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BACKGROUND: Urban particulate matter (UPM) in ambient air is implicated in a variety of human health issues worldwide, however, few studies exist on the effect of UPM on the olfactory system. This study aimed to identify the factors affecting the destruction of the olfactory system in a mouse model following UPM exposure. METHODS: Mice were divided into: control and four UPM-exposed groups (200 µg UPM at 1 and 2 weeks, and 400 µg UPM at 1 and 2 weeks [standard reference material 1649b; average particle diameter 10.5 µm]). The olfactory neuroepithelium was harvested for histologic examination, gene ontology, quantitative real-time polymerase chain reaction, and western blotting. RESULTS: Compared to the control group, olfactory marker protein, Olfr1507, ADCY3, and GNAL mRNA levels were lower, and S-100, CNPase, NGFRAP1, BDNF, and TACR3 mRNA levels were higher in the olfactory neuroepithelium of the UPM groups. Moderately positive correlation was present between the 1- and 2-week groups. After analyzing the 200 and 400 UPM groups separately, the strength of the association between the 200 UPM 1- and 2-week groups was moderately positive. No differences was present in the neuroepithelial inflammatory marker levels between the UPM and control groups. CONCLUSIONS: UPM could have cytotoxic effects on the olfactory epithelium. The exposure time and particular concentration of UPM exposure could affect the degree of destruction of the olfactory neuroepithelium. The olfactory regeneration mechanism could be related to the neurotrophic factors, olfactory ensheathing cell stimulation, and trigeminal nerve support.
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Material Particulado , Olfato , Animais , Camundongos , Mucosa Olfatória , Material Particulado/toxicidade , RNA MensageiroRESUMO
Large insertions and deletions (indels), including copy number variations (CNVs), are commonly seen in many diseases. Standard approaches for indel detection rely on well-established methods such as qPCR or short tandem repeat (STR) markers. Recently, a number of tools for CNV detection based on next-generation sequencing (NGS) data have also been developed; however, use of these methods is limited. Here, we used whole-exome sequencing (WES) in patients previously diagnosed with CMT1A or HNPP using STR markers to evaluate the ability of WES to improve the clinical diagnosis. Patients were evaluated utilizing three CNV detection tools including CONIFER, ExomeCNV and CEQer, and array comparative genomic hybridization (aCGH). We identified a breakpoint region at 17p11.2-p12 in patients with CMT1A and HNPP. CNV detection levels were similar in both 6 Gb (mean read depth = 80×) and 17 Gb (mean read depth = 190×) data. Taken together, these data suggest that 6 Gb WES data are sufficient to reveal the genetic causes of various diseases and can be used to estimate single mutations, indels, and CNVs simultaneously. Furthermore, our data strongly indicate that CNV detection by NGS is a rapid and cost-effective method for clinical diagnosis of genetically heterogeneous disorders such as CMT neuropathy.
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Artrogripose/genética , Doença de Charcot-Marie-Tooth/genética , Cromossomos Humanos Par 17/química , Variações do Número de Cópias de DNA , Exoma , Neuropatia Hereditária Motora e Sensorial/genética , Mutação INDEL , Artrogripose/diagnóstico , Artrogripose/patologia , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/patologia , Pontos de Quebra do Cromossomo , Hibridização Genômica Comparativa , Estudo de Associação Genômica Ampla , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Neuropatia Hereditária Motora e Sensorial/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Repetições de Microssatélites , SoftwareRESUMO
BACKGROUND: Berberine (Ber), used widely as an antibacterial, antifungal, and anti-inflammatory drug, has long been used as a gastrointestinal remedy in Chinese traditional medicine. Recent reports have suggested that Ber suppresses Th17 responses that was mediated by direct actions on T cells and thymic stromal lymphopoietin production in primary mast cells. It has been suggested that Ber may be useful in treating allergic response. The purpose of this study was to assess the effects of Ber treatment on allergic inflammation in an allergic rhinitis mouse model and to examine the underlying mechanism(s). METHODS: BALB/c mice were divided into control, Derf with no treated (Derf), Ber treated, and Ber with anti-C25 monoclonal antibody treated (Ber + anti-CD25) groups. All mice, with the exception of the control group, were sensitized with an intraperitoneal i.p. injection of Dermatophagoides farinae (Derf). Mice in the Ber and Ber + anti-CD25 group were treated intranasally with 10 #181;g/mL. Then, 1 week after sensitization, all mice were challenged intranasally with 20 #181;g Derf for 5 consecutive days. Mice in the anti-CD25 group were treated intraperitoneally with 250 #181;g anti-CD25 monoclonal antibody 1 day before the first intra-nasal challenge with Derf. Allergic symptom scores, eosinophil counts, and serum Derf-specific IgE levels were measured. T-bet, GATA-3, interferon-g (IFN-γ), interleukin (IL)-10, IL-13, and Foxp3 expression was examined by real-time polymerase chain reaction and Western blotting. CD4⺠CD25⺠Foxp3⺠T cells were assessed by flow cytometry. RESULTS: Symptom scores, serum Derf-specific IgE levels, GATA-3 mRNA levels, T-bet mRNA levels, and tissue eosinophil counts were decreased in the Ber versus the Derf group. In the Ber + anti-CD25 group, serum IL-10 levels were decreased versus the control, Derf, and Ber groups. In the Ber + anti-CD25 mAb groups, Foxp3 mRNA levels were decreased versus the control group. In the Ber group, Foxp3 mRNA levels were increased versus the control group. In the Ber group, the percentage of CD4⺠CD25⺠Foxp3⺠T cells was increased versus the Derf group. The percentage of CD4⺠CD25⺠Foxp3+ T cells was increased in the Ber versus the Derf groups. CONCLUSIONS: In our study, Ber reduced allergic inflammation significantly. Moreover, our findings suggest that the mechanism of action of Ber may be via CD4⺠CD25⺠Foxp3⺠Treg cells, possibly through not only by increasing their numbers but also altering their function.
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Berberina/uso terapêutico , Dermatophagoides farinae/imunologia , Fitoterapia , Rinite Alérgica/tratamento farmacológico , Animais , Berberina/farmacologia , Western Blotting , Citocinas/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Eosinófilos , Feminino , Citometria de Fluxo , Imunoglobulina E/sangue , Camundongos Endogâmicos BALB C , Mucosa/imunologia , Mucosa/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real , Rinite Alérgica/sangue , Rinite Alérgica/imunologiaRESUMO
BACKGROUND: Enlarged facial pores have been esthetic problems and have become a matter of cosmetic concern. Several factors are supposed to be related to the enlargement of facial pores, although scientific evaluations were not performed yet. OBJECTIVE: To assess the correlation between facial pores and possible relating factors such as age, gender, sebum secretion, skin elasticity, and the presence of acne, using objective bioengineering instruments. METHODS: Sixty volunteers, 30 males and 30 females, participated in this study. Various parameters of facial pores were assessed using the Robo Skin Analyzer. The facial sebum secretion and skin elasticity were measured using the Sebumeter and the Cutometer, respectively. These data were compared and correlated to examine the possible relationship between facial pores and age, sebum secretion and skin elasticity, according to gender and the presence of acne. RESULTS: Male gender and the existence of acne were correlated with higher number of facial pores. Sebum secretion levels showed positive correlation with facial pores. The R7 parameter of skin elasticity was negatively correlated with facial pores, suggesting increased facial pores with decreased skin elasticity. However, the age and the severity of acne did not show a definite relationship with facial pores. CONCLUSION: Male, increased sebum and decreased skin elasticity were mostly correlated with facial pore development. Further studies on population with various demographic profiles and more severe acne may be helpful to elucidate the potential effect of aging and acne severity on facial pores.
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Acne Vulgar/metabolismo , Acne Vulgar/patologia , Face , Sebo/metabolismo , Caracteres Sexuais , Pele/patologia , Adulto , Fatores Etários , Bioengenharia , Elasticidade , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Masculino , Sebo/citologia , Índice de Gravidade de Doença , Pele/metabolismo , Envelhecimento da Pele/patologia , Envelhecimento da Pele/fisiologia , Adulto JovemRESUMO
BACKGROUND: Assessment of psoriatic scales is important to determine the severity of psoriasis. However, there are very limited numbers of objective, quantitative and observer-independent tools for measuring the severity of psoriasis. OBJECTIVE: To determine whether the bioengineering parameters of the psoriatic scale can be used to assess the severity of psoriasis instead of the psoriatic severity index of scales (PSIs) score. METHODS: Thirty-four patients with psoriasis were included. A representative lesion from each patient was selected and bioengineering parameters were measured using the Corneofix(®). Simultaneously, the severity of the scales was assessed by the PSIs score using clinical photographs of the lesions. In addition, skin color and elasticity parameters were also measured using the Colorimeter(®), the Mexameter(®) and the Cutometer(®). RESULTS: Statistical differences in the scale parameters were observed between the PSIs 2 and 3 scores. Among the scale parameters, the percent area and area in µm(2) were negatively correlated with the PSIs score. In addition, the Colorimeter(®) a, b parameters and the Cutometer(®) R9 parameters were significantly correlated with the PSIs score. CONCLUSIONS: The results of this study showed that the severity of psoriatic scales could be measured objectively using the Corneofix(®).
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Colorimetria/métodos , Dermoscopia/métodos , Técnicas de Imagem por Elasticidade/métodos , Processamento de Imagem Assistida por Computador/métodos , Psoríase/patologia , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Bioengenharia/instrumentação , Bioengenharia/métodos , Bioengenharia/normas , Criança , Colorimetria/instrumentação , Colorimetria/normas , Dermoscopia/instrumentação , Dermoscopia/normas , Técnicas de Imagem por Elasticidade/instrumentação , Técnicas de Imagem por Elasticidade/normas , Feminino , Humanos , Processamento de Imagem Assistida por Computador/instrumentação , Processamento de Imagem Assistida por Computador/normas , Masculino , Pessoa de Meia-Idade , Fotografação , Padrões de Referência , Fita Cirúrgica , Adulto JovemRESUMO
The pathogenicity of a fowl adenovirus serotype-1 (FAdV-1, K181 strain) isolated from a case of gizzard erosion in layer chickens was investigated in specific-pathogen-free (SPF) chicks. One-week-old SPF chicks were inoculated orally or intramuscularly with the isolate of FAdV-1 and euthanized for necropsy at 7, 14, and 21 d postinoculation. Although there were no clinical signs after inoculation, gizzard erosions were observed grossly and the virus was recovered from the gizzards in the inoculated chickens. Histologically, in the chickens that were infected orally, the lesions found in the gizzard consisted of severe degeneration and necrosis of glandular epitheliums and eosinophilic inclusion bodies. These results indicate that the Korean FAdV-1 isolate could induce gizzard lesions in chickens. Moreover, the present investigation reproduced an outbreak of gizzard erosion caused by FAdV-1 infection and, for the first time, described the isolation of FAdV-1 from chickens in Korea. These findings provide important information on the epidemiology and pathogenesis of FAdV-1 infection in chickens.
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Infecções por Adenoviridae/veterinária , Galinhas , Adenovirus A das Aves/patogenicidade , Moela das Aves/patologia , Doenças das Aves Domésticas/patologia , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/patologia , Animais , Adenovirus A das Aves/genética , Filogeografia , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/virologia , República da Coreia/epidemiologia , VirulênciaRESUMO
Prevalence and antimicrobial resistance profiles of Salmonella serotypes isolated from 7 chicken meat brands produced by different integrated broiler operations in Korea were determined. In total, 210 samples were collected from retail supermarkets in Seoul, South Korea, and analyzed for the presence of Salmonella. Of 210 chicken meat samples, overall Salmonella prevalence was 22.4%. Salmonella Enteritidis was the dominant serovar, with an isolation rate of 57.4% from the Salmonella-positive chickens, followed by Salmonella Montevideo. Salmonella isolates frequently were resistant to various antibiotics, including 100% to erythromycin, 87% to cephalothin, 85% to nalidixic acid, and 70% to streptomycin. Of the 47 isolates, 41 (87.2%) isolates were resistant to 3 or more antibiotics. Moreover, the Salmonella profiles of each chicken meat brand were different by broiler operation. Brand A showed the highest prevalence of Salmonella (18 isolates, 60%), whereas brand G showed the lowest prevalence (one isolate, 3.3%). Eight among the 18 isolates of brand A were resistant to 11 antibiotics, whereas 5 of the 6 brand C isolates were resistant to only 2 antibiotics. This study demonstrates that a high proportion of chicken meat in Korea is contaminated with Salmonella and the prevalence and antimicrobial resistance patterns of Salmonella of chicken meat differ significantly according to the integrated broiler operation.
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Criação de Animais Domésticos/métodos , Antibacterianos/farmacologia , Carne/microbiologia , Salmonella/classificação , Salmonella/efeitos dos fármacos , Animais , Galinhas/microbiologia , Farmacorresistência Bacteriana , Prevalência , República da Coreia , SorotipagemAssuntos
Técnicas de Ablação , Carcinoma de Células Escamosas/cirurgia , Face/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/cirurgia , Retalho Perfurante/irrigação sanguínea , Procedimentos de Cirurgia Plástica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
A total of 140 weaning pigs ((Landrace×Yorkshire)×Duroc, BW = 6.47±0.86 kg) were used in a 5-wk growth trail to determine the effects of phytoncide supplementation on growth performance, nutrient apparent total tract digestibility (ATTD), blood profiles, diarrhea scores and fecal microflora shedding. Pigs were assigned randomly by BW into 5 treatments, dietary treatments were: i) NC, basal diet; ii) PC, NC+0.05% tylosin; iii) EO, NC+0.1% essential oil; iv) PP, NC+0.2% PP (phytoncide with 2% citric acid), and v) PA, NC+0.2% PA (phytoncide). Each treatment had 7 replicate pens with 4 pigs per pen. All pigs were housed in pens with a self-feeder and nipple drinker to allow ad libitum access to feed and water throughout the experimental period. During 0 to 2 wks, supplementation with essential oil and PA decreased (p<0.05) G/F compared with the other treatments. During 2 to 5 wks, supplementation with PA led to a higher (p<0.05) G/F than the other treatments. At 2 wk, ATTD of dry matter (DM) and gross energy (GE) in EO treatment were decreased (p<0.05) compared with NC treatment. Dietary PC treatment improved (p<0.05) ATTD of DM and E compared with the CON group, and PA and PP treatments showed a higher (p<0.05) ATTD of E than that in NC treatment. Pigs fed phytoncide (PA and PP) had a greater (p<0.05) ATTD of DM than those of NC and EO treatments at 5 wk. Moreover, supplementation with phytoncide elevated (p<0.05) the concentration of immunoglobulin (IgG) in blood at 2 wk. The inclusion of EO, PP and PA treatments showed a greater (p<0.05) amount of fecal Lactobacillus compared with CON group. However, no difference (p>0.05) was observed in diarrhea scores among treatments. In conclusion, phytoncide can elevate feed efficiency, nutrient digestibility, and improve the fecal Lactobacillus counts in weaning pigs. Our results indicated that the phytoncide could be used as a good antibiotics alternative in weaning pigs.
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BACKGROUND: Little is known about the clinical characteristics of acne based on the age of onset. OBJECTIVES: The aim of this study was to investigate the clinical characteristics of patients according to the age of onset of acne and evaluate whether the findings were related to regional differences in the density of Propionibacterium acnes or the levels of sebum secretion. METHODS: A total of 89 women were recruited. The acne lesions were assessed by counting the lesions using standard digital photographs. Digital fluorescent photography for the evaluation of the density of P. acnes were taken and quantitative measurements of facial sebum secretion were performed. RESULTS: In women with acne, the age of onset was negatively correlated with the number of comedones and the proportion of comedones. By comparing the number of comedones and the proportion of comedones, onset of acne after 21 years of age was defined as late onset acne. In the patients with late onset acne, the number of comedones, the total number of acne lesions and the proportions of comedones were significantly less than in the patients with early onset acne. However, there were no significant differences in the fluorescence density of P. acnes or the level of sebum secretion between the two groups. CONCLUSIONS: The results of this study, using objective evaluation tools, suggest that late onset acne has different clinical characteristics. Other possible factors might explain the clinical differences in late onset acne.
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Acne Vulgar/patologia , Idade de Início , Adolescente , Adulto , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Sebo/metabolismoRESUMO
OBJECTIVE: We aimed to analyze clinical characteristics, treatment patterns, and prognosis of patients with reversible cerebral vasoconstriction syndrome (RCVS). MATERIALS AND METHODS: Two investigators independently searched PubMed and EMBASE, and 191 cases were included in this study. Information regarding demographics, triggering factors, brain imaging findings, treatment modalities, recurrence, and clinical outcome was collected. RESULTS: The mean age of the patients was 39.9 years, and 155 (81.2%) were female. The most common triggering factor for RCVS was an exposure to vasoactive substances (41.4%), followed by pregnancy/postpartum (20.9%), and sexual intercourse (10.5%). Multifocal stenosis (84.0%) and beading shape (82.4%) were the leading abnormal findings on angiography, while cerebral ischemic lesions (47.6%) and cerebral hemorrhage (mainly subarachnoid hemorrhage) (35.1%) were the main findings on brain computed tomography (CT)/magnetic resonance imaging (MRI). Calcium channel blockers (nimodipine/verapamil) were the most commonly used medications (44.5%) in the treatment of RCVS. Multivariate analysis identified that RCVS was precipitated by trauma/surgery/procedure (hazard ratio (HR): 3.29, 95% confidence interval (CI) (1.21-8.88), p=0.019), and presence of aphasia/neglect/apraxia during the acute phase of the disease (HR: 3.83, 95% CI (1.33-11.05), p=0.013) were found to be the two independent risk factors for residual neurological deficit after RCVS. CONCLUSIONS: In our systematic review, vasoactive substances were the most frequent triggers for RCVS, which was most commonly accompanied by angiographic findings of multifocal stenotic lesions. Patients with RCVS precipitated by trauma or surgical procedures and those with focal cortical deficits had a higher risk of residual neurological deficits, and these patients should closely be monitored.
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Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos da Cefaleia Primários/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Humanos , VasoconstriçãoRESUMO
BACKGROUND: Eruptive pseudo-angiomatosis (EPA) is a rare, relatively newly described cutaneous disorder characterized by the sudden onset of several bright red, angioma-like papules surrounded by blanched halo. Its aetiology is unknown; however, viral infection or mosquito bites have been speculated as possible causes. OBJECTIVE: This study aims to determine the clinical and histopathological features of EPA, and whether it is associated with Epstein-Barr virus (EBV) infection. METHODS: We conducted a retrospective chart review of 25 EPA cases from 2006 to 2008. In order to determine latent EBV infection, EBV-encoded small RNA (EBER) in situ hybridization was performed in 18 subjects. To determine EPA's distinguishing histological characteristics, we compared the cases with 22 control cases of perivascular lymphocytic infiltration for haematoxylin and eosin, CD3, CD4, CD8, CD31 and c-kit staining patterns. RESULTS: The patient sample's female-to-male ratio was 2.1 : 1, and the patients' age ranged from 5 to 79 years (average 46 years). The lesions appeared during the months of July to September in all but 3 patients. Skin biopsies demonstrated capillary ectasia with perivascular mononuclear cellular infiltrates in the upper dermis. Most patients were otherwise healthy, and routine laboratory results were all normal except in one patient who had diabetes. The skin lesions faded without any treatment in 1-2 weeks. Results of EBER in situ hybridization were all negative. The only histological distinguishing feature of EPA was the presence of intravascular neutrophils, which was found to be present in 19 of the 20 EPA cases (95%), in contrast to only 3 of the 22 control subjects (14%) (P < 0.0001). CONCLUSION: The sudden onset of lesions during the summer months among our patients supports the 'paraviral eruption' concept of this probably underdiagnosed condition. The significant presence of intravascular neutrophils may be a diagnostic clue of EPA in South Korea.
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Angiomatose/patologia , Herpesvirus Humano 4/isolamento & purificação , Neutrófilos/patologia , Adulto , Idoso , Angiomatose/virologia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Herpesvirus Humano 4/genética , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , RNA Viral/genética , RNA Viral/isolamento & purificação , Estudos RetrospectivosRESUMO
AIM: This study investigated the clinical characteristics of diabetic ketoacidosis (DKA) and compared the DKA characteristics between patients treated with and without SGLT2 inhibitors. METHODS: Data were collected from patients aged ≥ 18 years admitted for DKA at nine centres in Korea between September 2014 and April 2017. The electronic medical records of these subjects were retrospectively reviewed. Based on their history of medications taken before admission, subjects were classified as either users or non-users of SGLT2 inhibitors and their clinical characteristics of DKA were compared. RESULTS: During the study, the main subtype of DKA episodes (n = 523) was identified as type 2 diabetes (51%). Average hospitalization duration was 11 days, and average intensive care unit (ICU) time was 2.5 days. The in-hospital mortality rate was 3%, but no users of SGLT2 inhibitors died during DKA treatment. In patients taking SGLT2 inhibitors (n = 15), DKA manifested at 124 days, on average, after starting the inhibitors (range: 7-380 days). Also, SGLT2 inhibitors users had significantly lower plasma glucose levels (413 mg/dL) compared with non-users (554 mg/dL), and longer ICU stays (4 vs. 2 days; P = 0.019). CONCLUSION: In this report of recent data on the clinical features of DKA in Korea, patients using SGLT2 inhibitors needed longer treatment in ICUs compared with non-users and had lower levels of blood glucose, whereas DKA associated with SGLT2 inhibitors was rare.
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Glicemia , Diabetes Mellitus/tratamento farmacológico , Cetoacidose Diabética/diagnóstico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Adulto , Diabetes Mellitus/sangue , Diabetes Mellitus/mortalidade , Cetoacidose Diabética/sangue , Cetoacidose Diabética/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Ion optics of three accelerator geometries was studied in terms of an analytic linear optics analysis, a numerical simulation using the IGUN program, an optical multichannel measurement of Doppler-shifted H(alpha) lines, and a water-flow calorimetry on the beam absorbing target. In general, there was a reasonable agreement observed between the four analysis methods and thus the theoretical analyses can be utilized with confidence for design iteration.
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Heparanase has been previously associated with the metastatic potential, inflammation, and angiogenesis of tumor cells. Heparanase activity has been detected by means of UV absorption, radiolabeled substrates, electrophoretic migration, and heparan sulfate affinity assays. However, those methods have proven to be somewhat problematic with regards to application to actual biological samples, the accessibility of the immobilized substrates, experimental sensitivity, and the separation of degraded products. Rather than focusing on heparanase activity, then, we have developed a rapid, alternative colorimetric heparinase assay, on the basis of the recent finding that sulfated disaccharides generated from heparin by bacterial heparinase exhibit biological properties comparable to those from heparan sulfate by mammalian heparanase. In this study, the concentrations of porcine heparin and bacterial heparinase I were determined using a Sigma Diagnostics Kit. Morus alba was selected as a candidate through this assay system, and an inhibitor, resveratrol, was purified from its methanol extract. Its anti-metastatic effects on the pulmonary metastasis of murine B16 melanoma cells were also evaluated. Our findings suggest that this assay may prove useful as a diagnostic tool for heparinase inhibition, as an alternative anti-metastatic target.
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Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Heparina Liase/análise , Metástase Neoplásica/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Bioensaio , Linhagem Celular Tumoral , Colorimetria/métodos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/análise , Feminino , Flavobacterium/enzimologia , Heparina/análise , Heparina/metabolismo , Heparina Liase/antagonistas & inibidores , Mucosa Intestinal , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/secundário , Camundongos , Camundongos Endogâmicos C57BL , Morus/química , Metástase Neoplásica/patologia , Organismos Livres de Patógenos EspecíficosRESUMO
A superconducting transition temperature (Tc) as high as 100 K was recently discovered in one monolayer FeSe grown on SrTiO3. The discovery ignited efforts to identify the mechanism for the markedly enhanced Tc from its bulk value of 8 K. There are two main views about the origin of the Tc enhancement: interfacial effects and/or excess electrons with strong electron correlation. Here, we report the observation of superconductivity below 20 K in surface electron-doped bulk FeSe. The doped surface layer possesses all the key spectroscopic aspects of the monolayer FeSe on SrTiO3. Without interfacial effects, the surface layer state has a moderate Tc of 20 K with a smaller gap opening of 4.2 meV. Our results show that excess electrons with strong correlation cannot induce the maximum Tc, which in turn reveals the need for interfacial effects to achieve the highest Tc in one monolayer FeSe on SrTiO3.
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The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently-expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.
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Transformação Celular Neoplásica/genética , Proteína Forkhead Box M1/genética , Fígado/metabolismo , Peroxirredoxinas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Animais , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Células Cultivadas , Feminino , Proteína Forkhead Box M1/metabolismo , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Knockout , Camundongos Nus , Camundongos Transgênicos , Células NIH 3T3 , Peptídeos/farmacologia , Peroxirredoxinas/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transplante HeterólogoRESUMO
Herbimycin A, an inhibitor of protein tyrosine kinases, dose-dependently reduced PDGF-induced inositol phosphates (IPt) accumulation without effect on phosphatidylethanol (PEt) formation in PLC-gamma 1-overexpressing NIH 3T3 (NIH 3T3 gamma 1) cells. The compound also reduced tyrosine phosphorylations of some proteins including PLC-gamma 1 in response to PDGF. On the other hand, phorbol 12-myristate 13-acetate (PMA)-induced phospholipase D (PLD) activation was reduced by herbimycin A in the cells, indicating that the pathways for PLD activation by PDGF and PMA are different from each other. Also, these results suggest that PLC-gamma 1 activation is not always an upstream event for PLD activation and that tyrosine phosphorylation of one or more proteins not affected by herbimycin A should be indispensable for PLD activation in PDGF-stimulated NIH 3T3 gamma 1 cells.
Assuntos
Glicerofosfolipídeos , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinonas/farmacologia , Fosfolipases Tipo C/metabolismo , Células 3T3 , Animais , Benzoquinonas , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Fosfatos de Inositol/biossíntese , Isoenzimas/metabolismo , Lactamas Macrocíclicas , Camundongos , Ácidos Fosfatídicos/biossíntese , Fosfolipase C gama , Fosfolipase D/metabolismo , Fosfoproteínas/análise , Fosforilação , Rifabutina/análogos & derivados , Acetato de Tetradecanoilforbol/farmacologia , Tirosina/metabolismoRESUMO
TSU-PR1 was originally reported as a prostatic carcinoma cell line derived from a lymph node metastasis. Recently, however, this cell line was reported to be derived from T24 bladder carcinoma cells, and thus further definition of its origin is needed. Conventional cytogenetic study of TSU-PR1 showed aneuploidy, ranging from 65 to 86 chromosome with a modal number of 80, and with 10 marker chromosomes, thus conventional cytogenetics cannot be used to determine which chromosomes or regions of chromosomes are critical in cancer development and progression of this cell line. The present study was conducted to characterize genetic changes of the cell line using comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), and flow cytometry. CGH results showed that green-to-red fluorescence ratios were within the range of 0.85-1.15, except for a few chromosomes, which reflected near tetraploidy in TSU-PR1. Flow cytometric analysis of TSU-PR1 revealed a DNA index of 3.46n, which is close to the 3.48n calculated from a modal number of 80. The copy numbers of chromosomes 4, 6, 7, 17, and 20 determined by the DNA index and the CGH analyses were 2.85 +/- 0.09, 3.22 +/- 0.77, 3.01 +/- 0.26, 4.05 +/- 0.44, and 4.99 +/- 0.48, respectively. These numbers are also in accordance with the chromosome copy numbers determined with FISH: 2.98 +/- 0.23, 2.91 +/- 0.44, 2.74 +/- 0.44, 3.93 +/- 0.38, and 5.05 +/- 0.78 for chromosomes 4, 6, 7, 17, and 20, respectively (P > 0.05).