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[PMID]:28549585
[Au] Autor:Fujita I; Nobunaga M; Seki T; Kurauchi Y; Hisatsune A; Katsuki H
[Ad] Endereço:Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
[Ti] Título:Cystamine-mediated inhibition of protein disulfide isomerase triggers aggregation of misfolded orexin-A in the Golgi apparatus and prevents extracellular secretion of orexin-A.
[So] Source:Biochem Biophys Res Commun;489(2):164-170, 2017 Jul 22.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Orexins (orexin-A and orexin-B) are neuropeptides that are reduced in narcolepsy, a sleep disorder that is characterized by excessive daytime sleepiness, sudden sleep attacks and cataplexy. However, it remains unclear how orexins in the brain and orexin neurons are reduced in narcolepsy. Orexin-A has two closely located intramolecular disulfide bonds and is prone to misfolding due to the formation of incorrect disulfide bonds. Protein disulfide isomerase (PDI) possesses disulfide interchange activity. PDI can modify misfolded orexin-A to its native form by rearrangement of two disulfide bonds. We have previously demonstrated that sleep deprivation and a high fat diet increase nitric oxide in the brain. This increase triggers S-nitrosation and inactivation of PDI, leading to aggregation of orexin-A and reduction of orexin neurons. However, the relationship between PDI inactivation and loss of orexin neurons has not yet been fully elucidated. In the present study, we used a PDI inhibitor, cystamine, to elucidate the precise molecular mechanism by which PDI inhibition reduces the number of orexin neurons. In rat hypothalamic slice cultures, cystamine induced selective depletion of orexin-A, but not orexin-B and melanin-concentrating hormone. Moreover, cystamine triggered aggregation of orexin-A, but not orexin-B in the Golgi apparatus of hypothalamic slice cultures and in vivo mouse brains. However, cystamine did not induce endoplasmic reticulum (ER) stress, and an ER stress inducer did not trigger aggregation of orexin-A in slice cultures. Finally, we demonstrated that cystamine significantly decreased extracellular secretion of orexin-A in AD293 cells overexpressing prepro-orexin. These findings suggest that cystamine-induced PDI inhibition induces selective depletion, aggregation in the Golgi apparatus and impaired secretion of orexin-A. These effects may represent an initial step in the pathogenesis of narcolepsy.
[Mh] Termos MeSH primário: Cistamina/farmacologia
Complexo de Golgi/efeitos dos fármacos
Orexinas/química
Orexinas/secreção
Agregados Proteicos/efeitos dos fármacos
Agregação Patológica de Proteínas
Isomerases de Dissulfetos de Proteínas/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Cistamina/administração & dosagem
Complexo de Golgi/metabolismo
Complexo de Golgi/secreção
Hipotálamo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Neurônios/efeitos dos fármacos
Neurônios/metabolismo
Isomerases de Dissulfetos de Proteínas/metabolismo
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Orexins); 0 (Protein Aggregates); EC 5.3.4.1 (Protein Disulfide-Isomerases); R110LV8L02 (Cystamine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170528
[St] Status:MEDLINE


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[PMID]:28323415
[Au] Autor:Guo R; Su Q; Zhang J; Dong A; Lin C; Zhang J
[Ad] Endereço:State Key Laboratory for Marine Corrosion and Protection, Luoyang Ship Material Research Institute (LSMRI) , Qingdao 266101, China.
[Ti] Título:Facile Access to Multisensitive and Self-Healing Hydrogels with Reversible and Dynamic Boronic Ester and Disulfide Linkages.
[So] Source:Biomacromolecules;18(4):1356-1364, 2017 Apr 10.
[Is] ISSN:1526-4602
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Multifunctional and multiresponsive hydrogels have presented a promising platform to design and fabricate smart devices for application in a wide variety of fields. However, their preparations often involve multistep preparation of multiresponsive polymer precursors, tedious reactions to introduce functional groups or sophisticated molecular designs. In this work, a multifunctional boronic acid-based cross-linker bis(phenylboronic acid carbamoyl) cystamine (BPBAC) was readily prepared from inexpensive commercially available 3-carboxylphenylboronic acid (CPBA) and cystamine dihydrochloride, which has the ability to cross-link the cis-diols and catechol-containing hydrophilic polymers to form hydrogels. Due to the presence of the reversible and dynamic boronate ester and disulfide bonds, the obtained hydrogels were demonstrated to not only possess pH, glucose, and redox triresponsive features, but also have autonomic self-healing properties under ambient conditions. Moreover, we can modulate the rheological and mechanical properties by simply adjusting the BPBAC amount. The features, such as commercially available starting materials, easy-to-implement approach, and versatility in controlling cross-linking network and mechanical properties, make the strategy described here a promising platform for fabricating multifunctional and smart hydrogels.
[Mh] Termos MeSH primário: Resinas Acrílicas/química
Ácidos Borônicos/química
Catecóis/química
Reagentes para Ligações Cruzadas/química
Cistamina/análogos & derivados
Dissulfetos/química
Dopamina/análogos & derivados
Hidrogéis/química
Hidrogéis/síntese química
[Mh] Termos MeSH secundário: Resinas Acrílicas/síntese química
Ácidos Borônicos/síntese química
Cistamina/síntese química
Cistamina/química
Ditiotreitol/química
Dopamina/síntese química
Dopamina/química
Glucose/química
Oxirredução
Transição de Fase
Propriedades de Superfície
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acrylic Resins); 0 (Boronic Acids); 0 (Catechols); 0 (Cross-Linking Reagents); 0 (Disulfides); 0 (Hydrogels); 0 (bis(phenylboronic acid carbamoyl)cystamine); 0 (poly(acrylamide-co-dopamine methacrylamide)); IY9XDZ35W2 (Glucose); LF3AJ089DQ (catechol); R110LV8L02 (Cystamine); T8ID5YZU6Y (Dithiothreitol); VTD58H1Z2X (Dopamine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biomac.7b00089


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[PMID]:28239785
[Au] Autor:Vasin MV; Ushakov IB; Kovtun VY; Komarova SN; Semenova LA; Galkin AA; Afanas'ev RV; Bukhtiyarov IV
[Ad] Endereço:Research Institute of Occupational Medicine, Russian Academy of Sciences, Moscow, Russia. mikhail-vvasin@yandex.ru.
[Ti] Título:Pharmacological Analysis of the Therapeutic Effect of Radioprotectors Cystamine and Indralin in the Capacity of Radiomitigators.
[So] Source:Bull Exp Biol Med;162(4):466-469, 2017 Feb.
[Is] ISSN:1573-8221
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The therapeutic radiomitigating effect of cystamine and indralin was studied in experiments on mice and rats and pharmacological analysis of these drugs was carried out. The animals were subjected to whole-body Co γ-irradiation. The mice were exposed to single (9-10 Gy) or double (8 Gy) irradiation with an interval of 1 month. The rats were exposed to 10 Gy with partial shielding of the upper quarter of the abdomen. In experiments on mice, pretreatment with reserpine abolished the therapeutic effect of cystamine administered repeatedly every 15 min over 1 h after irradiation. Moreover, summation of the radioprotective and therapeutic effects of the radioprotector was revealed under these conditions. In mice and rats, α -adrenoreceptor blocker terazosin did not abolish the therapeutic effect of indralin administrated after irradiation, but blocked the radioprotective effect of indralin applied prior to irradiation. At the same time, 5-HT serotonin receptor blocker tropoxin abolished the therapeutic effect of indralin without affecting its radioprotective activity.
[Mh] Termos MeSH primário: Cistamina/farmacologia
Raios gama
Fenóis/farmacologia
Lesões Experimentais por Radiação/prevenção & controle
Protetores contra Radiação/farmacologia
[Mh] Termos MeSH secundário: Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia
Animais
Compostos Aza/farmacologia
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia
Cistamina/antagonistas & inibidores
Relação Dose-Resposta à Radiação
Esquema de Medicação
Feminino
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos CBA
Fenóis/antagonistas & inibidores
Prazosina/análogos & derivados
Prazosina/farmacologia
Lesões Experimentais por Radiação/metabolismo
Lesões Experimentais por Radiação/patologia
Ratos
Receptores Adrenérgicos alfa 1/metabolismo
Receptores 5-HT2 de Serotonina/metabolismo
Reserpina/farmacologia
Irradiação Corporal Total
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-(3,4,5-trimethoxybenzoyloximino)-8-methyl-8-azabicyclo(3,2,1)octane); 0 (Adrenergic alpha-1 Receptor Antagonists); 0 (Aza Compounds); 0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (Phenols); 0 (Radiation-Protective Agents); 0 (Receptors, Adrenergic, alpha-1); 0 (Receptors, Serotonin, 5-HT2); 156799-03-0 (indralin); 8B1QWR724A (Reserpine); 8L5014XET7 (Terazosin); R110LV8L02 (Cystamine); XM03YJ541D (Prazosin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170315
[Lr] Data última revisão:
170315
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170228
[St] Status:MEDLINE
[do] DOI:10.1007/s10517-017-3641-1


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[PMID]:28219708
[Au] Autor:Angus JA; Rajasekaran P; Wright CE
[Ad] Endereço:Cardiovascular Therapeutics Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Victoria 3010, Australia. Electronic address: jamesaa@unimelb.edu.au.
[Ti] Título:Novel technique to determine the pK of clonidine at prejunctional α -adrenoceptors in cardiac and vascular sympathetic transmission.
[So] Source:Eur J Pharmacol;800:81-95, 2017 Apr 05.
[Is] ISSN:1879-0712
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Analytical pharmacology draws heavily on the concept of equilibrium of agonist and silent antagonist concentrations competing at a specific receptor site. This condition breaks down in nerve transmission when transmitter release is inhibited by prejunctional α -adrenoceptors activated by an agonist such as clonidine. We have developed a method that allows the agonist dissociation constant K of clonidine to be determined in a robust isolated right atrial assay of mouse, rat and guinea pig. By applying low numbers of field pulses 1-4 to prevent autoinhibitory feedback, clonidine shifted the nerve pulse stimulation-tachycardia curves to the right. These peak responses to field pulses were equated to responses to exogenous noradrenaline and the pK determined by global fitting and display in the Clark plot. The pK for clonidine ranged from 8.95 in the mouse, 7.8 in rat and 8.3 in guinea pig. The propranolol pK was 8.87 in mouse and 8.91 in rat atria, reading very similarly to those values from ß-adrenoceptor agonist assays under equilibrium conditions. In mesenteric resistance arteries mounted in a myograph for electrical field stimulation, clonidine again inhibited contractions to field pulses in mouse arteries with a pK of 7.12, but was inactive in rat arteries due to competing autoinhibitory feedback from nerve-released noradrenaline. In both species, prazosin inhibited the field pulses with a pK of 9.08 in rat and 9.03 in mouse arteries. We conclude that pK for antagonists and pK for the prejunctional inhibitors of nerve transmission can be determined with this novel analytical approach.
[Mh] Termos MeSH primário: Clonidina/farmacologia
Átrios do Coração/inervação
Artérias Mesentéricas/inervação
Receptores Adrenérgicos alfa 2/metabolismo
Sistema Nervoso Simpático/efeitos dos fármacos
Sistema Nervoso Simpático/fisiologia
Transmissão Sináptica/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Cistamina/análogos & derivados
Cistamina/farmacologia
Desipramina/farmacologia
Relação Dose-Resposta a Droga
Cobaias
Átrios do Coração/efeitos dos fármacos
Masculino
Artérias Mesentéricas/efeitos dos fármacos
Camundongos
Norepinefrina/farmacologia
Ratos
Ioimbina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Adrenergic, alpha-2); 2Y49VWD90Q (Yohimbine); 69790-18-7 (benextramine); MN3L5RMN02 (Clonidine); R110LV8L02 (Cystamine); TG537D343B (Desipramine); X4W3ENH1CV (Norepinephrine)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170425
[Lr] Data última revisão:
170425
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170222
[St] Status:MEDLINE


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[PMID]:27662029
[Au] Autor:Chen J; Liu J; Li J; Xu L; Qiao Y
[Ad] Endereço:Institute for Clean Energy & Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, China; Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest Universit
[Ti] Título:One-pot synthesis of nitrogen and sulfur co-doped carbon dots and its application for sensor and multicolor cellular imaging.
[So] Source:J Colloid Interface Sci;485:167-174, 2017 Jan 01.
[Is] ISSN:1095-7103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nitrogen and sulfur co-doped carbon dots (N, S/C-dots) were prepared via one-pot hydrothermal treatment of citric acid and cystamine dihydrochloride. The as-prepared N, S/C-dots exhibited excellent excitation-wavelength-independent photoluminescence property and higher fluorescence quantum yield (QY) of 39.7% compared to C,N-dots (QY=2.6%) prepared using citric acid and 1,6-diaminohexane dihydrochloride as the precursor. The N, S/C-dots were well-dispersed in aqueous solution and showed good photoluminescence stabilities in different pH and temperature without any surface modification. Additionally, the fluorescence of N, S/C-dots can be quenched based on inner filter effect (IFE) upon the addition of Cr(VI) and showed good selectivity and sensitivity to Cr(VI). The detection for Cr(VI) exhibited a good linear correlation ranging from 1 to 80µM with a detection limit of 0.86µM. What's more, in comparison with other quantum dots and organic dyes, these N, S/C-dots were much more eco-friendly and can be used for multicolor bioimaging.
[Mh] Termos MeSH primário: Carbono/química
Cromo/análise
Imagem Molecular/métodos
Nitrogênio/química
Pontos Quânticos/química
Enxofre/química
Poluentes da Água/análise
[Mh] Termos MeSH secundário: Ácido Cítrico/química
Cistamina/química
Células HeLa
Seres Humanos
Concentração de Íons de Hidrogênio
Limite de Detecção
Medições Luminescentes
Pontos Quânticos/ultraestrutura
Soluções
Temperatura Ambiente
Água
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Solutions); 0 (Water Pollutants); 059QF0KO0R (Water); 0R0008Q3JB (Chromium); 18540-29-9 (chromium hexavalent ion); 2968PHW8QP (Citric Acid); 70FD1KFU70 (Sulfur); 7440-44-0 (Carbon); N762921K75 (Nitrogen); R110LV8L02 (Cystamine)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170916
[Lr] Data última revisão:
170916
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160924
[St] Status:MEDLINE


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[PMID]:27654333
[Au] Autor:Du AW; Lu H; Stenzel M
[Ad] Endereço:Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, and ‡School of Chemistry, University of New South Wales , Sydney, NSW 2052, Australia.
[Ti] Título:Stabilization of Paclitaxel-Conjugated Micelles by Cross-Linking with Cystamine Compromises the Antitumor Effects against Two- and Three-Dimensional Tumor Cellular Models.
[So] Source:Mol Pharm;13(11):3648-3656, 2016 Nov 07.
[Is] ISSN:1543-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Paclitaxel (PTX)-conjugated micelles provide a promising tool for the treatment of prostate cancer. Core cross-linking by incorporating a disulfide bridge is a useful approach to improving the in vivo stability of polymeric micelles. This paper aims to investigate the effects of different degrees of cross-linking on the antitumor efficacy of micelles formed by poly(ethylene glycol methyl ether acrylate)-b-poly(carboxyethyl acrylate) (POEGMEA-b-PCEA-PTX) block copolymer. Both two-dimensional (2D) and three-dimensional (3D) in vitro prostate tumor cell models were used to evaluate the un-cross-linked and cross-linked micelles. The cytotoxicity decreased with an increase in the degree of cross-linking upon being tested with 2D cultured cells, and all micelles remained less cytotoxic than free PTX. In the 3D prostate MCTS model, however, there was no statistical difference between the performance of un-cross-linked micelles and free PTX, while increasing cross-linking densities led to significantly relevant decreases in the antitumor efficacy of micelles. These results are contradictory to our previous research using an irreversible cross-linker (1,8-diaminooctane) to stabilize POEGMEA-b-PCEA-PTX conjugate micelles where it was shown that cross-linking accelerates and improves the effects of the micelles when compared to those of un-cross-linked micelles. Further studies that aim to investigate the underlying mechanisms of disulfide bonds when micelles are internalized into cells are desired.
[Mh] Termos MeSH primário: Antineoplásicos/química
Antineoplásicos/farmacologia
Cistamina/química
Cistamina/farmacologia
Micelas
Paclitaxel/química
Paclitaxel/farmacologia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Portadores de Fármacos/química
Seres Humanos
Masculino
Modelos Teóricos
Polímeros/química
Neoplasias da Próstata/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drug Carriers); 0 (Micelles); 0 (Polymers); P88XT4IS4D (Paclitaxel); R110LV8L02 (Cystamine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160923
[St] Status:MEDLINE


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[PMID]:27574429
[Au] Autor:Yu J; Zhang J; Xing H; Yang Z; Cai C; Zhang C; Zhao X; Wei M; Yang L; Ding P
[Ad] Endereço:School of Pharmacy, Shenyang Pharmaceutical University.
[Ti] Título:Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery.
[So] Source:Int J Nanomedicine;11:4011-24, 2016.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Guanidinylated poly(amido amine)s with multiple disulfide linkages (Gua-SS-PAAs) were designed and constructed as nonviral gene carriers. The main chains of these novel carriers were synthesized based on monomers containing guanidino groups (guanidine hydrochloride and chlorhexidine), which could avoid complicated side-chain-modification reactions while introducing the guanidino groups. The synthesized Gua-SS-PAAs polymers were characterized by (1)H nuclear magnetic resonance, molecular weight, and polydispersity. Furthermore, Gua-SS-PAAs polymers were complexed with pDNA, and the properties of the complexes were determined, including entrapment efficiency, particle size, ζ-potential, atomic force microscopy images, stability, DNA complexation ability, reduction sensitivity, cytotoxicity, and transfection efficiency. The new Gua-SS-PAAs carriers exhibited higher transfection efficiency and lower cytotoxicity compared with two widely used gene delivery carriers, polyethylenimine and lipofectamine 2000. Furthermore, the relationship between the side-chain structure and morphological/biological properties was extrapolated, and the results showed that guanidine in the side chain aids in the improvement of transfection efficiency. In addition, the introduction of guanidino group might confer the new carriers with nuclear localization function compared to carriers without it.
[Mh] Termos MeSH primário: Núcleo Celular/metabolismo
Técnicas de Transferência de Genes
Guanidina/química
Poliaminas/química
[Mh] Termos MeSH secundário: Benzimidazóis/metabolismo
Sobrevivência Celular/efeitos dos fármacos
Clorexidina/farmacologia
Cistamina/química
DNA/genética
DNA/metabolismo
Eletroforese em Gel de Ágar
Endocitose/efeitos dos fármacos
Seres Humanos
Células MCF-7
Microscopia de Força Atômica
Peso Molecular
Tamanho da Partícula
Plasmídeos/metabolismo
Polietilenoimina/química
Eletricidade Estática
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzimidazoles); 0 (Poly(amidoamine)); 0 (Polyamines); 9002-98-6 (Polyethyleneimine); 9007-49-2 (DNA); JU58VJ6Y3B (Guanidine); P976261J69 (bisbenzimide ethoxide trihydrochloride); R110LV8L02 (Cystamine); R4KO0DY52L (Chlorhexidine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160831
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S109406


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[PMID]:27412922
[Au] Autor:Bockuviene A; Slavuckyte K; Vareikis A; Zigmantas S; Zaliauskiene L; Makuska R
[Ad] Endereço:Department of Polymer Chemistry, Vilnius University, Naugarduko 24, LT-03225, Vilnius, Lithuania. burvytealma@gmail.com.
[Ti] Título:Intracellular Delivery and Triggered Release of DNA Using Biodegradable Poly(2-hydroxypropylene imine)s Containing Cystamine Units.
[So] Source:Macromol Biosci;16(10):1497-1505, 2016 Oct.
[Is] ISSN:1616-5195
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Poly(2-hydroxypropylene imine)s containing segments of cystamine (PHPI-CA) are synthesized by polycondensation of 1,3-dibromo-2-propanol with a mixture of 1,3-diamino-2-propanol and cystamine. High molecular weight fractions of these polymers are collected by ultrafiltration and characterized by chemical analysis, H and C-NMR spectroscopy, size-exclusion chromatography with triple detection, and potentiometric titration, and are tested for DNA delivery in vitro. It is shown that PHPI-CA are highly branched polymers containing disulfide linkages. Transfection efficiency of PHPI-CA for DNA gives similar results to that of PHPI with GFP cell percent reaching 80-90%. Cytotoxicity levels for PHPI-CA are lower than that of PHPI. Novel polymers containing different amounts of disulfide linkages are able to disintegrate and release DNA following the treatment with reducing agent 1,4-dithiothreitol. Downstream application of PHPI-CA transfected cells for RNA purification shows that RNA yield is not affected even after the double transfection suggesting that these polymers could be great candidates for in vitro and in vivo transfection.
[Mh] Termos MeSH primário: Cistamina/química
DNA/química
Polipropilenos/química
Transfecção/métodos
[Mh] Termos MeSH secundário: Animais
Camundongos
Células NIH 3T3
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Polypropylenes); 9007-49-2 (DNA); R110LV8L02 (Cystamine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160715
[St] Status:MEDLINE
[do] DOI:10.1002/mabi.201600155


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[PMID]:27378395
[Au] Autor:Eligini S; Fiorelli S; Tremoli E; Colli S
[Ad] Endereço:Centro Cardiologico Monzino I.R.C.C.S., Milan, Italy. Electronic address: sonia.eligini@cardiologicomonzino.it.
[Ti] Título:Inhibition of transglutaminase 2 reduces efferocytosis in human macrophages: Role of CD14 and SR-AI receptors.
[So] Source:Nutr Metab Cardiovasc Dis;26(10):922-30, 2016 Oct.
[Is] ISSN:1590-3729
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND AIMS: Transglutaminase 2 (TGM2), a member of the transglutaminase family of enzymes, is a multifunctional protein involved in numerous events spanning from cell differentiation, to signal transduction, apoptosis, and wound healing. It is expressed in a variety of cells, macrophages included. Macrophage TGM2 promotes the clearance of apoptotic cells (efferocytosis) and emerging evidence suggests that defective efferocytosis contributes to the consequences of inflammation-associated diseases, including atherosclerotic lesion progression and its sequelae. Of interest, active TGM2 identified in human atherosclerotic lesions plays critical roles in plaque stability through effects on matrix cross-linking and TGFß activity. This study explores the mechanisms by which TGM2 controls efferocytosis in human macrophages. METHODS AND RESULTS: Herein we show that TGM2 increases progressively during monocyte differentiation towards macrophages and controls their efferocytic potential as well as morphology and viability. Two experimental approaches that took advantage of the inhibition of TGM2 activity and protein silencing give proof that TGM2 reduction significantly impairs macrophage efferocytosis. Among the mechanisms involved we highlighted a role of the receptors CD14 and SR-AI whose levels were markedly reduced by TGM2 inhibition. Conversely, CD36 receptor and αvß3 integrin levels were not influenced. Of note, lipid accumulation and IL-10 secretion were reduced in macrophages displaying defective efferocytosis. CONCLUSION: Overall, our data define a crucial role of TGM2 activity during macrophage differentiation via mechanisms involving CD14 and SR-AI receptors and show that TGM2 inhibition triggers a pro-inflammatory phenotype.
[Mh] Termos MeSH primário: Inibidores Enzimáticos/farmacologia
Proteínas de Ligação ao GTP/antagonistas & inibidores
Receptores de Lipopolissacarídeos/metabolismo
Macrófagos/efeitos dos fármacos
Fagocitose/efeitos dos fármacos
Fatores de Processamento de Serina-Arginina/metabolismo
Transglutaminases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Apoptose
Cadaverina/análogos & derivados
Cadaverina/farmacologia
Diferenciação Celular
Forma Celular
Sobrevivência Celular
Técnicas de Cocultura
Cistamina/farmacologia
Relação Dose-Resposta a Droga
Proteínas de Ligação ao GTP/genética
Proteínas de Ligação ao GTP/metabolismo
Seres Humanos
Interleucina-10/secreção
Células Jurkat
Macrófagos/enzimologia
Macrófagos/secreção
Fenótipo
Interferência de RNA
Transdução de Sinais/efeitos dos fármacos
Linfócitos T/patologia
Fatores de Tempo
Transfecção
Transglutaminases/genética
Transglutaminases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (IL10 protein, human); 0 (Lipopolysaccharide Receptors); 0 (SCAF1 protein, human); 130068-27-8 (Interleukin-10); 170974-22-8 (Serine-Arginine Splicing Factors); EC 2.3.2.- (transglutaminase 2); EC 2.3.2.13 (Transglutaminases); EC 3.6.1.- (GTP-Binding Proteins); I9N81SC5HD (monodansylcadaverine); L90BEN6OLL (Cadaverine); R110LV8L02 (Cystamine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160706
[St] Status:MEDLINE


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[PMID]:27281238
[Au] Autor:Yan T; Li D; Li J; Cheng F; Cheng J; Huang Y; He J
[Ad] Endereço:MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, State Key Laboratory of Urban Water Resource and Environment, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang 150010, China.
[Ti] Título:Effective co-delivery of doxorubicin and curcumin using a glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer micelle for combination cancer chemotherapy.
[So] Source:Colloids Surf B Biointerfaces;145:526-538, 2016 Sep 01.
[Is] ISSN:1873-4367
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer (PCL-SS-CTS-GA) micelle was developed for the co-delivery of doxorubicin (DOX) and curcumin (CCM) to hepatoma cells. Glycyrrhetinic acid (GA) was used as a targeting unit to ensure specific delivery. Co-encapsulation of DOX and CCM was facilitated by the incorporation of poly(ε-caprolactone) (PCL) groups. The highest drug loading content was 19.8% and 8.9% (w/w) for DOX and CCM, respectively. The PCL-SS-CTS-GA micelle presented a spherical or ellipsoidal geometry with a mean diameter of approximately 110nm. The surface charge of the micelle changed from negative to positive, when the pH value of the solution decreased from 7.4 to 6.8. Meanwhile, it also exhibited a character of redox-responsive drug release and GA/pH-mediated endocytosis in vitro. In simulated body fluid with 10mM glutathione, the release rate in 12h was 80.6% and 67.2% for DOX and CCM, respectively. The cell uptake of micelles was significantly higher at pH 6.8 than pH 7.4. The combined administration of DOX and CCM was facilitated by PCL-SS-CTS-GA micelle. Results showed that there was strong synergic effect between the two drugs. The PCL-SS-CTS-GA micelle might turn into a promising and effective carrier for improved combination chemotherapy.
[Mh] Termos MeSH primário: Quitosana/química
Curcumina/farmacologia
Cistamina/química
Doxorrubicina/farmacologia
Ácido Glicirretínico/química
Micelas
Neoplasias/tratamento farmacológico
Poliésteres/química
[Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Sobrevivência Celular/efeitos dos fármacos
Liberação Controlada de Fármacos
Endocitose/efeitos dos fármacos
Citometria de Fluxo
Células Hep G2
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
Seres Humanos
Concentração de Íons de Hidrogênio
Espaço Intracelular/metabolismo
Espectroscopia de Infravermelho com Transformada de Fourier
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Micelles); 0 (Polyesters); 24980-41-4 (polycaprolactone); 80168379AG (Doxorubicin); 9012-76-4 (Chitosan); IT942ZTH98 (Curcumin); P540XA09DR (Glycyrrhetinic Acid); R110LV8L02 (Cystamine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160610
[St] Status:MEDLINE



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