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1.
Cell Death Dis ; 10(6): 453, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186405

RESUMO

Hepatocellular carcinoma (HCC) has a high mortality rate due to the lack of effective treatments and drugs. Arsenic trioxide (ATO), which has been proved to successfully treat acute promyelocytic leukemia (APL), was recently reported to show therapeutic potential in solid tumors including HCC. However, its anticancer mechanisms in HCC still need further investigation. In this study, we demonstrated that ATO inhibits tumorigenesis and distant metastasis in mouse models, corresponding with a prolonged mice survival time. Also, ATO was found to significantly decrease the cancer stem cell (CSC)-associated traits. Minichromosome maintenance protein (MCM) 7 was further identified to be a potential target suppressed dramatically by ATO, of which protein expression is increased in patients and significantly correlated with tumor size, cellular differentiation, portal venous emboli, and poor patient survival. Moreover, MCM7 knockdown recapitulates the effects of ATO on CSCs and metastasis, while ectopic expression of MCM7 abolishes them. Mechanistically, our results suggested that ATO suppresses MCM7 transcription by targeting serum response factor (SRF)/MCM7 complex, which functions as an important transcriptional regulator modulating MCM7 expression. Taken together, our findings highlight the importance of ATO in the treatment of solid tumors. The identification of SRF/MCM7 complex as a target of ATO provides new insights into ATO's mechanism, which may benefit the appropriate use of this agent in the treatment of HCC.

2.
Zhongguo Zhong Yao Za Zhi ; 43(13): 2784-2788, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30111032

RESUMO

To study the effect of serum containing Xihuang pill on the proliferation of human breast cancer cell lines MDA-MB-435 and MCF-7 and the gene and protein expressions of Bcl-2, Bax, TP53, in order to explore the effect and mechanism of Xihuang pill in resisting breast cancer. The serum of the rats was prepared by the method of MTT assay. The expressions of Bcl-2 and Bax were detected by RT-PCR. The serum levels of Bcl-2 and Bax and the mRNA expression of TP53 were detected by immunofluorescence. The rats with serum containing Xihuang pill could inhibit the proliferation of MDA-MB-435 cells and MCF-7 cells (P<0.05). The serum containing Xihuang pill increased TP53 and Bax in MDA-MB-435 cells (P<0.05), and the ratio of Bcl-2/Bax was decreased (P<0.05). Meanwhile, the serum containing Xihuang pill could up-regulate the mRNA expression of Bax in MCF-7 cells and decrease the expression of Bcl (P<0.05), but there was no significant difference between the expression of TP53mRNA and Bax protein expressions after the treatment of MCF-7 cells with Xihuang pill serum. Serum containing Xihuang pill can induce the apoptosis of human breast cancer cells, and the mechanism of estrogen receptor-negative breast cancer cell apoptosis may be induced by up-regulating the mRNA expression of TP53, which can induce the expression of Bax and promote the metastasis of Bax to mitochondria, and ultimately play the role of inducing apoptosis.


Assuntos
Apoptose , Neoplasias da Mama , Animais , Proliferação de Células , Medicamentos de Ervas Chinesas , Humanos , Células MCF-7 , Ratos , Proteína X Associada a bcl-2
3.
Mol Med Rep ; 16(6): 8589-8594, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28990107

RESUMO

Bone marrow stromal cells (BMSCs) can differentiate into osteoblasts. The present study investigated the osteogenic effects of estradiol, as well as the role of the c­Jun N­terminal kinase (JNK) signaling pathway in promoting estradiol­enhanced osteogenesis of rat (r)BMSCs. rBMSCs were treated for 7 days with or without estradiol and further treated with or without the JNK­specific inhibitor SP600125. The role of estrogen during rBMSC osteogenesis was evaluated by alkaline phosphatase activity and mineralized nodule formation using the Gomori method and Alizarin red S staining, respectively. Subsequently, the mRNA expression levels of transforming growth factor-ß1 (TGF­ß1) and core­binding factor α1 (Cbfα1) were evaluated by reverse transcription­quantitative polymerase chain reaction, and TGF­ß1, Cbfα1 and phosphorylated (p)­JNK protein expression was detected by western blotting. All groups treated with SP600125 expressed low levels of TGF­ß1 and Cbfα1 mRNA and protein, and low p­JNK protein expression. Compared with the control cells, rBMSCs cultured with estradiol exhibited a significant upregulation in the expression levels of osteogenic genes and proteins. The present study demonstrated that estradiol enhanced osteogenic differentiation of rBMSCs and that the JNK signaling pathway was involved in this process, providing insights into the molecular mechanisms involved in rBMSC osteogenesis upon estradiol stimulation.


Assuntos
Estradiol/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/enzimologia , Osteogênese/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Biomarcadores/metabolismo , Forma Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Citometria de Fluxo , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Minerais/metabolismo , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
4.
Anal Biochem ; 537: 50-55, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28882747

RESUMO

A novel method, real-time reverse transcription PCR (real-time RT-PCR) coupled with probe-melting curve analysis, has been established to detect two kinds of samples within one fluorescence channel. Besides a conventional TaqMan probe, this method employs another specially designed melting-probe with a 5' terminus modification which meets the same label with the same fluorescent group. By using an asymmetric PCR method, the melting-probe is able to detect an extra sample in the melting stage effectively while it almost has little influence on the amplification detection. Thus, this method allows the availability of united employment of both amplification stage and melting stage for detecting samples in one reaction. The further demonstration by simultaneous detection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in one channel as a model system is presented in this essay. The sensitivity of detection by real-time RT-PCR coupled with probe-melting analysis was proved to be equal to that detected by conventional real-time RT-PCR. Because real-time RT-PCR coupled with probe-melting analysis can double the detection throughputs within one fluorescence channel, it is expected to be a good solution for the problem of low-throughput in current real-time PCR.


Assuntos
RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real , Sequência de Bases , Sondas de DNA/química , Sondas de DNA/metabolismo , HIV/genética , Hepacivirus/genética , Humanos , Transição de Fase , RNA Viral/genética , RNA Viral/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
5.
Sci Rep ; 6: 34854, 2016 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-27708385

RESUMO

Glycosylphosphatidyl inositol anchored proteins (GPI-APs) on fungal cell wall are essential for invasive infections. While the function of inositol deacylation of GPI-APs in mammalian cells has been previously characterized the impact of inositol deacylation in fungi and implications to host infection remains largely unexplored. Herein we describe our identification of BST1, an inositol deacylase of GPI-Aps in Candida albicans, was critical for GPI-APs cell wall attachment and host infection. BST1-deficient C. albicans (bst1Δ/Δ) was associated with severely impaired cell wall anchorage of GPI-APs and subsequen unmasked ß-(1,3)-glucan. Consistent with the aberrant cell wall structures, bst1Δ/Δ strain did not display an invasive ability and could be recognized more efficiently by host immune systems. Moreover, BST1 null mutants or those expressing Bst1 variants did not display inositol deacylation activity and exhibited severely attenuated virulence and reduced organic colonization in a murine systemic candidiasis model. Thus, Bst1 can facilitate cell wall anchorage of GPI-APs in C. albicans by inositol deacylation, and is critical for host invasion and immune escape.


Assuntos
Candida albicans/patogenicidade , Candidíase/microbiologia , Parede Celular/metabolismo , Inositol/química , Monoéster Fosfórico Hidrolases/genética , Acilação , Animais , Candida albicans/genética , Candida albicans/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Deleção de Genes , Glicosilfosfatidilinositóis/metabolismo , Camundongos , Monoéster Fosfórico Hidrolases/metabolismo
6.
Zhongguo Zhong Yao Za Zhi ; 41(4): 619-623, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-28871682

RESUMO

Terminalia chebula Retz, known as the "king" of Mongolian and Tibetan medicines, is a drug for a wide range of diseases. The main chemical components of myrobalan include triterpene acid, galloyl glucose, anthraquinonoid. The modern pharmacological studies show that myrobalan has multiple biological activities, including antimicrobial, anti-inflammatory, antioxidation as well as anti-tumor. Based on domestic and foreign literatures in recent years, this paper gave a review on the advance of studies for pharmacological activity of T. chebula. and its active components, so as to provide a reference for the in-depth studies on the pharmacological action of myrobalan, and the further development and utilization of myrobalan.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Terminalia/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/química , Humanos , Triterpenos/química , Triterpenos/farmacologia
7.
World J Gastroenterol ; 21(21): 6561-71, 2015 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-26074694

RESUMO

AIM: To determine the protective effect of triple viable probiotics on gastritis induced by Helicobacter pylori (H. pylori) and elucidate the possible mechanisms of protection. METHODS: Colonization of BIFICO strains in the mouse stomach was determined by counting colony-forming units per gram of stomach tissue. After treatment with or without BIFICO, inflammation and H. pylori colonization in the mouse stomach were analyzed by hematoxylin and eosin and Giemsa staining, respectively. Cytokine levels were determined by enzyme-linked immunosorbent assay and Milliplex. The activation of nuclear factor (NF)-κB and MAPK signaling in human gastric epithelial cells was evaluated by Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was used to quantify TLR2, TLR4 and MyD88 mRNA expression in the mouse stomach. RESULTS: We demonstrated that BIFICO, which contains a mixture of Enterococcus faecalis, Bifidobacterium longum and Lactobacillus acidophilus, was tolerant to the mouse stomach environment and was able to survive both the 8-h and 3-d courses of administration. Although BIFICO treatment had no effect on the colonization of H. pylori in the mouse stomach, it ameliorated H. pylori-induced gastritis by significantly inhibiting the expression of cytokines and chemokines such as TNF-α, IL-1ß, IL-10, IL-6, G-CSF and MIP-2 (P < 0.05). These results led us to hypothesize that BIFICO treatment would diminish the H. pylori-induced inflammatory response in gastric mucosal epithelial cells in vitro via the NF-κB and MAPK signaling pathways. Indeed, we observed a decrease in the expression of the NF-κB subunit p65 and in the phosphorylation of IκB-α, ERK and p38. Moreover, there was a significant decrease in the production of IL-8, TNF-α, G-CSF and GM-CSF (P < 0.05), and the increased expression of TLR2, TLR4 and MyD88 induced by H. pylori in the stomach was also significantly reduced following BIFICO treatment (P < 0.05). CONCLUSION: Our results suggest that the probiotic cocktail BIFICO can ameliorate H. pylori-induced gastritis by inhibiting the inflammatory response in gastric epithelial cells.


Assuntos
Mucosa Gástrica/microbiologia , Gastrite/prevenção & controle , Infecções por Helicobacter/terapia , Helicobacter pylori/patogenicidade , Probióticos , Animais , Bifidobacterium/crescimento & desenvolvimento , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Enterococcus faecalis/crescimento & desenvolvimento , Feminino , Mucosa Gástrica/metabolismo , Gastrite/genética , Gastrite/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Interações Hospedeiro-Patógeno , Mediadores da Inflamação/metabolismo , Lactobacillus acidophilus/crescimento & desenvolvimento , Sistema de Sinalização das MAP Quinases , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Fatores de Tempo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
8.
PLoS One ; 10(5): e0126393, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25992630

RESUMO

Our previous study demonstrated berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. We also suggested BBR played a major antifungal role in the synergism of FLC and BBR, while FLC increased intracellular BBR concentrations. Our following systematic structural modification and reconstruction of BBR core identified the novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acet-amide derivatives 7a-i, including B-7b and B-7d exhibiting remarkable synergistic antifungal activity and low cytotoxicity. Here, the study mainly investigated the synergistic activity of FLC and B-7b and the underlying mechanism. In vitro interaction of FLC and B-7b was investigated against 30 FLC-resistant clinical isolates of C. albicans and non-C. albicans species, including Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The potent synergistic activity of B-7b in combination with FLC against FLC-resistant C. albicans was found through the checkerboard microdilution assay. The findings of agar diffusion tests and time-kill curves confirmed its better synergism with FLC. And as expected, B-7b exhibited much lower cytotoxicity than BBR to human umbilical vein endothelial cells. In contrast to BBR, we found that endogenous ROS augmentation was not involved in the synergism of FLC and B-7b. According to the results from our present comparative proteomic study, it seemed that the disruption of protein folding and processing and the weakening of cells' self-defensive ability contributed to the synergism of FLC and B-7b. Together, these results suggested novel scaffold BBR derivative B-7b could be a promising synergist in combination with FLC for the treatment of invasive fungal infections.


Assuntos
Antifúngicos/farmacologia , Berberina/farmacologia , Fluconazol/farmacologia , Candida/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Farmacorresistência Fúngica , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana
9.
Hepatology ; 62(3): 801-15, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25953743

RESUMO

UNLABELLED: Emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) play important roles in tumor metastasis and recurrence. Understanding molecular mechanisms that regulate the EMT process is crucial for improving treatment of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play important roles in HCC; however, the mechanisms by which miRNAs target the EMT and their therapeutic potential remains largely unknown. To better explore the roles of miRNAs in the EMT process, we established an EMT model in HCC cells by transforming growth factor beta 1 treatment and found that several tumor-related miRNAs were significantly decreased. Among these miRNAs, miR-125b expression was most strongly suppressed. We also found down-regulation of miR-125b in most HCC cells and clinical specimens, which correlated with cellular differentiation in HCC patients. We then demonstrated that miR-125b overexpression attenuated EMT phenotype in HCC cancer cells, whereas knockdown of miR-125b promoted the EMT phenotype in vitro and in vivo. Moreover, we found that miR-125b attenuated EMT-associated traits, including chemoresistance, migration, and stemness in HCC cells, and negatively correlated with EMT and cancer stem cell (CSC) marker expressions in HCC specimens. miR-125b overexpression could inhibit CSC generation and decrease tumor incidence in the mouse xenograft model. Mechanistically, our data revealed that miR-125b suppressed EMT and EMT-associated traits of HCC cells by targeting small mothers against decapentaplegic (SMAD)2 and 4. Most important, the therapeutic delivery of synthetic miR-125b mimics decreased the target molecule of CSC and inhibited metastasis in the mice model. These findings suggest a potential therapeutic treatment of miR-125b for liver cancer. CONCLUSION: miR-125b exerts inhibitory effects on EMT and EMT-associated traits in HCC by SMAD2 and 4. Ectopic expression of miR-125b provides a promising strategy to treat HCC.


Assuntos
Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Células-Tronco Neoplásicas/patologia , Proteína Smad2/metabolismo , Proteína Smad4/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Distribuição Aleatória , Sensibilidade e Especificidade , Transfecção , Células Tumorais Cultivadas
10.
World J Gastroenterol ; 21(19): 5893-900, 2015 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-26019453

RESUMO

AIM: To validate the value of aspartate aminotransferase to platelet ratio index (APRI) in assessment of liver fibrosis and prediction of postoperative prognosis of biliary atresia (BA) infants from Mainland China. METHODS: Medical records of 153 BA infants who were hospitalized from January 2010 to June 2013 were reviewed. The efficacy of APRI for diagnosis of liver fibrosis was assessed using the receiver operator characteristic (ROC) curve compared to the pathological Metavir fibrosis score of the liver wedge specimens of 91 BA infants. The prognostic value of preoperative APRI for jaundice persistence, liver injury, and occurrence of cholangitis within 6 mo after KP was studied based on the follow-up data of 48 BA infants. RESULTS: APRI was significantly correlated with Metavir scores (rs = 0.433; P < 0.05). The mean APRI value was 0.76 in no/mild fibrosis group (Metavir score F0-F1), 1.29 in significant fibrosis group (F2-F3), and 2.51 in cirrhosis group (F4) (P < 0.001). The area under the ROC curve (AUC) of APRI for diagnosing significant fibrosis and cirrhosis was 0.75 (P < 0.001) and 0.81 (P = 0.001), respectively. The APRI cut-off of 0.95 was 60.6% sensitive and 76.0% specific for significant fibrosis diagnosis, and a threshold of 1.66 was 70.6% sensitive and 82.7% specific for cirrhosis. The preoperative APRI in infants who maintained jaundice around 6 mo after KP was higher than that in those who did not (1.86 ± 2.13 vs 0.87 ± 0.48, P < 0.05). The AUC of APRI for prediction of postoperative jaundice occurrence was 0.67. A cut-off value of 0.60 showed a sensitivity of 66.7% and a specificity of 83.3% for the prediction of jaundice persistence. Preoperative APRI had no significant association with later liver injury or occurrence of cholangitis. CONCLUSION: Our study demonstrated that APRI could diagnose significant liver fibrosis, especially cirrhosis in BA infants, and the elevated preoperative APRI predicts jaundice persistence after KP.


Assuntos
Aspartato Aminotransferases/sangue , Atresia Biliar/diagnóstico , Plaquetas , Ensaios Enzimáticos Clínicos , Cirrose Hepática/diagnóstico , Testes de Função Hepática , Área Sob a Curva , Atresia Biliar/sangue , Atresia Biliar/enzimologia , Atresia Biliar/patologia , Atresia Biliar/cirurgia , Biomarcadores/sangue , Biópsia , China , Feminino , Humanos , Lactente , Recém-Nascido , Cirrose Hepática/sangue , Cirrose Hepática/enzimologia , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Masculino , Registros Médicos , Contagem de Plaquetas , Portoenterostomia Hepática , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
11.
Infect Immun ; 83(7): 2694-704, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25895969

RESUMO

Fungi can shield surface pathogen-associated molecular patterns (PAMPs) for evading host immune attack. The most common and opportunistic human pathogen, Candida albicans, can shield ß-(1 3)-glucan on the cell wall, one of the major PAMPs, to avoid host phagocyte Dectin-1 recognition. The way to interfere in the shielding process for more effective antifungal defense is not well established. In this study, we found that deletion of the C. albicans GPI7 gene, which was responsible for adding ethanolaminephosphate to the second mannose in glycosylphosphatidylinositol (GPI) biosynthesis, could block the attachment of most GPI-anchored cell wall proteins (GPI-CWPs) to the cell wall and subsequently unmask the concealed ß-(1,3)-glucan. Neutrophils could kill the uncloaked gpi7 mutant more efficiently with an augmented respiratory burst. The gpi7 mutant also stimulated Dectin-1-dependent immune responses of macrophages, including activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways and secretion of specific cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-12p40. Furthermore, the gpi7 null mutant could induce an enhanced inflammatory response through promoting significant recruitment of neutrophils and monocytes and could stimulate stronger Th1 and Th17 cell responses to fungal infections in vivo. These in vivo phenotypes also were Dectin-1 dependent. Thus, we assume that GPI-CWPs are involved in the immune mechanism of C. albicans escaping from host recognition by Dectin-1. Our studies also indicate that the blockage of GPI anchor synthesis is a strategy to inhibit C. albicans evading host recognition.


Assuntos
Antígenos de Fungos/imunologia , Candida albicans/imunologia , Parede Celular/imunologia , Proteínas Fúngicas/imunologia , Glicosilfosfatidilinositóis/metabolismo , Lectinas Tipo C/metabolismo , Animais , Antígenos de Fungos/metabolismo , Candida albicans/metabolismo , Parede Celular/metabolismo , Feminino , Proteínas Fúngicas/metabolismo , Deleção de Genes , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , beta-Glucanas/imunologia , beta-Glucanas/metabolismo
12.
Zhonghua Nan Ke Xue ; 20(6): 490-4, 2014 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-25029851

RESUMO

OBJECTIVE: To observe the changes of the mechanical pain threshold in the rat model of autoimmune prostatitis, explore the mechanism of autoimmune prostatitis pain and offer some animal experimental evidence for the drug therapy of the condition. METHODS: Twenty male Wistar rats weighing 180 - 220 g were divided into a model and a control group. The autoimmune prostatitis model was established by subcutaneous injection of an extract of male rat prostate glands (RPG) at 60 mg/ml in Freund's complete adjuvant (FCA) and pertussis-diphtheria-tetanus vaccine at 0 and 30 days, respectively. Mechanical tactile hyperalgesia was measured once a week using Von Frey Filaments from the beginning of the study. At 8 weeks after modeling, the rats were sacrificed and the prostate tissues harvested for observation of histomorphological changes by HE staining. RESULTS: HE staining revealed different degrees of benign prostatitis in the model rats. Compared with the controls, the mechanical pain threshold in the model rats was significantly decreased with the increased time of modeling, from (65.52 +/- 6.27) g at 0 week to (23.67 +/- 4.09) g at 8 weeks (P < 0.01). Statistically significant differences were found in the variation trend at different time points between the two groups (P < 0.01). CONCLUSION: Autoimmune prostatitis models were successfully established in rats and hyperalgesia was induced after modeling.


Assuntos
Doenças Autoimunes/fisiopatologia , Limiar da Dor/fisiologia , Prostatite/fisiopatologia , Animais , Modelos Animais de Doenças , Masculino , Prostatite/imunologia , Ratos , Ratos Wistar
13.
PLoS One ; 9(7): e103442, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25058485

RESUMO

The incidence of invasive fungal infections is increasing in recent years. The present study mainly investigated glabridin (Gla) alone and especially in combination with fluconazole (FLC) against Cryptococcus neoformans and Candida species (Candida albicans, Candida tropicalis, Candida krusei, Candida parapsilosis and Candida Glabratas) by different methods. The minimal inhibitory concentration (MIC) and the minimal fungicidal concentration (MFC) indicated that Gla possessed a broad-spectrum antifungal activity at relatively high concentrations. After combining with FLC, Gla exerted a potent synergistic effect against drug-resistant C. albicans and C. tropicalis at lower concentrations when interpreted by fractional inhibitory concentration index (FICI). Disk diffusion test and time-killing test confirming the synergistic fungicidal effect. Cell growth tests suggested that the synergistic effect of the two drugs depended more on the concentration of Gla. The cell envelop damage including a significant decrease of cell size and membrane permeability increasing were found after Gla treatment. Together, our results suggested that Gla possessed a synergistic effect with FLC and the cell envelope damage maybe contributed to the synergistic effect, which providing new information for developing novel antifungal agents.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Fluconazol/farmacologia , Isoflavonas/farmacologia , Fenóis/farmacologia , Candida/classificação , Candida/crescimento & desenvolvimento , Parede Celular/efeitos dos fármacos , Cryptococcus neoformans/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Farmacorresistência Fúngica/efeitos dos fármacos , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana
14.
Sci China Life Sci ; 57(2): 188-94, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24448906

RESUMO

Due to the low number of collectable stem cells from single umbilical cord blood (UCB) unit, their initial uses were limited to pediatric therapies. Clinical applications of UCB hematopoietic stem and progenitor cells (HSPCs) would become feasible if there were a culture method that can effectively expand HSPCs while maintaining their self-renewal capacity. In recent years, numerous attempts have been made to expand human UCB HSPCs in vitro. In this study, we report that caffeic acid phenethyl ester (CAPE), a small molecule from honeybee extract, can promote in vitro expansion of HSPCs. Treatment with CAPE increased the percentage of HSPCs in cultured mononuclear cells. Importantly, culture of CD34(+) HSPCs with CAPE resulted in a significant increase in total colony-forming units and high proliferative potential colony-forming units. Burst-forming unit-erythroid was the mostly affected colony type, which increased more than 3.7-fold in 1 µg mL(-1) CAPE treatment group when compared to the controls. CAPE appears to induce HSPC expansion by upregulating the expression of SCF and HIF1-α. Our data suggest that CAPE may become a potent medium supplement for in vitro HSPC expansion.


Assuntos
Ácidos Cafeicos/farmacologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Cordão Umbilical/efeitos dos fármacos , Células Cultivadas , Citometria de Fluxo , Células-Tronco Hematopoéticas/citologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Técnicas In Vitro , Álcool Feniletílico/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Células-Tronco/metabolismo , Cordão Umbilical/citologia , Regulação para Cima/efeitos dos fármacos
15.
Genome Biol ; 14(12): R141, 2013 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-24359812

RESUMO

BACKGROUND: Fig pollinating wasps form obligate symbioses with their fig hosts. This mutualism arose approximately 75 million years ago. Unlike many other intimate symbioses, which involve vertical transmission of symbionts to host offspring, female fig wasps fly great distances to transfer horizontally between hosts. In contrast, male wasps are wingless and cannot disperse. Symbionts that keep intimate contact with their hosts often show genome reduction, but it is not clear if the wide dispersal of female fig wasps will counteract this general tendency. We sequenced the genome of the fig wasp Ceratosolen solmsi to address this question. RESULTS: The genome size of the fig wasp C. solmsi is typical of insects, but has undergone dramatic reductions of gene families involved in environmental sensing and detoxification. The streamlined chemosensory ability reflects the overwhelming importance of females finding trees of their only host species, Ficus hispida, during their fleeting adult lives. Despite long-distance dispersal, little need exists for detoxification or environmental protection because fig wasps spend nearly all of their lives inside a largely benign host. Analyses of transcriptomes in females and males at four key life stages reveal that the extreme anatomical sexual dimorphism of fig wasps may result from a strong bias in sex-differential gene expression. CONCLUSIONS: Our comparison of the C. solmsi genome with other insects provides new insights into the evolution of obligate mutualism. The draft genome of the fig wasp, and transcriptomic comparisons between both sexes at four different life stages, provide insights into the molecular basis for the extreme anatomical sexual dimorphism of this species.


Assuntos
Ficus/parasitologia , Genoma de Inseto , Análise de Sequência de DNA/métodos , Vespas/embriologia , Vespas/genética , Animais , Evolução Molecular , Feminino , Ficus/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Tamanho do Genoma , Masculino , Filogenia , Caracteres Sexuais , Simbiose , Vespas/classificação , Vespas/fisiologia
16.
Zhonghua Nan Ke Xue ; 19(4): 296-9, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23678705

RESUMO

OBJECTIVE: To explore the relationship between aging and erectile function changes in rats in order to establish a rat model of aging-related erectile dysfunction (ED). METHODS: Eighty male Wistar rats were equally divided into four age groups (3-, 6-, 12- and 18-month) and treated with intragastric administration of sildenafil citrate (Sn) for penile erection tests. Twenty 3-month-old female Wistar rats were randomized to four groups as oestrous rat models. We recorded the rate and frequency of penile erections of the male rats in different age groups. RESULTS: The rates of penile erection were 85%, 75%, 40% and 30% and erectile frequencies were 2.27 +/- 0.80, 2.00 +/- 0.61, 1.40 +/- 0.51 and 1.29 +/- 0.49 in the 3-, 6-, 12- and 18-month rats, respectively, with statistically significant differences among different age groups (P < 0.01). And their erectile function exhibited a tendency to decrease with the increase of age. Besides, comparison of the 3-month with the 6-, 12- and 18-month groups showed significantly reduced erectile function in the 18-month rats (P < 0.05) but no remarkable difference between the 3-month and the 6- and 12-month groups (P > 0.05). CONCLUSION: Aging is one of the main risk factors of rat erectile dysfunction, and 18-month-old male rats are qualified for the establishment of the rat model of aging-related erectile dysfunction.


Assuntos
Envelhecimento/fisiologia , Disfunção Erétil/fisiopatologia , Ereção Peniana/fisiologia , Animais , Masculino , Modelos Animais , Ratos , Ratos Wistar
17.
Hepatology ; 57(6): 2274-86, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23316018

RESUMO

UNLABELLED: Cancer-associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer-associated MSCs (LC-MSCs) and hepatocellular carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC-MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC-MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC-MSCs compared with liver normal MSCs (LN-MSCs) from adjacent cancer-free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC-MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)-155 in HCC cells was significantly up-regulated by coculture with LC-MSCs and by S100A4 ectopic overexpression. The invasion-promoting effects of S100A4 were significantly attenuated by a miR-155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR-155 expression in HCC cells. We demonstrate that S100A4 secreted from LC-MSCs promotes the expression of miR-155, which mediates the down-regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness. CONCLUSION: S100A4 secreted from LC-MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target. (HEPATOLOGY 2013).


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Proteínas S100/metabolismo , Animais , Carcinoma Hepatocelular/patologia , Proliferação de Células , Progressão da Doença , Humanos , Neoplasias Hepáticas/patologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Proteína A4 de Ligação a Cálcio da Família S100 , Fator de Transcrição STAT3/metabolismo , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/metabolismo
18.
Mol Phylogenet Evol ; 65(2): 757-64, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22877644

RESUMO

Thelypteridaceae is one of the largest families of polypodioid ferns. The generic classification of the family is still controversial because of high levels of convergent or parallel evolution of morphological characters and a lack of molecular phylogenetic studies. In the present study, phylogenetic analyses of three chloroplast regions (rbcL, rps4 and trnL-trnF intergenic spacer region) for 115 taxa, representing 27 recognized segregates in the family, were conducted to explore infrafamilial relationships and gain further understanding of generic boundaries. The phylogenetic reconstructions resolved six distinct clades (Clade I-VI) with strong support. Seven genera: Cyclogramma, Macrothelypteris, Oreopteris, Phegopteris, Pseudophegopteris, Stegnogramma, and Thelypteris are recognized from Clades I, II, IV, and V. In Clade III, Metathelypteris was supported as monophyletic, but the other segregates Amauropelta, Coryphopteris, and Parathelypteris were polyphyletic or paraphyletic, preventing clear recognition of generic boundaries within this clade without additional sampling. Considering great morphological homoplasy within Clade VI, a large genus Cyclosorus is recognized to comprise several small recognized segregates. Within this clade, Pronephrium, and Christella were revealed to be polyphyletic, but several Asian-endemic segregates, such as Glaphyropteridopsis, Mesopteris, and Pseudocyclosorus were strongly supported as monophyletic. Analyses of the evolution of morphological character states on the molecular phylogeny showed extremely high levels of homoplastic evolution for many diagnostic characters.


Assuntos
Evolução Molecular , Gleiquênias/classificação , Filogenia , Teorema de Bayes , DNA de Cloroplastos/genética , DNA de Plantas/genética , Gleiquênias/anatomia & histologia , Gleiquênias/genética , Funções Verossimilhança , Modelos Genéticos , Alinhamento de Sequência , Análise de Sequência de DNA
19.
Cell Reprogram ; 14(1): 88-97, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22313114

RESUMO

Blood cells transfusion and hematopoietic stem cells (HSCs) transplantation are important methods for cell therapy. They are widely used in the treatment of incurable hematological disorder, infectious diseases, genetic diseases, and immunologic deficiency. However, their availability is limited by quantity, capacity of proliferation and the risk of blood transfusion complications. Recently, human embryonic stem cells (hESCs) have been shown to be an alternative resource for the generation of hematopoietic cells. In the current study, we describe a novel method for the efficient production of hematopoietic cells from hESCs. The stable human fetal liver stromal cell lines (hFLSCs) expressing erythropoietin (EPO) were established using the lentiviral system. We observed that the supernatant from the EPO transfected hFLSCs could induce the hESCs differentiation into hematopoietic cells, especially erythroid cells. They not only expressed fetal and embryonic globins but also expressed the adult-globin chain on further maturation. In addition, these hESCs-derived erythroid cells possess oxygen-transporting capacity, which indicated hESCs could generate terminally mature progenies. This should be useful for ultimately developing an animal-free culture system to generate large numbers of erythroid cells from hESCs and provide an experimental model to study early human erythropoiesis.


Assuntos
Células-Tronco Embrionárias/citologia , Eritropoetina/metabolismo , Feto/citologia , Hematopoese/fisiologia , Fígado/citologia , Células Estromais/citologia , Células Estromais/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Células-Tronco Embrionárias/fisiologia , Células Eritroides/citologia , Células Eritroides/metabolismo , Eritropoetina/genética , Globulinas Fetais/metabolismo , Humanos , Lentivirus/genética , Fígado/embriologia , Fígado/metabolismo , Transfecção
20.
J Mol Med (Berl) ; 90(4): 389-400, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22038097

RESUMO

Human mesenchymal stem cells (MSCs) have therapeutic potential because of their ability to self-renew and differentiate into multiple tissues. However, senescence often occurs in MSCs when they are cultured in vitro and the molecular mechanisms underlying this effect remain unclear. In this study, we found that NAD-dependent protein deacetylase SIRT1 is differentially expressed in both human bone marrow-derived MSCs (B-MSCs) and adipose tissue-derived MSCs after increasing passages of cell culture. Using lentiviral shRNA we demonstrated that selective knockdown of SIRT1 in human MSCs at early passage slows down cell growth and accelerates cellular senescence. Conversely, overexpression of SIRT1 delays senescence in B-MSCs that have undergone prolonged in vitro culturing and the cells do not lose adipogenic and osteogenic potential. In addition, we found that the delayed accumulation of the protein p16 is involved in the effect of SIRT1. However, resveratrol, which has been used as an activator of SIRT1 deacetylase activity, only transiently promotes proliferation of B-MSCs. Our findings will help us understand the role of SIRT1 in the aging of normal diploid cells and may contribute to the prevention of human MSCs senescence thus benefiting MSCs-based tissue engineering and therapies.


Assuntos
Células-Tronco Mesenquimais/citologia , Sirtuína 1/metabolismo , Tecido Adiposo/citologia , Adulto , Células da Medula Óssea/citologia , Diferenciação Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Senescência Celular , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Resveratrol , Sirtuína 1/genética , Estilbenos/farmacologia , Regulação para Cima , Adulto Jovem
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