Effect of 3 mg melatonin on jet lag syndrome in an 8-h eastward flight

In order to assess the effect of melatonin on jet lag a field study was undertaken. The process of re-entrainment of circadian melatonin rhythm was investigated in six subjects. Except during 24-h blood sampling, the subjects were exposed to natural zeitgeber (time giver) outdoors and given 3 mg melatonin at 23:00 h. The subjects were exposed to bright sunlight from 3000 to 12000 lx. All of them showed orthodromic re-entrainment with taking melatonin, while two out of the six did not show orthodromic re-entrainment without taking melatonin. Melatonin accelerated the rate of the re-entrainment of the circadian melatonin rhythm. Melatonin was useful to jet travel from Tokyo to Los Angeles.     

In vivo and in vitro effects of melatonin or ganglioside GT1B on L-cysteine-induced brain mitochondrial DNA damage in mice.

The effects of L-cysteine on mitochondrial DNA (mtDNA) in mouse brain were investigated both in vivoandin vitro. An intracerebroventricular (icv) injection of L-cysteine (1.25 micromol/animal) caused mtDNA damage in brain frontal and central portions of the cortex, broad-spectrum limbic and severe sustained seizures in mice, and increased lipid peroxidation in the whole brain. The L-cysteine-mediated effects were prevented by an intraperitoneal (ip) preinjection of melatonin (20 mg/kg) or an intracerebroventricular preinjection of ganglioside GT1b (90 nmol/animal). Furthermore, in in vitroexperiments, L-cysteine (0.05, 0.5, or 1.0 mM) caused damage to brain mtDNA and increased lipid peroxidation in a concentration-dependent manner when incubated at 37 degrees C for 20 or 60 min with a homogenate prepared from whole mouse brains. However, the mtDNA damage and the increased lipid peroxidation were completely abolished by a cotreatment with melatonin (1.5 mM), a potent scavenger of the hydroxyl radical (*OH), or ganglioside GT1b (60 microM), a potent inhibitor of glutamate-receptor-mediated activation and translocation of protein kinase C and lipid peroxidation. These results suggest that reactive oxygen species including the *OH may be involved in l-cysteine-induced brain mtDNA damage, lipid peroxidation, and development of seizures in mice. Therefore, we concluded that *OH scavengers, such as the pineal hormone melatonin and ganglioside GT1b, can protect against brain mtDNA damage, seizures, and lipid peroxidation induced by reactive oxygen species producers such as L-cysteine.     

大鼠出生前接触苯妥英和褪黑素对仔代反射功能发育及自发运动的影响

目的 :探讨苯妥英 (DPH)神经发育毒性与胚胎脑组织中自由基产生和氧化应激反应的关系。方法 :Wistar孕鼠于妊娠d 11～ 14经 0 ,10 0 ,2 0 0mg·kg-1DPH或合并 4 0mg·kg-1褪黑素 (MT)染毒处理 ,研究MT对DPH的仔代反射功能发育及自发运动损害作用的拮抗效应。结果 :孕鼠在染毒期及染毒后增重下降 ,仔代体重减轻 ,哺乳期死亡率增高 ;DPH染毒仔鼠的转身运动增多 ,空中翻正反射及游泳能力发育延迟 ,成年后行走次数、站立次数、刻板动作等自发活动增多 ,旋转手比率增多 ,对阿朴吗啡“激发”反应性增强。MT和DPH合并处理可明显拮抗上述DPH仔鼠的行为异常。结论 :氧化性损伤在DPH神经发育毒性发生中发挥重要作用 ,而MT可拮抗其毒性作用。     

Melatonin inhibits EMT and PD‐L1 expression through the ERK1/2/FOSL1 pathway and regulates anti‐tumor immunity in HNSCC

Melatonin is an endogenous hormone with various biological functions and possesses anti‐tumor properties in multiple malignancies. Immune evasion is one of the most important hallmarks of head and neck squamous cell carcinoma (HNSCC) and is closely related to tumor progression. However, as an immune modulator under physiological conditions, the roles of melatonin in tumor immunity in HNSCC remains unclear. In this study, we found that the endogenous melatonin levels in patients with HNSCC were lower than those in patients with benign tumors in head and neck. Importantly, lower melatonin levels were related to lymph node metastasis among patients with HNSCC. Moreover, melatonin significantly suppressed programmed death‐ligand 1 (PD‐L1) expression and inhibited epithelial–mesenchymal transition (EMT) of HNSCC through the ERK1/2/FOSL1 pathway in vitro and in vivo. In SCC7/C3H syngeneic mouse models, anti‐programmed death‐1 (PD‐1) antibody combined with melatonin significantly inhibited tumor growth and modulated anti‐tumor immunity by increasing CD8⁺ T cell infiltration and decreasing the regulatory T cell (Treg) proportion in the tumor microenvironment. Taken together, melatonin inhibited EMT and downregulated PD‐L1 expression in HNSCC through the ERK1/2/FOSL1 pathway and exerted synergistic effects with anti‐PD‐1 antibody in vivo, which could provide promising strategies for HNSCC treatment.     

Melatonin protects N2a against ischemia/reperfusion injury through autophagy enhancement

Researches have shown that melatonin is neuroprotectant in ischemia/reperfusion-mediated injury.Although melatonin is known as an effective antioxidant,the mechanism of the protection cannot be explained merely by antioxidation.This study was devoted to explore other existing mechanisms by investigating whether melatonin protects ischemia/reperfusion-injured neurons through elevating autophagy,since autophagy has been frequently suggested to play a crucial role in neuron survival.To find it out,an ischemia/...     

褪黑素缺乏影响脊柱侧弯的研究进展

脊柱侧弯是一种常见的脊柱畸形,可能会增加发生背痛的风险,导致肩部不平衡和胸部畸形,甚至影响到患者的心肺功能或对神经造成不可逆的损伤。褪黑素可以改善骨代谢平衡和增加骨密度,目前关于褪黑素干预骨代谢有许多假说,对于褪黑素缺乏是否会导致脊柱侧弯的发生仍存在争议。血清褪黑素水平较低的脊柱侧弯患者,使用褪黑素进行补充,或许在一定程度上能防止脊柱侧弯的发展,并存在一定的治疗效果。本文综述了近年来关于褪黑素缺乏与脊柱侧弯的关系的相关研究,以期为脊柱侧弯的治疗提供参考。     

Nose to brain delivery of melatonin lipidic nanocapsules as a promising post-ischemic neuroprotective therapeutic modality

Ischemic stroke accounts for about 87% of all strokes, causing long-term disability in adults, and is the second leading cause of death worldwide. In search of new therapeutic modalities, the use of neuroprotective agents loaded in nanocarriers to be delivered by noninvasive means (i.e. via intranasal route) became a popular approach. In the current study, melatonin (MEL) was loaded in lipidic nanocapsules (LNCs) prepared using the phase inversion method, and characterized in terms of size, polydispersity, zeta potential, in vitro drug release, viscosity, storage stability, and ex vivo permeation across sheep nasal mucosa. Moreover, MEL-LNCs were tested for efficacy in cerebral ischemia/reperfusion (I/R/) injury model through histopathological assessment, and analysis of oxidative stress markers, pro-inflammatory cytokines, and apoptotic markers. Results showed that LNCs exhibited particle size ranging from 18.26 to 109.8 nm, negative zeta potential, good storage stability, spherical morphology, and a burst release followed by a sustained release pattern. LNCs exhibited 10.35 folds higher permeation of MEL than the drug solution across sheep nasal mucosa. Post-ischemic intranasal administration of MEL-LNCs revealed lowering of oxidative stress manifested by a decrease in malondialdehyde levels, and elevation of glutathione and superoxide dismutase levels, lowering of the inflammatory markers tumor necrosis factor-α, NO, myeloperoxidase, and significant inhibition of Caspase-3 activity as an apoptotic marker. Western blot analysis delineated a recovery of protein expression Nrf-2 and HO-1 with downregulation in the parent inflammatory markers nuclear factor kappa B p65, inducible nitric oxide synthase, Bax, and Cytochrome C expressions, and upregulation of B-cell lymphoma-2 Bcl-2, hence promoting neuronal survival. This was supported by histological evidence, revealing significant restoration of hippocampal neurons. In light of the above, it can be concluded that MEL-LNCs could be a promising delivery system for nose to brain delivery for treatment of cerebral ischemia.     

褪黑激素抗氧化作用的研究进展

褪黑激素是松果体分泌的一类激素，对其研究起初主要集中在调节睡眠的作用，但近年发现其具有强大的抗氧化应激作用。实验研究表明,褪黑激素不仅本身具有明显的抗氧化作用,且被氧化后的多级代谢产物亦有强大的抗氧化功能;还具有同时清除氧族和氮族自由基的双重功效及上调多种抗氧化酶活性的功能。目前对于它在缺血再灌注损伤、抗癌、抗退行性变等领域的应用研究取得众多进展。本文主要综述近年来褪黑激素抗氧化机制及其应用的研究进展。     

胰胆管合流异常肝损伤抗氧化治疗的实验研究

目的 研究胰胆管合流异常(APBDU)肝损伤的抗氧化治疗.方法 采用13只健康杂种猫,建立胰胆管合流异常的动物模型后随机分为:A组7只,不进行抗氧化治疗;B组6只,抗氧化治疗;术前的13只作为对照组.饲养6个月观察肝脏的病理和肝脏过氧化产物丙二醛(maleic dialdehyde,MDA)变化.结果 13只猫均成活6...     

调和阴阳法针灸对老年不寐患者睡眠质量及MT、NE、5-HT水平的影响

目的 探讨调和阴阳法针灸对老年不寐患者睡眠质量及褪黑素（MT）、去甲肾上腺素（NE）、5-羟色胺（5-HT）水平的影响。方法 选取2020年7月—2022年7月河北医科大学第一医院收治的老年不寐患者120例,采用随机数表法分为观察组和对照组,每组60例。对照组采取常规药物治疗,观察组在对照组基础上联合调和阴阳法针灸。比较两组临床疗效,同时评估其中医证候积分和匹兹堡睡眠质量指数（PSQI）评分,测定MT、NE、5-HT、多巴胺（DA）、γ-氨基丁酸（GABA）水平,观察记录不良反应发生情况。结果 观察组总有效率高于对照组（P <0.05）;观察组治疗前后入睡困难、多梦易醒、神疲食少、目赤口苦、舌红少津、脉弦数、舌苔黄评分的差值均高于对照组（P <0.05）。观察组与对照组治疗前及治疗后2、4周的PSQI评分比较,结果 ①不同时间点PSQI评分比较,差异有统计学意义（F =17.894,P =0.000）;②两组PSQI评分比较,差异有统计学意义（F =26.894,P =0.000）,观察组PSQI评分较低,相对睡眠质量较好;③观察组与对照组PSQI评分变化趋势比较,差异有统计学意义（F =45.247,P =0.000）。观察组治疗前后睡眠总时间、快速眼动睡眠期、睡眠潜伏期、醒觉时间、睡眠效率的差值均高于对照组（P <0.05）;观察组治疗前后MT、NE、5-HT的差值均高于对照组（P <0.05）;观察组治疗前后DA、GABA的差值均高于对照组（P <0.05）;两组不良反应总发生率比较,差异无统计学意义（P >0.05）。结论 调和阴阳法针灸治疗老年失眠症疗效显著,不仅能有效改善患者中医症状、睡眠质量及睡眠结构,还能改善血清MT、NE、5-HT、DA、GABA水平,安全性较高。