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Rice is a staple crop providing a significant portion of the global food supply. It is then crucial to develop strategies for breeding high-yield cultivars to meet global food security challenges, including the UN's zero-hunger goal. In this study, QTL mapping was employed to pinpoint key genomic regions linked to traits influencing rice yield, with a focus on panicle structure-a critical determinant of grain number. Over two consecutive years, QTLs were identified using 88 JJ625LG/Namchan Recombinant Inbred Lines (JNRILs), revealing several candidate genes. Notably, Gn1a, a known regulator of grain number, was mapped within qNS1 and qNSSr1-1, while the sd1 gene, linked to plant height, was detected across multiple QTLs. Furthermore, a novel gene, OsNSMq3 (Os03g0843800), encoding a methyltransferase, was identified in various QTLs, with haplotype and sequence homology analysis suggesting its role in enhancing yield by influencing panicle structure development. The increase in primary and secondary branches, driven by these genes, leads to a higher number of spikelets per panicle, thereby boosting yield. These findings underscore the potential of candidate genes from stable QTLs as valuable tools in molecular breeding to develop high-yield rice cultivars, addressing global hunger and aiding food supply in refugee crises.
Assuntos
Mapeamento Cromossômico , Oryza , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Oryza/genética , Oryza/crescimento & desenvolvimento , Locos de Características Quantitativas/genética , Polimorfismo de Nucleotídeo Único/genética , Genes de Plantas/genética , Fenótipo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Recent studies have highlighted the potential of Mesenchymal Stem Cells (MSCs) as an alternative treatment for Alopecia Areata (AA) due to their immunosuppressive properties. While MSCs have shown promise in cell experiments, their effectiveness in vivo remains uncertain. This study aims to validate local administration of MSC therapy's efficacy in AA treatment through animal experiments. AA was induced through Interferon-gamma (IFN-γ) administration in mice, and MSC treatment (MSCT)'s effects were assessed visually and through tissue analysis. The MSC-treated group showed more hair regrowth compared to the control (CTL) group. MSCT notably reduced local inflammatory cytokines (JAK1, JAK2, STAT1, STAT3, IFN-γR, IL-1ß, IL-16, IL-17α, and IL-18) in AA-induced mice's skin, but systemic cytokine levels remained unchanged. Furthermore, MSC treatment normalized the expression of Wnt/ß-catenin signaling pathway genes (LEF1 and ß-catenin) and growth factors (FGF7 and FGF2), which are crucial for hair cycle regulation. This study lays the groundwork for further exploring MSCs as a potential treatment for AA, but more research is needed to fully understand their therapeutic potential.
Assuntos
Alopecia em Áreas , Citocinas , Modelos Animais de Doenças , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Alopecia em Áreas/terapia , Alopecia em Áreas/metabolismo , Camundongos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Citocinas/metabolismo , Via de Sinalização Wnt , Interferon gama/metabolismo , beta Catenina/metabolismo , beta Catenina/genética , Feminino , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/genéticaRESUMO
Rice is a major crop, providing calories and food for most of the world's population. Currently, the global population is rapidly increasing, and securing a yield of rice that can satisfy everyone is an ongoing challenge. The yield of rice can be increased by controlling 1000-grain weight as one of the important determining factors. Grain length, grain width, grain thickness, and 1000-grain weight, which determine grain size, are controlled by QTLs. To identify QTLs related to grain size, we screened and then mapped 88 RIL individuals derived from a cross between JJ625LG, which has a long grain size, long spindle-shaped grains, and low 1000-grain weight, and Namchan, which has short grains with round shape and heavy 1000-grain weight. In 2021 and 2022, 511 SNP markers were used to map QTLs related to grain size to a physical map. The QTLs found to be related to grain size are evenly distributed on chromosomes 2, 3, 5, 10, and 11. The mapping results also show that the QTLs qGl3-2, qRlw3, and qRlw3-2 of chromosome 3, and qGt5 and qRlw5 of chromosome 5 are, respectively, associated with GS3 and qSW5, which are the major genes previously cloned and found to be related to grain size. In addition, qGw10 and qGw10-1, which were additionally detected in this study, were found to be associated with Os10g0525200 (OsCPq10), a potential candidate gene involved in controlling grain size. This gene codes for a cytochrome P450 family protein and is reported to have a positive effect on grain size by interacting with proteins related to mechanisms determining grain size. In particular, OsCPq10 was screened in the same identified QTL region for 2 consecutive years, which is expected to have a positive effect on grain size. These results will be helpful for breeding elite rice cultivars with high yields through additional fine mapping related to grain size.
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Several studies have reported the pathogenic role of Malassezia in atopic dermatitis (AD); the significance of Malassezia's influence on AD needs to be further investigated. Dupilumab, a monoclonal antibody to anti-Interleukin (IL) 4Rα, and ruxolitinib, a Janus kinase (JAK)1/2 inhibitor, are the first approved biologics and inhibitors widely used for AD treatment. In this study, we aimed to investigate how Malassezia Restricta (M. restricta) affects the skin barrier and inflammation in AD and interacts with the AD therapeutic agents ruxolitinib and anti-IL4Rα. To induce an in vitro AD model, a reconstructed human epidermis (RHE) was treated with IL-4 and IL-13. M. restricta was inoculated on the surface of RHE, and anti-IL4Rα or ruxolitinib was supplemented to model treated AD lesions. Histological and molecular analyses were performed. Skin barrier and ceramide-related molecules were downregulated by M. restricta and reverted by anti-IL4Rα and ruxolitinib. Antimicrobial peptides, VEGF, Th2-related, and JAK/STAT pathway molecules were upregulated by M. restricta and suppressed by anti-IL4Rα and ruxolitinib. These findings show that M. restricta aggravated skin barrier function and Th2 inflammation and decreased the efficacy of anti-IL4Rα and ruxolitinib.
Assuntos
Dermatite Atópica , Malassezia , Humanos , Dermatite Atópica/tratamento farmacológico , Janus Quinases , Fatores de Transcrição STAT , Transdução de Sinais , Epiderme , InflamaçãoRESUMO
Alopecia areata (AA) is an autoimmune condition related to the collapse of the immune privilege of hair follicles. Certain AA populations present severe clinical manifestations, such as total scalp hair or body hair loss and a treatment refractory property. The aim of this study was to assess the effects of allogenic human mesenchymal stem cells (hMSCs) from healthy donors on the peripheral blood mononuclear cells (PBMCs) of severe AA patients, with a focus on the change in the cell fraction of Th1, Th17, and Treg cells and immunomodulatory functions. PBMCs of 10 AA patients and eight healthy controls were collected. Levels of Th17, Th1, and Treg subsets were determined via flow cytometry at baseline, activation status, and after co-culturing with hMSCs. All participants were severe AA patients with SALT > 50 and with a long disease duration. While the baseline Th1 and Treg levels of AA patients were comparable to those of healthy controls, their Th17 levels were significantly lower than those of the controls. When stimulated, the levels of CD4+IFN-γ+ T cells of the AA patients rose sharply compared to the baseline, which was not the case in those of healthy controls. The cell fraction of CD4+Foxp3+ regulatory T cells also abruptly increased in AA patients only. Co-culturing with allogenic hMSCs in activated AA PBMCs slightly suppressed the activation levels of CD4+INF-γ+ T cells, whereas it significantly induced the differentiation of CD4+Foxp3+ regulatory T cells. However, these changes were not prominent in the PBMCs of health controls. To examine the pathomechanisms, PBMCs of healthy donors were treated with IFN-γ to induce AA-like environment and then treated with allogenic grants and compared with ruxolitinib as a positive treatment control. hMSC treatment was shown to significantly inhibit the mRNA levels of proinflammatory cytokines, such as IFN-γ, TNF-α, IL-1α, IL-2R, IL-15, and IL-18, and chemokines, such as CCR7 and CCR10, in IFN-treated PBMCs. Interestingly, hMSCs suppressed the activation of JAK/STAT signaling by IFN in PBMCs with an effect that was comparable to that of ruxolitinib. Furthermore, the hMSC treatment showed stronger efficacy in inducing Foxp3, IL-10, and TGF-ß mRNA transcription than ruxolitinib in IFN-treated PBMCs. This study suggests that allogenic hMSC treatments have therapeutic potential to induce immune tolerance and anti-inflammatory effects in severe AA patients.
Assuntos
Alopecia em Áreas , Células-Tronco Mesenquimais , Humanos , Alopecia em Áreas/terapia , Fatores de Transcrição Forkhead , Leucócitos Mononucleares , RNA Mensageiro , Linfócitos T Reguladores , Transplante de Células-Tronco Mesenquimais/métodos , Tolerância ImunológicaRESUMO
Road speed is an important indicator of traffic congestion. Therefore, the occurrence of traffic congestion can be reduced by predicting road speed because predicted road speed can be provided to users to distribute traffic. Traffic congestion prediction techniques can provide alternative routes to users in advance to help them avoid traffic jams. In this paper, we propose a machine-learning-based road speed prediction scheme using road environment data analysis. The proposed scheme uses not only the speed data of the target road, but also the speed data of neighboring roads that can affect the speed of the target road. Furthermore, the proposed scheme can accurately predict both the average road speed and rapidly changing road speeds. The proposed scheme uses historical average speed data from the target road organized by the day of the week and hour to reflect the average traffic flow on the road. Additionally, the proposed scheme analyzes speed changes in sections where the road speed changes rapidly to reflect traffic flows. Road speeds may change rapidly as a result of unexpected events such as accidents, disasters, and construction work. The proposed scheme predicts final road speeds by applying historical road speeds and events as weights for road speed prediction. It also considers weather conditions. The proposed scheme uses long short-term memory (LSTM), which is suitable for sequential data learning, as a machine learning algorithm for speed prediction. The proposed scheme can predict road speeds in 30 min by using weather data and speed data from the target and neighboring roads as input data. We demonstrate the capabilities of the proposed scheme through various performance evaluations.
Assuntos
Acidentes de Trânsito , Tempo (Meteorologia) , Acidentes de Trânsito/prevenção & controle , Algoritmos , Aprendizado de MáquinaRESUMO
No effective therapeutic strategies have been developed against food allergies. Immunomodulation during early infant period could prevent the development of food allergies. We investigated the preventive effects of human hematopoietic mesenchymal stem cells (hHMSCs) in mice with ovalbumin (OVA)-induced food allergy. BALB/c mice with OVA-induced food allergy were divided into 3 groups, and each group was treated with hHMSCs or hHMSC culture medium (hHMSC-CM) or saline. Ear thickness, allergy score, rectal temperature, and diarrhea occurrence were checked. Total IgE, OVA-specific IgE, and mucosal mast cell protease-1 (mMCP-1) were measured by ELISA. Other allergic parameters were analyzed using histology specimens, RT-PCR, and flow cytometry. Treatment with hHMSCs or hHMSC-CM significantly suppressed the frequency of anaphylactic response and rectal temperature decline, reduced diarrhea, total IgE, OVA-specific IgE, and mMCP-1. While the treatment decreased the level of Th2 cytokines, it enhanced IL-10 and TGF-ß1 mRNA. Exposure to hHMSC or hHMSC-CM did not generate regulatory T cells, but reduced mast cells. The immunomodulatory effect on the Th2 cytokines was greater in hHMSC-CM than in hHMSCs. hHMSC treatment may be a promising preventive intervention against food allergy. Further studies are needed to elucidate the key substances released from hHMSC to induce immune tolerance.
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Mesenchymal stem cell therapy (MSCT) has been shown to be a new therapeutic option for treating alopecia areata (AA). Outer root sheath cells (ORSCs) play key roles in maintaining the hair follicle structure and supporting the bulge area. In human ORSCs (hORSCs), the mechanism for this process has not been extensively studied. In this study, we aimed to examine the influence of human hematopoietic mesenchymal stem cells (hHMSCs) in the hORSCs in vitro model of AA and determine the mechanisms controlling efficacy. Interferon-gamma (IFN-γ) pretreatment was used to induce an in vitro model of AA in hORSCs. The effect of MSCT on the viability and migration of hORSCs was examined using co-cultures, the MTT assay, and migration assays. We investigated the expression of molecules related to the Wnt/ß-catenin pathway, JAK/STAT pathway, and growth factors in hHMSC-treated hORSCs by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. hHMSCs increased hORSC viability and migration when they were co-cultured. hHMSCs reverted IFN-γ-induced expression-including NLRP3, ASC, caspase-1, CXCL-9 through 11, IL-1ß, and IL-15-and upregulated several growth factors and hair stem cell markers. hHMSCs activated several molecules in the Wnt/ß-catenin signaling pathway, such as in the Wnt families, ß-catenin, phosphorylated GSK-3ß and cyclin D1, and suppressed the expression of DKK1 induced by IFN-γ in hORSCs. hHMSCs suppressed the phosphorylation of JAK1 to 3, STAT1, and STAT3 compared to the controls and IFN-γ-pretreated hORSCs. These results demonstrate that hHMSCs increased hORSC viability and migration in the in vitro AA model. Additionally, MSCT definitely stimulated anagen survival and hair growth in an HF organ culture model. MSCT appeared to be associated with the Wnt/ß-catenin and JAK/STAT pathways in hORSCs.
Assuntos
Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Interferon gama/farmacologia , Células-Tronco Mesenquimais/metabolismo , Alopecia em Áreas/metabolismo , Alopecia em Áreas/patologia , Animais , Movimento Celular , Técnicas de Cocultura , Dermatite/metabolismo , Feminino , Expressão Gênica , Folículo Piloso/metabolismo , Humanos , Interferon gama/metabolismo , Janus Quinases/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Técnicas de Cultura de Órgãos , Fatores de Transcrição STAT/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismoRESUMO
Since 2016, the invasive halophyte Spartina anglica has been colonizing mudflats along the western coast of South Korea. In order to minimize costs on S. anglica expansion management and waste-treatment of collected biomass, the potential application of the collected biomass of S. anglica was investigated. Ethanolic extracts and subfractions thereof (hexanes, methylene chloride, ethyl acetate, 1-butanol, and water-soluble) of the aerial and belowground parts of S. anglica showed free radical-scavenging [2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)], tyrosinase inhibitory, and pancreatic lipase inhibitory activities. An ethyl acetate fraction derived from aerial parts (EA-a) showed the most potent radical-scavenging and pancreatic lipase inhibitory activities, whereas tyrosinase inhibition was mainly observed in the methylene chloride soluble fractions (MC-bg) and other lipophilic fractions (ethyl acetate and hexanes layers) obtained from belowground parts. The major EA-a compound isolated and identified was 1,3-di-O-trans-feruloyl quinic acid (1) based on spectroscopic analysis, whereas the two major MC-bg compounds were identified as p-hydroxybenzaldehyde (2) and N-trans-feruloyltyramine (3). Compounds 1 and 3 scavenged both DPPH and ABTS radicals, whereas 1 and 2 inhibited pancreatic lipase activity. These results indicate that extracts and fractions of S. anglica have antioxidant, anti-obesity, and whitening properties with potential pharmaceutical, cosmeceutical, and functional food applications.
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Two new chlorinated secondary metabolites, saccharochlorines A and B (1 and 2), were isolated from the saline cultivation of a marine-derived bacterium Saccharomonospora sp. (KCTC-19160). The chemical structures of the saccharochlorines were elucidated by 2D NMR and MS spectroscopic data. Saccharochlorines A and B (1 and 2) exhibit weak inhibition of ß-secretase (BACE1) in biochemical inhibitory assay, but they induced the release of Aß (1-40) and Aß (1-42) in H4-APP neuroglial cells. This discrepancy might be derived from the differences between the cellular and sub-cellular environments or the epigenetic stimulation of BACE1 expression.
Assuntos
Acrilatos/química , Actinobacteria/química , Acrilatos/isolamento & purificação , Acrilatos/metabolismo , Acrilatos/farmacologia , Actinobacteria/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Neuroglia/citologia , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Fragmentos de Peptídeos/metabolismoRESUMO
BACKGROUND: Korean Red Ginseng (KRG) has been widely used as an herbal medicine to normalize and strengthen body functions. Although many researchers have focused on the biological effects of KRG, more studies on the action mechanism of red ginseng are still needed. Previously, we investigated the proteomic changes of the rat spleen while searching for molecular signatures and the action mechanism of KRG. The proteomic analysis revealed that differentially expressed proteins (DEPs) were involved in the increased immune response and phagocytosis. The aim of this study was to evaluate the biological activities of KRG, especially the immune-enhancing response of KRG. METHODS: Rats were divided into 4 groups: 0 (control group), 500, 1000, and 2000 mg/kg administration of KRG powder for 6 weeks, respectively. Isobaric tags for relative and absolute quantitation was performed with Q-Exactive LC-MS/MS to compare associated proteins between the groups. The putative DEPs were identified by a current UniProt rat protein database search and by the Gene Ontology annotations. RESULTS: The DEPs appear to increase the innate and acquired immunity as well as immune cell movement. These results suggest that KRG can stimulate immune responses. This analysis refined our targets of interest to include the potential functions of KRG. Furthermore, we validated the potential molecular targets of the functions, representatively LCN2, CRAMP, and HLA-DQB1, by Western blotting. CONCLUSION: These results may provide molecular signature candidates to elucidate the mechanisms of the immune response by KRG. Here, we demonstrate a strategy of tissue proteomics for the discovery of the molecular function of KRG.
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HPLC-UV guided isolation of the culture broth of a marine bacterium Saccharomonospora sp. CNQ-490 has led to the isolation of two new natural products, lodopyridones B and C (1 and 2) along with the previously reported lodopyridone A (3). Their chemical structures were established from the interpretation of 2D NMR spectroscopic data and the comparison of NMR data with the lodopyridone A (3). Lodopyridones B and C (1 and 2) possess the thiazole, and chloroquinoline groups which are characteristic features of these molecules. Lodopyridones A-C show weak inhibitory activities on the ß-site amyloid precursor protein cleaving enzyme 1 (BACE1).
Assuntos
Actinobacteria/metabolismo , Sedimentos Geológicos/microbiologia , Piridonas/química , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fragmentos de Peptídeos/metabolismo , Piridonas/isolamento & purificação , Piridonas/farmacologiaRESUMO
A Gram-negative, strictly aerobic, chemoheterotrophic, beige-pigmented, ovoid bacterium, designated YP194T, was isolated from marine sediment in the Republic of Korea. A phylogenetic analysis based on the 16S rRNA gene sequence indicated that the novel marine strain belongs to the family Rhodobacteraceae of the class Alphaproteobacteria, with high sequence similarity (98.4%) to Marinovum algicola FF3T. The DNA-DNA relatedness values between strains YP194T and M. algicola FF3T were 34.1 ± 2.7%. The DNA G+C content of strain YP194T was 63.1 mol%. Ubiquinone 10 (Q-10) was the sole respiratory quinone. The predominant cellular fatty acid was C18:1 ω7c (77.6%). Strain YP194T produced phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an unidentified aminolipid, an unidentified phospholipid and two unidentified lipids as polar lipids. From the combination of genotypic and phenotypic characteristics and the distinct phylogenetic position, the strain is considered to represent a novel species of the genus Marinovum for which the name Marinovum faecis sp. nov. is proposed. The type strain of M. faecis sp. nov. is YP194T (= KCCM 90263T = NBRC 111905T).
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Alphaproteobacteria/isolamento & purificação , DNA Bacteriano , Sedimentos Geológicos/microbiologia , Água do Mar , Composição de Bases , Ácidos Graxos/metabolismo , Filogenia , RNA Ribossômico 16S , República da Coreia , Rhodobacteraceae , Análise de Sequência de DNARESUMO
PURPOSE: To investigate the association between vision improvement with refractive correction in the visually impaired eyes and the prevalence of ocular comorbidities in the South Korean population. MATERIALS AND METHODS: The data of 24,620 individuals in the Korea National Health and Nutrition Examination Survey (KNHANES 2009-2011) were reviewed. Visual impairment was defined as a presenting visual acuity < 20/60. The participants with visual impairment in at least one eye were divided into 3 groups according to the best-corrected visual acuity (group 1: <20/30, group 2: ≥20/30 but <20/25, and group 3: ≥20/25). The prevalence of ocular comorbidities was estimated and compared between the three groups. RESULTS: Visual impairment in at least one eye was found in 3031 individuals. Groups 1, 2, and 3 comprised 23.5%, 22.2%, and 54.3% of these visually impaired eyes, respectively. The prevalence of cataract, diabetic retinopathy, age-related macular degeneration, corneal opacity, blepharoptosis, and pterygium was similar to or even higher in group 2 compared to group 1. The prevalence of glaucoma and age-related macular degeneration was 5.40% and 11.39%, respectively, in group 2 and 3.31% and 3.76%, respectively, in group 3. CONCLUSIONS: Appropriate ophthalmologic examination is necessary even if people exhibit vision improvement after optical correction.
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PURPOSE: To investigate changes in the spherical equivalent (SE) refractive error and astigmatism in a pediatric referral population in Korea with longitudinal follow-up and to evaluate the effect of risk factors on changes in refractive error. METHODS: This was a retrospective case series. In total, 221 patients who presented to a tertiary care hospital when aged 3 to 9 years and who underwent at least 10 years of follow-up were enrolled. The patients were divided into groups in terms of the initial extent of SE refractive error, the initial extent of astigmatism, sex, and ocular alignment. Changes in SE and astigmatism were compared among the groups. RESULTS: The patients were followed up for a mean of 11.19 ± 1.81 years. An overall negative shift in SE refractive error and increasing tendency in astigmatism during the follow-up period were noted. The negative shift in SE refractive error in the myopia group was significantly greater than those in the emmetropia and hyperopia groups. The change in astigmatism in the myopia group was significantly greater than that in the hyperopia group. The change in astigmatism in the low astigmatism group was significantly greater than those in the moderate and high astigmatism groups. Sex did not influence the changes in SE refractive error or astigmatism. CONCLUSIONS: A pediatric referral population in Korea showed a negative shift in SE refractive error and increasing tendency in astigmatism during childhood. Changes in refractive error may be influenced by the initial degree of SE refractive error and astigmatism. [J Pediatr Ophthalmol Strabismus. 2017;54(1):43-51.].
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Previsões , Encaminhamento e Consulta , Erros de Refração/epidemiologia , Acuidade Visual , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Prevalência , Erros de Refração/fisiopatologia , Refratometria , República da Coreia/epidemiologia , Estudos RetrospectivosRESUMO
The nucleosomal protein high-mobility group box-1 (HMGB1), which has recently been established as a late mediator of lethal systemic inflammation, has a relatively wide therapeutic window for pharmacological interventions. Compounds produced by marine-derived microbes have been widely investigated for their potential use as bioactive natural products. Cyclic dipeptides, which are also known as diketopiperazines, are molecules that are frequently found in marine-derived microorganisms. While their pharmacological potential has been well established, their biological activities against septic responses have not yet been reported. Here, three diketopiperazines (1-3) isolated from two strains of marine-derived bacteria were investigated for their potential activities against HMGB1-mediated septic responses. The data showed that 1-3 effectively inhibited the lipopolysaccharide (LPS)-induced release of HMGB1 and suppressed the HMGB1-mediated septic responses, including hyperpermeability, leukocyte adhesion and migration, and cell adhesion molecule expression. In addition, 1-3 inhibited the HMGB1-mediated production of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text] and interleukin (IL)-6 and the activation of nuclear factor-[Formula: see text]B (NF-[Formula: see text]B) and extracellular signal-regulated kinase (ERK) 1 and ERK2. Collectively, these results indicated that 1-3 might act as potential therapeutic agents for various severe vascular inflammatory diseases through the inhibition of the HMGB1 signaling pathway.
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Actinomycetales/química , Anti-Infecciosos Locais/farmacologia , Bacillus/química , Dicetopiperazinas/farmacologia , Proteína HMGB1/efeitos adversos , Poríferos/microbiologia , Sepse/tratamento farmacológico , Actinomycetales/isolamento & purificação , Animais , Anti-Infecciosos Locais/química , Anti-Infecciosos Locais/isolamento & purificação , Anti-Infecciosos Locais/uso terapêutico , Bacillus/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Dicetopiperazinas/química , Dicetopiperazinas/isolamento & purificação , Dicetopiperazinas/uso terapêutico , Modelos Animais de Doenças , Sedimentos Geológicos/microbiologia , Proteína HMGB1/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos Endogâmicos C57BL , Sepse/genética , Choque Séptico/tratamento farmacológico , Choque Séptico/genéticaRESUMO
The drug resistance of microorganisms isolated from laboratory animals never treated with antibiotics is being reported consistently, while the number of laboratory animals used in medicine, pharmacy, veterinary medicine, agriculture, nutrition, and environmental and health science has increased rapidly in Korea. Therefore, this study examined the development of antimicrobial resistance in bacteria isolated from laboratory animals bred in Korea. A total of 443 isolates (7 species) containing 5 Sphingomonas paucimobilis, 206 Escherichia coli, 60 Staphylococcus aureus, 15 Staphylococcus epidermidis, 77 Enterococcus faecalis, 27 Citrobacter freundii, 35 Acinetobacter baumannii were collected from the nose, intestine, bronchus and reproductive organs of ICR mice and SD rats. Of these species, Acinetobacter baumannii and Enterococcus faecalis showed significant antimicrobial resistance according to the minimum inhibition concentration (MIC) in E-test. In case of Acinetobacter baumannii, several isolates showed MIC values 16-128 µg/mL for cefazolin and cefoxitin, and higher resistance (128-512 µg/mL) to nitrofurantoin than that of standard type. Resistance to cefazolin, cefoxitin and nitrofurantoin was detected in 17.14, 20.00, and 8.57% of the Acinetobacter baumannii isolates, respectively. In addition, 44.1% of the Enterococcus faecalis isolates collected from the laboratory animals were resistant to oxacillin concentration of 16-32 µg/mL range, while MIC value of standard type was below oxacillin concentration of 6 µg/mL. These results suggest that in rodent species of laboratory animals, Acinetobacter baumannii are resistance to cefazolin, cefoxitin and nitrofurantoin, whereas those of Enterococcus faecalis were resistance to oxacillin.
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PURPOSE: To report a case of congenital sudoriferous cyst of the orbit with esotropia. METHODS: A 20-day-old male, born prematurely presented with a palpable lump on left upper lid. Orbital ultrasonography including color doppler image and orbital magnetic resonance image were performed to evaluate the lid lesion. The mass was excised and histologically examined. Complete ocular examination including visual acuity, duction, version, and the presence of strabismus were performed. RESULTS: A well circumscribed round cystic mass, measuring 1.4 x 1.3 cm was noted at medial superior aspect of the left orbit. It compressed and displaced the left globe to inferior posterior position with intact optic nerve. Histopathologic examination showed the lesion to be a solitary sudoriferous cyst lined by two layers of cuboidal epithelial cells with eosinophilic cytoplasm. After the excision of the mass, limitations of extraocular muscle movements, esotropia, and amblyopia were noted. CONCLUSIONS: If an orbital cyst affects the globe or extraocular muscles, it should be excised as soon as possible to prevent strabismus and amblyopia especially in infant.
Assuntos
Cistos/congênito , Esotropia/etiologia , Doenças Orbitárias/congênito , Glândulas Sudoríparas , Cistos/complicações , Cistos/diagnóstico , Diagnóstico Diferencial , Esotropia/diagnóstico , Seguimentos , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Doenças Orbitárias/complicações , Doenças Orbitárias/diagnóstico , Ultrassonografia Doppler em CoresRESUMO
A sensitive validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for gabapentin (GB) in human plasma has been developed and applied to pharmacokinetic (PK) and bioequivalence (BE) studies in human. In a randomized crossover design with a 1-week period, each subject received a 300 mg GB capsule. The procedure involves a simple protein precipitation with acetonitrile and separated by LC with a Gemini C(18) column using acetonitrile-10 mm ammonium acetate (20:80, v/v, pH 3.2) as mobile phase. The GB and internal standard [(S)-(+)-alpha-aminocyclohexanepropionic acid hydrate] were analyzed using an LC-API 2000 MS/MS in multiple reaction monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved using MS/MS analysis, m/z 172.0 --> 154.0 and m/z 172.0 --> 126.0 for GB and IS, respectively. The assay exhibited good linearity over a working range of 20-5000 ng/mL for GB in human plasma with a lower limit of quantitation of 20 ng/mL. No endogenous compounds were found to interfere with the analysis. The accuracy and precision were shown for concentrations over the standard ranges. This method was successfully applied for the PK and BE studies by analysis of blood samples taken up to 36 h after an oral dose of 300 mg of GB in 24 healthy volunteers.