Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
1.
Surg Endosc ; 37(11): 8682-8689, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37500921

RESUMO

BACKGROUND: Conversion from sleeve gastrectomy (SG) to single anastomosis duodeno-ileal bypass (SADI) is becoming increasingly common, but data regarding safety is of these conversions is scarce. As such, the objective of this study was to compare the 30-day rate of serious complications and mortality of primary SADI (p-SADI-S) with SG to SADI (SG-SADI) conversions. METHODS: This retrospective cohort study analyzed the MBSAQIP database. Patients undergoing p-SADI-S and SG-SADI were included. Data collection was limited to 2020 and 2021. A multivariable logistic regression analysis was performed between groups to determine if SG-SADI was an independent predictor of 30-day serious complications or mortality. RESULTS: A total of 783 patients were included in this study, 488 (62.3%) underwent p-SADI-S and 295 (37.6%) underwent SG-SADI. The mean body mass index (BMI) at the time of surgery was lower in the SG-SADI cohort (45.1 vs 51.4 kg/m2, p < 0.001). Indications for revision in the SG-SADI cohort included weight recurrence (50.8%), inadequate weight loss (41.0%), other (3.0%), GERD (2.7%), and persistent comorbidities (2.5%). SG-SADI had longer operative times (156.7 vs 142.1 min, p < 0.001) and was not associated with a higher rate of serious complications (5.7 vs 6.9%, p = 0.508) compared to p-SADI-S. p-SADI-S was associated with a higher rate of pneumonia (1.2 vs 0.0%, p < 0.001), and SG-SADI was not correlated with higher rates of reoperation (3.0 vs 3.2%, p = 0.861), readmission (5.4 vs 5.5%, p = 0.948) and death (0.0 vs 0.2%, p = 0.437). On multivariable analysis, SG-SADI was not independently predictive of serious complications (OR 0.81, 95% CI 0.43 to 1.52, p = 0.514) when adjusting for age, sex, BMI, comorbidities, and operative time. CONCLUSIONS: The prevalence of SG-SADI is high, representing 37.6% of SADI-S procedures. Conversion from sleeve to SADI, is safe, and as opposed to other studies of revisional bariatric surgery, has similar 30-day complication rates to primary SADI-S.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Obesidade Mórbida/epidemiologia , Derivação Gástrica/métodos , Estudos Retrospectivos , Prevalência , Gastrectomia/métodos
2.
Chem Biodivers ; 14(2)2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27505410

RESUMO

Bioassay-guided fractionation of the MeOH extract of the tubers of Bletilla striata led to the isolation of two new C-methylated flavan-3-ols, bletillanols A (1) and B (2), along with ten known compounds (3 - 12). Their structures were determined by using extensive spectroscopic analysis including 1D-, 2D-NMR, and circular dichroism data. All of the isolated compounds were tested for their inhibitory potential on the nitric oxide generation in LPS-stimulated RAW 264.7 cells.


Assuntos
Macrófagos/citologia , Óxido Nítrico/metabolismo , Orchidaceae/química , Extratos Vegetais/farmacologia , Tubérculos/química , Animais , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Células RAW 264.7
3.
PLoS One ; 11(2): e0150431, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26919231

RESUMO

Cadmium (Cd) stress may cause serious morphological and physiological abnormalities in addition to altering the proteome in plants. The present study was performed to explore Cd-induced morpho-physiological alterations and their potential associated mechanisms in Sorghum bicolor leaves at the protein level. Ten-day-old sorghum seedlings were exposed to different concentrations (0, 100, and 150 µM) of CdCl2, and different morpho-physiological responses were recorded. The effects of Cd exposure on protein expression patterns in S. bicolor were investigated using two-dimensional gel electrophoresis (2-DE) in samples derived from the leaves of both control and Cd-treated seedlings. The observed morphological changes revealed that the plants treated with Cd displayed dramatically altered shoot lengths, fresh weights and relative water content. In addition, the concentration of Cd was markedly increased by treatment with Cd, and the amount of Cd taken up by the shoots was significantly and directly correlated with the applied concentration of Cd. Using the 2-DE method, a total of 33 differentially expressed protein spots were analyzed using MALDI-TOF/TOF MS. Of these, treatment with Cd resulted in significant increases in 15 proteins and decreases in 18 proteins. Major changes were absorbed in the levels of proteins known to be involved in carbohydrate metabolism, transcriptional regulation, translation and stress responses. Proteomic results revealed that Cd stress had an inhibitory effect on carbon fixation, ATP production and the regulation of protein synthesis. Our study provides insights into the integrated molecular mechanisms involved in responses to Cd and the effects of Cd on the growth and physiological characteristics of sorghum seedlings. We have aimed to provide a reference describing the mechanisms involved in heavy metal damage to plants.


Assuntos
Cloreto de Cádmio/toxicidade , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/biossíntese , Sorghum/metabolismo , Trifosfato de Adenosina/biossíntese , Cloreto de Cádmio/administração & dosagem , Ciclo do Carbono , Relação Dose-Resposta a Droga , Eletroforese em Gel Bidimensional , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Proteoma , Plântula/efeitos dos fármacos , Plântula/metabolismo , Sorghum/efeitos dos fármacos , Sorghum/crescimento & desenvolvimento , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Estresse Fisiológico/genética , Espectrometria de Massas em Tandem
4.
Oncotarget ; 6(38): 40452-63, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26564962

RESUMO

Multiple sclerosis (MS), also known as disseminated sclerosis or encephalomyelitis disseminate, is an inflammatory disease in which myelin in the spinal cord and brain are damaged. IL-32α is known as a critical molecule in the pathophysiology of immune-mediated chronic inflammatory disease such as rheumatoid arthritis, chronic pulmonary disease, and cancers. However, the role of IL-32α on spinal cord injuries and demyelination is poorly understood. Recently, we reported that the release of proinflammatory cytokines were reduced in IL-32α-overexpressing transgenic mice. In this study, we investigated whether IL-32α plays a role on MS using experimental autoimmune encephalomyelitis (EAE), an experimental mouse model of MS, in human IL-32α Tg mice. The Tg mice were immunized with MOG35-55 suspended in CFA emulsion followed by pertussis toxin, and then EAE paralysis of mice was scored. We observed that the paralytic severity and neuropathology of EAE in IL-32α Tg mice were significantly decreased compared with that of non-Tg mice. The immune cells infiltration, astrocytes/microglials activation, and pro-inflammatory cytokines (IL-1ß and IL-6) levels in spinal cord were suppressed in IL-32α Tg mice. Furthermore, NG2 and O4 were decreased in IL-32α Tg mice, indicating that spinal cord damaging was suppressed. In addition, in vitro assay also revealed that IL-32α has a preventive role against Con A stimulation which is evidenced by decrease in T cell proliferation and inflammatory cytokine levels in IL-32α overexpressed Jurkat cell. Taken together, our findings suggested that IL-32α may play a protective role in EAE by suppressing neuroinflammation in spinal cord.


Assuntos
Encefalomielite Autoimune Experimental/prevenção & controle , Inflamação/prevenção & controle , Interleucinas/fisiologia , Glicoproteína Mielina-Oligodendrócito/administração & dosagem , Traumatismos da Medula Espinal/prevenção & controle , Animais , Apoptose , Western Blotting , Proliferação de Células , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/etiologia , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Células Jurkat , Ativação Linfocitária , Camundongos , Camundongos Transgênicos , Glicoproteína Mielina-Oligodendrócito/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia
5.
Arch Pharm Res ; 38(6): 991-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25502561

RESUMO

Belamcanda chinensis (L.) DC., which belongs to the family of Iridaceae, has been used as a folk medicine for the treatment of inflammation, asthma, tonsillitis, and many other throat disorders. Bioactivity-guided purification of the methylene chloride-soluble fraction of the rhizomes of B. chinensis based on the inhibition of nitric oxide production led to the identification of seventeen known compounds. Their structures were elucidated on the basis of extensive spectroscopic measurement such as NMR and ESI-MS. All of the isolated compounds were evaluated for their inhibitory effects on nitric oxide production in LPS-induced RAW 264.7 macrophage cells.


Assuntos
Iridaceae/química , Macrófagos/metabolismo , Óxido Nítrico/biossíntese , Animais , Sobrevivência Celular/efeitos dos fármacos , Isoflavonas/farmacologia , Macrófagos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , Extratos Vegetais/química , Células RAW 264.7 , Rizoma/química , Espectrometria de Massas por Ionização por Electrospray
6.
AJR Am J Roentgenol ; 203(1): 223-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24951219

RESUMO

OBJECTIVE: The purpose of this article is to evaluate the correlations between breast-specific gamma imaging (BSGI) findings and mammographic and clinicopathologic characteristics of breast cancer. MATERIALS AND METHODS: Our study included 56 breast cancers that had undergone BSGI between August 2010 and December 2012. We reviewed imaging findings (BSGI and mammography) with histopathologic findings, including tumor size, histologic type, nuclear grade, presence of ductal carcinoma in situ (DCIS), and presence of extensive intraductal component (EIC); and immunochemical features, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (ERBB2, formerly HER2), Ki67, and p53. We classified cancers into positive or negative groups on the basis of BSGI visibility and investigated the statistical differences in mammographic and histopathologic characteristics between the BSGI-positive and -negative groups. RESULTS: Among 56 malignancies, 48 (85.7%) were shown to be BSGI positive. Patients in the BSGI-positive group were statistically significantly older than those in the BSGI-negative group (p = 0.027). BSGI-positive cancers were statistically significantly larger than BSGI-negative cancers (p = 0.002). Cancers 1.0 cm or larger, unlike those of subcentimeter size, were statistically significantly more visible on BSGI (p = 0.004). The mammographic findings and mammographic densities did not statistically significantly differ between the BSGI-positive and -negative groups. Invasiveness of cancer showed no statistically significant difference on BSGI finding. Cancers with a DCIS component tended to be BSGI positive, but without statistical significance (p = 0.051). Visibility on BSGI was not statistically significantly associated with EIC, nuclear grade, ER, PR, ERBB2, Ki67, and p53. CONCLUSION: The sensitivity of BSGI for breast cancer was 85.7%. Breast cancers in older patients, cancers larger than 1.0 cm, and cancers with the DCIS component tended to be visible on BSGI. BSGI was an equally sensitive tool to detect the breast cancer in women with fatty and dense breast.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Biópsia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Cintilografia , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia de Intervenção
7.
Toxicol Appl Pharmacol ; 277(1): 67-76, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24631338

RESUMO

Although recent study has shown tricin 4'-O-(threo-ß-guaiacylglyceryl) ether (TTGE), an isolated compound from Njavara rice, to have the most potent anti-inflammatory effects, the action mechanism has not been fully understood. Here, we examined the effect of TTGE on the inflammation and elucidated the potential mechanism. We demonstrated that TTGE significantly inhibited LPS-induced NO and ROS generation in RAW264.7 cells, which was correlated with the down-regulating effect of TTGE on the iNOS and COX-2 expression via NF-κB and STAT3. TPA-induced ear edema was also efficiently inhibited by the TTGE treatment. TTGE blocked the induction of iNOS and COX-2 through the regulation of NF-κB and STAT3, which could explain the reduced TPA-induced edema symptoms. Moreover, the introduction of ERK inhibitor abrogated the anti-inflammatory effect of TTGE via the recovery of NF-κB and STAT3 signalings. Taken together, these results suggest that TTGE has anti-inflammatory properties through down-regulation of NF-κB and STAT3 pathways.


Assuntos
Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Flavonas/farmacologia , Flavonolignanos/farmacologia , Mediadores da Inflamação/metabolismo , Oryza , Animais , Ciclo-Oxigenase 2 , Relação Dose-Resposta a Droga , Regulação para Baixo , Lipopolissacarídeos/toxicidade , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Prostaglandinas E/metabolismo , Espécies Reativas de Oxigênio/metabolismo
8.
Mol Neurobiol ; 48(3): 941-51, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23771816

RESUMO

The amyloid beta (Aß) peptide in the brains of patients with Alzheimer's disease (AD) is cytotoxic to neurons and has a central role in the pathogenesis of the disease. Peroxiredoxin 6 (Prdx6) is an antioxidant protein and could act as a cytoprotective protein. However, the role of Prdx6 in neurodegenerative disease has not been studied. Thus, the roles and action mechanisms in the development of AD were examined. Aß1-42-induced memory impairment in Prdx6 transgenic mice was worse than C57BL/6 mice, and the expression of amyloid precursor protein cleavage, C99, ß-site APP-cleaving enzyme 1, inducible nitric oxide synthase, and cyclooxygenase-2 was greatly increased. In addition, the astrocytes and microglia cells of Aß-infused Prdx6 transgenic mice were more activated, and Aß also significantly increased lipid peroxidation and protein carbonyl levels, but decreased glutathione levels. Furthermore, we found that translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus was increased in Aß-infused Prdx6 transgenic mice. These results suggest that the overexpression of Prdx6 could accelerate the development of AD through increased amyloidogenesis through independent PLA2 activation and Nrf2 transcription.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/toxicidade , Progressão da Doença , Peroxirredoxina VI/metabolismo , Doença de Alzheimer/complicações , Doença de Alzheimer/enzimologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/enzimologia , Astrócitos/patologia , Ciclo-Oxigenase 2/metabolismo , Feminino , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Transtornos da Memória/complicações , Transtornos da Memória/enzimologia , Transtornos da Memória/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/enzimologia , Microglia/patologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfolipases A2/metabolismo , Carbonilação Proteica/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos
9.
AJR Am J Roentgenol ; 196(1): 71-6, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21178049

RESUMO

OBJECTIVE: In glioblastoma multiforme, the peritumoral region may be infiltrated with malignant cells in addition to vasogenic edema, whereas in a metastatic deposit, the peritumoral areas comprise predominantly vasogenic edema. The purpose of this study was to determine whether the minimum apparent diffusion coefficient (ADC) can be used to differentiate glioblastoma from solitary metastasis on the basis of cellularity levels in the enhancing tumor and in the peritumoral region. MATERIALS AND METHODS: Seventy-three patients underwent conventional MRI and diffusion-weighted imaging (DWI) before undergoing treatment. The minimum ADC was measured in the enhancing tumor, peritumoral region, and contralateral normal white matter. To determine whether there was a statistical difference between metastasis and glioblastoma, we analyzed patient age and sex, minimum ADC value, and ADC ratio of the two groups. A receiver operating characteristic (ROC) curve analysis was used to determine the cutoff value of the minimum ADC that had the best combination of sensitivity and specificity for distinguishing between glioblastoma and metastasis. RESULTS: The mean minimum ADC values and mean ADC ratios in the peritumoral regions of glioblastomas were significantly higher than those in metastases. However, the mean minimum ADC values and mean ADC ratios in enhancing tumors showed no statistically significant difference between the two groups. According to ROC curve analysis, a cutoff value of 1.302 × 10(-3) mm(2)/s for the minimum peritumoral ADC value generated the best combination of sensitivity (82.9%) and specificity (78.9%) for distinguishing between glioblastoma and metastasis. CONCLUSION: Although the characteristics of solitary metastasis and glioblastoma multiforme may be similar on conventional MRI, DWI can offer diagnostic information to distinguish between the tumors.


Assuntos
Neoplasias Encefálicas/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Glioblastoma/diagnóstico , Glioblastoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Distribuição de Qui-Quadrado , Diagnóstico Diferencial , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico , Curva ROC , Sensibilidade e Especificidade , Estatísticas não Paramétricas
10.
Arch Pharm Res ; 33(3): 381-5, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20361302

RESUMO

Bioassay-guided fractionation of a CH2Cl2-soluble fraction of the stems of Catalpa ovata led to isolation of a new naphthoquinone, 4-hydroxy-2-(2-methoxy-3-hydroxy-3-methyl-but-1-enyl)-4-hydro-1H-naphthalen-1-one (10), together with nine known compounds, catalponol (1), catalponone (2), catalpalactone (3), alpha-lapachone (4), 9-hydroxy-alpha-lapachone (5), 4,9-dihydroxy-alpha-lapachone (6), 9-methoxy-alpha-lapachone (7), 4-oxo-alpha-lapachone (8), and 9-methoxy-4-oxo-alpha-lapachone (9). The structures were elucidated on the basis of spectroscopic analyses. The inhibitory effects of these isolates on lipopolysaccharide-induced NO synthesis in RAW 264.7 cells were evaluated. Among them, catapalactone (3), 9-hydroxy-alpha-lapachone (5) and 4,9-dihydroxy-alpha-lapachone (6) exhibited potent inhibitory effects, with IC(50) values of 9.80, 4.64 and 2.73 microM, respectively.


Assuntos
Bignoniaceae , Macrófagos/efeitos dos fármacos , Naftoquinonas/farmacologia , Óxido Nítrico/metabolismo , Bignoniaceae/química , Bioensaio , Linhagem Celular , Fracionamento Químico , Cromatografia Líquida de Alta Pressão , Regulação para Baixo , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Naftoquinonas/química , Naftoquinonas/isolamento & purificação , Caules de Planta , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade
11.
Arch Pharm Res ; 32(4): 501-4, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19407966

RESUMO

A new sesamin type furofuran lignan, (-)-sesamin-2,2'-diol (1), along with two known flavonoids (2 and 3) and three phenolic compounds (4-6) were isolated from the aerial parts of Isodon japonicus. The structures of these compounds were determined by analysis of spectroscopic data (1D-, 2D-NMR, HRMS and CD) and by comparison of the data with those of related metabolites.


Assuntos
Anti-Inflamatórios/química , Isodon , Lignanas/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Linhagem Celular , Cromatografia Líquida , Dicroísmo Circular , Isodon/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Componentes Aéreos da Planta , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
12.
J Toxicol Environ Health A ; 72(21-22): 1475-83, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20077221

RESUMO

Repetitive exposure of the skin to ultraviolet (UV) radiation induces various adverse effects, including skin thickening, wrinkle formation, inflammation, and pigmentation. Various natural and synthetic compounds were studied to determine whether they might prevent UV induction of these adverse effects. In particular, naturally occurring antioxidants were used for regulating skin damage induced by UV radiation since several antioxidants were found to inhibit photoaging through prevention of collagen synthesis via inhibition of matrix metalloproteinases (MMP) and/or decrease of melanin synthesis. The L values in pigmented skin were lower at 4 wk (52.97 +/- 2.09) than at the start of this study (0 wk, 62.89 +/- 0.56) in the control. In the proanthocyanidin mixture group, the L value was increased (56.83 +/- 1.71) similar to the control (52.97 +/- 2.09). Proanthocyanidin also suppressed the expression levels of tyrosinase by 20-40%, and blocked the expression of MITF, TRP-1, and TRP-2, which are factors implicated in the control of melanogenesis. Taken together, these data indicate that proanthocyanidin may be useful to attenuate UVB-induced melanogenesis.


Assuntos
Melaninas/metabolismo , Pigmentação/efeitos dos fármacos , Proantocianidinas/farmacologia , Raios Ultravioleta , Agaricales/enzimologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Cobaias , Humanos , Melanoma , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Pigmentação/efeitos da radiação
13.
Mediators Inflamm ; 2007: 93148, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17541474

RESUMO

Inflexinol, an ent-kaurane diterpenoid, was isolated from the leaves of Isodon excisus. Many diterpenoids isolated from the genus Isodon (Labiatae) have antitumor and antiinflammatory activities. We investigated the antiinflammatory effect of inflexinol in RAW 264.7 cells and astrocytes. As a result, we found that inflexinol (1, 5, 10 microM) suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 cells and astrocytes. Consistent with the inhibitory effect on iNOS and COX-2 expression, inflexinol also inhibited transcriptional and DNA binding activity of NF-kappaB via inhibition of IkappaB degradation as well as p50 and p65 translocation into nucleus. These results suggest that inflexinol inhibits iNOS and COX-2 expression through inhibition of NF-kappaB activation, thereby inhibits generation of inflammatory mediators in RAW 264.7 cells and astrocytes, and may be useful for treatment of inflammatory diseases.


Assuntos
Diterpenos do Tipo Caurano/farmacologia , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Western Blotting , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , DNA/metabolismo , Diterpenos do Tipo Caurano/química , Ensaio de Desvio de Mobilidade Eletroforética , Luciferases/genética , Luciferases/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Estrutura Molecular , NF-kappa B/genética , Polissacarídeos Bacterianos/farmacologia , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transfecção
14.
Biochem Biophys Res Commun ; 357(1): 174-80, 2007 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-17418105

RESUMO

The learning and memory impairment of presenilin 2 transgenic mice was mentioned previously. In this study, exposing the presenilin 2 transfected PC12 cells to the 50 microM Abeta(25-35), 30 mM l-glutamate and 50 microM H(2)O(2) resulted in significant increase 8-oxodG and p53 levels of the cells expressing the mutant gene. The increase was also found in the mutant presenilin 2 transgenic mice brains age-dependently in comparison to that in the wild-type presenilin 2-transgenic mice and non-transgenic ones. These findings indicated that mutant presenilin 2 clearly increases oxidative stress and p53 expression, which could be implicated in promoting mutant presenilin 2-induced neurodegeneration in Alzheimer's disease, and the influence of mutant presenilin 2 in Alzheimer's disease may be brain regional and age related effects.


Assuntos
Doença de Alzheimer/metabolismo , Neurônios/metabolismo , Presenilina-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Mutação , Estresse Oxidativo , Células PC12 , Presenilina-2/genética , Ratos
15.
Mol Cancer Ther ; 6(2): 675-83, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17308063

RESUMO

We investigated whether the snake venom toxin (SVT) from Vipera lebetina turanica inhibits cell growth of human prostate cancer cells by inducing apoptosis and also studied possible signaling pathways involved in this cell death. SVT inhibited growth of PC-3 and DU145 cells, androgen-independent prostate cancer cells, but not LNCaP cells, a human androgen-dependent prostate cancer cell. Cells were arrested in the G(2)-M phase by SVT with a concomitant decrease in the expression of the G(2)-M phase regulatory protein cyclin B1 and were also arrested in the G(1)-S phase with decreasing expression of cyclin-dependent kinase 4, cyclin D1 and cyclin E. In addition to the growth-inhibitory effect, SVT increased the induction of apoptotic cell death. Untreated PC-3 cells show high DNA binding activity of nuclear factor kappaB (NF-kappaB), an antiapoptotic transcriptional factor, but this was inhibited by SVT and accompanied by a significant inhibition of p50 translocation into the nucleus, as well as phosphorylation of inhibitory kappaB. Consistent with the induction of apoptosis and inhibition of NF-kappaB, this toxin increased the expression of proapoptotic proteins such as p53, Bax, caspase-3, and caspase-9, but down-regulated antiapoptotic protein Bcl-2. However, SVT did not show an inhibitory effect on cell growth and caspase-3 activity in cells carrying mutant p50 and inhibitory kappaB kinase plasmids. Confocal microscopy analysis showed that SVT is taken up into the nucleus of the cells. These findings suggest that a nanogram concentration range of SVT from V. lebetina turanica could inhibit hormone-refractory human prostate cancer cell growth, and the effect may be related to NF-kappaB signal-mediated induction of apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , NF-kappa B/metabolismo , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Venenos de Serpentes/farmacologia , Toxinas Biológicas/farmacologia , Viperidae , Animais , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Núcleo Celular , Ciclinas/metabolismo , Humanos , Masculino , NF-kappa B/genética , Fosforilação/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transporte Proteico
16.
Arch Pharm Res ; 28(9): 1073-8, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16212240

RESUMO

A presenilin 2 mutation is believed to be involved in the development of Alzheimer's disease. In addition, transgenic mice with a presenilin 2 mutation have been reported to have learning and memory impairments. In this study, exposing PC12 cells expressing mutant presenilin 2 to 50 microM AP25-35, 30 mM L-glutamate and 50 microM H2O2 caused a significant increase in acetylcholine esterase activity. An in vivo study revealed high levels of this enzyme activity in the mutant presenilin 2 transgenic brains compared with the wild type presenilin 2 transgenic and nontransgenic samples. These results suggest that a mutant presenilin 2-induced neurodegeneration in Alzheimer's disease might be involved in the increase in acetylcholinesterase activity. These findings might help in the development of an appropriate therapeutic intervention targeting mutant presenilin 2-induced Alzheimer's disease.


Assuntos
Acetilcolinesterase/metabolismo , Proteínas de Membrana/fisiologia , Mutação , Neurônios/enzimologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/enzimologia , Doença de Alzheimer/etiologia , Animais , Encéfalo/enzimologia , Proteínas de Membrana/genética , Camundongos , Camundongos Transgênicos , Células PC12 , Presenilina-2 , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA