RESUMO
Two new secolignans, 3,4-trans-3-hydroxymethyl-4-[bis(4-hydroxy-3- methoxyphenyl)methyl]butyrolactone (1) and 3,4-trans-3-hydroxymethyl-4- [bis(3,4-dimethoxyphenyl)methyl]butyrolactone (2) have been isolated from the roots of Urtica fissa E.Pritz. Their structures were determined on the basis of spectroscopic methods, especially 1H NMR, 13C NMR, 2D NMR, and HR-ESI-MS. The inhibitory effects on N1 and N2, two subtypes of neuraminidases (NAs), of these two compounds were assayed.
Assuntos
Lignanas/química , Raízes de Plantas/química , Urticaceae/química , Estrutura MolecularRESUMO
BACKGROUND/OBJECTIVES: It seems that global DNA hypomethylation in CD4+T cells is linked to the pathogenesis of systemic lupus erythematosus (SLE). However, the underlying mechanism by which SLE patients show hypomethylated DNA remains unclear. This study explored the relationship between DNA methylation patterns and expression levels of DNA methyltransferases (DNMT1) and MBD2 in CD4+T cells of SLE patients. METHODS: CD4+T cells were obtained from 30 patients with SLE and 18 normal controls. The global DNA methylation levels in CD4+T cells were evaluated by the Methyflash DNA methylation quantification kit. The mRNA levels of DNMT1 and MBD2 were quantified by quantitative real-time polymerase chain reaction. RESULTS: SLE patients had significantly lower global DNA methylation levels than controls, and the global DNA methylation was inversely correlated with the SLE disease activity index (SLEDAI). The mRNA levels of DNMT1 in SLE patients were significantly lower than that of controls and there was no correlation between DNMT1 mRNA levels and SLEDAI but there was a positive correlation between DNMT1 mRNA levels and global DNA methylation. The mRNA levels of MBD2 in SLE patients were significantly higher than in controls, and there was positive correlation between MBD2 mRNA levels and SLEDAI and an inverse correlation between MBD2 mRNA levels and global DNA methylation. CONCLUSIONS: Global DNA hypomethylation may play a pivotal role in the pathogenesis of SLE. Abnormal expression levels of DNMT1 and MBD2 mRNA may be important causes of the global hypomethylation observed in CD4+T cells in SLE.
Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Lúpus Eritematoso Sistêmico/genética , Adolescente , Adulto , Linfócitos T CD4-Positivos/metabolismo , Estudos de Casos e Controles , DNA (Citosina-5-)-Metiltransferase 1 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Índice de Gravidade de Doença , Transcrição Gênica , Adulto JovemRESUMO
BACKGROUND: Localized senile pruritus is a continued health problem for the elderly. This study aimed to evaluate the efficacy and safety of artemether emulsion on localized senile pruritus. METHODS: Sixty patients diagnosed with senile pruritus were randomized into the artemether emulsion (1%) group or emulsion base group in a 1:1 ratio (the artemether group vs the control group). The patients used artemether emulsion or emulsion base for pruritus twice daily for 2 weeks. The pruritus visual analog scale (VAS) and the rate of adverse events were evaluated in week 0 and week 2. RESULTS: The VAS scores in week 2 after treatment decreased significantly compared with those before treatment in both groups (Pâ <â .05). After treatment, patients receiving the artemether emulsion had significantly lower mean VAS scores compared to those who received the emulsion base (1.21â ±â 1.64 vs 3.67â ±â 2.97, Pâ <â .05). When the VAS scores were compared between the 2 groups before treatment, the effective rate of the artemether group was significantly higher than that of the control group (χ2â =â 55, Pâ <â .05) in week 2 after treatment. Besides, no adverse events occurred in both groups. CONCLUSIONS: Both artemether emulsion and emulsion base were effective in treating localized senile pruritus, and artemether emulsion was superior to emulsion base.
Assuntos
Prurido , Idoso , Artemeter , Emulsões , Humanos , Projetos Piloto , Prurido/tratamento farmacológico , Prurido/etiologia , Escala Visual AnalógicaRESUMO
BACKGROUND: Tissue resident memory T (TRM) cells have been reported to play a significant role in the pathogenesis and relapse of chronic eczema. AIM: To compare the efficacy and safety of the intralesional injection of 5-fluorouracil (5-FU) and triamcinolone (TA) with those associated with TA alone for the treatment of chronic eczema. METHODS: A total of 168 patients were randomized to 5-FU+TA or TA groups and received a one-time intralesional injection of 5-FU+TA or TA only. Biopsies were collected before and 2 wk after treatment for evaluation of histopathological changes. All patients were followed up monthly for up to 1 year. RESULTS: No serious adverse event was observed in either group. Although the mean atopic dermatitis severity index scores and effective rates were comparable between the two groups after 2 wk of treatment, the relapse rate was significantly lower in the 5-FU+TA group than in the TA group. Histological examination showed significantly fewer CD8+ and CD103+ T cells but not CD4+ T cells in the 5-FU+TA group. CONCLUSION: One-time intralesional injection of 5-FU+TA is effective and safe for chronic eczema treatment and can further reduce the retention of TRM cells in the lesional skin and the relapse rate of chronic eczema.
RESUMO
OBJECTIVE: To evaluate the efficacy and safety of artemether emulsion treating patients with mild-to-moderate acne vulgaris. METHODS: A total of 73 (randomized 1:1) patients were externally administered either artemether emulsion (1%) or fusidic acid emulsion (5g: 0.1g) twice daily for 12 weeks. Efficacy and safety evaluations were performed at weeks 0 and 12 by Global acne Grading System (GAGS), the number of acne and papule, as well as the rate of clinical respond. RESULTS: After 12 weeks, patients randomized to the artemether emulsion group received artemether emulsion had significantly lower GAGS scores (5.08 ± 1.99 versus 13.75 ± 4.87, p < .001) compared to patients who received fusidic acid emulsion. Patients in the artemether emulsion group had comparable baseline acne scores (11.11 ± 3.73 versus 10.75 ± 4.66, p = .626) and papule score (16.11 ± 5.58 versus 17.03 ± 6.34, p = .356), but significantly lower acne score (3.00 ± 1.55 versus 9.08 ± 4.90, p < .001) and comparable papule score (2.81 ± 1.61 versus 12.69 ± 5.45, p < .001) compared to the fusidic acid emulsion group at 12 weeks. No major adverse events were noted in either treatment group through 12 weeks. CONCLUSIONS: Artemether emulsion had better effect in improving mild-to-moderate AV compared to fusidic acid emulsion with barely AEs.
Assuntos
Acne Vulgar , Acne Vulgar/tratamento farmacológico , Artemeter , Emulsões , Humanos , Projetos Piloto , Resultado do TratamentoRESUMO
Objective: To assess the efficacy and safety of artemether emulsion in patients with papulopustular rosacea. Methods: A total of 130 (randomized 1:1) were externally administered either artemether emulsion (1%) or metronidazole emulsion (3%) twice daily for 4 weeks with an open-label 8-week follow-up. The primary endpoints included the proportion of patients who achieved clinical effective responses, as well as erythema and papule and pustule score at week 4. Results: Numerically more patients achieved an effective response at week 4 with artemether emulsion (87.1%) than metronidazole emulsion (80.0%) (p > .05). Patients with artemether emulsion had comparable baseline erythema score (2.45 ± 0.67 versus 2.42 ± 0.70, p = .809) and papule and pustule score (2.11 ± 0.96 versus 2.32 ± 0.83, p = .264), but significantly lower papule and pustule score (0.21 ± 0.52 versus 0.42 ± 0.83, p = .001) and comparable erythema score (0.53 ± 0.88 versus 0.62 ± 0.88, p = .999) compared to patients with metronidazole emulsion at week 4. There was a significantly higher proportion of patients with metronidazole emulsion relapse compared to metronidazole emulsion during the open-label 8-week follow-up period (21.6% versus 2.4%, p < .01). Conclusions: Artemether emulsion improved papulopustular rosacea in the metronidazole emulsion group as early as 4 weeks, but its beneficial effect was maintained through the 8-week follow-up period compared to metronidazole emulsion.
Assuntos
Artemeter/uso terapêutico , Rosácea/tratamento farmacológico , Adulto , Artemeter/efeitos adversos , Artemeter/química , Esquema de Medicação , Emulsões/química , Feminino , Humanos , Masculino , Metronidazol/química , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Projetos Piloto , Prurido/etiologia , Rosácea/patologia , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemAssuntos
Linfócitos T CD4-Positivos/metabolismo , Lúpus Eritematoso Sistêmico/genética , MicroRNAs/genética , Adulto , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , RNA Longo não Codificante , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
BACKGROUND: Candida albicans (C. albicans) infection, often occurring in genital candidiasis, has increased dramatically recently. Developing an efficient C. albicans typing method may contribute to understanding its epidemiological characteristics and guiding efficient treatment. We used rapid microsatellite genotyping assay for interstrain differentiation of C. albicans isolates and explored some characteristics of its spread. METHODS: DNA was extracted from C. albicans isolates from gentalia, recta and mouths of 39 female cases and 27 male cases of genital candidiasis. Three fluorescent primers for the microsatellite markers in conserved genes (CDC3, EF3 and HIS3) of C. albicans were used to amplify the isolates DNA by PCR. Fluorescent signals were read with an automatic sequencer and analyzed with GeneScan software. RESULTS: Analysis of the three microsatellites markers showed 18 gene allelic associations in genital C. albicans infected patients: 10 allelic associations in female and 11 allelic associations in male, of which 3 allelic associations shared by both genders covered 71% of infections. The most dominant allele association of pathogenic strains for both genders was 116:124, 122:131, 160:200 that covered about 50% of infection. Gentalia and recta shared the same strains in 80% of female patients, but in only 3.8% of male patients. There were 2.7% female patients, but no males, with same strain in both gentalia and mouths. Five of seven genital C. albicans infected couples had the same allelic associations of which 4 were the dominant pathogenic C. albicans susceptible for both genders. CONCLUSIONS: The predominant allelic association of the pathogenic strain in genital C. albicans infection is 116:124, 122:131, 160:200. Vaginal pathogenic strains are probably maintained from the rectal reservoir. Pathogenic strains of male patients are probably from frequent sexual intercourse. The aggressiveness of some strains varies with gender.
Assuntos
Candida albicans/genética , Candidíase Vulvovaginal/diagnóstico , Candidíase/diagnóstico , Doenças dos Genitais Masculinos/diagnóstico , Repetições de Microssatélites , Adulto , Candida albicans/classificação , Feminino , Genótipo , Humanos , Masculino , Reto/microbiologia , Sensibilidade e Especificidade , Língua/microbiologiaRESUMO
OBJECTIVE: To study the effect of zinc on mRNA expression of ZIP4 in human intestinal Caco2 cells and its regularity. METHODS: Low zinc cell model was established by TPEN, a kind of chelating agent which chelates specially to zinc. ZIP4 cDNA fragment was obtained by RT-PCR. Expression of ZIP4 on 10 micromol/L TPEN exposure after 0, 2, 4, 6, 8 and 10 hours in Caco2 cells and its expression on various concentration of TPEN exposure (0,2.5,5,7.5 and 10 micromol/L) was measured by RT-PCR. RESULTS: A proper single fragment is obtained with the sequence conformable to the design. A proper single ZIP4 cDNA fragment was obtained. The mRNA expression of ZIP4 increased in accordance with the duration of low zinc. The peak mRNA level appeared at about 6h. And the ZIP4 mRNA increased in accordance with the concentration of TPEN in Caco2 cells. CONCLUSION: Zinc can regulate the mRNA expression of ZIP4 in Caco2 cells. And ZIP4 may play a role in the absorption of zinc in human intestine.
Assuntos
Proteínas de Transporte de Cátions/metabolismo , Zinco/farmacologia , Células CACO-2 , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/farmacologia , Etilenodiaminas/farmacologia , Humanos , Absorção Intestinal/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Zinco/farmacocinéticaRESUMO
Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy accounting for approximately 1-2% of vulvar cancers. The rarity of this disease has caused difficulties in characterization and the molecular mechanism underlying EMPD development remains largely unclear. Here we used microarray analysis to identify differentially expressed genes in EMPD of the scrotum comparing with normal epithelium from healthy donors. Agilent single-channel microarray was used to compare the gene expression between 6 EMPD specimens and 6 normal scrotum epithelium samples. A total of 799 up-regulated genes and 723 down-regulated genes were identified in EMPD tissues. Real-time PCR was conducted to verify the differential expression of some representative genes, including ERBB4, TCF3, PAPSS2, PIK3R3, PRLR, SULT1A1, TCF7L1, and CREB3L4. Generally, the real-time PCR results were consistent with microarray data, and the expression of ERBB4, PRLR, TCF3, PIK3R3, SULT1A1, and TCF7L1 was significantly overexpressed in EMPD (P<0.05). Moreover, the overexpression of PRLR in EMPD, a receptor for the anterior pituitary hormone prolactin (PRL), was confirmed by immunohistochemistry. These data demonstrate that the differentially expressed genes from the microarray-based identification are tightly associated with EMPD occurrence.
RESUMO
OBJECTIVE: To study the effect of DNMT1 on CD4(+) T cells in the peripheral blood of systemic lupus erythematosus (SLE) patients. METHODS: To investigate the differential expression of DNMT1 in CD4(+) T cells of SLE patients and healthy individuals, a DNMT1 lentiviral plasmid (pLenti6.3/V5-DNMT1) and a control plasmid (pLenti6.3/V5-GW/LacZ) were constructed and transfected into CD4(+) T cells from the peripheral blood of SLE patients. The transcriptional and translational expression of DNMT1, global genomic DNA methylation, and the production of IgG antibody in the CD4(+) T cells in the peripheral blood of SLE patients were assessed using qPCR analysis, western blotting, flow cytometry, and ELISA, respectively. RESULTS: The expression level of DNMT1 in SLE patients was significantly lower than that in normal humans. The expression of DNMT1 was found to be positively correlated with the methylation level of genomic DNA and negatively correlated with the IgG titration level. DNA sequencing results confirmed that the DNMT1 lentiviral plasmid was successfully constructed. After the CD4(+) T cells from the peripheral blood of SLE patients were transfected with the pLenti6.3/V5-DNMT1 plasmid, the transcription level of the DNMT1 gene was upregulated and abundance of DNMT1 protein significantly increased. Global genomic DNA methylation was enhanced, while the production of IgG antibody was reduced. CONCLUSION: DNMT1 can inhibit the autoimmune response in SLE patients by reversing the abnormally low DNA methylation level in the CD4(+) T cells.
RESUMO
AIM: DNA methylation plays important roles in various kinds of carcinogenesis. Vitamin C could induce Tet-dependent DNA demethylation in embryonic stem cells. Therefore, the antagonizing activity of vitamin C on ultraviolet (UV)-induced apoptosis was investigated in this study. METHODS: Apoptosis of human epidermoid carcinoma A431 cells and p16-knockout (KO) or p21-KO fibroblasts was assessed by a fluorescence-activated cell sorter. Real-time PCR and western blot were used to determine the relative expression levels of p12, p21, and Tet1/2/3 genes. The global DNA methylation levels were determined using MethylFlash Methylated DNA Quantification Kit in A431 cells with or without vitamin C treatment. To examine the DNA demethylation activity of vitamin C, DNA immunoprecipitation (DIP)-qPCR was performed to determine the relative levels of 5-methylcytosine (5mC) or 5-hydroxymethylcytosine (5hmC) in p16 and p21 promoter regions containing cytosine-phosphorothiolated guanine (CpG) islands. RESULTS: The increasing apoptosis of A431 cells under prolonged UV irradiation was remarkably decreased by the combination of vitamin C treatment, suggesting that vitamin C protects against UV-induced apoptosis. Concurrently, vitamin C induced a significant reduction of global DNA methylation in a time- and dose-dependent manner in A431 cells. Vitamin C also reactivated the expression of p16 and p21 at mRNA and protein levels. Mechanistically, about 27% 5hmC-positive cells were observed in vitamin C-treated A431 cells, and the 5hmC enrichment at p16 and p21 promoter regions was also largely increased by vitamin C. Moreover, the expression of p16 and p21 was decreased in Tet1/2 double-knockdown cells, in which the inhibitory effect of vitamin C on UV-induced apoptosis was dismissed. Furthermore, the inhibition of UV-induced apoptosis on vitamin C treatment nearly disappeared in p16- or p21-knockout primary cultured fibroblasts. CONCLUSION: These results demonstrate that vitamin C effectively antagonizes UV-induced apoptosis through regulation of Tet activity, DNA demethylation, and subsequent tumor suppressor gene activation in skin cancer cells.
Assuntos
Ácido Ascórbico/farmacologia , Inibidor de Quinase Dependente de Ciclina p21/genética , Metilação de DNA/efeitos dos fármacos , Proteínas de Neoplasias/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Inibidor p16 de Quinase Dependente de Ciclina , Metilação de DNA/efeitos da radiação , Técnicas de Inativação de Genes , Genes Supressores de Tumor , Humanos , Camundongos Knockout , Neoplasias Cutâneas/metabolismo , Transfecção , Raios UltravioletaRESUMO
Motion sickness is caused by exposure to unfamiliar motions and typical symptoms of motion sickness include nausea and vomiting. To observe the metabolic and hormonal differences between nausea/vomiting (NAV) subjects and non-nausea/vomiting (NNV) ones, and to understand how the differences in metabolites and hormones affect the tolerance of organism to acceleration, 60 volunteers were exposed to repetitive acceleration using a 6-degree-of-freedom ship motion simulator. Meanwhile, 36 rats were randomly divided into three groups: an acceleration model group (n=14, exposed to acceleration), insulin group (n=14, intraperitoneal injection of insulin 30 min before exposure to acceleration), and control group (n=8). Gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF/MS) was applied to analyze the serum metabolites in human subjects. Serum glucocorticoid, insulin, and glucagon levels were determined by radioimmunoassay in the NAV and NNV subjects as well as in rats, and serum epinephrine level was determined by ELISA. After acceleration exposure, 9 metabolites, including L-histidine, L-ornithine, L-serine, L-tyrosine, pyroglutamic acid, fumaric acid, urea, n-dodecanoic acid and n-tetradecanoic acid, had different changes in the NAV and NNV groups. The serum levels of 4-hydroxy-L-proline, glucose, oleic acid and urea were significantly higher in the NAV group than in the NNV group after exposure; however, only the elevation degree of serum glucose was significantly greater in the NAV group than in the NNV group (P<0.05). Serum cortisol and epinephrine were increased in both groups. Before exposure, insulin level in the NAV group was significantly lower than that in the NNV group (P<0.05). After rotation exposure, rat serum glucose in the insulin group was significantly lower than that in the acceleration model group (P<0.001), and the motion sickness index was significantly lower than that in the acceleration model group (P<0.05). Our study provides the first evidence that stable glucose level can help to relieve gastrointestinal symptoms in motion sickness, and suggests that acute hyperglycemia is related to gastrointestinal symptoms in motion sickness.
Assuntos
Gastroenteropatias/etiologia , Hiperglicemia/complicações , Hiperglicemia/etiologia , Enjoo devido ao Movimento/complicações , Aceleração/efeitos adversos , Animais , Glicemia , Modelos Animais de Doenças , Hormônios/sangue , Humanos , Hidrocortisona , Masculino , Enjoo devido ao Movimento/sangue , Enjoo devido ao Movimento/etiologia , Análise de Componente Principal , Radioimunoensaio , Ratos , Índice de Gravidade de Doença , Adulto JovemRESUMO
Three new secolignan glycosides {3,4-trans-4-[bis(3,4-dimethoxyphenyl)methyl]-2-oxotetrahydrafuran-3-yl}methyl-O-ß-glucopyranoside (1), {3,4-trans-4-[(3-methoxy-4-hydroxyphenyl)(3,4-dimethoxyphenyl)methyl]-2-oxotetrahydrafuran-3-yl}methyl-O-ß-glucopyranoside (2) and {3,4-cis-4-[(3-methoxy-4-hydroxyphenyl)(3,4-dimethoxyphenyl)methyl]-2-oxotetrahydrafuran-3-yl}methyl-O-ß-glucopyranoside (3) were isolated from the roots of Urtica fissa E. Pritz. Their structures were identified by spectral methods including 1D NMR, 2D NMR and HR-EI-MS.