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1.
Chem Pharm Bull (Tokyo) ; 72(8): 747-750, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39111846

RESUMO

The gastric stability of eight barbiturates (BARs) (barbital, primidone, allobarbital, phenobarbital, cyclobarbital, pentobarbital, secobarbital, and thiobutabarbital (TBB)) was examined in artificial gastric juice using LC/UV detection. Among the eight BARs, only TBB was degraded at higher temperatures. Furthermore, the degradation product of TBB was isolated, structurally analyzed, and finally identified as 5-butan-2-yl-5-ethyl-1,3-diazinane-2,4,6-trione, also known as butabarbital. The study elucidated that butabarbital was formed by substituting the sulfur atom of the carbonyl group at the 2-position of TBB with an oxygen atom under acidic condition.


Assuntos
Barbitúricos , Suco Gástrico , Humanos , Barbitúricos/química , Estabilidade de Medicamentos , Suco Gástrico/química , Suco Gástrico/metabolismo , Estrutura Molecular , Estômago/química
2.
Mod Rheumatol ; 33(2): 392-397, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35137159

RESUMO

OBJECTIVES: Due to the low prevalence of HLA-B27 and ankylosing spondylitis (AS) in Japan, rheumatologists have little experience with AS. We conducted a multicentre study to identify the characteristics and frequency of HLA-B types. METHODS: We analysed epidemiological and clinical data, blood tests, spine radiographs, and HLA-B types in Japanese AS patients. RESULTS: We evaluated 111 AS patients, predominantly men (82.9%). The mean age, disease onset, diagnosis, and time from onset to diagnosis were 43.7, 24.2, 36.0, and 11.6 years, respectively. Inflammatory low back pain was found in 96 cases (86.5%); peripheral arthritis in 59 (53.2%), enthesitis in 35 (31.5%), and dactylitis in 6 (5.4%). Extra-articular symptoms included uveitis, psoriasis, and inflammatory bowel disease in 41 (36.9%), 1 (0.9%), and 5 (4.5%) cases, respectively. HLA-B27 was positive in 83 cases (74.8%; odds ratio, 1146.0); and HLA-B48 in 9 (8.1%; odds ratio, 3.0). HLA-B27-positive patients were younger at onset and had a shorter diagnostic delay. CONCLUSIONS: AS clinical symptoms were almost the same as other countries except for the low coexistence of psoriasis. HLA-B27 positivity in Japanese patients was 78%. HLA-B27-positive patients were younger and diagnosed earlier. In addition to HLA-B27, a relationship with HLA-B48 was suggested.


Assuntos
Psoríase , Espondilite Anquilosante , Feminino , Humanos , Masculino , Diagnóstico Tardio , População do Leste Asiático , Teste de Histocompatibilidade , Antígeno HLA-B27/genética , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/genética , Adulto
3.
J Am Chem Soc ; 144(31): 14090-14100, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35860845

RESUMO

The pursuit of a high surface area while maintaining high catalytic performance remains a challenge due to a trade-off relationship between these two features in some cases. In this study, mesoporous todorokite-type manganese oxide (OMS-1) nanoparticles with high specific surface areas were synthesized in one step by a new synthesis approach involving crystallization (i.e., solid-state transformation) of a precursor produced by a redox reaction between MnO4- and Mn2+ reagents. The use of a low-crystallinity precursor with small particles is essential to achieve this solid-state transformation into OMS-1 nanoparticles. The specific surface area reached up to ca. 250 m2 g-1, which is much larger than those (13-185 m2 g-1) for Mg-OMS-1 synthesized by previously reported methods including multistep synthesis or dissolution/precipitation processes. Despite ultrasmall nanoparticles, a linear correlation between the catalytic reaction rates of OMS-1 and the surface areas was observed without a trade-off relationship between particle size and catalytic performance. These OMS-1 nanoparticles exhibited the highest catalytic activity among the Mn-based catalysts tested for the oxidation of benzyl alcohol and thioanisole with molecular oxygen (O2) as the sole oxidant, including highly active ß-MnO2 nanoparticles. The present OMS-1 nanomaterial could also act as a recyclable heterogeneous catalyst for the aerobic oxidation of various aromatic alcohols and sulfides under mild reaction conditions. The mechanistic studies showed that alcohol oxidation proceeds with oxygen species caused by the solid, and the high surface area of OMS-1 significantly contributes to an enhancement of the catalytic activity for aerobic oxidation.


Assuntos
Compostos de Manganês , Nanopartículas , Catálise , Cristalização , Compostos de Manganês/química , Oxirredução , Óxidos/química , Oxigênio
4.
Rheumatology (Oxford) ; 59(10): 2939-2946, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32125422

RESUMO

OBJECTIVES: Although T cells are thought to be involved in the pathogenesis of PMR, whether innate-like T cells are involved in the process remains unknown. METHODS: The serum levels of 27 cytokines/chemokines in patients with PMR were measured by a multiplex immunoassay (Bio-Plex Assay). The cytokine-producing capacity of T and innate-like T cells was assessed by intracellular cytokine staining and flow cytometry. The frequency and activated status of T and innate-like T cells were investigated by flow cytometry and their associations with clinical parameters were assessed. RESULTS: The levels of inflammatory cytokines were associated with disease activity in PMR. The cytokine-producing capacity by CD8+ T and innate-like T cells was associated with disease activity. The frequency of HLA-DR+ CD38+ cells among CD8+ T cells was increased in patients with active disease. The frequencies of HLA-DR+ CD38+ cells among CD4+ T, mucosal-associated invariant T (MAIT) and γδ T cells were higher in patients with inactive disease. The frequency of HLA-DR+ CD38+ MAIT cells was associated with the PMR activity score and CRP levels in patients in remission. CONCLUSION: The inflammatory cytokine-producing capacity and expression of activation markers of CD8+ T and innate-like T cells were associated with the disease activity of PMR. MAIT cell activation in patients in remission may contribute to the subclinical activity of the disease.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/sangue , Células T Invariantes Associadas à Mucosa/imunologia , Polimialgia Reumática/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Quimiocinas/sangue , Feminino , Citometria de Fluxo , Humanos , Imunidade Celular , Ativação Linfocitária , Masculino , Polimialgia Reumática/sangue , Polimialgia Reumática/patologia
5.
BMC Musculoskelet Disord ; 21(1): 41, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31954409

RESUMO

BACKGROUND: Studies on characteristic spinal deformities in Japanese patients with ankylosing spondylitis (AS) and data demonstrating a relationship between health-related quality of life (HRQOL) and spinopelvic alignment in these patients are lacking. METHODS: In this cross-sectional study, 50 patients with AS and without a surgical history, vertebral body fracture, or scoliosis as well as 30 control patients with degenerative lumbar kyphoscoliosis (DLKS) were included. Data collected included patient sex, age, spinopelvic parameters on sagittal full-spine standing radiographs, and HRQOL questionnaire responses. Student's t-test was used to compare the characteristics of spinopelvic parameters between the groups. A multiple regression analysis was performed to analyze correlations between spinopelvic parameters and HRQOL in the AS group. RESULTS: Global kyphosis (GK; T1-12 angle) was significantly greater in the AS group than in the DLKS group (P < 0.001), whereas the pelvic tilt (PT; posterior PT angle) was smaller in the AS group (P = 0.006). Radiographic parameters correlated with HRQOL in the AS group. Multiple regression analysis identified the sagittal vertical axis (SVA) and sacral slope (SS) as factors influencing the SRS-22 total score and SVA and GK as factors influencing Japanese Orthopaedic Association Back Pain Evaluation Questionnaire mental health (subdomain). CONCLUSIONS: Patients with AS did not use lumbar lordosis or posterior PT to compensate for their large thoracic kyphosis due to spinopelvic ankylosis. These patients showed a unique compensation pattern. The correlation/regression analysis revealed a correlation between radiographic parameters and HRQOL in patients with AS, with particular importance of SVA, SS, and GK for clinical results in AS.


Assuntos
Ossos Pélvicos/diagnóstico por imagem , Equilíbrio Postural/fisiologia , Qualidade de Vida , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/epidemiologia , Adulto , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Espondilite Anquilosante/cirurgia
6.
J Am Chem Soc ; 141(2): 890-900, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30612429

RESUMO

Aerobic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) as a bioplastics monomer is efficiently promoted by a simple system based on a nonprecious-metal catalyst of MnO2 and NaHCO3. Kinetic studies indicate that the oxidation of 5-formyl-2-furancarboxylic acid (FFCA) to FDCA is the slowest step for the aerobic oxidation of HMF to FDCA over activated MnO2. We demonstrate through combined computational and experimental studies that HMF oxidation to FDCA is largely dependent on the MnO2 crystal structure. Density functional theory (DFT) calculations reveal that vacancy formation energies at the planar oxygen sites in α- and γ-MnO2 are higher than those at the bent oxygen sites. ß- and λ-MnO2 consist of only planar and bent oxygen sites, respectively, with lower vacancy formation energies. Consequently, ß- and λ-MnO2 are likely to be good candidates as oxidation catalysts. On the other hand, experimental studies reveal that the reaction rates per surface area for the slowest step (FFCA oxidation to FDCA) decrease in the order of ß-MnO2 > λ-MnO2 > γ-MnO2 ≈ α-MnO2 > δ-MnO2 > ε-MnO2; the catalytic activity of ß-MnO2 exceeds that of the previously reported activated MnO2 by three times. The order is in good agreement not only with the DFT calculation results, but also with the reduction rates per surface area determined by the H2-temperature-programmed reduction measurements for MnO2 catalysts. The successful synthesis of high-surface-area ß-MnO2 significantly improves the catalytic activity for the aerobic oxidation of HMF to FDCA.


Assuntos
Ácidos Dicarboxílicos/síntese química , Furaldeído/análogos & derivados , Furanos/síntese química , Compostos de Manganês/química , Óxidos/química , Catálise , Teoria da Densidade Funcional , Furaldeído/química , Modelos Químicos , Oxirredução , Oxigênio/química , Bicarbonato de Sódio/química
7.
Proc Natl Acad Sci U S A ; 110(41): 16492-7, 2013 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-24067652

RESUMO

Piwi-interacting RNAs (piRNAs) are gonad-specific small RNAs that provide defense against transposable genetic elements called transposons. Our knowledge of piRNA biogenesis is sketchy, partly due to an incomplete inventory of the factors involved. Here, we identify Tudor domain-containing 12 (TDRD12; also known as ECAT8) as a unique piRNA biogenesis factor in mice. TDRD12 is detected in complexes containing Piwi protein MILI (PIWIL2), its associated primary piRNAs, and TDRD1, all of which are already implicated in secondary piRNA biogenesis. Male mice carrying either a nonsense point mutation (reproductive mutant 23 or repro23 mice) or a targeted deletion in the Tdrd12 locus are infertile and derepress retrotransposons. We find that TDRD12 is dispensable for primary piRNA biogenesis but essential for production of secondary piRNAs that enter Piwi protein MIWI2 (PIWIL4). Cell-culture studies with the insect ortholog of TDRD12 suggest a role for the multidomain protein in mediating complex formation with other participants during secondary piRNA biogenesis.


Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Metilação de DNA/fisiologia , Elementos de DNA Transponíveis/fisiologia , Células Germinativas/fisiologia , RNA Interferente Pequeno/biossíntese , Complexo de Inativação Induzido por RNA/fisiologia , Sequência de Aminoácidos , Animais , Northern Blotting , Bombyx , Clonagem Molecular , Biologia Computacional , Primers do DNA/genética , Elementos de DNA Transponíveis/genética , DNA Complementar/genética , Imunofluorescência , Vetores Genéticos/genética , Imunoprecipitação , Masculino , Camundongos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Complexo de Inativação Induzido por RNA/genética
8.
Nihon Shokakibyo Gakkai Zasshi ; 113(5): 828-36, 2016 05.
Artigo em Japonês | MEDLINE | ID: mdl-27151480

RESUMO

A 51-year-old woman was diagnosed with mixed connective tissue disease (MCTD) in 2011. She underwent treatment with prednisolone. Her hepatobiliary enzyme level increased, and multiple nodules were found in both liver lobes in abdominal imaging studies. Ultrasonography revealed large and small hyperechoic lesions with indistinct or well-defined borders. No findings of classic hepatocellular carcinoma or liver cirrhosis were observed on contrast-enhanced computed tomography, but some nodules showed an enhanced effect of the central lesion that was characteristic of focal nodular hyperplasia (FNH) in an arterial phase. On gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging, slightly high-intensity nodules, 10-40mm in size, were observed on T1- and T2-weighted images. The nodules showed highest intensities in the hepatocyte phase and were enhanced with the uptake of Gd-EOB-DTPA as compared with the background liver. FNH was suspected based on the imaging findings, but we performed a liver tumor biopsy for differential diagnosis of the malignant lesion. Based on the immunohistopathological examination results, the final diagnosis was idiopathic portal hypertension associated with nodular regenerative hyperplasia (NRH)-like nodule of the liver. Benign nodular hepatocellular lesions are caused by abnormal hepatic circulation and were previously known as anomalous portal tract syndrome. Our case of atypical NRH with large nodules may be included in this disease entity. Here, we report a rare case of MCTD with NRH-like nodules and idiopathic portal hypertension with a review of literature.


Assuntos
Hiperplasia Nodular Focal do Fígado/patologia , Hipertensão Portal/patologia , Doença Mista do Tecido Conjuntivo/complicações , Doença Mista do Tecido Conjuntivo/dietoterapia , Feminino , Humanos , Fígado/patologia , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/patologia
10.
Proc Natl Acad Sci U S A ; 108(26): 10579-84, 2011 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-21670278

RESUMO

In the male germline in mammals, chromatoid bodies, a specialized assembly of cytoplasmic ribonucleoprotein (RNP), are structurally evident during meiosis and haploidgenesis, but their developmental origin and regulation remain elusive. The tudor domain containing proteins constitute a conserved class of chromatoid body components. We show that tudor domain containing 7 (Tdrd7), the deficiency of which causes male sterility and age-related cataract (as well as glaucoma), is essential for haploid spermatid development and defines, in concert with Tdrd6, key biogenesis processes of chromatoid bodies. Single and double knockouts of Tdrd7 and Tdrd6 demonstrated that these spermiogenic tudor genes orchestrate developmental programs for ordered remodeling of chromatoid bodies, including the initial establishment, subsequent RNP fusion with ubiquitous processing bodies/GW bodies and later structural maintenance. Tdrd7 suppresses LINE1 retrotransposons independently of piwi-interacting RNA (piRNA) biogenesis wherein Tdrd1 and Tdrd9 operate, indicating that distinct Tdrd pathways act against retrotransposons in the male germline. Tdrd6, in contrast, does not affect retrotransposons but functions at a later stage of spermiogenesis when chromatoid bodies exhibit aggresome-like properties. Our results delineate that chromatoid bodies assemble as an integrated compartment incorporating both germline and ubiquitous features as spermatogenesis proceeds and that the conserved tudor family genes act as master regulators of this unique RNP remodeling, which is genetically linked to the male germline integrity in mammals.


Assuntos
Cromatina/metabolismo , Ribonucleoproteínas/metabolismo , Espermatogênese , Animais , Cromossomos Artificiais Bacterianos , Masculino , Camundongos , Camundongos Knockout , Microscopia Imunoeletrônica , Ribonucleoproteínas/genética , Ribonucleoproteínas/fisiologia
11.
J Biol Chem ; 287(51): 43156-69, 2012 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-23105111

RESUMO

The glycosphingolipid biosynthesis is initiated by monoglycosylation of ceramides, the action of which is catalyzed either by UDP-glucose:ceramide glucosyltransferase or by UDP-galactose:ceramide galactosyltransferase (CGalT). CGalT is expressed predominantly at the endoplasmic reticulum (ER) of oligodendrocytes and is responsible for synthesizing galactosylceramides (GalCer) that play an important role in regulation of axon conductance. However, despite the importance of ceramide monoglycosylation enzymes in a spectrum of cellular functions, the mechanism that fine tunes activities of those enzymes is largely unknown. In the present study, we demonstrated that the sigma-1 receptor (Sig-1R) chaperone, the mammalian homologue of a yeast C8-C7 sterol isomerase, controls the protein level and activity of the CGalT enzyme via a distinct ER-associated degradation system involving Insig. The Sig-1R forms a complex with Insig via its transmembrane domain partly in a sterol-dependent manner and associates with CGalT at the ER. The knockdown of Sig-1Rs dramatically prolonged the lifetime of CGalT without affecting the trimming of N-linked oligosaccharides at CGalT. The increased lifetime leads to the up-regulation of CGalT protein as well as elevated enzymatic activity in CHO cells stably expressing CGalT. Knockdown of Sig-1Rs also decreased CGalT degradation endogenously expressed in D6P2T-schwannoma cells. Our data suggest that Sig-1Rs negatively regulate the activity of GalCer synthesis under physiological conditions by enhancing the degradation of CGalT through regulation of the dynamics of Insig in the lipid-activated ER-associated degradation system. The GalCer synthesis may thus be influenced by sterols at the ER.


Assuntos
Degradação Associada com o Retículo Endoplasmático , Chaperonas Moleculares/metabolismo , N-Acilesfingosina Galactosiltransferase/metabolismo , Receptores sigma/metabolismo , Animais , Células CHO , Cricetinae , Regulação para Baixo , Galactosilceramidas/metabolismo , Técnicas de Silenciamento de Genes , Proteínas de Membrana/metabolismo , Camundongos , Ratos , Frações Subcelulares/metabolismo , Especificidade por Substrato , Receptor Sigma-1
12.
Nihon Shokakibyo Gakkai Zasshi ; 110(5): 839-45, 2013 May.
Artigo em Japonês | MEDLINE | ID: mdl-23648540

RESUMO

A 48-year-old man was admitted to our hospital complaining of acute severe abdominal pain and constipation. He had received bone marrow transplantation for acute myelogenous leukemia 5 months previously and immunosuppressant treatment for chronic graft-versus-host disease. Abdominal X-ray and CT scan films revealed his large intestine widely dilated and filled with air, and colonic pseudo-obstruction was diagnosed. It was difficult to ascertain the cause of the symptoms until 6 days after onset of the abdominal pain when disseminated zoster eruption appeared over his whole body. It was disseminated varicella-zoster and complicated with colonic pseudo-obstruction. He was treated with acyclovir. It is important to suspect disseminated varicella-zoster and treat early immunocompromised patients complaining of severe acute abdominal pain and colonic pseudo-obstruction.


Assuntos
Dor Abdominal/etiologia , Pseudo-Obstrução do Colo/etiologia , Herpes Zoster/complicações , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade
13.
Mod Rheumatol Case Rep ; 8(1): 112-116, 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-37572090

RESUMO

The European League Against Rheumatism and the American College of Rheumatology have stated that the halo sign on vascular ultrasonography (v-US) is relevant in diagnosing giant cell arteritis (GCA) and is equivalent to temporal artery biopsy. However, there are only a few reports about transitions in v-US findings after glucocorticoid (GC) therapy. We report the transitions in the v-US findings in a case of GCA after GC therapy. The patient had rapidly progressive symptoms, and there were concerns about blindness. After GC therapy, we first observed improvement in headache and visual impairment symptoms within 1 week, followed by rapid improvement in laboratory findings within 2 weeks. Subsequently, there were improvements in v-US findings after more than 2 months. In conclusion, these findings showed a dissociation between improvements in clinical symptoms and v-US findings of the temporal artery. Additionally, this case suggests that regular examination of v-US findings is useful in evaluating GCA with evident vascular wall thickness before GC therapy.


Assuntos
Arterite de Células Gigantes , Humanos , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/patologia , Cefaleia/etiologia , Ultrassonografia , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Transtornos da Visão/patologia
14.
Chem Sci ; 14(20): 5453-5459, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37234904

RESUMO

Cation-uptake has been long researched as an important topic in materials science. Herein we focus on a molecular crystal composed of a charge-neutral polyoxometalate (POM) capsule [MoVI72FeIII30O252(H2O)102(CH3CO2)15]3+ encapsulating a Keggin-type phosphododecamolybdate anion [α-PMoVI12O40]3-. Cation-coupled electron-transfer reaction occurs by treating the molecular crystal in an aqueous solution containing CsCl and ascorbic acid as a reducing reagent. Specifically, multiple Cs+ ions and electrons are captured in crown-ether-like pores {MoVI3FeIII3O6}, which exist on the surface of the POM capsule, and Mo atoms, respectively. The locations of Cs+ ions and electrons are revealed by single-crystal X-ray diffraction and density functional theory studies. Highly selective Cs+ ion uptake is observed from an aqueous solution containing various alkali metal ions. Cs+ ions can be released from the crown-ether-like pores by the addition of aqueous chlorine as an oxidizing reagent. These results show that the POM capsule functions as an unprecedented "redox-active inorganic crown ether", clearly distinguished from the non-redox-active organic counterpart.

15.
ACS Appl Mater Interfaces ; 14(5): 6528-6537, 2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35080862

RESUMO

Heterogeneously catalyzed aerobic oxidative C-H functionalization under mild conditions is a chemical process to obtain desired oxygenated products directly. Nanosized murdochite-type oxide Mg6MnO8 (Mg6MnO8-MA) was successfully synthesized by the sol-gel method using malic acid. The specific surface area reached up to 104 m2 g-1, which is about 7 times higher than those (2-15 m2 g-1) of Mg6MnO8 synthesized by previously reported methods. Mg6MnO8-MA exhibited superior catalytic performance to those of other Mn- and Mg-based oxides, including manganese oxides with Mn-O-Mn active sites for the oxidation of fluorene with molecular oxygen (O2) as the sole oxidant under mild conditions (40 °C). The present catalytic system was applicable to the aerobic oxidation of various substrates. The catalyst could be recovered by simple filtration and reused several times without obvious loss of its high catalytic performance. The correlation between the reactivity and the pKa of the substrates, basic properties of catalysts, and kinetic isotope effects suggest a basicity-controlled mechanism of hydrogen atom transfer. The 18O-labeling experiments, kinetics, and mechanistic studies showed that H abstraction of the hydrocarbon proceeds via a mechanism involving O2 activation. The structure of Mg6MnO8 consisting of isolated Mn4+ species located in a basic MgO matrix plays an important role in the present oxidation.

16.
Histochem Cell Biol ; 135(6): 627-37, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21573736

RESUMO

Molecular chaperones localized at the endoplasmic reticulum (ER) lumen constitutively or cellular stress-dependently associate with a variety of proteins to promote their proper folding or to inhibit protein misfolding. ER chaperones preferentially form large complexes with co-chaperones and/or misfolded proteins in a highly crowded cellular environment that often hampers their detection by immunocytochemistry (ICC). This study establishes an antigen retrieval (AR) protocol to improve the ICC detection of ER chaperones in cultured cells using widely available antibodies against synthetic peptides. Among ten different antigen retrieval/fixation conditions, only the AR with Tris-HCl (pH 9.5) containing 6 M urea (80°C for 10 min) significantly improved the ICC detection of the novel ER chaperone sigma-1 receptor (Sig-1R) in Chinese hamster ovary cells. Extended fixation with 4% paraformaldehyde for 1 h effectively preserved the morphology of the ER under the AR condition. This method greatly enhanced the signal-to-noise ratio in Sig-1R ICC, thus allowing for semi-quantitative detection of protein upregulation under ER stress. The AR similarly improved the ICC detection of a series of other major ER chaperones, including BiP/GRP78, GRP94, calnexin, calreticulin, ERp57, protein disulfide isomerase, and cyclophilin B. The improved ICC methodology using the urea AR at 80°C may improve ICC of ER molecules as well as visualization of ER structure and substructures.


Assuntos
Retículo Endoplasmático/metabolismo , Imuno-Histoquímica/métodos , Chaperonas Moleculares/metabolismo , Receptores sigma/metabolismo , Animais , Antígenos/metabolismo , Células CHO , Cricetinae , Cricetulus , Receptor Sigma-1
17.
J Pharmacol Exp Ther ; 332(3): 1054-63, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19940104

RESUMO

sigma-1 Receptors are endoplasmic reticulum (ER) chaperones that are implicated in the neuroplasticity associated with psychostimulant abuse. We immunocytochemically examined the distribution of sigma-1 receptors in the brain of drug-naive rats and then examined the dynamics of sigma-1 receptors and other ER chaperones in specific brain subregions of rats that self-administered methamphetamine, received methamphetamine passively, or received only saline injections. sigma-1 Receptors were found to be expressed in moderate to high levels in the olfactory bulb, striatum, nucleus accumbens shell, olfactory tubercle, amygdala, hippocampus, red nucleus, ventral tegmental area, substantia nigra, and locus ceruleus. Methamphetamine, whether self-administered or passively received, significantly elevated ER chaperones including the sigma-1 receptor, BiP, and calreticulin in the ventral tegmental area and substantia nigra. In the olfactory bulb, however, only the sigma-1 receptor chaperone was increased, and this increase occurred only in rats that actively self-administered methamphetamine. Consistent with an increase in sigma-1 receptors, extracellular signal-regulated kinase was found to be activated and protein kinase A attenuated in the olfactory bulb of methamphetamine self-administering rats. sigma-1 Receptors in the olfactory bulb were found to be colocalized with dopamine D1 receptors. These results indicate that methamphetamine induces ER stress in the ventral tegmental area and substantia nigra in rats whether the drug is received actively or passively. However, the changes seen only in rats that actively self-administered methamphetamine suggest that D1 and sigma-1 receptors in the olfactory bulb might play an important role in the motivational conditioning/learning aspects of methamphetamine self-administration in the rat.


Assuntos
Encéfalo/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Retículo Endoplasmático/metabolismo , Metanfetamina/farmacologia , Chaperonas Moleculares/biossíntese , Receptores sigma/biossíntese , Animais , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Células CHO , Estimulantes do Sistema Nervoso Central/administração & dosagem , Cricetinae , Cricetulus , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Masculino , Metanfetamina/administração & dosagem , Ratos , Ratos Sprague-Dawley , Autoadministração , Receptor Sigma-1
18.
ACS Appl Mater Interfaces ; 12(32): 36004-36013, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32805787

RESUMO

Mesoporous ß-MnO2 nanoparticles were synthesized by a template-free low-temperature crystallization of Mn4+ precursors (low-crystallinity layer-type Mn4+ oxide, c-distorted H+-birnessite) produced by the reaction of MnO4- and Mn2+. The Mn starting materials, pH of the reaction solution, and calcination temperatures significantly affect the crystal structure, surface area, porous structure, and morphology of the manganese oxides formed. The pH conditions during the precipitation of Mn4+ precursors are important for controlling the morphology and porous structure of ß-MnO2. Nonrigid aggregates of platelike particles with slitlike pores (ß-MnO2-1 and -2) were obtained from the combinations of NaMnO4/MnSO4 and NaMnO4/Mn(NO3)2, respectively. On the other hand, spherelike particles with ink-bottle shaped pores (ß-MnO2-3) were formed in NaMnO4/Mn(OAc)2 with pH adjustment (pH 0.8). The specific surface areas for ß-MnO2-1, -2, and -3 were much higher than those for nonporous ß-MnO2 nanorods synthesized using a typical hydrothermal method (ß-MnO2-HT). On the other hand, c-distorted H+-birnessite precursors with a high interlayer metal cation (Na+ and K+) content led to the formation of α-MnO2 with a 2 × 2 tunnel structure. These mesoporous ß-MnO2 materials acted as effective heterogeneous catalysts for the aerobic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) as a bioplastic monomer and for the transformation of aromatic alcohols to the corresponding aldehydes, where the catalytic activities of ß-MnO2-1, -2, and -3 were approximately 1 order of magnitude higher than that of ß-MnO2-HT. ß-MnO2-3 exhibited higher catalytic activity (especially for larger molecules) than the other ß-MnO2 materials, and this is likely attributed to the nanometer-sized spaces.

19.
Chem Commun (Camb) ; 56(14): 2095-2098, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31995042

RESUMO

High-surface-area ß-MnO2 (ß-MnO2-HS) nanoparticles could act as effective heterogeneous catalysts for the one-pot oxidative sulfonamidation of various aromatic and heteroaromatic thiols to the corresponding sulfonamides using molecular oxygen (O2) and ammonia (NH3) as respective oxygen and nitrogen sources, without the need for any additives.

20.
Membranes (Basel) ; 9(7)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277497

RESUMO

The development of suitable separation technologies for the separation of carbon dioxide is a pressing technological requirement. The application of ion gel membranes for this purpose continues to stimulate a great deal of research, and in this study we focus on the chemical structure of the ionic liquid component in the ion gel, and its interactions with the sulfonated polyimide polymer. Whilst such membranes are known to give promising carbon dioxide separation properties together with mechanical strength and thin-film-processability, we further elaborate on how changing the cation of the ionic liquid from a typical imidazolium cation to a protic variant effects the physicochemical, thermal, and structural properties of the membranes, and how these changes further influence the carbon dioxide separation properties. We compare and contrast our findings with our earlier study on protic and aprotic ammonium-based ionic liquids, and highlight that for CO2 absorption behavior in the imidazolium systems, the importance of directionality of interactions (ion pairs exhibit a large energy stabilization only for a specific geometrical arrangement of cation and anion, e.g., hydrogen bonding rather than Coulombic interaction) between cation and anion applies not only to the protic system, but also to the nominally aprotic cation. Finally, we demonstrate that the phase separation behavior in the ion gels is an important factor in determining the carbon dioxide separation behavior.

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