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Erratum to: Mitochondrial cytochrome P450 (CYP) 1B1 is responsible for melatonin-induced apoptosis in neural cancer cells 勘误:线粒体细胞色素P450(CYP)1B1负责美拉通素诱导的神经癌症细胞凋亡。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-03 DOI: 10.1111/jpi.12917

DOI: 10.1111/jpi.12478

Zhenlong Yu1,+, Xiangge Tian1,+, Yuling Peng1,+, Zheng Sun1, Chao Wang 1, Ning Tang1, Bin Li2, Yuqing Jian2, Wei Wang2,*, Xiaokui Huo1, Xiaochi Ma1,*

*Correspondence: Professor Xiaochi Ma, E-mail: [email protected] (Xiaochi Ma); Professor Wei Wang, E-mail: [email protected] (Wei Wang).

+These authors equally contributed to this work.

Correction:

Unfortunately, the original version of this article1 contained the errors. The band of p-p38 in Figure 1F (SH-SY5Y) was mistakenly uploaded, during the arrangement of the figure panels. The mistake did not affect our results or discussion as the text refers to the correct experimental values. The corrected Figure 1F is provided here. Additionally, an error was also identified in the authors' names, where Yulin Peng's name was mistakenly written as “Yuling Peng”.

We regret any inconvenience this has caused.

Corrected Figure 1F

DOI: 10.1111/jpi.12478Zhenlong Yu1,+, Xiangge Tian1,+, Yuling Peng1,+, Zheng Sun1, Chao Wang 1, Ning Tang1, Bin Li2, Yuqing Jian2, Wei Wang2,*, Xiaokui Huo1, Xiaochi Ma1,**Correspondence:马晓驰教授,电子邮件:[email protected] (马晓驰电子邮件:[email protected] (Xiaochi Ma);王伟教授,电子邮件:[email protected] (Wei Wang):[Correction:Unfortunately, the original version of this article1 contained the errors.图1F(SH-SY5Y)中p-p38的条带在编排时被错误上传。这个错误并不影响我们的结果或讨论,因为文中提到的是正确的实验值。现提供更正后的图 1F。此外,我们还发现了作者姓名中的一处错误,彭玉林的名字被误写为 "Yuling Peng"。
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引用次数: 0
Melatonin, a potentially effective drug for the treatment of infected bone nonunion 褪黑素,一种治疗感染性骨不连的潜在有效药物。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-27 DOI: 10.1111/jpi.12914
Han-jun Qin, Si-ying He, Ke Shen, Qing-rong Lin, Yan-jun Hu, Zi-lin Chen, Bin Yu, Nan Jiang

Osteomyelitis (OM), characterized by heterogeneity and complexity in treatment, has a high risk of infection recurrence which may cause limb disability. Management of chronic inactive osteomyelitis (CIOM) without typical inflammatory symptoms is a great challenge for orthopedic surgeons. On the basis of data analysis of 1091 OM cases, we reported that latent osteogenic decline in CIOM patients was the main cause of secondary surgery. Our research shows that impairment of osteoblasts capacity in CIOM patients is associated with ferroptosis of osteoblasts caused by internalization of Staphylococcus aureus. Further studies show that melatonin could alleviate ferroptosis of osteoblasts in infected states through Nox4/ROS/P38 axis and protect the osteogenic ability of CIOM patients. Knockout of NADPH oxidase 4 (Nox4) in vivo could effectively relieve ferroptosis of osteoblasts in the state of infection and promote osteogenesis. Through a large number of clinical data analyses combined with molecular experiments, this study clarified that occult osteogenic disorders in CIOM patients were related to ferroptosis of osteoblasts. We revealed that melatonin might be a potential therapeutic drug for CIOM patients and provided a new insight for the treatment of OM.

骨髓炎(OM)具有治疗的异质性和复杂性,感染复发的风险很高,可能导致肢体残疾。没有典型炎症症状的慢性非活动性骨髓炎(CIOM)的治疗对骨科医生来说是一个巨大的挑战。在对1091例OM病例进行数据分析的基础上,我们报告了CIOM患者潜在的成骨能力下降是二次手术的主要原因。我们的研究表明,CIOM患者成骨细胞能力受损与金黄色葡萄球菌内化引起的成骨细胞脱铁性贫血有关。进一步的研究表明,褪黑素可以通过Nox4/ROS/P38轴减轻感染状态下成骨细胞的脱铁性贫血,并保护CIOM患者的成骨能力。体内敲除NADPH氧化酶4(Nox4)可有效缓解感染状态下成骨细胞的脱铁性,促进成骨。通过大量临床数据分析结合分子实验,本研究阐明CIOM患者的隐性成骨性疾病与成骨细胞脱铁性贫血有关。我们发现褪黑素可能是CIOM患者的一种潜在治疗药物,并为OM的治疗提供了新的见解。
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引用次数: 0
Orchestrated feedback regulation between melatonin and sex hormones involving GPER1-PKA-CREB signaling in the placenta 褪黑激素和性激素之间的协调反馈调节,涉及胎盘中GPER1-PKA-CREB信号传导
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-25 DOI: 10.1111/jpi.12913
Xuan Shao, Yun Yang, Yanlei Liu, Yongqing Wang, Yangyu Zhao, Xin Yu, Juan Liu, Yu-Xia Li, Yan-Ling Wang

Maintaining placental endocrine homeostasis is crucial for a successful pregnancy. Pre-eclampsia (PE), a gestational complication, is a leading cause of maternal and perinatal morbidity and mortality. Aberrant elevation of testosterone (T0) synthesis, reduced estradiol (E2), and melatonin productions have been identified in preeclamptic placentas. However, the precise contribution of disrupted homeostasis among these hormones to the occurrence of PE remains unknown. In this study, we established a strong correlation between suppressed melatonin production and decreased E2 as well as elevated T0 synthesis in PE placentas. Administration of the T0 analog testosterone propionate (TP; 2 mg/kg/day) to pregnant mice from E7.5 onwards resulted in PE-like symptoms, along with elevated T0 production and reduced E2 and melatonin production. Notably, supplementation with melatonin (10 mg/kg/day) in TP-treated mice had detrimental effects on fetal and placental development and compromised hormone synthesis. Importantly, E2, but not T0, actively enhanced melatonin synthetase AANAT expression and melatonin production in primary human trophoblast (PHT) cells through GPER1-PKA-CREB signaling pathway. On the other hand, melatonin suppressed the level of estrogen synthetase aromatase while promoting the expressions of androgen synthetic enzymes including 17β-HSD3 and 3β-HSD1 in PHT cells. These findings reveal an orchestrated feedback mechanism that maintains homeostasis of placental sex hormones and melatonin. It is implied that abnormal elevation of T0 synthesis likely serves as the primary cause of placental endocrine disturbances associated with PE. The suppression of melatonin may represent an adaptive strategy to correct the imbalance in sex hormone levels within preeclamptic placentas. The findings of this study offer novel evidence that identifies potential targets for the development of innovative therapeutic strategies for PE.

维持胎盘内分泌稳态对成功怀孕至关重要。先兆子痫(PE)是一种妊娠并发症,是孕产妇和围产期发病率和死亡率的主要原因。在先兆子痫胎盘中发现了睾酮(T0)合成异常升高、雌二醇(E2)减少和褪黑素产生异常。然而,这些激素中稳态紊乱对PE发生的确切贡献仍然未知。在这项研究中,我们在PE胎盘中建立了褪黑素产生抑制与E2降低以及T0合成升高之间的强相关性。T0类似物丙酸睾酮(TP;2 mg/kg/天)导致PE样症状,同时T0产生增加,E2和褪黑素产生减少。值得注意的是,补充褪黑激素(10 mg/kg/天)对胎儿和胎盘发育具有不利影响,并损害激素合成。重要的是,E2,而不是T0,通过GPER1-PKA-CREB信号通路,积极增强原代人类滋养层(PHT)细胞中褪黑素合成酶AANAT的表达和褪黑素的产生。另一方面,褪黑素抑制了PHT细胞中雌激素合成酶芳香化酶的水平,同时促进了包括17β-HSD3和3β-HSD1在内的雄激素合成酶的表达。这些发现揭示了维持胎盘性激素和褪黑激素稳态的协调反馈机制。这意味着T0合成的异常升高可能是PE相关胎盘内分泌紊乱的主要原因。褪黑素的抑制可能是纠正先兆子痫胎盘性激素水平失衡的一种适应性策略。这项研究的发现为PE创新治疗策略的开发提供了新的证据。
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引用次数: 0
Corrigendum to “melatonin ameliorates PM2.5-induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis” “褪黑激素通过调节线粒体氧化还原稳态改善PM2.5诱导的心脏血管周围纤维化”更正。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-20 DOI: 10.1111/jpi.12915

After publication of the paper “Melatonin ameliorates PM2.5-induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis” by Jinjin Jiang et al. it was noticed that the paper contains error in Figure 4D and Figure 6D. During the assembly of certain figure panel of this article showing representative immunoblot, Ac-SOD2 and GPADH (Figure 4D) and GAPDH (Figure 6D) were presented incorrectly, due to unintended duplication mistake. Using the original source data, the rectified version of the incorrectly presented panel of Figure 4D and Figure 6D were generated and is shown below. Here we provided the revised Figure 4 and Figure 6. The authors apologize for the oversight and declare that the correction does not affect the description, interpretation, or conclusions detailed in the original manuscript.

蒋津津等人的论文《褪黑素通过调节线粒体氧化还原稳态改善PM2.5诱导的心脏血管周围纤维化》发表后,我们发现论文中的图4D和图6D有误。在组装本文某些显示代表性免疫印迹的图板时,由于无意中的重复错误,Ac-SOD2 和 GPADH(图 4D)以及 GAPDH(图 6D)的显示不正确。利用原始数据,我们生成了图 4D 和图 6D 的更正版本,如下所示。在此,我们提供了修改后的图 4 和图 6。作者对疏忽表示歉意,并声明更正并不影响原稿中详细的描述、解释或结论。
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引用次数: 0
Biosynthesis of neuroprotective melatonin is dysregulated in Huntington's disease 神经保护性褪黑激素的生物合成在亨廷顿舞蹈症中失调
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-18 DOI: 10.1111/jpi.12909
Jinho Kim, Wei Li, Jingjing Wang, Sergei V. Baranov, Brianna E. Heath, Jiaoying Jia, Yalikun Suofu, Oxana V. Baranova, Xiaomin Wang, Timothy M. Larkin, William R. Lariviere, Diane L. Carlisle, Robert M. Friedlander

Huntington's disease (HD) is a progressive neurodegenerative brain disorder associated with uncontrolled body movements, cognitive decline, and reduced circulating melatonin levels. Melatonin is a potent antioxidant and exogenous melatonin treatment is neuroprotective in experimental HD models. In neurons, melatonin is exclusively synthesized in the mitochondrial matrix. Thus, we investigated the integrity of melatonin biosynthesis pathways in pineal and extrapineal brain areas in human HD brain samples, in the R6/2 mouse model of HD and in full-length mutant huntingtin knock-in cells. Aralkylamine N-acetyltransferase (AANAT) is the rate-limiting step enzyme in the melatonin biosynthetic pathway. We found that AANAT expression is significantly decreased in the pineal gland and the striatum of HD patients compared to normal controls. In the R6/2 mouse forebrain, AANAT protein expression was decreased in synaptosomal, but not nonsynaptosomal, mitochondria and was associated with decreased synaptosomal melatonin levels compared to wild type mice. We also demonstrate sequestration of AANAT in mutant-huntingtin protein aggregates likely resulting in decreased AANAT bioavailability. Paradoxically, AANAT mRNA expression is increased in tissues where AANAT protein expression is decreased, suggesting a potential feedback loop that is, ultimately unsuccessful. In conclusion, we demonstrate that pineal, extrapineal, and synaptosomal melatonin levels are compromised in the brains of HD patients and R6/2 mice due, at least in part, to protein aggregation.

亨廷顿舞蹈症(HD)是一种进行性神经退行性脑疾病,与身体运动失控、认知能力下降和循环褪黑素水平降低有关。褪黑素是一种强效抗氧化剂,外源性褪黑素治疗对实验性HD模型具有神经保护作用。在神经元中,褪黑激素仅在线粒体基质中合成。因此,我们研究了人类HD脑样本、HD的R6/2小鼠模型和全长突变亨廷顿蛋白敲除细胞中松果体和线外脑区域褪黑素生物合成途径的完整性。阿拉伯烷基胺N-乙酰转移酶(AANAT)是褪黑激素生物合成途径中的限速步进酶。我们发现,与正常对照组相比,HD患者松果体和纹状体中AANAT的表达显著降低。在R6/2小鼠前脑中,与野生型小鼠相比,AANAT蛋白在突触体、线粒体中的表达减少,但在非突触体和线粒体中没有,并且与突触体褪黑素水平降低有关。我们还证明了AANAT在突变亨廷顿蛋白聚集体中的螯合可能导致AANAT生物利用度降低。矛盾的是,在AANAT蛋白表达降低的组织中,AANAT mRNA表达增加,这表明潜在的反馈回路最终是不成功的。总之,我们证明HD患者和R6/2小鼠大脑中的松果体、松果体外和突触体褪黑素水平受损,至少部分原因是蛋白质聚集。
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引用次数: 0
iMS-Bmal1−/− mice show evident signs of sarcopenia that are counteracted by exercise and melatonin therapies iMS-Bmal1-/- 小鼠表现出明显的肌肉疏松症状,而运动和褪黑激素疗法可抵消这种症状
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-13 DOI: 10.1111/jpi.12912
José Fernández-Martínez, Yolanda Ramírez-Casas, Paula Aranda-Martínez, Alba López-Rodríguez, Ramy K. A. Sayed, Germaine Escames, Darío Acuña-Castroviejo

Sarcopenia is an age-related disease characterized by a reduction in muscle mass, strength, and function and, therefore, a deterioration in skeletal muscle health and frailty. Although the cause of sarcopenia is still unknown and, thus, there is no treatment, increasing evidence suggests that chronodisruption, particularly alterations in Bmal1 clock gene, can lead to those deficits culminating in sarcopenia. To gain insight into the cause and mechanism of sarcopenia and the protective effect of a therapeutic intervention with exercise and/or melatonin, the gastrocnemius muscles of male and female skeletal muscle-specific and inducible Bmal1 knockout mice (iMS-Bmal1−/−) were examined by phenotypic tests and light and electron microscopy. Our results revealed a disruption of the normal activity/rest rhythm, a drop in skeletal muscle function and mass, and increased frailty in male and female iMS-Bmal1−/− animals compared to controls. A reduction in muscle fiber size and increased collagenous tissue were also detected, accompanied by reduced mitochondrial oxidative capacity and a compensatory shift towards a more oxidative fiber type. Electron microscopy further supports mitochondrial impairment in mutant mice. Melatonin and exercise ameliorated the damage caused by loss of Bmal1 in mutant mice, except for mitochondrial damage, which was worsened by the latter. Thus, iMS-Bmal1−/− mice let us to identify Bmal1 deficiency as the responsible for the appearance of sarcopenia in the gastrocnemius muscle. Moreover, the results support the exercise and melatonin as therapeutic tools to counteract sarcopenia, by a mechanism that does not require the presence of Bmal1.

肌肉疏松症是一种与年龄有关的疾病,其特点是肌肉质量、力量和功能下降,因此骨骼肌健康状况恶化,身体虚弱。虽然肌肉疏松症的病因尚不清楚,因此也没有治疗方法,但越来越多的证据表明,时序紊乱,特别是 Bmal1 时钟基因的改变,可导致这些缺陷,最终导致肌肉疏松症。为了深入了解肌肉疏松症的成因和机制,以及运动和/或褪黑激素的治疗干预的保护作用,我们通过表型测试、光镜和电子显微镜检查了雌雄骨骼肌特异性和诱导性 Bmal1 基因敲除小鼠(iMS-Bmal1-/-)的腓肠肌。结果显示,与对照组相比,iMS-Bmal1-/-雄性和雌性小鼠的正常活动/休息节律被打乱,骨骼肌功能和质量下降,体弱程度增加。此外,还发现肌肉纤维尺寸缩小,胶原组织增加,同时线粒体氧化能力降低,代偿性地转向氧化能力更强的纤维类型。电子显微镜进一步证实了突变小鼠线粒体功能受损。褪黑素和运动可改善突变小鼠因 Bmal1 缺失而造成的损伤,但线粒体损伤除外,后者会加重线粒体损伤。因此,iMS-Bmal1-/-小鼠让我们确定 Bmal1 缺乏是导致腓肠肌出现肌肉疏松症的原因。此外,研究结果还支持将运动和褪黑激素作为治疗工具,通过一种不需要 Bmal1 存在的机制来对抗肌少症。
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引用次数: 0
Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification 松果体区肿瘤的原发性伽玛刀放射治疗:一项系统综述和组织学分层的文献汇总分析
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-13 DOI: 10.1111/jpi.12910
Filippo Gagliardi, Pierfrancesco De Domenico, Enrico Garbin, Silvia Snider, Pietro Mortini

Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-year OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-year progression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.

松果体区域肿瘤(PT)代表了极其罕见的病理,其特征是高度异质的组织学模式。伽玛刀放射外科(GKSR)治疗PT的大多数可用证据来自多模式方案,包括GKSR作为辅助模式或复发时的挽救治疗。我们旨在收集有关该主题的现有证据,并分析单个患者水平的数据,以解决原发性GKSR的疗效和安全性问题。这是对文献(PubMed、Embase、Cochrane、Science Direct)和单患者水平数据的汇总分析的系统综述。共检索到1054件原创作品。在排除重复和无关作品后,我们纳入了13篇论文(n = 64名患者)。另外12名患者来自作者的原始系列。共有76名患者达到最终分析;56.5%(n = 43)接受组织学诊断。已确诊的病变包括世界卫生组织I级(60.5%)、世界卫生组织II级(14%)、世界卫生组织IV级(7%)、中分化松果体瘤世界卫生组织II/III(4.7%)、松果体区乳头状瘤世界卫生组织II/III(4.7%)、生殖细胞瘤(2.3%)、世界卫生组织I级(2.3%)神经细胞瘤、星形细胞瘤世界卫生组织II(2.3%)和世界卫生组织III(2.3%)。其余43.5%(n = 33)例,包括松果细胞瘤(9%)、生殖细胞瘤(6%)、低级别神经胶质瘤(6%。GKSR时的平均年龄为38.7岁,平均病变体积为4.2 ± 4毫升。所有患者均接受GKSR,平均边际剂量为14.7 ± 2.1 Gy(50%等剂量)。在中位36个月的随访中,80.3%的病例实现了局部控制。13名患者在中位时间14个月后出现进展。总死亡率为13.2%。除高级别胶质瘤(8mo)外,所有纳入的病变均未达到中位OS。LGG和中等分化的松果体肿瘤的3年OS为100%,低级别松果体病变为91%,高级别松果体损伤为66%,生殖细胞肿瘤(GCTs)为60%,HGG为50%,未确定肿瘤为82%。LGG和松果体中间肿瘤的3年无进展生存率(PFS)为100%,低度松果体为86%,高度松果体为66%,GCT为33.3%,HGG为0%。HGG的中位PFS为5个月,GCT为34个月。放射性坏死率为6%,囊性变性率为2%。共济失调作为一种表现症状有力地预测了死亡率(比值比[OR]104,p = .02),而GCT和HGG组织学很好地预测了PD(OR:13,p = .04)。这些结果支持GKSR治疗PT的有效性和安全性。需要进一步的研究来验证这些结果,这些结果强调了初步推定诊断对选择最佳治疗策略的重要性。
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引用次数: 0
Correction to human transporters, PEPT1/2, facilitate melatonin transportation into mitochondria of cancer cells: An implication of the therapeutic potential 纠正人类转运蛋白PEPT1/2,促进褪黑素运输到癌细胞的线粒体:治疗潜力的暗示。
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-09-11 DOI: 10.1111/jpi.12911

Huo X, Wang C, Yu Z, Peng Y, Wang S, Feng S, Zhang S, Tian X, Sun C, Liu K, Deng S, Ma X. Human transporters, PEPT1/2, facilitate melatonin transportation into mitochondria of cancer cells: An implication of the therapeutic potential. J Pineal Res. 2017;62(4):12390. https://doi.org/10.1111/jpi.12390

In Figure 10B, the C-casp3 bands of PC3 cells and Bax bands of U118 cells were accidentally wrongly used during the figure preparation. The corrected figures are provided below.

This corrected figure does not change the conclusions of this study. This correction does not modify the data interpretation of the original article. We apologize for this error.

Huo X, Wang C, Yu Z, Peng Y, Wang S, Feng S, Zhang S, Tian X, Sun C, Liu K, Deng S, Ma X. Human transporters, PEPT1/2, facilitate melatonin transportation into mitochondria of cancer cells:对治疗潜力的影响。J Pineal Res. 2017;62(4):12390。https://doi.org/10.1111/jpi.12390In 图10B中,PC3细胞的C-casp3条带和U118细胞的Bax条带在制图过程中被意外错用。更正后的图表如下。此更正不会修改原文的数据解释。我们对此错误深表歉意。
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引用次数: 0
From gestational chronodisruption to noncommunicable diseases: Pathophysiological mechanisms of programming of adult diseases, and the potential therapeutic role of melatonin 从妊娠期时间中断到非传染性疾病:成人疾病编程的病理生理机制和褪黑素的潜在治疗作用
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-08-31 DOI: 10.1111/jpi.12908
Natalia Méndez, Fernando Corvalan, Diego Halabi, Pamela Ehrenfeld, Rodrigo Maldonado, Karina Vergara, Maria Seron-Ferre, Claudia Torres-Farfan

During gestation, the developing fetus relies on precise maternal circadian signals for optimal growth and preparation for extrauterine life. These signals regulate the daily delivery of oxygen, nutrients, hormones, and other biophysical factors while synchronizing fetal rhythms with the external photoperiod. However, modern lifestyle factors such as light pollution and shift work can induce gestational chronodisruption, leading to the desynchronization of maternal and fetal circadian rhythms. Such disruptions have been associated with adverse effects on cardiovascular, neurodevelopmental, metabolic, and endocrine functions in the fetus, increasing the susceptibility to noncommunicable diseases (NCDs) in adult life. This aligns with the Developmental Origins of Health and Disease theory, suggesting that early-life exposures can significantly influence health outcomes later in life. The consequences of gestational chronodisruption also extend into adulthood. Environmental factors like diet and stress can exacerbate the adverse effects of these disruptions, underscoring the importance of maintaining a healthy circadian rhythm across the lifespan to prevent NCDs and mitigate the impact of gestational chronodisruption on aging. Research efforts are currently aimed at identifying potential interventions to prevent or mitigate the effects of gestational chronodisruption. Melatonin supplementation during pregnancy emerges as a promising intervention, although further investigation is required to fully understand the precise mechanisms involved and to develop effective strategies for promoting health and preventing NCDs in individuals affected by gestational chronodisruption.

在妊娠期间,发育中的胎儿依靠精确的母体昼夜节律信号来实现最佳生长和为宫外生活做准备。这些信号调节氧气、营养物质、激素和其他生物物理因素的每日输送,同时使胎儿节律与外部光周期同步。然而,光污染和轮班工作等现代生活方式因素会导致妊娠时间中断,导致母体和胎儿昼夜节律不同步。这种干扰与胎儿心血管、神经发育、代谢和内分泌功能的不良影响有关,增加了成年后对非传染性疾病的易感性。这与健康与疾病的发展起源理论一致,该理论表明,早期接触会对日后的健康结果产生重大影响。妊娠期时间中断的后果也会延伸到成年期。饮食和压力等环境因素会加剧这些干扰的不利影响,强调在整个生命周期中保持健康的昼夜节律对预防非传染性疾病和减轻妊娠时间干扰对衰老的影响的重要性。目前的研究工作旨在确定预防或减轻妊娠时间中断影响的潜在干预措施。妊娠期补充褪黑激素是一种很有前途的干预措施,尽管需要进一步的研究来充分了解所涉及的确切机制,并制定有效的策略来促进受妊娠时间中断影响的个体的健康和预防非传染性疾病。
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引用次数: 0
The mammalian gastro-intestinal tract is a NOT a major extra-pineal source of melatonin 哺乳动物的胃肠道不是褪黑激素的主要松果体外来源
IF 10.3 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-08-31 DOI: 10.1111/jpi.12906
David J. Kennaway

In 1992, a paper reported that the melatonin content of the rat duodenum was 24 000 ± 2000 pg/g tissue (range: 4000–100 000 pg/g) while the pineal melatonin content was 580 000 ± 36 000 pg/g. The data has been used for the last 30 years to infer that the gut produces 400 hundred times more melatonin than the pineal gland and that it is the source of plasma melatonin during the daytime. No-one has ever challenged the statement. In this review, evidence is summarised from the literature that pinealectomy eliminates melatonin from the circulation and that studies to the contrary have relied upon poorly validated immunoassays that overstate the levels. Similarly studies that have reported increases in plasma melatonin following tryptophan administration failed to account for cross reactivity of tryptophan and its metabolites in immunoassays. The most extraordinary observation from the literature is that in those studies that have measured melatonin in the gut since 1992, the tissue content is vastly lower than the original report, even when the methodology used could be overestimating the melatonin content due to cross reactivity. Using the more contemporary results we can calculate that rather than a 400:1 ratio of duodenum: pineal melatonin, a ratio of 0.05–0.19: 1 is likely. The gut is not a major extra-pineal source of melatonin; indeed it may well not produce any.

1992年,一篇论文报道,大鼠十二指肠的褪黑素含量为24 000 ± 2000 pg/g组织(范围:4000-100 000 pg/g),而松果体褪黑素含量为580 000 ± 36 000 pg/g。在过去的30年里,这些数据一直被用来推断肠道产生的褪黑激素是松果体的400倍,并且它是白天血浆褪黑激素的来源。从来没有人质疑过这一说法。在这篇综述中,文献中总结了松果体切除术可消除循环中的褪黑激素的证据,相反,研究依赖于夸大水平的未经验证的免疫测定。类似的研究报告了色氨酸给药后血浆褪黑素的增加,但未能解释免疫测定中色氨酸及其代谢物的交叉反应性。文献中最不同寻常的观察结果是,自1992年以来,在那些测量肠道中褪黑素的研究中,组织含量远低于原始报告,即使使用的方法可能由于交叉反应而高估了褪黑素含量。使用更现代的结果,我们可以计算出十二指肠与松果体褪黑素的比例可能不是400:1,而是0.05–0.19:1。肠道并不是褪黑激素的主要松果体外来源;事实上,它很可能不会产生任何结果。
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Journal of Pineal Research
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