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Melatonin,tunneling nanotubes,mesenchymal cells,and tissue regeneration

Neural Regeneration Research 2023年第4期18卷 760-762页

作者： Francesca Luchetti Silvia Carloni Maria G.Nasoni russel j.reiter Walter Balduini Department of Biomolecular Sciences University of Urbino Carlo BoUrbinoItaly Department of Cell Systems and Anatomy Long School of MedicineUT HealthSan AntonioTXUSA

Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and *** stem cells are widely used in experimental and clinical regenerative medicine due to their capability to transdifferentiate into various ***,when transplanted,they lose part of their multipotency and immunomodulatory properties,and most of them die after injection into the damaged *** this review,we discuss the potential utility of melatonin in preserving mesenchymal stem cells’survival and function after *** is a pleiotropic molecule regulating critical cell functions including apoptosis,endoplasmic reticulum stress,and *** is also synthesized in the mitochondria where it reduces oxidative stress,the opening of the mitochondrial permeability transition pore and the downstream caspase activation,activates uncoupling proteins,and curtails the proinflammatory *** addition,recent findings showed that melatonin also promotes the formation of tunneling nanotubes and the transfer of mitochondria between cells through the connecting *** mitochondrial dysfunction is a primary cause of mesenchymal stem cells death and senescence and a critical issue for survival after transplantation,we propose that melatonin by favoring mitochondria functionality and their transfer through tunneling nanotubes from healthy to suffering cells could improve mesenchymal stem cellbased therapy in a large number of diseases for which basic and clinical trials are underway.

关键词： brain ischemia cell transplantation melatonin mesenchymal stem cell mitochondria mitochondrial transplantation regenerative therapy senescence tunneling nanotubes

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Promotion of liquid-to-solid phase transition of cGAS by Baicalein suppresses lung tumorigenesis

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1392-1395页

作者： Tiansheng Zheng Haipeng Liu Yifan Hong Yajuan Cao Qing Xia Chengge Qin Ming Li russel j.reiter Yidong Bai Lihong Fan Department of Respiratory Medicine Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China Department of Integrated Traditional Chinese&Western Medicine Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China Clinical Translational Research Center Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433China Institute of Energy Metabolism and Health Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China Institute of Molecular Physiology Institue of Cancer ResearchShenzhen Bay LaboratoryShenzhen 518132China Medical School of Nantong University NantongJiangsu 22601China Department of Cell Systems and Anatomy University of Texas Health San AntonioSan AntonioTexas 78229USA

Dear Editor,Kras and p53 mutation are among the most common gene mutations in lung cancer,which has both the highest incidence and mortality rate among cancers.1 Kras/p53 mutation also causes mitochondrial dysfunction,which has been implicated to promote the inflammation-to-cancer transition.2 We established a lung adenocarcinoma model by using conditional alleles of KrasLSLG12D/p53flox/flox in mice3 to evaluate the effect of Baicalein(5,6,7-trihydroxyflavone),a principal component of Scutellaria baicalensis in traditional Chinese medicine,4 on the initiation and progression of lung ***-mediated expression of KrasG12D and deletion of p53 caused obvious tumor lesions in the lung,which were strongly inhibited by the administration of Baicalein(Fig.1a,b and Supplementary Fig.1a,b),indicating that Baicalein is highly potent in inhibiting the progression of primary lung cancer.

关键词： lung Baicalein inhibited

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Melatonin enhances radiofrequency-induced NK antitumor immunity,causing cancer metabolism reprogramming and inhibition of multiple pulmonary tumor development

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Signal Transduction and Targeted Therapy 2021年第10期6卷 3019-3032页

作者： Ming Li Bingjie Hao Menghuan Zhang russel j.reiter Shumeng Lin Tiansheng Zheng Xiangyun Chen Yanbei Ren Liduo Yue Baigenzhin Abay Guojie Chen Xiao Xu Yufeng Shi Lihong Fan Department of Respiratory Medicine Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina Institute of Energy Metabolism and Health Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina Tongji University Cancer Center Shanghai Tenth People's Hospital of Tongji UniversitySchool of MedicineTongji UniversityShanghaiChina Clinical Center For Brain And Spinal Cord Research Tongji UniversityShanghaiChina Department of Cell Systems and Anatomy University of Texas Health San AntonioSan AntonioTexasUSA National Scientific Medical Research Center AstanaKazakhstan State Key Laboratory of Molecular Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghaiChina

Surgery is the comm on treatme nt for early lung cancer with multiple pulm onary no dules,but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic *** this study,we found that a combined treatment of local rad iofreq ue ncy ablati on(RFA)and melatonin(MLT)greatly improved clinical outcomes for early lung cancer patie nts with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated ***,as demonstrated in an associated mouse lung tumor model,RFA not only effectively remove treated tumors but also stimulate antitumor immunity,which could inhibit tumor growth in non-ablated *** enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with *** and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment,which suggests reprogrammed tumor metabolism after combined treatment with RFA and *** of residual tumor further revealed the depressed activity of MAPK,NF-kappa B,Wnt,and Hedgehog pathways and upregulated P53 pathway in tumors,which was in line with the inhibited tumor *** RFA and MLT treatment also reversed the Warburg effect and decreased tumor *** findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary *** registration:***,identifier ChiCTR2100042695,http://***/***?proj=120931.

关键词： metabolism immunity inhibited

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Secretion of melatonin and 6-sulfatoxymelatonin urinary excretion in functional dyspepsia

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World journal of Gastroenterology 2011年第21期17卷 2646-2651页

作者： Cezary Chojnacki Tomasz Poplawski Grazyna Klupinska janusz Blasiak jan Chojnacki russel j reiter Department of Gastroenterology Medical University of Lodz90-647 LodzPoland Department of Molecular Genetics University of Lodz90-131 LodzPoland Department of Cellular and Structural Biology University of Texas Health Science CenterSan AntonioTX 78229-3901United States

To evaluate blood concentration of melatonin and urinary excretion of its metabolite, 6-sulfatoxymelatonin （6-OHMS）, in functional dyspepsia （FD）. METHODS： Ninety individuals were enrolled in the study： 30 in each study group： patients with postprandial distress syndrome （PDS）, epigastric pain syndrome （EPS）, and controls. Blood samples were drawn at 02：00 and 09：00 h and 24-h urine collection was performed. Serum melatonin and urinary 6-OHMS concentrations were measured by enzyme-linked immunosorbent assay. RESULTS： Serum melatonin concentration at night and in the morning was significantly （P 〈 0.001） higher inPDS patients [at 02：00 h-93.3 pg/mL, quartile range （QR）： 79.8-116.2; at 09.00 h-14.3 pg/mL, QR： 7.06-19.0] than in EPS （57.2 pg/mL, QR： 42.6-73.1, 8.1 pg/mL, QR： 4.2-9.3） and control patients （57.7 pg/mL, QR： 51.2-62.5; 8.1 pg/mL, QR： 5.4-10.3）. A similar relationship was observed for urinary 6-OHMS excretion. Patients with severe PDS symptoms had a higher melatonin concentration than these with moderate syndromes, whereas patients with severe EPS had a lower urinary 6-OHMS excretion than patients with moderate ***： Evaluation of melatonin serum concentrations and 24-h urinary 6-OHMS excretion are useful methods for differential diagnosis of various clinical forms of FD.

关键词： Functional dyspepsia Postprandial distress syndrome Epigastric pain syndrome Melatonin 6-sulfatoxymelatonin

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ALDH2 contributes to melatonin-induced protection against APP/PS1 mutation-prompted cardiac anomalies through cGAS-STING-TBK1-mediated regulation of mitophagy

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1335-1347页

作者： Shuyi Wang Lin Wang Xing Qin Subat Turdi Dongdong Sun Bruce Culver russel jreiter Xiaoming Wang Hao Zhou jun Ren Department of Emergency Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China Center for Cardiovascular Research and Alternative Medicine University of Wyoming College of Health SciencesLaramieWY 82071USA Department of Cardiology and Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan UniversityShanghai 200032China Department of Geriatrics Xijing HospitalThe Air Force Military Medical UniversityXi’anChina Department of Cardiology Xijing HospitalThe Air Force Military Medical UniversityXi’an 710032China Department of Cellular and Structural Biology UT Health San AntonioSan AntonioTXUSA Chinese PLA General Hospital Medical School of Chinese PLABeijing 100853China

Ample clinical evidence suggests a high incidence of cardiovascular events in Alzheimer’s disease(AD),although neither precise etiology nor effective treatment is *** study was designed to evaluate cardiac function in AD patients and APP/PS1 mutant mice,along with circulating levels of melatonin,mitochondrial aldehyde dehydrogenase(ALDH2)and *** patients and APP/PS1 mice displayed cognitive and myocardial deficits,low levels of circulating melatonin,ALDH2 activity,and autophagy,ultrastructural,geometric(cardiac atrophy and interstitial fibrosis)and functional(reduced fractional shortening and cardiomyocyte contraction)anomalies,mitochondrial injury,cytosolic mtDNA buildup,apoptosis,and suppressed autophagy and ***/PS1 mutation downregulated cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)levels and TBK1 phosphorylation,while promoting Aβ*** with melatonin overtly ameliorated unfavorable APP/PS1-induced changes in cardiac geometry and function,apoptosis,mitochondrial integrity,cytosolic mtDNA accumulation(using both immunocytochemistry and qPCR),mitophagy,and cGAS-STING-TBK1 signaling,although these benefits were absent in APP/PS1/ALDH2−/−*** vitro evidence indicated that melatonin attenuated APP/PS1-induced suppression of mitophagy and cardiomyocyte function,and the effect was negated by the nonselective melatonin receptor blocker luzindole,inhibitors or RNA interference of cGAS,STING,TBK1,and *** data collectively established a correlation among cardiac dysfunction,low levels of melatonin,ALDH2 activity,and autophagy in AD patients,with compelling support in APP/PS1 mice,in which melatonin rescued myopathic changes by promoting cGAS-STING-TBK1 signaling and mitophagy via an ALDH2-dependent mechanism.

关键词： APP/PS1 cardiac ALDH2

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Night-time Rise in Rat Pineal N-Acetyltransferase due to Carbaryl Administration Is Reduced by Propranolol Treatment

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Biomedical and Environmental Sciences 1995年第1期8卷 45-53页

作者： AHMED M. ATTIA MOSTAFA H. MOSTAFA BRUCE A. RICHARDSON AND russel j. reiter(Department of Environmental Studies, Institute of Graduate Studies and Research, P.O.Box 832, Alexandria, Egypt Department of Cellular and Structural Biology, University of Texas, Department of Environmental Studies Institute of Graduate Studies and Research Alexandria Egypt.

The purpose of the present study was to examine the effects of administration of sublethal doses of carbaryl on nighttime rat pineal melatonin synthesis in the presence and absence of propranolol, a β-adrenergic receptor antagonist. Two groups of adult male albino rats were administered orally N-methyl-l-naphthylcarbamate (carbaryl) (8. 33mg/kg BW daily in corn oil) for six successive days; another two groups received corn oil *** the last day of carbaryl treatment, half of the animals received an intraperitoneal injection of propranolol (20 mg/kg body weight, one hour before lights off). The other two groups were given a saline injection. Four hours after darkness onset, pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) activities as well as pineal concentrations of 5-hydroxytryptophan (5HTP), serotonin (5HT),5-hydroxyindole acetic acid (5HIAA) and pineal and serum melatonin levels were measured. Nocturnal NAT activity was increased due to carbaryl administration but the pesticide was ineffective in stimulating NAT activity in rats treated with *** 5HT was decreased due to carbaryl administration but 5HTP and 5HIAA levels were unaffected. Pineal and serum melatonin levels were decreased due to propranolol treatment. The results indicate that carbaryl may influence pineal NAT activity by a mechanism that involves β-adrenergic neural transmission.

关键词： time Night-time Rise in Rat Pineal N-Acetyltransferase due to Carbaryl Administration Is Reduced by Propranolol Treatment

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Evaluation of enterochromaffin cells and melatonin secretion exponents in ulcerative colitis

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World journal of Gastroenterology 2013年第23期19卷 3602-3607页

作者： Cezary Chojnacki Maria Wisniewska-jarosińska Grazyna Kulig Ireneusz Majsterek russel j reiter jan Chojnacki Department of Gastroenterology Medical University of Lodz90-647 Lodz Poland Department of Clinical Chemistry and Biochemistry Medical University of Lodz90-647 Lodz Poland Department of Cellular and Structural Biology University of Texas Health Science CenterSan Antonio TX 78229 United States

AIM: To study an assessment of the number of enterochromaffin cells and expression of hydroxyindole-Omethyltransferase in colonic mucosa and urine excretion of 6-sulfatoxymelatonin in patients with ulcerative colitis. METHODS: The study included 30 healthy subjects (groupⅠ-C), 30 patients with ulcerative proctitis [group Ⅱ-ulcerative proctitis (UP)] and 30 patients with ulcerative colitis [group Ⅲ-ulcerative colitis (UC)] in acute phases of these diseases. The number of enterochromaffin cells (EC) was estimated in rectal and colonic mucosa. Bioptates were assembled from many different parts of the large intestine. Immunorective cells collected from various parts of the colon were counted according to the Eurovision DAKO (Dako A/S, Copenhagen, Denmark) System in the range of 10 fields in each bioptate at × 200 magnification. The level of mRNA expression of hydroxyindole-O-methyltransferase (HIOMT) in colonic mucosa was estimated with RT-PCR. Urine 6-sulfatoxymelatonin (6-HMS) excretion was determined immunoenzymatically using an IBL (IBL International GmbH, Hamburg, Germany) kit (RE 54031). RESULTS: The number of EC cells in healthy subjects (C) was 132.40 ± 31.26. In patients of group Ⅱ (UP) and group Ⅲ (UC) the number of these cells was higher 225.40 ± 37.35 (P < 0.001) and 225.24 ± 40.50 (P < 0.001) respectively. Similar differences were related to HIOMT expression, which was 1.04 ± 0.36 in group C, 1.56 ± 0.56 (P < 0.01) in group UP and 2.00 ± 0.35 (P < 0.001) in group UC. Twenty-four hour 6-HMS urinary excretion was as follows: C 16.32 ± 4.95 μg/24 h, UP 26.30 ± 7.29 μg/24 h (P < 0.01), UC 42.30 ± 12.56 μg/24h (P < 0.001). A correlation between number of EC cells and 6-HMS excretion was noted in all groups: r = 0.766 in patients with UP, r = 0.703 with UC and r = 0.8551 in the control group; the correlation between the results is statistically significant. CONCLUSION: In the acute phases of both UP and UC, proliferation of EC cells and high expression of HIOMT a

关键词： Enterochromaffin cells 5-hydroxyindoleO-methyltransferase 6-sulfatoxymelatonin Ulcerative proctitis Ulcerative colitis

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Melatonin inhibits Gram-negative pathogens by targeting citrate synthase

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Science China(Life Sciences) 2022年第7期65卷 1430-1444页

作者： Fang He Yuan Liu Pan Li Xiaoyan Wu Yaoyao Xia Dong Zhang Nengzhang Li Yuanyi Peng Guoqiang Zhu Rüdiger Hardeland russel jreiter Wenkai Ren College of Veterinary Medicine Southwest UniversityChongqing 400715China State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources Guangdong Laboratory of Lingnan Modern AgricultureGuangdong Provincial Key Laboratory of Animal Nutrition ControlNational Engineering Research Center for Breeding Swine IndustryCollege of Animal ScienceSouth China Agricultural UniversityGuangzhou 510642China joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China Jiangsu Co-innovation Center for Important Animal Infectious Diseases and ZoonosesCollege of Veterinary MedicineInstitute of Comparative MedicineYangzhou UniversityYangzhou 225009China johann Friedrich Blumenbach Institute of Zoology and Anthropology University of GöttingenGöttingen 37073Germany Department of Cellular and Structural Biology University of Texas Health Science CenterSan AntonioTX 78229USA

Bacterial infections caused by Gram-negative pathogens represent a growing burden for public health *** the urgent need for new antibiotics that effectively fight against pathogenic bacteria,very few compounds are currently under development or approved in the clinical *** compounds for other uses offers a productive strategy for the development of new *** we report that the multifaceted melatonin effectively improves survival rates of mice and decreases bacterial loads in the lung during ***,melatonin specifically inhibits the activity of citrate synthase of Gram-negative pathogens through directly binding to the R300,D363,and H265 sites,particularly for the notorious Pasteurella *** findings highlight that usage of melatonin is a feasible and alternative therapy to tackle the increasing threat of Gram-negative pathogen infections via disrupting metabolic flux of bacteria.

关键词： citrate synthase citric acid Gram-negative pathogens melatonin P.multocida

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Effect of melatonin on the severity of L-arginine-induced experimental acute pancreatitis in rats

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World journal of Gastroenterology 2006年第2期12卷 251-258页

作者： Annamaria Szabolcs russel j reiter Tamas Letoha Peter Hegyi Gabor Papai Ilona Varga Katalin jarmay jozsef Kaszaki Reka Sari Zoltan Rakonczay jr janos Lonovics Tamas Takacs st Department of Medicine University of SzegedHungary Department of Cellular and Structural Biology University of TexasHealth Science CentreSan AntonioTexasUnited States Institute of Chemistry University of SzegedHungary Biological Research Centre Hungarian Academy of SciencesSzegedHungary Biological Isotope Laboratory University of SzegedHungary Institute of Experimental Surgery University of SzegedHungary

AIM： To determine the effect of melatonin pre- and post-treatment on the severity of L-arginine （L-Arg） -induced experimental pancreatitis in rats. METHODS： Male Wistar rats （25） were divided into five groups. Those in group A received two injections of 3.2 g/kg body weight L-Arg i.p. at an interval of 1 h. In group MA, the rats were treated with 50 mg/kg body weight melatonin i.p. 30 min prior to L-Arg administration. In group AM, the rats received the same dose of melatonin 1 h after L-Arg was given. In group M, a single dose of melatonin was administered as described previously. In group C the control animals received physiological saline injections i.p. All rats were exsanguinated 24 h after the second L-Arg injection. RESULTS： L-Arg administration caused severe necrotizing pancreatitis confirmed by the significant elevations in the serum amylase level, the pancreatic weight/body weight ratio （pw/bw）, the pancreatic IL-6 content and the myeloperoxidase activity, relative to the control values. Elevation of the serum amylase level was significantly reduced in rats given melatonin following L-Arg compared to rats injected with L-Arg only. The activities of the pancreatic antioxidant enzymes （Cu/Zn-superoxide dismutase （CulZn-SOD） and catalase （CAT）） were significantly increased 24 h after pancreatitis induction. Melatonin given in advance of L-Arg significantly reduced the pancreatic CAT activity relative to that in the rats treated with L-Arg alone. In the liver, L-Arg significantly increased the lipid peroxidation level, and the glutathione peroxidase and Cu/Zn-SOD activities, whereas the Mn-SOD activity was reduced as compared to the control rats. Melatonin pre-treatment prevented these changes. CONCLUSION： Melatonin is an antioxidant that is able to counteract some of the L-Arg-induced changes during acute pancreatitis, and may therefore be helpful in the supportive therapy of patients with acute necrotizing pancreatitis.

关键词： Acute pancreatitis Melatonin Scavengers

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Melatonin alleviates brain injury in mice subjected to cecal ligation and puncture via attenuating inflammation, apoptosis, and oxidative stress: the role of SIRT1 signaling

Melatonin alleviates brain injury in mice subjected to cecal...

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第十四届中国医师协会神经外科医师年会

作者： Lei Zhao Rui An Yang Yang Xiangmin Yang Haixiao Liu Liang Yue Xia Li Yan Lin russel j.reiter Yan Qu Department of Neurosurgery Tangdu HospitalThe Fourth Military Medical University Department of Radiology Xijing HospitalThe Fourth Military Medical University Department of Scientific Research The Fourth Military Medical University Department of Cellular and Structural Biology UT Health Science Center

Sepsis is a systemic inflammatory response to infection that causes severe neurological complications. Previous studies have suggested that melatonin is protective during sepsis. Additionally, silent information regulator 1（SIRT1） was reported to be beneficial in sepsis. However, the role of SIRT1 signaling in the protective effect of melatonin against septic encephalopathy remains unclear. This study aimed to investigate the role of SIRT1 in the protective effect of melatonin. EX527, a SIRT1 inhibitor, was used to reveal the role of SIRT1 in melatonin’s action. Cecal ligation and puncture or sham operation was performed in male C57BL/6j *** was administrated intraperitoneally（30 mg/kg）. The survival rate of mice was recorded for the 7-day period following the sham or CLP operation. The blood–brain barrier（BBB） integrity, brain water content, levels of inflammatory cytokines（TNF-a, IL-1b, and HMGB1）, and the level of oxidative stress（superoxide dismutase（SOD）, catalase（CAT）, and malondialdehyde（MDA）） and apoptosis were assessed. The expression of SIRT1, Ac-FoxO1, Ac-p53, Ac-NF-jB, Bcl-2, and Bax was detected by Western blot. The results suggested that melatonin improved survival rate,attenuated brain edema and neuronal apoptosis, and preserved BBB *** decreased the production of TNF-a, IL-1b, and *** increased the activity of SOD and CAT and decreased the MDA production. Additionally, melatonin upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of Ac-FoxO1, Ac-p53, Ac-NF-jB,and Bax. However, the protective effects of melatonin were abolished by EX527. In conclusion, our results demonstrate that melatonin attenuates sepsis-induced brain injury via SIRT1 signaling activation.

关键词： cecal ligation and puncture inflammation melatonin oxidative stress septic encephalopathy SIRT1 signaling

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