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1.
Cells Tissues Organs ; 207(3-4): 165-176, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31726456

RESUMO

OBJECTIVE: To elaborate the mechanism of miR-150 in the regulation of the NF-κB signal pathway in intervertebral disc degeneration (IDD) by targeting P2X7. METHODS: The degenerative and normal intervertebral disc tissues were collected to detect the expressions of miR-150 and P2X7. Nucleus pulposus cells were transfected and divided into different groups. Cell apoptosis was determined by flow cytometry and TUNEL staining. The expressions of IL-6, TNF-α, MMP-3, MMP-13, Cox-2, iNOS, collagen II and aggrecan, as well as NF-κB-associated proteins were measured by qRT-PCR and Western blotting. Furthermore, IDD rat models were established to validate the role of miR-150 in vivo. RESULTS: miR-150 was down-regulated but P2X7 was up-regulated in the degenerative intravertebral disc tissues. The apoptosis of nucleus pulposus cells in the IL-1ß-induced group with the transfection of miR-150 mimic and siP2X7 was significantly decreased, with reduced levels of IL-6, TNF-α, MMP-3, MMP-13, Cox-2 and iNOS, increased levels of collagen II and aggrecan, as well as decreased P2X7, p-p65/p65 and cleaved caspase-3. However, the above factors showed an opposite tendency after treatment with miR-150 inhibitor. Furthermore, the P2X7 siRNA transfection could reverse the effects caused by miR-150 inhibitor. Simultaneously, pcDNA P2X7 transfection also inhibited the function of miR-150 mimic in IL-1ß-induced nucleus pulposus cells. In vivoexperiments further verified the protective role of miR-150 in IDD rats. CONCLUSION: miR-150 may alleviate the degeneration of the intervertebral disc partially since it could restrict the NF-κB pathway by targeting P2X7, and thereby inhibiting IL-1ß-induced matrix catabolism, inflammatory responses and apoptosis of the nucleus pulposus cells.

2.
Sci Transl Med ; 11(502)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31341059

RESUMO

TYK2 is a nonreceptor tyrosine kinase involved in adaptive and innate immune responses. A deactivating coding variant has previously been shown to prevent receptor-stimulated activation of this kinase and provides high protection from several common autoimmune diseases but without immunodeficiency. An agent that recapitulates the phenotype of this deactivating coding variant may therefore represent an important advancement in the treatment of autoimmunity. BMS-986165 is a potent oral agent that similarly blocks receptor-stimulated activation of TYK2 allosterically and with high selectivity and potency afforded through optimized binding to a regulatory domain of the protein. Signaling and functional responses in human TH17, TH1, B cells, and myeloid cells integral to autoimmunity were blocked by BMS-986165, both in vitro and in vivo in a phase 1 clinical trial. BMS-986165 demonstrated robust efficacy, consistent with blockade of multiple autoimmune pathways, in murine models of lupus nephritis and inflammatory bowel disease, supporting its therapeutic potential for multiple immune-mediated diseases.

3.
J Control Release ; 308: 119-129, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31325471

RESUMO

Exosomes, which are nano-vesicles produced by most cell types, play an irreplaceable role in cell-cell communication. They are extracellular small vesicles that can delivery various cargos of DNA, RNAs, proteins, and lipids. Because exosomes have different secretory components under physiological conditions and pathological conditions, it has been extensively studied in the field of diseases as a therapeutic target, as a drug/gene delivery vector and as a novel cancer marker. Despite the great development in recent decades, there are still many obstacles to be overcome, for example, the separation method is not standardized with low yield and poor stability, which limit its medical application. This review mainly summarizes the main progresses of isolation and identification techniques, diversity function and medical application of exosomes in recent years.

4.
Int J Biol Macromol ; 131: 378-386, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30851326

RESUMO

The desmosome is a member of intercellular junctions that named 'anchoring junction', which contributes to the integrity and homeostasis of tissue structure and function of multicellular living organisms. As an important component of the desmosome and the most widely distributed isoform of desmocollins (DSCs), desmocollin2 (DSC2) has been demonstrated to be essential for the unity of epithelial cells, and served as a vital regulator in signaling processes such as epithelial morphogenesis, differentiation, wound healing, cell apoptosis, migration, and proliferation. Recent studies suggested that the aberrant expression or disruption of DSC2 might lead to some disorders, including heart disorders, certain cancers, and some other human diseases. The distinctions in expression and regulation mechanisms of DSC2 in different human diseases provided a potential target for diagnosis and individualized treatment. Further research is required to certify the signaling capacity of DSC2 and to shed light on the down-stream consequences of the signaling for us to understand the new area of DSC2 biology and the development of certain diseases. This review summarizes the molecular structure and dynamics of desmosome and DSC2, the relationship between the disruption or aberrant expression of DSC2 and human diseases and related molecular mechanisms, as well as the possible prospects.


Assuntos
Desmocolinas/genética , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Animais , Cálcio/metabolismo , Desmocolinas/química , Desmocolinas/metabolismo , Desmossomos/genética , Desmossomos/metabolismo , Humanos , Mutação , Transporte Proteico , Transdução de Sinais , Relação Estrutura-Atividade
5.
Anticancer Drugs ; 29(6): 503-512, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29697412

RESUMO

Galaxamide is a rare cyclic homopentapeptide composed of three leucines and two N-methyl leucines isolated from marine algae Galaxaura filamentosa. The strong antitumor activity of this compound makes it a promising candidate for tumor therapy. The synthesis of galaxamide, however, is a complex process, and it has poor water solubility. On the basis of its special chemical composition, we designed a series of linear leucine homopeptides. Among seven dipeptide derivatives, five compounds with terminal protection groups and methyl substitution of the hydrogen in the amido group showed remarkable inhibitory effects against various cancer cells. N-tertbutyl-D-leucine-N-methyl-D-leucinebenzyl (A7), the only stereomer condensed by two D-leucines, showed the highest antineoplastic activity. A7-treated cells showed cell cycle arrest and morphological changes typical of cells undergoing apoptosis. The population of Annexin-V positive/propidium iodide-negative cells also increased, indicating the induction of early apoptosis. A7 promoted the cleavage of caspase-9 and caspase-3, as well as increased intracellular Ca levels and decreased the mitochondrial membrane potential. Collectively, certain linear leucine dipeptides derived from cyclic pentapeptide are able to inhibit tumor cell proliferation through cell cycle arrest and apoptosis induction. The N-methyl group in the side chain and the D/L conformation of the amino-acid residue are critical for their activity.


Assuntos
Dipeptídeos/química , Dipeptídeos/farmacologia , Neoplasias/tratamento farmacológico , Células A549 , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Compostos de Benzil/síntese química , Compostos de Benzil/química , Compostos de Benzil/farmacologia , Ciclo Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ésteres/síntese química , Ésteres/química , Ésteres/farmacologia , Células HeLa , Células Hep G2 , Humanos , Células MCF-7 , Neoplasias/patologia
6.
Zhongguo Gu Shang ; 30(4): 349-352, 2017 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-29349986

RESUMO

OBJECTIVE: To observe the curative effect of musculoskeletal ultrasound-guided needle-knife on the degenerative meniscus disease, and to provide a new method in the treatment of degenerative meniscus disease. METHODS: Seventy-seven patients with degenerative meniscus disease treated in the Third Affiliated Hospital of Beijing University of Chinese Medicine from January 2015 to September 2015 were selected, including 30 males and 47 females, aged from 44 to 66 years old, with an average of 57.5 years old. VAS scores, Lysholm scores and distance of meniscal protrusion were analyzed and compared before treatment, 2 weeks and 1 month after treatment. The curative effect was summarized at last. RESULTS: The mean Lysholm scores were 51.63±15.26(before treatment), 77.13±11.82(2 weeks after treatment) and 87.56±8.65(1 month after treatment). The mean VAS scores were 7.080±1.574 (before treatment), 2.630±0.310(2 weeks after treatment) and 0.850±0.177(1 month after treatment). The mean of the distance of meniscal protrusion scores were 0.400±0.156 (before treatment), 0.298±0.140 (2 weeks after treatment) and 0.240±0.110 (1 month after treatment). VAS scores and Lysholm scores were improved significantly compared with preoperative results. The distance of meniscal protrusion showed an obvious improvement after treatment. CONCLUSIONS: The treatment of musculoskeletal ultrasound-guided needle-knife has advantages of high accuracy position and excellent effectiveness for degenerative meniscus disease. The treatment provides safety operation and significantly improves quality of life in patients without any complications.


Assuntos
Doenças das Cartilagens/cirurgia , Meniscos Tibiais , Instrumentos Cirúrgicos , Adulto , Idoso , Artroscopia , Feminino , Humanos , Articulação do Joelho , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento , Ultrassonografia de Intervenção
7.
Zhonghua Nan Ke Xue ; 22(1): 6-11, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-26931018

RESUMO

OBJECTIVE: To investigate the effects of single heat stress treatment on spermatogenic cells in mice. METHODS: We randomly divided 36 C57 male mice into a control and a heat stress treatment group and submerged the lower part of the torso in water at 25 °C and 43 °C, respectively, both for 15 minutes. At 1, 7, and 14 days after treatment, we obtained the testicular organ indexes, observed the changes in testicular morphology by HE staining, and determined the location and expression levels of the promyelocytic leukemia zinc finger (PLZF) and synaptonemal comlex protein-3 (SCP-3) in the testis tissue by immunohistochemistry and Western blot. RESULTS: The testicular organ index was significantly lower in the heat stress treatment than in the control group (P < 0.05). Compared with the controls, the heat shock-treated mice showed loosely arranged spermatogenic cells scattered in the seminiferous tubules at 1 day after heat stress treatment, atrophied, loosely arranged and obviously reduced number of spermatogenic cells at 7 days, and relatively closely arranged seminiferous tubules and increased number and layers of spermatogenic cells at 14 days. The number of SCP-3 labelled spermatocytes obviously decreased in the heat stress-treated animals at 1 and 7 days and began to increase at 14 days. The PLZF protein expression was significantly reduced in the heat stress treatment group at 1 day as compared with that in the control (0.19 ± 0.12 vs 0.64 ± 0.03, P < 0.01), but elevated to 0.77 ± 0.02 at 7 and 14 days, even remarkably higher than in the control animals (P < 0.01). CONCLUSION: Heat stress treatment can induce short-term dyszoospermia in mice, which can be recovered with the prolonged time after treatment.


Assuntos
Temperatura Alta , Proteínas Nucleares/metabolismo , Espermatócitos/patologia , Testículo/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Western Blotting , Proteínas de Ligação a DNA , Imuno-Histoquímica , Masculino , Camundongos , Proteína da Leucemia Promielocítica , Túbulos Seminíferos/citologia , Espermatócitos/citologia
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(5): 763-767, 2016 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-28598095

RESUMO

OBJECTIVES: To determine the prevalence and determinants of depressive symptoms in the mid- and old-aged people in China. METHODS: Data were extracted from the 2013 China Health and Retirement Longitudinal Study (CHARLS),which containthe Center Epidemiologic Studies-Depression scale(CES-D). Binary logistic regression models were developed to identify factors associated with the prevalence of depression symptoms. These included socio-economic status of the respondents (gender, age, education),health-related factors (chronic diseases, disability, accident injury, and fall in recent two years),and family events over the past two years (deaths of a parent, spouse or child). RESULTS: About 31.9% of respondents had depressive symptoms, with a mean CES-D score of 8.0±4.9.Women and those who were younger than 75 years, widowed, resided in a rural area, had low levels of education, and suffered from multiple chronic conditions were more likely to have depressive symptoms than the others. CONCLUSIONS: High prevalence of depressive symptoms in the mid- and old-aged population in China is evident, which is associated with the health and socio-economic status of the population.


Assuntos
Depressão/epidemiologia , Classe Social , Idoso , China/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Prevalência , Escalas de Graduação Psiquiátrica , Fatores de Risco
9.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(6): 4142-4143, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-25799352

RESUMO

Animal models play an important role in osteoarthritis studies. Here, the complete mitochondrial genome sequence of the spontaneous mice DBA/1 strain was reported for the first time. The total length of the mitogenome was 16,769 bp. It contained the typical structure, including two ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes, and one non-coding control region (D-loop region). The overall GC content of the mitogenome was estimated to be 39.2%. This mitochondrial genome sequence will provide new genetic resource into osteoarthritis disease.


Assuntos
Mitocôndrias/genética , Osteoartrite/genética , Sequenciamento Completo do Genoma/métodos , Animais , Composição de Bases , Modelos Animais de Doenças , Tamanho do Genoma , Genoma Mitocondrial , Camundongos , Camundongos Endogâmicos DBA , Fases de Leitura Aberta , RNA Ribossômico/genética , RNA de Transferência/genética
10.
J Pharmacol Exp Ther ; 354(2): 152-65, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26015463

RESUMO

Therapies targeting either interleukin (IL)-23 or IL-17 have shown promise in treating T helper 17 (Th17)-driven autoimmune diseases. Although IL-23 is a critical driver of IL-17, recognition of nonredundant and independent functions of IL-23 and IL-17 has prompted the notion that dual inhibition of both IL-23 and IL-17 could offer even greater efficacy for treating autoimmune diseases relative to targeting either cytokine alone. To test this hypothesis, we generated selective inhibitors of IL-23 and IL-17 and tested the effect of either treatment alone compared with their combination in vitro and in vivo. In vitro, using a novel culture system of murine Th17 cells and NIH/3T3 fibroblasts, we showed that inhibition of both IL-23 and IL-17 completely suppressed IL-23-dependent IL-22 production from Th17 cells and cooperatively blocked IL-17-dependent IL-6 secretion from the NIH/3T3 cells to levels below either inhibitor alone. In vivo, in the imiquimod induced skin inflammation model, and in the myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis model, we demonstrated that dual inhibition of IL-17 and IL-23 was more efficacious in reducing disease than targeting either cytokine alone. Together, these data support the hypothesis that neutralization of both IL-23 and IL-17 may provide enhanced benefit against Th17 mediated autoimmunity and provide a basis for a therapeutic strategy aimed at dual targeting IL-23 and IL-17.


Assuntos
Autoimunidade/imunologia , Encefalomielite Autoimune Experimental/imunologia , Interleucina-17/antagonistas & inibidores , Interleucina-17/imunologia , Interleucina-23/antagonistas & inibidores , Interleucina-23/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Autoimunidade/efeitos dos fármacos , Técnicas de Cocultura , Encefalomielite Autoimune Experimental/tratamento farmacológico , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Distribuição Aleatória
11.
Proteins ; 82(10): 2455-71, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24854765

RESUMO

Computational prediction of RNA-binding residues is helpful in uncovering the mechanisms underlying protein-RNA interactions. Traditional algorithms individually applied feature- or template-based prediction strategy to recognize these crucial residues, which could restrict their predictive power. To improve RNA-binding residue prediction, herein we propose the first integrative algorithm termed RBRDetector (RNA-Binding Residue Detector) by combining these two strategies. We developed a feature-based approach that is an ensemble learning predictor comprising multiple structure-based classifiers, in which well-defined evolutionary and structural features in conjunction with sequential or structural microenvironment were used as the inputs of support vector machines. Meanwhile, we constructed a template-based predictor to recognize the putative RNA-binding regions by structurally aligning the query protein to the RNA-binding proteins with known structures. The final RBRDetector algorithm is an ingenious fusion of our feature- and template-based approaches based on a piecewise function. By validating our predictors with diverse types of structural data, including bound and unbound structures, native and simulated structures, and protein structures binding to different RNA functional groups, we consistently demonstrated that RBRDetector not only had clear advantages over its component methods, but also significantly outperformed the current state-of-the-art algorithms. Nevertheless, the major limitation of our algorithm is that it performed relatively well on DNA-binding proteins and thus incorrectly predicted the DNA-binding regions as RNA-binding interfaces. Finally, we implemented the RBRDetector algorithm as a user-friendly web server, which is freely accessible at http://ibi.hzau.edu.cn/rbrdetector.


Assuntos
Algoritmos , Biologia Computacional/métodos , Conformação Proteica , Proteínas de Ligação a RNA/química , RNA/química , Software , Bases de Dados de Proteínas , Humanos , Modelos Moleculares
12.
J Int Med Res ; 41(4): 1258-65, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23860014

RESUMO

OBJECTIVE: To explore the correlation between the level of social support and the extent of anxiety and depression in Chinese men undergoing in vitro fertilization embryo transfer (IVF-ET) for the first time, in order to provide a basis for male mental health counselling. METHODS: Self-administered questionnaires covering general health status, anxiety (self-rating anxiety scale), depression (self-rating depression scale) and social support (social support rating scale) were completed by men undergoing their first round of IVF-ET. RESULTS: A total of 502 completed questionnaires were considered valid and were analysed. The anxiety, depression and social support scores for men undergoing their first round of IVF-ET were significantly higher than those for Chinese normative data. Social support was inversely correlated with anxiety and depression. CONCLUSIONS: These findings suggest that health care professionals should provide specific psychological counselling to Chinese men undergoing their first round of IVF-ET, in order to improve their psychological health and to facilitate increased levels of social support.


Assuntos
Ansiedade/psicologia , Depressão/psicologia , Transferência Embrionária , Infertilidade Masculina/psicologia , Apoio Social , Adulto , Feminino , Fertilização In Vitro , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Autorrelato , Estresse Psicológico , Inquéritos e Questionários
13.
Bioorg Med Chem ; 20(8): 2747-61, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22410249

RESUMO

A series of novel angiotensin II type 1 receptor antagonists were prepared. Radioligand binding assay suggested that compounds 1b and 1c could be recognized by the AT(1) receptor with an IC(50) value of 1.6 ± 0.09 nM and 2.64 ± 0.7 nM, respectively. In vivo anti-hypertension experiments showed that compounds (1a, 1b, 1c, 1e) elicited a significant decrease in SBP and DBP of spontaneous hypertensive rats (SHRs). The antihypertensive effects maintained for 10 h, which indicated that these compounds had a favorable blood pressure-lowering effect. Acute toxicity testing suggested that the LD(50) value of compound 1b was 2316.8 mg/kg which was lower than valsartan (LD(50)=307.50 mg/kg) but higher than losartan (LD(50)=2248 mg/kg). So they could be considered as novel anti-hypertension candidates and deserved for further investigation.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/síntese química , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Anti-Hipertensivos/síntese química , Anti-Hipertensivos/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/química , Animais , Anti-Hipertensivos/química , Pressão Sanguínea/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Conformação Molecular , Estrutura Molecular , Ratos , Ratos Endogâmicos SHR
14.
Bioorg Med Chem Lett ; 21(23): 7006-12, 2011 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-22018461

RESUMO

The synthesis, structure-activity relationships (SAR), and biological results of pyridyl-substituted azaindole based tricyclic inhibitors of IKK2 are described. Compound 4m demonstrated potent in vitro potency, acceptable pharmacokinetic and physicochemical properties, and efficacy when dosed orally in a mouse model of inflammatory bowel disease.


Assuntos
Acetamidas/química , Descoberta de Drogas , Inibidores Enzimáticos/química , Compostos Heterocíclicos com 3 Anéis/química , Quinase I-kappa B/antagonistas & inibidores , Acetamidas/síntese química , Acetamidas/farmacologia , Administração Oral , Animais , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Compostos Heterocíclicos com 3 Anéis/síntese química , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Concentração Inibidora 50 , Camundongos , Estrutura Molecular , Ratos , Relação Estrutura-Atividade
15.
Bioorg Med Chem ; 18(17): 6282-91, 2010 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-20691601

RESUMO

Photodynamic therapy (PDT) represents a promising method for treatment of cancerous tumors. The chemical and physical properties of used photosensitizer play key roles in the treatment efficacy. In this study, a novel photosensitizer, Chlorin-H [-13,15-N-(cyclohexyl)cycloimide] which displayed a characteristic long wavelength absorption peak at 698nm was synthesized. Following flash photolysis with 355nm laser, Chlorin-H is potent to react with O(2) and then produce (1)O(2). This finding indicates that Chlorin-H takes its effects through type II mechanism in PDT. Generally, Chlorin-H is localized in mitochondria and nucleus of cell. After light irradiation with 698nm laser, it can kill many types of cell, inhibit cell proliferation and colony formation, suppress cancer cell invasiveness and trigger apoptosis via the mitochondrial pathway in A549 cells in vitro. In addition, Chlorin-H-PDT can destroy A549 tumor in nude mice and a necrotic scab was formed eventually. The expression levels of many genes which regulated cell growth and apoptosis were determined by RT-PCR following Chlorin-H-PDT. The results showed that it either increased or decrease. Among which, the expression level of TNFSF13, a member of tumor necrosis factor superfamily, increased significantly. Silencing of TNFSF13 caused by RNA interference decreased the susceptibility of A549 cells to Chlorin-H-PDT. In general, Chlorin-H is an effective antitumor photosensitizer in vitro and in vivo and is worthy of further study as a new drug candidate. TNFSF13 will be an important molecular target for the discovery of new photosensitizers.


Assuntos
Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Fármacos Fotossensibilizantes/síntese química , Porfirinas/síntese química , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
Br J Pharmacol ; 159(4): 909-18, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20067467

RESUMO

BACKGROUND AND PURPOSE: Many bromopyrrole compounds have been reported to have in vitro antineoplastic activity. In a previous study, we isolated N-(4, 5-dibromo-pyrrole-2-carbonyl)-L-amino isovaleric acid methyl ester (B6) from marine sponges. Here, we investigated the in vitro and in vivo antineoplastic activity of B6 and its potential mechanism. EXPERIMENTAL APPROACH: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine the in vitro antineoplastic activity of B6. Flow cytometry, western blot analysis and morphological observations were used to investigate its mechanism of action. A mouse xenograft model was used to determine its in vivo activity. KEY RESULTS: B6 inhibited the proliferation of various human cancer cells in vitro, with highest activity on LOVO and HeLa cells. B6 also exhibited significant growth inhibitory effects in vivo in a xenograft mouse model. Acute toxicity analysis suggested that B6 has low toxicity. B6-treated cells arrested in the G1 phase of the cell cycle and had an increased fraction of sub-G1 cells. In addition, the population of Annexin V-positive/propidium iodide-negative cells increased, indicating the induction of early apoptosis. Indeed, B6-treated cells exhibited morphologies typical of cells undergoing apoptosis. Western blotting showed cleaved forms of caspase-9 and caspase-3 in cells exposed to B6. Moreover, B6-promoted Ca(2+) release and apoptosis was associated with elevated intracellular Ca(2+)concentration. CONCLUSIONS AND IMPLICATIONS: B6 has significant antineoplastic activity in vitro as well as in vivo. It inhibits tumour cell proliferation by arresting the cell cycle and inducing apoptosis. With its low toxicity, B6 represents a promising antineoplastic, primary compound.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Poríferos , Pirróis/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Western Blotting , Cálcio/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Citometria de Fluxo , Células HeLa , Hemiterpenos , Células Hep G2 , Humanos , Dose Letal Mediana , Masculino , Camundongos , Neoplasias/patologia , Poríferos/química , Pirróis/isolamento & purificação , Pirróis/toxicidade , Fatores de Tempo , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Nanotechnology ; 20(13): 135102, 2009 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19420486

RESUMO

Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic targeting. Nevertheless, no previous attempt has been reported to develop an in vivo magnetic drug delivery system with chitosan nanoparticles for magnetic resonance imaging (MRI) monitored targeting photodynamic therapy. In this study, magnetic targeting chitosan nanoparticles (MTCNPs) were prepared and tailored as a drug delivery system and imaging agents for PS, designated as PHPP. Results showed that PHPP-MTCNPs could be used in MRI monitored targeting PDT with excellent targeting and imaging ability. Non-toxicity and high photodynamic efficacy on SW480 carcinoma cells both in vitro and in vivo were achieved with this method at the level of 0-100 microM. Notably, localization of nanoparticles in skin and hepatic tissue was significantly less than in tumor tissue, therefore photosensitivity and hepatotoxicity can be attenuated.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Imagem por Ressonância Magnética/métodos , Nanopartículas/uso terapêutico , Fotoquimioterapia/métodos , Animais , Linhagem Celular Tumoral , Quitosana , Campos Eletromagnéticos , Humanos , Camundongos , Camundongos Nus , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Porfirinas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 1): m69, 2009 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-21579963

RESUMO

In the title mononuclear complex, [Cu(C(14)H(10)O(3))(C(12)H(8)N(2))(H(2)O)], the Cu(II) atom is five-coordinated by two N atoms from a 1,10-phenanthroline (phen) ligand, two O atoms from a benzilate ligand and one O atom from a water mol-ecule in a distorted square-pyramidal geometry. The crystal structure is stabilized via inter-molecular O-H⋯O and C-H⋯O hydrogen bonds, C-H⋯π inter-actions and π-π stacking inter-actions between the pyridine and benzene rings of neighboring phen ligands [centroid-centroid distances = 3.684 (2), 3.564 (2) and 3.380 (1) Å].

19.
Nanoscale Res Lett ; 4(5): 400-408, 2009 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-20596490

RESUMO

As a fast developing alternative of traditional therapeutics, photodynamic therapy (PDT) is an effective, noninvasive, nontoxic therapeutics for cancer, senile macular degeneration, and so on. But the efficacy of PDT was compromised by insufficient selectivity and low solubility. In this study, novel multifunctional silica-based magnetic nanoparticles (SMNPs) were strategically designed and prepared as targeting drug delivery system to achieve higher specificity and better solubility. 2,7,12,18-Tetramethyl-3,8-di-(1-propoxyethyl)-13,17-bis-(3-hydroxypropyl) porphyrin, shorted as PHPP, was used as photosensitizer, which was first synthesized by our lab with good PDT effects. Magnetite nanoparticles (Fe(3)O(4)) and PHPP were incorporated into silica nanoparticles by microemulsion and sol-gel methods. The prepared nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and fluorescence spectroscopy. The nanoparticles were approximately spherical with 20-30 nm diameter. Intense fluorescence of PHPP was monitored in the cytoplasm of SW480 cells. The nanoparticles possessed good biocompatibility and could generate singlet oxygen to cause remarkable photodynamic anti-tumor effects. These suggested that PHPP-SMNPs had great potential as effective drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy. GRAPHICAL ABSTRACT: Novel multifunctional photosensitizer loaded magnetic silica nanoparticles were strategically prepared with low toxicity, good biocompatibility and remarkable photodynamic anti-tumor efficacy. The nanoparticles were believed to be of great value as drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy.

20.
Huan Jing Ke Xue ; 29(9): 2606-12, 2008 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-19068651

RESUMO

The genetic and eco-toxic effects of Cd (0-10 mg x kg(-1)) were studied with Vicia faba (broad bean) as the test species using meadow brown soil in pot experiments by means of several indexes, such as Vicia faba root tip micronucleus frequency (MCN), mitosis index (MI), and chromosomal aberrations frequency (CAF), antioxidant enzymes superoxide dismutases (SOD), peroxidases (POD), catalase (CAT) and phytohormone abscisic acid (ABA), gibberellic acid (GA3) and zeatin and zeatin riboside (Z&ZR). Results indicated the significant positive dose-response correlations were found between Cd2+ concentrations and the tested indexes (MI, MCN and CAF). Among of them, MCN is the most sensitive, and the MCN frequencies were 1.43-3.22 times higher in Cd treatment soils than that of in the controls. SOD and POD in seedling leaves of broad bean were response to the Cd stress, showing a trend of increase with Cd concentrations initially and then decreased. The CAT response to Cd in soils was opposite to that of SOD and POD. In addition, there were stimulation and inhabitation effects between Cd and ABA, GA3 and Z&ZR in lower and higher Cd concentrations. The highest contents of phytohormone (ABA, GA3 and Z&ZR) were found when Cd was at 2.5 mg x kg(-1), which was 6.6%, 4.0% and 12.6% higher than that in the control, respectively. Our study indicated that all indexes were response to the Cd stress in soils, but the sensitivity of each index was different from each other. All these indexes combined should be more efficiency in the diagnosis of geno-, and eco-toxicity of cadmium in soils.


Assuntos
Cádmio/toxicidade , Poluentes do Solo/toxicidade , Vicia faba/efeitos dos fármacos , Cádmio/análise , Testes para Micronúcleos , Reguladores de Crescimento de Planta/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Poluentes do Solo/análise , Superóxido Dismutase/metabolismo , Vicia faba/genética , Vicia faba/metabolismo
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