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1.
J Voice ; 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32576525

RESUMO

OBJECTIVES: The present study translated the Vocal Tract Discomfort Scale (VTDS) into Korean (K-VTDS) and evaluated its reliability and validity. STUDY DESIGN: This was a prospective study. METHODS: The VTDS was first translated into Korean and validated. One hundred and fifty-nine patients with voice disorders were divided into three different diagnostic groups (functional, structural, and neurologic voice disorder) and 131 vocally healthy adults were also included. All participants completed the K-VTDS and the Korean version of the Voice Handicap Index (K-VHI) and Korean versions of the Voice-Related Quality of Life (K-VRQOL). The internal consistency of the K-VTDS was analyzed through Cronbach's α coefficient. The VTDS score differences related to the diagnostic groups were assessed with t test and analysis of variance. We assessed the correlation between the K-VTDS, the K-VHI, and the K-VRQOL using Pearson's correlation analysis. RESULTS: High internal consistency and the test-retest reliability of the K-VTDS were found. The voice disorder group had significantly higher K-VTDS scores for the subscales and total scores than those in the healthy group (P < 0.001). The K-VTDS scores for the subscale of frequency and total scores were highest in the functional voice disorder group. We found a significant difference in frequency and total score of the K-VTDS between the functional voice disorder group and the structural voice disorder group (P < 0.05). We observed a strong positive correlation among the scores for the subscales of frequency and severity, and total scores in the K-VTDS. The K-VTDS showed moderate correlation with the K-VHI and the K-VRQOL. CONCLUSION: The K-VTDS is a reliable and valid instrument for voice assessment for voice disorders in Korean-speaking patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32530793

RESUMO

a rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) clean-up for a variety of foods and dietary supplements (DS). QuEChERS is widely used in extraction or clean-up procedures to eliminate interference of matrices such as sugars, organic acids, lipids, and fatty acids. The samples were categorised into three types, and various pretreatment methods were compared for each type. In all types, the QuEChERS was superior and selected as the final pretreatment method. The optimised method was validated for specificity, limit of detection (LOD), limit of quantification (LOQ), linearity, recovery, precision and accuracy. All of the validation results met the requirements of the international guidelines for all types of samples. The validated method was applied to 30 commercial food samples, CBD was detected in 17 samples, with 2 of them detected below the LOQ level and the rest detected in a range of 70 µg/kg to 31305 mg/kg (3.1%, w/w). Meanwhile, THC was detected in 14 samples; 2 of them were detected below the LOQ level and the rest detected in a 0.08-98.62 µg/g range. These results indicated that the validated method can be successfully applied for the determination of cannabinoids in a variety of samples. Furthermore, it will be useful for controlling the illegal distribution of cannabinoids.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32569530

RESUMO

Anabolic-androgenic steroids (AASs) are very potent muscle builders, and professional sportsmen often take protein supplements to improve their performance. Several studies have emphasised that protein supplements may contain undeclared AASs banned by the International Olympic Committee/World Anti-Doping Agency. The widespread occurrence and abuse of contaminated protein supplements is extremely dangerous because of their side effects. To minimise the chances of an unattended positive doping test or to avoid serious health problems, adequate screening methods for the detection of a wide range of steroids is essential. To address this requirement, a rapid and effective modified QuEChERS (quick, easy, cheap, effective, rugged and safe) method was developed and validated to screen and quantify the simultaneous analysis of twenty-eight AASs in protein supplements using LC-MS/MS. The validated method was applied to 198 protein supplements collected from on-line and, off-line markets, and direct purchase from overseas between 2019 and 2020. Of the 198 samples, two samples contained testosterone and stanozolol at concentrations of 0.27 µg/g and 0.023 µg/g, respectively. In addition, 5α-hydroxylaxogenin was detected for the first time in three products purchased in Korea from overseas. The modified QuEChERS method was established and successfully applied to screen and determine AASs as a measure of continuous control and supervision in protein supplements.

4.
J Korean Med Sci ; 35(21): e163, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32476302

RESUMO

BACKGROUND: The digits-in-noise (DiN) test is a speech-in-noise test to measure speech recognition threshold in noise adaptively. Herein, we aimed to develop the Korean version of the DiN test to provide a useful hearing screening tool for clinical as well as research purposes. METHOD: Spoken monosyllabic digits from 0 to 9 were recorded by a female speaker. The test list was constructed such that each digit was placed in three different positions. An optimization procedure was conducted to equate the audibility of each digit. After the optimization, the smartphone application for the Korean DiN (K-DiN) test was developed. For the adaptive measurement procedure, 180 new DiN triplets separated into six lists of 30 were created. Mean speech recognition threshold values for each list and session were measured to examine the test-retest and training effects of the test materials. In addition, speech recognition threshold values measured by different devices were compared to determine whether the speech recognition threshold levels differed. RESULTS: Optimization results showed that the mean speech recognition threshold and slope were ?11.55 dB signal-to-noise ratio and 10.21%/dB, respectively, which are comparable to levels shown in different-language versions of the DiN test. The results of the test-retest and training effects revealed no significant differences among the test sessions and lists. Additionally, the mean speech recognition threshold values measured by four different devices were not different, indicating the reliability of the test materials. CONCLUSION: We believe this study is the first to attempt to develop a K-DiN test. Our results indicate that this test can be used as a potentially reliable hearing screening tool.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32423185

RESUMO

Techniques used for the regulation of gene expression facilitate studies of gene function and treatment of diseases via gene therapy. Many tools have been developed for the regulation of gene expression in mammalian cells. The Lac operon system induced with isopropyl ß-D-1-thiogalactopyranoside (IPTG) is one of the employed inducible systems. IPTG mimics the molecular structure of allolactose and has a strong affinity for the corresponding repressor. IPTG is known to rapidly penetrate into mammalian cells and exhibits low toxicity. In the present study, we developed an inducible expression system that could regulate the expression of genes in mammalian cells using IPTG. Here, we confirm that unlike other vector systems based on the Lac operon, this expression system allows regulation of gene expression with lactose in the mammalian cells upon transfection. The co-treatment with IPTG and lactose could improve the efficiency of gene expression regulation. The regulation of gene expression with lactose has several benefits. Lactose is safe in humans as compared to other chemical substances and is easily available, making this technique very cost-effective.

6.
J Obes Metab Syndr ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32045514

RESUMO

Background: Growing evidence suggests links between sugar-sweetened beverages (SSBs) and metabolic disorders. We investigated the effects of SSBs commonly consumed by adolescents and their relationships to glucose metabolism and fatty liver. Methods: We treated 7-week old male C57BL/6 mice with water (control) or one of three different SSBs, carbonated soda (Coca-Cola®), milk-sweetened milk coffee (Maxwell®), or chocolate-added cocoa (Choco-Latte®), for 13 weeks (n=10 in each group). Half of the animals were fed a regular chow diet and the other half a high-fat diet (40% fat). Body composition and biochemical variables were investigated at the end of treatment. Histology of the liver and adipose tissue, as well as molecular signaling related to glucose and lipid metabolism, were also evaluated. Results: During the 13-week treatment, mice treated with chocolate-added cocoa or milk-sweetened coffee showed significantly greater increases in body weight compared with controls, especially when fed a high-fat diet. Fasting glucose level was higher in the three SSB-treated groups compared with the control group. Lipid droplets in the liver, fat cell size, and number of CD68-positive cells in adipose tissue were greater in the SSB-treated groups than in the control group. SSB treatments increased the expression of genes related to inflammatory processes in the liver and adipose tissue. Phosphorylation of AKT and glycogen synthase kinase in muscle was significantly reduced in SSB-treated groups. Conclusion: Daily consumption of SSBs over 3 months lead to metabolic impairment and weight gain and may contribute to development of metabolic diseases.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31902201

RESUMO

Objectives: Cochlear implant (CI) users typically report impaired ability to understand speech in noise. Speech understanding in CI users decreases with noise due to reduced temporal processing ability, and speech perceptual errors involve stop consonants distinguished by voice onset time (VOT). The current study examined the effects of noise on various speech perception tests while at the same time used cortical auditory evoked potentials (CAEPs) to quantify the change of neural processing of speech sounds caused by noise. We hypothesized that the noise effects on VOT processing can be reflected in N1/P2 measures, the neural changes relate to behavioral speech perception performances. Methods: Ten adult CI users and 15 normal-hearing (NH) people participated in this study. CAEPs were recorded from 64 scalp electrodes in both quiet and noise (signal-to-noise ratio +5 dB) and in passive and active (requiring consonant discrimination) listening. Speech stimulus was synthesized consonant-vowels with VOTs of 0 and 50 ms. N1-P2 amplitudes and latencies were analyzed as a function of listening condition. For the active condition, the P3b also was analyzed. Behavioral measures included a variety of speech perception tasks. Results: For good performing CI users, performance in most speech test was lower in the presence of noise masking. N1 and P2 latencies became prolonged with noise masking. The P3b amplitudes were smaller in CI groups compared to NH. The degree of P2 latency change (0 vs. 50 ms VOT) was correlated with consonant perception in noise. Conclusion: The effects of noise masking on temporal processing can be reflected in cortical responses in CI users. N1/P2 latencies were more sensitive to noise masking than amplitude measures. Additionally, P2 responses appear to have a better relationship to speech perception in CI users compared to N1.

8.
J Pept Sci ; 26(3): e3237, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31852026

RESUMO

Delivering biomolecules, such as antibodies, proteins, and peptides, to the cytosol is an important and challenging aspect of drug development and chemical biology. Polyarginine-a well-known cell-penetrating peptide (CPP)-is capable of exploiting its positive charge and guanidium groups to carry a fused cargo into the cytosol. However, the precise mechanism by which this occurs remains ambiguous. In the present study, we established a new method of quantitatively assessing cell penetration. The method involves inducing cell death by using a polyarginine (R8) to deliver a peptide-ie, mitochondrial targeting domain (MTD)-to the cytosol. We found that 4,4'-diisothiocyanatostilbene-2,2'-di-sulfonate (DIDS)-an anion channel blocker-inhibited the ability of octa-arginine (R8)-fused MTD to penetrate cells. Other anion channel blockers did not inhibit the penetration of peptides fused with R8. Comparison of DIDS with other structurally similar chemicals revealed that the isothiocyanate group of DIDS may be primarily responsible for the inhibitory effect than its stilbene di-sulfonate backbone. These results imply that the inhibitory effect of DIDS may not be derived from the interaction between stilbene di-sulfonate and the anion channels, but from the interaction between the isothiocyanate groups and the cell membrane. Our new MTD method enables the quantitative assessment of cell penetration. Moreover, further studies on the inhibition of CPPs by DIDS may help clarify the mechanism by which penetration occurs and facilitate the design of new penetrative biomolecules.

9.
Front Aging Neurosci ; 11: 287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31736738

RESUMO

Neuroinflammation is important in the pathogenesis and development of Alzheimer's disease (AD). In the AD brain, microglial activation and upregulation of pro-inflammatory mediators both induce amyloid beta (Aß) accumulation. Regulatory T cells (Tregs) and nuclear factor-kappa B (NF-κB) signaling have been implicated in AD development through their effects on neuroinflammation and microglial activation. The bee venom soluble phospholipase A2 (bv-sPLA2) enzyme is known to exert anti-inflammatory and anti-immune effects. Here, we investigated the inhibitory effects of bv-sPLA2 on memory deficiency in a lipopolysaccharide (LPS)-induced mouse model of AD. We examined whether bv-sPLA2 (0.02, 0.2, and 2 mg/kg by i.p. injection three times for 1 week) could inhibit neuroinflammation and memory impairment in LPS-treated mice (250 µg/kg by i.p. injection daily for 1 week). We also assessed the effects of bv-sPLA2 administration (0.01, 0.1, and 1 µg/ml) on LPS (1 µg/ml)-treated microglial BV-2 cells. In the LPS-injected mouse brain, sPLA2 treatment rescued memory dysfunction and decreased Aß levels, through the downregulation of amyloidogenic proteins, and decreased the expression of inflammatory proteins and pro-inflammatory cytokines. Moreover, the LPS-mediated increase in inflammatory protein expression was attenuated bv-sPLA2 treatment in BV-2 cells. Treatment with bv-sPLA2 also downregulated signaling by NF-κB, which is considered to be an important factor in the regulation of neuroinflammatory and amyloidogenic responses, both in vivo and in vitro. Additionally, co-treatment with NF-κB (5 µM) and bv-sPLA2 (0.1 µg/ml) exerted more marked anti-inflammatory effects, compared to bv-sPLA2 treatment alone. These results indicate that bv-sPLA2 inhibits LPS-induced neuroinflammation and amyloidogenesis via inhibition of NF-κB.

10.
Biochem Biophys Res Commun ; 518(1): 80-86, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31421829

RESUMO

Noxa is a weak apoptosis activator consisting of a BH3 domain and a mitochondrial-targeting domain (MTD). BH3 binds Mcl-1 and Bcl2A1 and inactivates their anti-apoptotic activities, while MTD delivers BH3 to mitochondria. Previously we revealed that MTD may also function as an inducer of necrosis via conjugation with octa-arginine, which induces cytosolic Ca2+ influx from mitochondria. However, the mechanism(s) underlying this process has not been elucidated yet. Here, we show that calcium influx induced by an MTD peptide fused with octa-arginine residue (R8:MTD) originates not only from mitochondria but also from the extracellular space. However, calcium spikes were not sufficient for necrosis. R8:MTD induced mitochondrial permeability transition pore opening, fragmentation, and swelling. These mitochondrial events induced by MTD appeared to be necessary for necrosis induction, since DIDS, a VDAC inhibitor, inhibited the mitochondrial swelling and cell death induced by MTD. We show that R8:MTD disrupted endoplasmic reticulum (ER) structures but not peroxisomes or Golgi, indicating that R8:MTD causes necrosis by inducing ER events as well.

11.
Indian J Hematol Blood Transfus ; 35(3): 531-537, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31388269

RESUMO

ABO genotyping is a molecular diagnostic technique important for transfusion and transplantation in medicine, and human identification in forensic science. Because ABO genotyping are labor intensive and time consuming, the genotyping cannot be firstly used to resolve the serological ABO discrepancy in blood bank. For rapid one-step ABO genotyping, we developed direct, real-time, allele-specific polymerase chain reaction (PCR), and melting curve analysis (DRAM assay) without DNA preparation. In DRAM assay, we used a special PCR buffer for direct PCR, a rapid RBC lysis buffer, white blood cells as template without DNA preparation, allele-specific primers for discriminating three ABO alleles (261G/del, 796C/A, and 803G/C), and melting curve analysis as a detection method. There was 100% concordance among the results of ABO genotyping by the DRAM assay, serologic typing, PCR-RFLP and PCR-direct sequencing of 96 venous blood samples. We were able to reduce the number of manual steps to three and the hands-on time to 12 min, compared to seven steps and approximately 40 min for conventional ABO genotyping using allele-specific PCR with purified DNA and agarose gel electrophoresis. We have established and validated the DRAM assay for rapid and reliable one-step ABO genotyping in a closed system. The DRAM assay with an appropriate number of allele-specific primers could help in resolving ABO discrepancies and should be valuable in clinical laboratory and blood bank.

12.
Cell Death Dis ; 10(7): 519, 2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285435

RESUMO

Noxa, a Bcl-2 homology 3 (BH3)-only protein of the Bcl-2 family, is responsive to cell stresses and triggers apoptosis by binding the prosurvival Bcl-2-like proteins Mcl1, BclXL, and Bcl2A1. Although the Noxa BH3 domain is necessary to induce apoptosis, the mitochondrial targeting domain (MTD) of Noxa functions as a pronecrotic domain, an inducer of mitochondrial fragmentation, and delivery to mitochondria. In this study, we demonstrate that the extended MTD (eMTD) peptide induces necrotic cell death by interaction with the VDAC2 protein. The eMTD peptide penetrates the cell membrane, causing cell membrane blebbing, cytosolic calcium influx, and mitochondrial swelling, fragmentation, and ROS generation. The MTD domain binds VDACs and opens the mitochondrial permeability transition pore (mPTP) in a CypD-independent manner. The opening of mPTP induced by eMTD is inhibited either by down-regulation of VDAC2 or by the VDACs inhibitor DIDS. These results indicate that the MTD domain of Noxa causes mitochondrial damage by opening mPTP through VDACs, especially VDAC2, during necrotic cell death.

13.
Acta Neuropathol Commun ; 7(1): 68, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046837

RESUMO

Accumulating evidence indicates that endoplasmic reticulum (ER) stress is a common feature of Parkinson's disease (PD) and further suggests that several PD-related genes are responsible for ER dysfunction. However, the underlying mechanisms are largely unknown. Here, we defined the mechanism by which LRRK2-G2019S (LRRK2-GS), a pathogenic mutation in the PD-associated gene LRRK2, accelerates ER stress and cell death. Treatment of cells with α-synuclein increased the expression of ER stress proteins and subsequent cell death in LRRK2-GS astrocytes. Intriguingly, we found that LRRK2-GS localizes to the ER membrane, where it interacts with sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and suppress its activity by preventing displacement of phospholamban (PLN). LRRK2-GS-mediated SERCA malfunction leads to ER Ca2+ depletion, which induces the formation of mitochondria-ER contacts and subsequent Ca2+ overload in mitochondria, ultimately resulting in mitochondrial dysfunction. Collectively, our data suggest that, in astrocytes, LRRK2-GS impairs ER Ca2+ homeostasis, which determines cell survival, and as a result, could contribute to the development of PD.


Assuntos
Astrócitos/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Doença de Parkinson/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Animais , Apoptose , Células Cultivadas , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Camundongos Transgênicos , Mutação , Neurônios/metabolismo
14.
Metabolism ; 95: 46-56, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30935969

RESUMO

OBJECTIVE: Alcohol overconsumption and abuse lead to alcoholic liver disease (ALD), which is a major chronic liver disease worldwide. Chitinase-3-like protein 1 (CHI3L1) have an important role in the pathogenesis of inflammatory disease. However, the role of CHI3L1 in ALD has not yet been reported. In the present study, we investigated the effect of CHI3L1 on chronic plus binge ethanol-induced liver injury. METHODS: CHI3L1 knock out (KO) mice and their littermate control mice based on C57BL/6 (10-12 weeks old) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 10 days. And, CHI3L1 siRNA or CHI3L1 expressing vector was transfected HepG2 cells were treated with ethanol or without. RESULTS: Ethanol-induced hepatic triglyceride (TG) levels and the mRNA levels of TG synthesis-related genes such as acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD1) were decreased in the liver of CHI3L1 knock out (KO) mice and the HepG2 cells transfected with CHI3L1 siRNA. Increased mRNA level and activation of SREBP1 which is transcription factor of ACC, FAS and SCD1 by ethanol feeding were reduced in the liver of ethanol-fed CHI3L1 KO mice. Moreover, ethanol-induced SREBP1 luciferase activity and mRNA level of SREBP1, ACC, FAS and SCD1 were also decreased in the HepG2 cells transfected with CHI3L1 siRNA, while those were further increased in the HepG2 cells treated with recombinant human CHI3L1. Furthermore, oxidative stress and up-regulated pro-inflammatory cytokines by ethanol were recovered in the liver of ethanol-fed CHI3L1 KO mice. CONCLUSION: Our finding suggest that inhibition of CHI3L1 suppressed ethanol-induced liver injury through inhibition of TG synthesis, and the blocking of oxidative stress and hepatic inflammation induced SREBP1 activity could be significant.


Assuntos
Proteína 1 Semelhante à Quitinase-3/deficiência , Hepatopatias Alcoólicas/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/biossíntese , Animais , Bebedeira/complicações , Linhagem Celular , Depressores do Sistema Nervoso Central/farmacologia , Proteína 1 Semelhante à Quitinase-3/genética , Citocinas/metabolismo , Etanol/farmacologia , Feminino , Humanos , Inflamação/genética , Inflamação/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo
15.
Front Hum Neurosci ; 13: 38, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30837852

RESUMO

Sensory plasticity, which is associated with deafness, has not been as thoroughly investigated in the adult brain as it has in the developing brain. In this study, we examined the brain reorganization induced by auditory deprivation in people with adult-onset deafness and its clinical relevance by measuring glucose metabolism before cochlear implant (CI) surgery. F-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scans were performed in 37 postlingually deafened patients during the preoperative workup period, and in 39 normal-hearing (NH) controls. Behavioral CI outcomes were measured at 1 year after implantation using a phoneme identification test with auditory cueing only. In the deaf individuals, areas involved in the auditory pathway such as the inferior colliculus and bilateral superior temporal gyri were hypometabolic compared to the NH controls. The hypometabolism observed in the deaf auditory cortices gradually returned to levels similar to the controls as the duration of deafness increased. However, contrary to our previous findings in congenitally deaf children, this metabolic recovery failed to have a significant prognostic value for the recovery of the speech perception ability in adult CI patients. In a broad occipital area centered on the primary visual cortices, glucose metabolism was higher in the deaf patients than the controls, suggesting that the area had become visually hyperactive for sensory compensation immediately after the onset of deafness. In addition, a negative correlation between the metabolic activity and behavioral speech perception outcomes was observed in the visual association areas. In the medial frontal cortices, cortical metabolism in most patients decreased, but patients who had preserved metabolic activities showed better speech performance. These results suggest that the auditory cortex in people with adult-onset deafness is relatively resistant to cross-modal plasticity, and instead, individual traits in late-stage visual processing and cognitive control seem to be more reliable prognostic markers for adult-onset deafness.

16.
Mar Drugs ; 17(2)2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30781690

RESUMO

Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer's disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide (LPS) administered mice model. Additionally, we investigated the anti-oxidant activity and the anti-neuroinflammatory response of AXT in LPS-treated BV-2 microglial cells. The AXT administration ameliorated LPS-induced memory loss. This effect was associated with the reduction of LPS-induced expression of inflammatory proteins, as well as the production of reactive oxygen species (ROS), nitric oxide (NO), cytokines and chemokines both in vivo and in vitro. AXT also reduced LPS-induced ß-secretase and Aß1⁻42 generation through the down-regulation of amyloidogenic proteins both in vivo and in vitro. Furthermore, AXT suppressed the DNA binding activities of the signal transducer and activator of transcription 3 (STAT3). We found that AXT directly bound to the DNA- binding domain (DBD) and linker domain (LD) domains of STAT3 using docking studies. The oxidative stress and inflammatory responses were not downregulated in BV-2 cells transfected with DBD-null STAT3 and LD-null STAT3. These results indicated AXT inhibits LPS-induced oxidant activity, neuroinflammatory response and amyloidogenesis via the blocking of STAT3 activity through direct binding.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Lipopolissacarídeos , Transtornos da Memória/prevenção & controle , Fator de Transcrição STAT3/efeitos dos fármacos , Precursor de Proteína beta-Amiloide/antagonistas & inibidores , Precursor de Proteína beta-Amiloide/biossíntese , Animais , Antioxidantes/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Linhagem Celular , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Rememoração Mental/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Microglia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Xantofilas/uso terapêutico
17.
J Microbiol ; 57(5): 356-361, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30796748

RESUMO

A Gram-stain-negative, mucus-forming, motile by gliding, non-spore-forming and short rod-shaped bacterial strain designated R1-15T was isolated from soil and its taxonomic position was evaluated using a polyphasic approach. Strain R1-15T grew at 15-37°C (optimum, 30°C), at pH 6-7 (optimum, pH 6) and in the presence of 0-1% (w/v) NaCl (optimum, 0%) on 0.1X TSA. On the basis of 16S rRNA gene sequence similarity, the novel strain was assigned to the family Chitinophagaceae of the phylum Bacteroidetes, and its closest related taxa were species of the genera Taibaiella (88.76-90.02% sequence similarity), Lacibacter (89.24-90.00%), Chitinophaga (88.61-89.76%), and Terrimonas (89.04%). Flexirubin- type pigments were produced. The only isoprenoid quinone was MK-7, and the major polar lipid was phosphatidylethanolamine. Based on whole genome comparisons between the strain R1-15T and the type strains of relatives, the orthologous average nucleotide identity values were 66.9-67.0%. The DNA G + C content of strain R1-15T was 43.8 mol%. The combination of phylogenetic, chemotaxonomic and phenotypic data clearly supported separation of strain R1-15T from related taxa, and thus the name Mucibacter soli gen. nov., sp. nov. is proposed. The type strain is R1-15T (= KCTC 62274T = JCM 31190T).


Assuntos
Bacteroidetes , Mucinas/biossíntese , Técnicas de Tipagem Bacteriana , Bacteroidetes/classificação , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Bacteroidetes/metabolismo , Composição de Bases/genética , DNA Bacteriano/genética , Locomoção/fisiologia , Fosfatidiletanolaminas/metabolismo , RNA Ribossômico 16S/genética , Microbiologia do Solo
18.
FASEB J ; 33(3): 4314-4326, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30566396

RESUMO

The overactivity of cannabinoid 1 receptor (CB1R) is associated with obesity and type 2 diabetes. First-generation CB1R antagonists, such as rimonabant, offered therapeutic advantages for the control of obesity and related metabolic abnormalities, but their therapeutic potential was limited by undesirable neuropsychiatric side effects. Here, we evaluated AJ5012 as a novel potent peripheral CB1R antagonist and, using this antagonist, investigated the role of peripheral CB1R on adipose tissue inflammation in obese mouse models. AJ5012 had a high degree of CB1R and cannabinoid 2 receptor selectivity but a low brain:plasma concentration ratio without eliciting centrally mediated neurobehavioral effects. In diet-induced obese (DIO) mice, AJ5012 did not reduce food intake but did induce a significant weight loss, likely owing to an increased energy expenditure. It was as effective as rimonabant for the improvement of hormonal or metabolic abnormalities, glycemic control, and insulin sensitivity. The treatment of DIO and leptin receptor-deficient mice with AJ5012 also exhibited effects comparable to rimonabant for the prevention of macrophage infiltration, activation of the nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome, and production of proinflammatory cytokines, which resulted in the suppression of adipose tissue inflammation. In addition to macrophage, activation of CB1R in 3T3-L1 adipocytes induced the expression of proinflammatory genes, which was fully inhibited by AJ5012. Our findings identified AJ5012 as a novel peripheral CB1R antagonist and suggest that peripheral CB1R blockade might break the links between insulin resistance and adipose tissue inflammation.-Han, J. H., Shin, H., Park, J.-Y., Rho, J. G., Son, D. H., Kim, K. W., Seong, J. K., Yoon, S.-H., Kim, W. A novel peripheral cannabinoid 1 receptor antagonist, AJ5012, improves metabolic outcomes and suppresses adipose tissue inflammation in obese mice.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Receptor CB1 de Canabinoide/antagonistas & inibidores , Células 3T3 , Tecido Adiposo/metabolismo , Animais , Células CHO , Cricetulus , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Resistência à Insulina/fisiologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Células RAW 264.7 , Receptor CB2 de Canabinoide/metabolismo , Rimonabanto/metabolismo , Perda de Peso/efeitos dos fármacos
20.
J Microbiol Biotechnol ; 28(12): 2064-2070, 2018 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-30301322

RESUMO

Pseudomonas tolaasii 6264 is a representative strain that causes bacterial blotch disease on the cultivated oyster mushroom, Pleurotus ostreatus. Bacteriophages are able to sterilize the pathogenic P. tolaasii strains, and therefore, they can be applied in creating disease-free mushroom cultivation farms, through a method known as "phage therapy". For successful phage therapy, the characterization of phage-resistant strains is necessary, since they are frequently induced from the original pathogenic bacteria in the presence of phages. When 10 different phages were incubated with P. tolaasii 6264, their corresponding phage-resistant strains were obtained. In this study, changes in pathogenic, genetic, and biochemical characteristics as well as the acquired phage resistance of these strains were investigated. In the phylogenetic analyses, all phage-resistant strains were identical to the original parent strain based on the sequence comparison of 16S rRNA genes. When various phage-resistant strains were examined by three different methods, pitting test, white line test, and hemolytic activity, they were divided into three groups: strains showing all positive results in three tests, two positive in the first two tests, and all negative. Nevertheless, all phage-resistant strains showed that their pathogenic activities were reduced or completely lost.


Assuntos
Terapia por Fagos , Pleurotus , Fagos de Pseudomonas/fisiologia , Pseudomonas/patogenicidade , Pseudomonas/virologia , Proteínas de Bactérias , Toxinas Bacterianas , Contagem de Colônia Microbiana , Produtos Agrícolas/microbiologia , DNA Bacteriano/genética , Depsipeptídeos , Fazendas , Genes Bacterianos/genética , Hemólise , Filogenia , Pseudomonas/classificação , Pseudomonas/genética , RNA Ribossômico 16S/genética , Esterilização
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