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Journal of Pineal Research

Rüdiger Hardeland
Dynamic aspects of melatonin's actions merit increasing future attention. This concerns particularly entirely different effects in senescent, weakened oscillators and in dysregulated oscillators of cancer cells that may be epigenetically blocked. This is especially obvious in the case of sirtuin 1 (SIRT1) which is upregulated by melatonin in aged tissues, but strongly downregulated in several cancer cells. These findings are not at all controversial, but are explained on the basis of divergent changes in weakened and dysregulated oscillators...
October 20, 2016: Journal of Pineal Research
Liming Yu, Chongxi Fan, Zhi Li, Jian Zhang, Xiaodong Xue, Yinli Xu, Guolong Zhao, Yang Yang, Huishan Wang
Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague-Dawley rats were subjected to MI/R surgery and high glucose (HG, 500 g/L) infusion (4 ml/kg/h) to induce temporary hyperglycemia...
October 18, 2016: Journal of Pineal Research
Alberto Dominguez-Rodriguez, Pedro Abreu-Gonzalez, Jose M de la Torre-Hernandez, Julia Gonzalez-Gonzalez, Tamara Garcia-Camarero, Luciano Consuegra-Sanchez, Maria Del Mar Garcia-Saiz, Ana Aldea-Perona, Tirso Virgos-Aller, Agueda Azpeitia, Russel J Reiter
The MARIA randomized trial evaluated the efficacy and safety of melatonin for the reduction of reperfusion injury in patients undergoing revascularization for ST-elevation myocardial infarction (STEMI). This was a prespecified interim analysis. A total of 146 patients presenting with STEMI within 6 hours of chest pain onset were randomized to receive intravenous and intracoronary melatonin (n=73) or placebo (n=73) during primary pecutaneous coronary intervention (PPCI). Primary endpoint was myocardial infarct size as assessed by magnetic resonance imaging (MRI) at 6±2 days...
October 13, 2016: Journal of Pineal Research
Juan C Mayo, David Hevia, Isabel Quiros-Gonzalez, Aida Rodriguez-Garcia, Pedro Gonzalez-Menendez, Vanesa Cepas, Iván Gonzalez-Pola, Rosa M Sainz
Treatment of prostate cancer (PCa), a leading cause of cancer among males lacks successful strategies especially in advanced, hormone-refractory stages. Some clinical studies have shown an increase in neuroendocrine like cells parallel to the tumor progression but their exact role is a matter of debate. The prostate is a well-known target for melatonin, which reduces PCa cells proliferation and induces neuroendocrine differentiation. To evaluate the mechanisms underlying the indole effects on neuroendocrine differentiation and its impact on PCa progression, we used a cell culture model (LNCaP) and a murine model (TRAMP)...
October 13, 2016: Journal of Pineal Research
Mel S Lee, Tsung-Cheng Yin, Pei-Hsun Sung, John Y Chiang, Cheuk-Kwan Sun, Hon-Kan Yip
Despite state-of-the-art pharmaceutical regimens, continuous improvements in diagnostic techniques as well as refinements in equipment and interventional procedures, many diseases remain refractory to conventional therapies. Recent advances in stem cell (SC) biology have opened an avenue to exploring its therapeutic potential in various disease entities, especially those that are ischemia-related and refractory to conventional treatment. A number of experimental studies and clinical trials have already demonstrated promising outcomes...
October 13, 2016: Journal of Pineal Research
Shih-Chi Su, Ming-Ju Hsieh, Wei-En Yang, Wen-Hung Chung, Russel J Reiter, Shun-Fa Yang
Melatonin is a naturally occurring molecule secreted by the pineal gland and known as a gatekeeper of circadian clocks. Mounting evidence indicates that melatonin, employing multiple and interrelated mechanisms, exhibits a variety of oncostatic properties in a myriad of tumors during different stages of their progression. Tumor metastasis, which commonly occurs at the late stage is responsible for the majority of cancer deaths; metastases lead to the development of secondary tumors distant from a primary site...
October 5, 2016: Journal of Pineal Research
Hai-Feng Pei, Juan-Ni Hou, Fei-Peng Wei, Qiang Xue, Fan Zhang, Cheng-Fei Peng, Yi Yang, Yue Tian, Juan Feng, Jin Du, Lei He, Xiu-Chuan Li, Er-He Gao, De Li, Yong-Jian Yang
Mitochondrial dysfunction leads to reactive oxygen species (ROS) overload, exacerbating injury in myocardial infarction (MI). As a receptor for translocases in the outer mitochondrial membrane (Tom) complex, Tom70 has an unknown function in MI, including in melatonin-induced protection against MI injury. We delivered specific small interfering RNAs against Tom70 or lentivirus vectors carrying Tom70a sequences into the left ventricles of mice or to cultured neonatal murine ventricular myocytes (NMVMs). At 48 h post-transfection, the left anterior descending coronary arteries of mice were permanently ligated, while the NMVMs underwent continuous hypoxia...
October 5, 2016: Journal of Pineal Research
Jianqiang Hu, Lei Zhang, Yang Yang, Yanjie Guo, Yanhong Fan, Mingming Zhang, Wanrong Man, Erhe Gao, Wei Hu, Russel J Reiter, Haichang Wang, Dongdong Sun
Melatonin reportedly protects against several cardiovascular diseases including ischemia/reperfusion (I/R), atherosclerosis and hypertension. The present study investigated the effects and mechanisms of melatonin on cardiomyocyte autophagy, apoptosis and mitochondrial injury in the context of MI. We demonstrated that melatonin significantly alleviated cardiac dysfunction after MI. Four weeks after MI, echocardiography and Masson staining indicated that melatonin notably mitigated adverse left ventricle remodeling...
October 1, 2016: Journal of Pineal Research
Diana I Sánchez, Bárbara González-Fernández, Beatriz San-Miguel, Juan Ortiz de Urbina, Irene Crespo, Javier González-Gallego, María J Tuñón
The sphingosine kinase (SphK)/sphingosine1-phosphate (S1P) pathway is involved in multiple biological processes, including carcinogenesis. Melatonin shows beneficial effects in cell and animal models of hepatocellular carcinoma (HCC), but it is unknown if they are associated with the modulation of the SphK/S1P system, along with different downstream signaling pathways modified in cancer. We investigated effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight i.p) once a week for 8 weeks...
October 1, 2016: Journal of Pineal Research
Yunxie Wei, Wei Hu, Qiannan Wang, Hongqiu Zeng, Xiaolin Li, Yu Yan, Russel J Reiter, Chaozu He, Haitao Shi
As one popular fresh fruit, banana (Musa acuminata) is cultivated in the world's subtropical and tropical areas. In recent years, pathogen Fusarium oxysporum f. sp. cubense (Foc) has been widely and rapidly spread to banana cultivated areas, causing substantial yield loss. However, the molecular mechanism of banana response to Foc remains unclear, and functional identification of disease-related genes is also very limited. In this study, nine 90 kDa heat-shock proteins (HSP90s) were genomewide identified. Moreover, the expression profile of them in different organs, developmental stages, and in response to abiotic and fungal pathogen Foc were systematically analyzed...
September 14, 2016: Journal of Pineal Research
Jana Kudová, Ondřej Vašíček, Milan Číž, Lukáš Kubala
Melatonin, a molecule involved in the regulation of circadian rhythms, has protective effects against myocardial injuries. However, its capability to regulate the maturation of cardiac progenitor cells is unclear. Recently, several studies have shown that melatonin inhibits the stabilization of hypoxia-inducible factors (HIFs), important signaling molecules with cardioprotective effects. In this study, by employing differentiating mouse embryonic stem cells, we report that melatonin significantly upregulated the expression of cardiac cell-specific markers (myosin heavy chains six and seven) as well as the percentage of myosin heavy chain-positive cells...
September 7, 2016: Journal of Pineal Research
Hsin-Yu Ho, Chiao-Wen Lin, Ming-Hsien Chien, Russel J Reiter, Shih-Chi Su, Yi-Hsien Hsieh, Shun-Fa Yang
Nasopharyngeal carcinoma (NPC), a disease common in the South-East Asian population, has high lymph node metastatic ability. Melatonin, an endogenously produced substance present in animals, plants, fungi, and bacteria, has oncotstatic activity via several mechanisms. The molecular mechanisms involved in melatonin-mediated tumor inhibitory potential are not completely defined. Here, we show that melatonin treatment inhibits TPA-induced cell motility by regulating matrix metalloproteinase-9 (MMP-9) expression in NPC...
September 7, 2016: Journal of Pineal Research
Kyoungwhan Back, Dun-Xian Tan, Russel J Reiter
Melatonin is an animal hormone as well as a signaling molecule in plants. It was first identified in plants in 1995, and almost all enzymes responsible for melatonin biosynthesis had already been characterized in these species. Melatonin biosynthesis from tryptophan requires four-step reactions. However, six genes, i.e., TDC, TPH, T5H, SNAT, ASMT, and COMT, have been implicated in the synthesis of melatonin in plants, suggesting the presence of multiple pathways. Two major pathways have been proposed based on the enzyme kinetics: one is the tryptophan/tryptamine/serotonin/N-acetylserotonin/melatonin pathway, which may occur under normal growth conditions; the other is the tryptophan/tryptamine/serotonin/5-methoxytryptamine/melatonin pathway, which may occur when plants produce large amounts of serotonin, e...
September 7, 2016: Journal of Pineal Research
Azam Hosseinzadeh, Seyed Kamran Kamrava, Mohammad Taghi Joghataei, Radbod Darabi, Ali Shakeri-Zadeh, Mansour Shahriari, Russel J Reiter, Habib Ghaznavi, Saeed Mehrzadi
Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of articular cartilage. As chondrocytes are the only cell type forming the articular cartilage, their gradual loss is the main cause of OA. There is a substantial body of published research that suggests reactive oxygen species (ROS) are major causative factors for chondrocyte damage and OA development. Oxidative stress elicited by ROS is capable of oxidizing and subsequently disrupting cartilage homeostasis, promoting catabolism via induction of cell death and damaging numerous components of the joint...
August 24, 2016: Journal of Pineal Research
Kyungjin Lee, Zbigniew Czarnocki, Russel J Reiter, Kyoungwhan Back
Melatonin is metabolized in animals to cyclic 3-hydroxymelatonin (3-OHM) not by an enzymatic pathway, but by interaction with hydroxyl radicals. The production of 3-OHM in animals suggests the possible presence of 3-OHM in plants. Prior to identification of 3-OHM in plants, we directly cloned the corresponding gene(s) responsible for 3-OHM synthesis using Escherichia coli library strains expressing genes belonging to the 2-oxoglutarate-dependent dioxygenase (2-ODD) superfamily from rice. Three of 35 E. coli library strains supplemented with1 mm melatonin were found to produce 3-OHM in their extracellular medium, suggestive of three 2-ODD genes involved in 3-OHM production...
August 8, 2016: Journal of Pineal Research
Wen Xu, Shu-Yu Cai, Yun Zhang, Yu Wang, Golam Jalal Ahammed, Xiao-Jian Xia, Kai Shi, Yan-Hong Zhou, Jing-Quan Yu, Russel J Reiter, Jie Zhou
Melatonin is a pleiotropic signaling molecule that provides physiological protection against diverse environmental stresses in plants. Nonetheless, the mechanisms for melatonin-mediated thermotolerance remain largely unknown. Here we report that endogenous melatonin levels increased with a rise in ambient temperature and that peaked at 40 °C. Foliar pretreatment with an optimal dose of melatonin (10 μM) or the overexpression of N-acetylserotonin methyltransferase (ASMT) gene effectively ameliorated heat-induced photoinhibition and electrolyte leakage in tomato plants...
August 2, 2016: Journal of Pineal Research
Sarah Chua, Fan-Yen Lee, Hsin-Ju Chiang, Kuan-Hung Chen, Hung-I Lu, Yen-Ta Chen, Chih-Chao Yang, Kun-Chen Lin, Yi-Ling Chen, Gour-Shenq Kao, Chih-Hung Chen, Hsueh-Wen Chang, Hon-Kan Yip
We investigated the cardioprotective effect of melatonin (Mel) and exendin-4 (Ex4) treatment in a rat model of cardiorenal syndrome (CRS). Male-adult SD rats (n=48) were randomly and equally divided into sham-control (SC), dilated cardiomyopathy (DCM) (doxorubicin 7 mg/kg i.p. every five days/ 4 doses), CRS (defined as DCM + CKD) only, CRS-Mel (20 mg/kg/day), CRS-Ex4 (10 μg/kg/day) and CRS-Mel-Ex4. In-vitro results showed protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), DNA/mitochondrial-damaged (γ-H2AX/cytosolic cytochrome-C) and apoptotic (cleaved caspase-3/PARP) biomarkers, and senescence (β-galactosidase cells) were upregulated, whereas mitochondrial ATP level was decreased in doxorubicin/ p-Cresol-treated H9C2 cells that were revised by Mel and Ex4 treatments (all p<0...
July 28, 2016: Journal of Pineal Research
Russel J Reiter, Juan C Mayo, Dun-Xian Tan, Rosa M Sainz, Moises Alatorre-Jimenez, Lilian Qin
Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress...
October 2016: Journal of Pineal Research
Néstor Prieto-Domínguez, Raquel Ordóñez, Anna Fernández, Carolina Méndez-Blanco, Anna Baulies, Carmen Garcia-Ruiz, José C Fernández-Checa, José L Mauriz, Javier González-Gallego
Effects of sorafenib in hepatocellular carcinoma (HCC) are frequently transient due to tumor-acquired resistance, a phenotype that could be targeted by other molecules to reduce this adaptive response. Because melatonin is known to exert antitumor effects in HCC cells, this study investigated whether and how melatonin reduces resistance to sorafenib. Susceptibility to sorafenib (10 nmol/L to 50 μmol/L) in the presence of melatonin (1 and 2 mmol/L) was assessed in HCC cell lines HepG2, HuH7, and Hep3B. Cell viability was reduced by sorafenib from 1 μmol/L in HepG2 or HuH7 cells, and 2...
October 2016: Journal of Pineal Research
Carlos Quintana, Javier Cabrera, Juan Perdomo, Francisco Estévez, Juan F Loro, Russel J Reiter, José Quintana
Melatonin is an endogenous indoleamine with a wide range of biological functions. In addition to modulating circadian rhythms, it plays important roles in the health as an antioxidant. Melatonin has also the ability to induce apoptosis in cancer cells and to enhance the antitumoral activity of chemotherapeutic agents. In this study, the effect of melatonin on hyperthermia-induced apoptosis was explored using human leukemia cells. The results demonstrate that melatonin greatly improved the cytotoxicity of hyperthermia in U937 cells...
October 2016: Journal of Pineal Research
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