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Therapeutic use of melatonin in schizophrenia:A systematic review

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World Journal of Psychiatry 2021年第8期11卷 463-476页

作者： Cathy Duan zoe M Jenkins David Castle Department of Psychiatry University of MelbourneParkville 3010VICAustralia Mental health Service St.Vincent's HospitalMelbourne 3065VICAustralia Centre for Complex Interventions Centre for Addictions and Mental HealthToronto ON M6J 1H4Canada Department of Psychiatry University of TorontoToronto ON M5SCanada

BACKGROUND Sleep dysfunction is a common problem in people with schizophrenia,and side effects of treatment often exacerbate metabolic and cardiovascular risk and may induce extrapyramidal side ***(N-acetyl-5-methoxytryptamine)is an endogenously produced hormone which has demonstrated direct and indirect antioxidant and neuroprotective *** studies have explored the use of exogenous melatonin in improving sleep outcomes in the general population,yet indications for use in schizophrenia are *** To synthesize the evidence from clinical trials investigating prescribed melatonin as an adjunctive therapy in patients with *** A systematic literature review of MEDLINE(Ovid),Embase,PsychINFO,and PubMed on the 27/08/20;and CINAhL and Cochrane Library databases,was *** criteria were:a peer-reviewed clinical trial published in English;included a group of patients with schizophrenia;used melatonin as an adjunctive therapy;and reported any outcome of any *** criteria were:neurodegenerative diseases,primary sleep disorders,co-morbid substance use or animal *** Fifteen studies were included in the current review with the following primary outcomes:sleep(n=6),metabolic profile(n=3),tardive dyskinesia(n=3),cognitive function(n=2)and benzodiazepine discontinuation(n=1).CONCLUSION Adjunctive melatonin therapy has some positive outcomes for sleep,metabolic profile and tardive dyskinesia in patients with *** beneficial effect of melatonin was observed on outcomes of cognition or benzodiazepine *** studies utilizing larger samples and investigations specifically comparing the effect of melatonin as adjunctive therapy with different antipsychotics in patients with schizophrenia are required.

关键词： Schizophrenia Melatonin Clinical trials Sleep Metabolic syndrome Tardive dyskinesia

Clinical laboratory and imaging evidence for effectiveness of agarose-agarose macrobeads containing stem-like cells derived from a mouse renal adenocarcinoma cell population (RMBs) in treatment-resistant, advanced metastatic colorectal cancer:Evaluation of

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Chinese Journal of Cancer Research 2018年第1期30卷 72-83页

作者： Barry h.Smith Lawrence S.Gazda Thomas J.Fahey Angelica Nazarian Melissa A.Laramore Prithy Martis zoe P.Andrada Joanne Thomas Tapan Parikh Sudipta Sureshbabu Nathaniel Berman Allyson J.Ocean Richard D.hall David J.Wolf The Rogosin Institute New York NY 10021 USA The Rogosin Institute-Xenia Division Xenia OH 45385 USA New York Presbyterian-Weill Cornell Medical Center New York NY 10021 USA Bob Evans Farms Inc. New Albany OH 43054 USA

Objective： The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival（OS） responses, to the use of one such system, implantable macrobeads [RENCA macrobeads（RMBs）], in phase I and IIa clinical trials in advanced,treatment-resistant metastatic colorectal cancer（m CRC） are described ***： Forty-eight m CRC patients（30 females; 18 males）, who had failed all available, approved treatments,underwent RMB implantation（8 RMB/kg body weight） up to 4 times in phase I and phase IIa open-label ***, labs [tumor and inflammation markers, lactate dehydrogenase（LDh）] and positron emission tomography-computed tomography（PET-CT） imaging to measure number/volume and metabolic activity of the tumors were performed pre-and 3-month-post-implantation to evaluate safety and initial efficacy（as defined by biological responses）. PET-CT maximum standard uptake value（SUVmax）（baseline and d 90; SUVmax ≥2.5）, LDh,and carcinoembryonic antigen（CEA） and/or cancer antigen 19-9（CA 19-9） response（baseline, d 30 and/or d 60）were assessed and compared to ***： Responses after implantation were characterized by an at least 20% decrease in CEA and/or CA 19-9 in75% of patients. Fluorodeoxyglucose（FDG）-positive lesions（phase I, 39; 2 a, 82） were detected in 37/48 evaluable patients, with 35% stable volume and stable or decreased SUV（10） plus four with necrosis; 10, increased tumor volume, SUV. LDh levels remained stable and low in Responders（R）（d 0–60, 290.4–333.9）, but increased steadily in Non-responders（NR）（d 0–60, 382.8–1,278.5）（d 60, P=0.050）. Responders to RMBs, indicated by the changes in the above markers, correlated with OS（R mean OS=10.76 months; NR mean OS=4.9 months; P=0.0006）.Conclusions： The correlations of the tumor marker, tumor volume

关键词： Clinical trial systems-biology RENCA macrobeads metastatic colorectal cancer colon cancer

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French For Dummies 2

Particle elasticity influences polymeric artificial antigen presenting cell effectiveness in vivo via CD8+T cell activation,macrophage uptake,and the protein corona

丛书名： -For dummies

2011年

作者： Erotopoulos zoe Schmidt Dodi-Katrin Williams Michelle M. Wenzel Dominique

ISBN: (数字)9781118138649

ISBN: (纸本)9781118004647

The fast, informal way to learn to speak French - with integrated audio clips throughout. Listen to pronunciations and conversations. French is a beautiful language but quite difficult to learn. Whether you need to learn the language for a French class, or you travel overseas for business or leisure, this enhanced edition of French for Dummies can help. Written in an easy-to-follow format, with integrated audio clips, it gives you just what you need for basic communication in French. The enhanced edition includes: Expanded coverage of necessary grammar, vocabulary, and pronunciations Useful exercises, practice questions, and a mini-dictionary Business, an upcoming class, travel – whatever your reason for wanting to learn a new language but don't have time to take a class, this enhanced edition of French For Dummies can get you well on your way to becoming fluent in no time!

关键词： French For Dummies book on learning French books on learning French introduction to French French language book French language books how to speak French learn how to speak French learn to speak French French language book French language books French immersion

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Nano Research 2024年第10期17卷 9052-9064页

作者： Savannah E.Est-Witte Sydney R.Shannon Dennis h.Gong Kaitlyn G.Calabresi Jawaun J.harris Kaitlyn Storm Edwin J.Yoo Ariel Isser Vivek P.Jani Natalie K.Livingston Mary O.Omotoso Kelly Rhodes Elana Ben-Akiva Randall A.Meyer zoe T.hsieh Simone Sidoli Stephany Y.Tzeng Jonathan P.Schneck Jordan J.Green Translational Tissue Engineering Center Institute for NanobiotechnologyDepartment of Biomedical EngineeringJohns Hopkins School of Medicine400 N BroadwayBaltimoreMD 21231USA Institute for Cell Engineering Department of PathologyJohns Hopkins School of Medicine733 N BroadwayBaltimoreMD 21205USA Department of Biochemistry Albert Einstein College of MedicineThe BronxNew York CityNY 10461USA

Adoptive cell therapy(ACT)is an immunotherapy strategy for cancer that has seen widespread clinical *** ACT,patient-derived lymphocytes are stimulated with the antigen of interest ex vivo,proliferated,then returned to the patient to initiate an antigen-specific antitumor *** effective,this process is resource-intensive and logistically impossible for many *** artificial antigen presenting cells(aAPCs)offer a potential“off-the-shelf”alternative to ex vivo *** particulate aAPCs perform well in vitro,they have had limited success in vivo due to poor bioavailability after *** to bioavailability include rapid clearance,unfavorable biodistribution,and inadequate interactions with CD8+T cells at sites of *** properties such as elasticity have been shown to vastly impact the bioavailability and particle-cell interactions,but this has yet to be investigated in the context of aAPCs for in vivo T-cell *** literature likewise indicates that biomaterial properties,especially elasticity,can modulate T-cell activation in *** the goal of creating a more biomimetic,next-generation particulate aAPC,we developed a poly(ethylene)glycol hydrogel particle platform with tunable elasticity to investigate the impact of elasticity on antigen-specific T cell activation for in vivo adoptive *** this knowledge,we were able to gain more precise control over in vivo T cell activation and investigate possible mechanisms including the effects of aAPC elasticity on T cell binding,macrophage uptake,and the protein corona.

关键词： adoptive cell therapy artificial antigen presenting cells particle drug delivery elasticity protein corona poly(ethylene glycol)

Secure Chained Threshold Proxy Signature without and with Supervision

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Journal of Software Engineering and Applications 2009年第4期2卷 267-275页

作者： zoe L. JIANG S. M. YIU Y. DONG L. C. K. hUI S. h. Y. WONG 不详

Threshold Proxy Signature (TPS) scheme facilitates a manager to delegate his signing capability to a group of n2 sub-ordinates without revealing his own private key, such that a subgroup of at least t2 ≤ n2 subordinates is required to generate a proxy signature. In reality, the situation can be more complicated. First of all, the subgroup may further delegate their proxy signing capabilities to another group of n3 subordinates such that at least another subgroup of at least t3 ≤ n3 subordinates are of the proxy signing capabilities (in the form of a chain). t2 can be unequal to t3 depending on the concrete requirement. This is a group-to-group delegation problem. In addition, a supervising agent (SA) may be introduced in the above chain to supervise the subordinates, such that proxy signing can only be successfully executed with SA’s agreement. This is a delegation with supervision problem in the threshold delegation chain described above. These two extensions of delegation problems are not solved yet. This paper designs two provably secure cryptographic schemes Chained Threshold Proxy Signature (CTPS) scheme and Chained Threshold Proxy Signature with Supervision (CTPSwS) scheme to solve these two delegation problems.

关键词： Delegation Threshold Proxy Signature Chained Threshold Proxy Signature with Supervision

LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson’s disease

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Translational Neurodegeneration 2022年第1期11卷 790-808页

作者： Eunice Eun Seo Chang Philip Wing-Lok ho hui-Fang Liu Shirley Yin-Yu Pang Chi-Ting Leung Yasine Malki zoe Yuen-Kiu Choi David Boyer Ramsden Shu-Leong ho Division of Neurology Department of MedicineQueen Mary HospitalUniversity of Hong KongPok Fu LamHong KongChina Institute of Metabolism and Systems Research University of BirminghamBirminghamUK.

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are one of the most frequent genetic causes of both familial and sporadic Parkinson’s disease (PD). Mounting evidence has demonstrated pathological similarities between LRRK2-associated PD (LRRK2-PD) and sporadic PD, suggesting that LRRK2 is a potential disease modulator and a thera-peutic target in PD. LRRK2 mutant knock-in (KI) mouse models display subtle alterations in pathological aspects that mirror early-stage PD, including increased susceptibility of nigrostriatal neurotransmission, development of motor and non-motor symptoms, mitochondrial and autophagy-lysosomal defects and synucleinopathies. This review provides a rationale for the use of LRRK2 KI mice to investigate the LRRK2-mediated pathogenesis of PD and implications from current findings from different LRRK2 KI mouse models, and ultimately discusses the therapeutic potentials against LRRK2-associated pathologies in PD.

关键词： Parkinson’s disease LRRK2 Knock-in mouse model Neurotransmission Motor dysfunction Autophagy Lysosome Mitochondrial dysfunction Synucleinopathy hyperkinase activity LRRK2 inhibitor

LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson’s disease

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Translational Neurodegeneration 2022年第1期11卷 869-882页

作者： Shirley Yin-Yu Pang Rachel Cheuk Nam Lo Philip Wing-Lok ho hui-Fang Liu Eunice Eun Seo Chang Chi-Ting Leung Yasine Malki zoe Yuen-Kiu Choi Wing Yan Wong Michelle hiu-Wai Kung David Boyer Ramsden Shu-Leong ho Division of Neurology Department of MedicineQueen Mary HospitalUniversity of Hong KongHong KongChina School of Biomedical Sciences Li Ka Shing Faculty of MedicineUniversity of Hong KongHong KongChina Institute of Metabolism and Systems Research University of BirminghamBirminghamUK.

Mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) represent two most common genetic causes of Parkinson’s disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which are associated with α-synuclein (α-syn) accumulation. LRRK2 regulates macroautophagy via activation of the mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) and the calcium-dependent adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways. Phosphorylation of Rab GTPases by LRRK2 regulates lysosomal homeostasis and endosomal trafficking. Mutant LRRK2 impairs chaperone-mediated autophagy, resulting in α-syn binding and oligomerization on lysosomal membranes. Mutations in GBA reduce glucocerebrosidase (GCase) activity, leading to glucosylceramide accumulation, α-syn aggregation and broad autophagic abnormalities. LRRK2 and GBA influence each other: GCase activity is reduced in LRRK2 mutant cells, and LRRK2 kinase inhibition can alter GCase activity in GBA mutant cells. Clinically, LRRK2 G2019S mutation seems to modify the effects of GBA mutation, resulting in milder symptoms than those resulting from GBA mutation alone. however, dual mutation carriers have an increased risk of PD and earlier age of onset compared with single mutation carriers, suggesting an additive deleterious effect on the initiation of PD pathogenic processes. Crosstalk between LRRK2 and GBA in PD exists, but its exact mechanism is unclear. Drugs that inhibit LRRK2 kinase or activate GCase are showing efficacy in pre-clinical models. Since LRRK2 kinase and GCase activities are also altered in idiopathic PD (iPD), it remains to be seen if these drugs will be useful in disease modification of iPD.

关键词： Parkinson’s disease Interaction LRRK2 GBA GCase Mutation Autophagy α-Synuclein