物生长速度加快。在对照、盐和镉处理的植株中,EH143 可使嫩枝中的 ABA 含量分别明显减少 13%、20% 和 34%,并使嫩枝中的 SA 生物合成量分别增加 14.8%、31% 和 48.2%,同时上调 CYP707A1 和 CYP707A2 以及 PAL1 和 ICS。经 EH143 处理后,褪黑激素含量明显降低,ASMT3 的表达量也有所减少;此外,在盐+镉胁迫下,过氧化物酶(POD)和超氧化物歧化酶(SOD)的表达量分别减少了 134.5% 和 39%,总氨基酸的含量也有所增加。对 EH143 进行的全基因组测序和注释发现了褪黑激素前体色氨酸合成酶(trpA、trpB、trpS)、金属和其他离子调节剂(镉:cadA,钾:KtrA 和 KtrB,镉:cadA,钾:cadA 和 KtrB)的存在:此外,EH143 还提供了可能参与植物代谢系统编程的酶激活剂(包括苷元转运蛋白 yfiZ 和 yfhA、SOD sodA、过氧化氢酶 katA1 和谷胱甘肽调节剂 KefG)。因此,EH143 能显著降低盐+镉胁迫下植物的脂质过氧化物(O2-、MDA 和 H2O2)含量,降幅分别高达 69%、46% 和 29%。这些研究结果表明,EH143 是一种有效的生物肥料,可以减轻作物的氯化钠和镉毒性,并可替代外源褪黑激素的应用。
{"title":"Novel melatonin-producing Bacillus safensis EH143 mitigates salt and cadmium stress in soybean","authors":"Eun-Hae Kwon,&nbsp;Arjun Adhikari,&nbsp;Muhammad Imran,&nbsp;Adil Hussain,&nbsp;Ho-Jun Gam,&nbsp;Ji-In Woo,&nbsp;Jin Ryeol Jeon,&nbsp;Da-Sol Lee,&nbsp;Chung-Yeol Lee,&nbsp;Liny Lay,&nbsp;Sang-Mo Kang,&nbsp;Won-Chan Kim,&nbsp;Byung-Wook Yun,&nbsp;In-Jung Lee","doi":"10.1111/jpi.12957","DOIUrl":"10.1111/jpi.12957","url":null,"abstract":"<p>Recently, microorganism and exogenous melatonin application has been recognized as an efficient biological tool for enhancing salt tolerance and heavy metal detoxification in agriculture crops. Thus, the goal of this study was to isolate and evaluate a novel melatonin-producing plant growth promoting bacterium. With high-throughput whole genome sequencing, phytohormone measurements, expression profiling, and biochemical analysis, we can identify a novel PGPB that produces melatonin and unravel how it promotes soybean growth and development and protects against salt and Cd stress. We identify the melatonin synthesis pathway (tryptophan→tryptamine→serotonin melatonin) of the halotolerant (NaCl &gt; 800 mM) and heavy metal-resistant (Cd &gt;3 mM) rhizobacterium <i>Bacillus safensis</i> EH143 and use it to treat soybean plants subjected to Cd and NaCl stresses. Results show that EH143 will highly bioaccumulate heavy metals and significantly improve P and Ca<sup>2+</sup> uptake and the K<sup>+</sup>/Na<sup>+</sup> (93%↑under salt stress) ratio while reducing Cd uptake (49% under Cd stress) in shoots. This activity was supported by the expression of the ion regulator HKT1, MYPB67, and the calcium sensors CDPK5 and CaMK1 which ultimately led to increased plant growth. EH143 significantly decreased ABA content in shoots by 13%, 20%, and 34% and increased SA biosynthesis in shoots by 14.8%, 31%, and 48.2% in control, salt, and Cd-treated plants, upregulating CYP707A1 and CYP707A2 and PAL1 and ICS, respectively. The melatonin content significantly decreased along with a reduced expression of ASMT3 following treatment with EH143; moreover, reduced expression of peroxidase (POD) and superoxide dismutase (SOD) by 134.5% and 39% under salt+Cd stress, respectively and increased level of total amino acids were observed. Whole-genome sequencing and annotation of EH143 revealed the presence of the melatonin precursor tryptophan synthase (trpA, trpB, trpS), metal and other ion regulators (Cd: cadA, potassium: KtrA and KtrB, phosphate: glpT, calcium: yloB, the sodium/glucose cotransporter: sgIT, and the magnesium transporter: mgtE), and enzyme activators (including the siderophore transport proteins yfiZ and yfhA, the SOD sodA, the catalase katA1, and the glutathione regulator KefG) that may be involved in programming the plant metabolic system. As a consequence, EH143 treatment significantly reduced the contents of lipid peroxidation (O<sup>2-</sup>, MDA, and H<sub>2</sub>O<sub>2</sub>) up to 69%, 46%, and 29% in plants under salt+Cd stress, respectively. These findings suggest that EH143 could be a potent biofertilizer to alleviate NaCl and Cd toxicity in crops and serve as an alternative substitute for exogenous melatonin application.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":null,"pages":null},"PeriodicalIF":10.3,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12957","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156976","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}
引用次数: 0
Correction to “Melatonin suppresses platelet activation and function against cardiac ischemia/reperfusion injury via PPARγ/FUNDC1/mitophagy pathways” 更正为 "褪黑素通过 PPARγ/FUNDC1/mitophagy 途径抑制血小板活化和功能,防止心脏缺血/再灌注损伤"。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-27 DOI: 10.1111/jpi.12947

Zhou H, Li D, Zhu P, et al. Melatonin suppresses platelet activation and function against cardiac ischemia/reperfusion injury via PPARγ/FUNDC1/mitophagy pathways. J. Pineal Res. 2017;63:e12438. https://doi.org/10.1111/jpi.12438

An incorrect version of the Ctrl+IR+GW group was inadvertently included in Figure 2A,I and Figure 4F of the published article. Please find the corrected figures below. It is important to note that these corrections do not affect the conclusions drawn from this study.

We apologize for this error.

Zhou H, Li D, Zhu P, et al. Melatonin inhibes platelet activation and function against cardiac ischemia/reperfusion injury via PPARγ/FUNDC1/mitophagy pathways.J. Pineal Res. 2017;63:e12438。https://doi.org/10.1111/jpi.12438An,发表文章的图2A,I和图4F中不慎包含了Ctrl+IR+GW组的错误版本。更正后的图如下。需要注意的是,这些更正并不影响本研究得出的结论。
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引用次数: 0
Circadian light/dark cycle reversal exacerbates the progression of chronic kidney disease in mice 昼夜节律光/暗周期逆转会加剧小鼠慢性肾脏病的进展。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-27 DOI: 10.1111/jpi.12964
Jiayang Zhang, Lejia Qiu, Zhaiyi Liu, Jiaxin Liu, Bo Yu, Chengcheng Liu, Baoyin Ren, Jiaqi Zhang, Shuyao Li, Youfei Guan, Feng Zheng, Guangrui Yang, Lihong Chen

Circadian disruption such as shift work, jet lag, has gradually become a global health issue and is closely associated with various metabolic disorders. The influence and mechanism of circadian disruption on renal injury in chronic kidney disease (CKD) remains inadequately understood. Here, we evaluated the impact of environmental light disruption on the progression of chronic renal injury in CKD mice. By using two abnormal light exposure models to induce circadian disruption, we found that circadian disruption induced by weekly light/dark cycle reversal (LDDL) significantly exacerbated renal dysfunction, accelerated renal injury, and promoted renal fibrosis in mice with 5/6 nephrectomy and unilateral ureteral obstruction (UUO). Mechanistically, RNA-seq analysis revealed significant immune and metabolic disorder in the LDDL-conditioned CKD kidneys. Consistently, renal content of ATP was decreased and ROS production was increased in the kidney tissues of the LDDL-challenged CKD mice. Untargeted metabolomics revealed a significant buildup of lipids in the kidney affected by LDDL. Notably, the level of β-NMN, a crucial intermediate in the NAD+ pathway, was found to be particularly reduced. Moreover, we demonstrated that both β-NMN and melatonin administration could significantly rescue the light-disruption associated kidney dysfunction. In conclusion, environmental circadian disruption may exacerbate chronic kidney injury by facilitating inflammatory responses and disturbing metabolic homeostasis. β-NMN and melatonin treatments may hold potential as promising approaches for preventing and treating light-disruption associated CKD.

昼夜节律紊乱,如轮班工作、时差,已逐渐成为一个全球性的健康问题,并与各种代谢紊乱密切相关。昼夜节律紊乱对慢性肾脏病(CKD)肾损伤的影响和机制仍未得到充分了解。在这里,我们评估了环境光干扰对慢性肾脏病小鼠慢性肾损伤进展的影响。通过使用两种异常光照模型来诱导昼夜节律紊乱,我们发现每周光/暗周期逆转(LDDL)诱导的昼夜节律紊乱会显著加重5/6肾切除术和单侧输尿管梗阻(UUO)小鼠的肾功能障碍、加速肾损伤并促进肾纤维化。从机理上讲,RNA-seq分析表明,LDDL调节的CKD肾脏存在明显的免疫和代谢紊乱。LDDL挑战CKD小鼠肾脏组织中ATP含量减少,ROS产生增加。非靶向代谢组学显示,受 LDDL 影响的肾脏中脂类物质明显增多。值得注意的是,我们发现 NAD+ 通路中的重要中间体 β-NMN 的水平尤其降低。此外,我们还证明,服用β-NMN和褪黑激素可显著缓解与光干扰相关的肾功能障碍。总之,环境昼夜节律紊乱可能会通过促进炎症反应和扰乱代谢平衡而加剧慢性肾损伤。β-NMN和褪黑激素治疗可能是预防和治疗与光干扰相关的慢性肾脏病的有效方法。
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引用次数: 0
Melatonin restores hepatic lipid metabolic homeostasis disrupted by blue light at night in high-fat diet-fed mice 褪黑素可恢复高脂饮食小鼠夜间被蓝光破坏的肝脏脂质代谢平衡。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-23 DOI: 10.1111/jpi.12963
Qingyun Guan, Zixu Wang, Jing Cao, Yulan Dong, Shusheng Tang, Yaoxing Chen

Artificial light at night (ALAN) is an emerging environmental pollutant that threatens public health. Recently, ALAN has been identified as a risk factor for obesity; however, the role of ALAN and its light wavelength in hepatic lipid metabolic homeostasis remains undetermined. We showed that chronic dim (~5 lx) ALAN (dLAN) exposure significantly promoted hepatic lipid accumulation in obese or diabetic mice, with the most severe effect of blue light and little effect of green or red light. These metabolic phenotypes were attributed to blue rather than green or red dLAN interfering with hepatic lipid metabolism, especially lipogenesis and lipolysis. Further studies found that blue dLAN disrupted hepatic lipogenesis and lipolysis processes by inhibiting hepatic REV-ERBs. Mechanistically, feeding behavior mediated the regulation of dLAN on hepatic REV-ERBs. In addition, different effects of light wavelengths at night on liver REV-ERBs depended on the activation of the corticosterone (CORT)/glucocorticoid receptor (GR) axis. Blue dLAN could activate the CORT/GR axis significantly while other wavelengths could not. Notably, we demonstrated that exogenous melatonin could effectively inhibit hepatic lipid accumulation and restore the hepatic GR/REV-ERBs axis disrupted by blue dLAN. These findings demonstrate that dLAN promotes hepatic lipid accumulation in mice via a short-wavelength-dependent manner, and exogenous melatonin is a potential therapeutic approach. This study strengthens the relationship between ALAN and hepatic lipid metabolism and provides insights into directing ambient light.

夜间人造光(ALAN)是一种威胁公众健康的新兴环境污染物。最近,ALAN 被确定为肥胖症的一个风险因素;然而,ALAN 及其光波长在肝脏脂质代谢平衡中的作用仍未确定。我们的研究表明,长期暴露于暗光(约 5 lx)ALAN(dLAN)会显著促进肥胖或糖尿病小鼠肝脏脂质的积累,其中蓝光的影响最为严重,而绿光或红光的影响很小。这些代谢表型归因于蓝色而非绿色或红色 dLAN 干扰了肝脏脂质代谢,尤其是脂肪生成和脂肪分解。进一步研究发现,蓝色 dLAN 通过抑制肝脏 REV-ERBs 干扰了肝脏脂肪生成和脂肪分解过程。从机理上讲,摄食行为介导了dLAN对肝脏REV-ERBs的调节。此外,夜间光波长对肝脏REV-ERB的不同影响取决于皮质酮(CORT)/糖皮质激素受体(GR)轴的激活。蓝色 dLAN 能显著激活 CORT/GR 轴,而其他波长则不能。值得注意的是,我们证明外源性褪黑素能有效抑制肝脏脂质积累,并恢复被蓝色 dLAN 破坏的肝脏 GR/REV-ERBs 轴。这些研究结果表明,dLAN 通过短波长依赖性方式促进小鼠肝脏脂质积累,而外源性褪黑激素是一种潜在的治疗方法。这项研究加强了 ALAN 与肝脏脂质代谢之间的关系,并为引导环境光提供了启示。
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引用次数: 0
Melatonin reduces brain injury following inflammation-amplified hypoxia–ischemia in a translational newborn piglet study of neonatal encephalopathy 在一项新生儿脑病转化研究中,褪黑素能减轻炎症加重缺氧缺血后的脑损伤。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-22 DOI: 10.1111/jpi.12962
Raymand Pang, Christopher Meehan, George Maple, Georgina Norris, Ellie Campbell, Katie Tucker, Alison Mintoft, Francisco Torrealdea, Alan Bainbridge, Mariya Hristova, John Barks, Xavier Golay, Joseph Standing, Nicola J. Robertson

There is a need to develop therapies for neonatal encephalopathy (NE) in low- and middle-income countries (LMICs) where the burden of disease is greatest and therapeutic hypothermia (HT) is not effective. We aimed to assess the efficacy of melatonin following inflammation-amplified hypoxia–ischaemia (IA-HI) in the newborn piglet. The IA-HI model accounts for the contribution of infection/inflammation in this setting and HT is not cytoprotective. We hypothesised that intravenous melatonin (5% ethanol, at 20 mg/kg over 2 h at 1 h after HI + 10 mg/kg/12 h between 24 and 60 h) is safe and associated with: (i) reduction in magnetic resonance spectroscopy lactate/N-acetylaspartate (MRS Lac/sNAA); (ii) preservation of phosphorus MRS phosphocreatine/phosphate exchange pool (PCr/Epp); (iii) improved aEEG/EEG recovery and (iv) cytoprotection on immunohistochemistry. Male and female piglets underwent IA-HI by carotid artery occlusion and reduction in FiO2 to 6% at 4 h into Escherichia coli lipopolysaccharide sensitisation (2 μg/kg bolus + 1 μg/kg/h over 12 h). At 1 h after IA-HI, piglets were randomised to HI-saline (n = 12) or melatonin (n = 11). There were no differences in insult severity between groups. Target melatonin levels (15–30 mg/L) were achieved within 3 h and blood ethanol levels were <0.25 g/L. At 60 h, compared to HI-saline, melatonin was associated with a reduction of 0.197 log10 units (95% CrI [−0.366, −0.028], Pr(sup) 98.8%) in basal-ganglia and thalamic Lac/NAA, and 0.257 (95% CrI [−0.676, 0.164], Pr(sup) 89.3%) in white matter Lac/NAA. PCr/Epp was higher in melatonin versus HI-saline (Pr(sup) 97.6%). Melatonin was associated with earlier aEEG/EEG recovery from 19 to 24 h (Pr(sup) 95.4%). Compared to HI-saline, melatonin was associated with increased NeuN+ cell density (Pr(sup) 99.3%) across five of eight regions and reduction in TUNEL-positive cell death (Pr(sup) 89.7%). This study supports the translation of melatonin to early-phase clinical trials. Melatonin is protective following IA-HI where HT is not effective. These data guide the design of future dose-escalation studies in the next phase of the translational pipeline.

中低收入国家(LMICs)的新生儿脑病(NE)负担最重,而治疗性低温疗法(HT)效果不佳,因此有必要在这些国家开发新生儿脑病疗法。我们的目的是评估褪黑素在新生仔猪发生炎症-加重缺氧-缺血(IA-HI)后的疗效。IA-HI模型考虑了感染/炎症在这种情况下的作用,而HT不具有细胞保护作用。我们假设,静脉注射褪黑素(5% 乙醇,20 毫克/千克,2 小时,HI 后 1 小时 + 10 毫克/千克/12 小时,24 至 60 小时)是安全的,并且与以下方面有关:(i) 磁共振波谱乳酸/N-乙酰天冬氨酸(MRS Lac/sNAA)减少;(ii) 磷MRS磷酸肌酸/磷酸盐交换池(PCr/Epp)保留;(iii) aEEG/EEG恢复改善;(iv) 免疫组化的细胞保护。在大肠杆菌脂多糖致敏(2 μg/kg 注射+1 μg/kg/h 12小时)4小时后,雌雄仔猪通过颈动脉闭塞接受IA-HI,并将FiO2降至6%。IA-HI后1小时,仔猪随机接受HI-盐水(n = 12)或褪黑素(n = 11)治疗。各组之间的损伤严重程度没有差异。褪黑素在 3 小时内达到目标水平(15-30 毫克/升),血液乙醇水平在基底神经节和丘脑 Lac/NAA 中为 10 单位(95% CrI [-0.366, -0.028],Pr(sup) 98.8%),在白质 Lac/NAA 中为 0.257 单位(95% CrI [-0.676, 0.164],Pr(sup) 89.3%)。PCr/Epp 在褪黑激素与 HI-saline 相比更高(Pr(sup) 97.6%)。褪黑素与 19 至 24 小时内较早的 aEEG/EEG 恢复有关(Pr(sup) 95.4%)。与HI-saline相比,褪黑激素与八个区域中五个区域的NeuN+细胞密度增加(Pr(sup) 99.3%)和TUNEL阳性细胞死亡减少(Pr(sup) 89.7%)有关。这项研究支持将褪黑素应用于早期临床试验。褪黑素对IA-HI后HT无效的情况具有保护作用。这些数据为下一阶段转化研究中未来剂量递增研究的设计提供了指导。
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引用次数: 0
Melatonin in energy control: Circadian time-giver and homeostatic monitor 能量控制中的褪黑激素:昼夜节律时间提供者和平衡监测器。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-15 DOI: 10.1111/jpi.12961
Etienne Challet, Paul Pévet

Melatonin is a neurohormone synthesized from dietary tryptophan in various organs, including the pineal gland and the retina. In the pineal gland, melatonin is produced at night under the control of the master clock located in the suprachiasmatic nuclei of the hypothalamus. Under physiological conditions, the pineal gland seems to constitute the unique source of circulating melatonin. Melatonin is involved in cellular metabolism in different ways. First, the circadian rhythm of melatonin helps the maintenance of proper internal timing, the disruption of which has deleterious effects on metabolic health. Second, melatonin modulates lipid metabolism, notably through diminished lipogenesis, and it has an antidiabetic effect, at least in several animal models. Third, pharmacological doses of melatonin have antioxidative, free radical-scavenging, and anti-inflammatory properties in various in vitro cellular models. As a result, melatonin can be considered both a circadian time-giver and a homeostatic monitor of cellular metabolism, via multiple mechanisms of action that are not all fully characterized. Aging, circadian disruption, and artificial light at night are conditions combining increased metabolic risks with diminished circulating levels of melatonin. Accordingly, melatonin supplementation could be of potential therapeutic value in the treatment or prevention of metabolic disorders. More clinical trials in controlled conditions are needed, notably taking greater account of circadian rhythmicity.

褪黑素是一种神经激素,由饮食中的色氨酸在松果体和视网膜等多个器官中合成。在松果体中,褪黑激素是在位于下丘脑上核的主时钟控制下于夜间产生的。在生理条件下,松果体似乎是循环褪黑激素的唯一来源。褪黑激素以不同方式参与细胞代谢。首先,褪黑激素的昼夜节律有助于维持适当的体内时间,而昼夜节律的破坏会对新陈代谢健康产生有害影响。其次,褪黑激素可调节脂质代谢,特别是通过减少脂肪生成,至少在几种动物模型中具有抗糖尿病作用。第三,在各种体外细胞模型中,药理剂量的褪黑激素具有抗氧化、清除自由基和抗炎特性。因此,褪黑素既可被视为昼夜节律时间的提供者,也可被视为细胞新陈代谢的稳态监测器,其作用机制多种多样,但尚未完全定性。衰老、昼夜节律紊乱和夜间人工光照是新陈代谢风险增加和褪黑激素循环水平降低的综合条件。因此,补充褪黑激素对治疗或预防代谢紊乱具有潜在的治疗价值。需要在受控条件下进行更多的临床试验,特别是要更多地考虑昼夜节律性。
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引用次数: 0
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Journal of Pineal Research
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