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1.
ACS Nano ; 13(7): 7556-7567, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31259530

RESUMO

Bone metastasis, a clinical complication of patients with advanced breast cancer, seriously reduces the quality of life. To avoid destruction of the bone matrix, current treatments focus on inhibiting the cancer cell growth and the osteoclast activity through combination therapy. Therefore, it could be beneficial to develop a bone-targeted drug delivery system to treat bone metastasis. Here, a bone-targeted nanoplatform was developed using gold nanorods enclosed inside mesoporous silica nanoparticles (Au@MSNs) which were then conjugated with zoledronic acid (ZOL). The nanoparticles (Au@MSNs-ZOL) not only showed bone-targeting ability in vivo but also inhibited the formation of osteoclast-like cells and promoted osteoblast differentiation in vitro. The combination of Au@MSNs-ZOL and photothermal therapy (PTT), triggered by near-infrared irradiation, inhibited tumor growth both in vitro and in vivo and relieved pain and bone resorption in vivo by inducing apoptosis in cancer cells and improving the bone microenvironment. This single nanoplatform combines ZOL and PTT to provide an exciting strategy for treating breast cancer bone metastasis.

2.
Neuroscience ; 371: 469-483, 2018 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-29292077

RESUMO

Fragile X syndrome (FXS), the leading cause of inherited forms of mental retardation and autism, is caused by the transcriptional silencing of fmr1 encoding the fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that is a widely expressed, but primarily in the brain and testis, and associated approximately 4% of transcripts. Macro-orchidism is a common symptom associated with FXS both in humans and mice. Thus, we analyze the pooled samples of cerebral cortex, hippocampus and testis from both the fmr1-KO and wild-type mice by a LC-MS/MS proteomic study. Among the identified proteins, most of those showing significant changes in expression were up- or downregulated in the absence of FMRP. Proteins (FMRP, RPS8, RPL23a and ATPIF1, RPL6, GAP43, MTCH2 and MPZ in brain, and FMRP, CAH3, AKR1B7 and C9 in testis) identified by MS/MS were also verified by Western blotting. The Gene Ontology and WikiPathways analysis revealed that the differentially expressed proteins were clustered in the polyribosome and RNA-binding protein categories in both cerebral cortex and hippocampus, but not in testis. Although this study was limited by the little number of samples, our results provide detailed insights into the ribosomal protein profiles of cerebral cortex, hippocampus and testis in the absence of FMRP. Our studies also provide a better understanding of protein profile changes and the underlying dysregulated pathways arising from fmr1 silencing in FXS.


Assuntos
Córtex Cerebral/metabolismo , Síndrome do Cromossomo X Frágil/metabolismo , Hipocampo/metabolismo , Proteoma , Proteínas Ribossômicas/metabolismo , Testículo/metabolismo , Animais , Western Blotting , Cromatografia Líquida , Modelos Animais de Doenças , Masculino , Espectrometria de Massas , Camundongos Knockout , Proteômica
3.
J Xray Sci Technol ; 25(1): 79-91, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27802249

RESUMO

OBJECTIVE: To investigate the differences in imaging quality and radiation dose in CT pulmonary angiography (CTPA) by using fast-kV switching dual energy CT imaging and 3D Smart mA modulation at different body mass indices (BMIs) and at different noise index (NI) values with an adaptive statistical iterative reconstruction (ASIR) algorithm. METHODS: Four hundred patients who underwent CTPA were equally divided into two groups: A (18.5 kg/m2 ≦ BMI <24.9 kg/m2) and B (24.9 kg/m2 ≦ BMI ≦ 4.9 kg/m2). The groups were randomly subdivided into four subgroups (n = 50): A1-A4 and B1-B4. The patients in subgroups A1 and B1 underwent fast-kV switching dual energy CT imaging. The other patients underwent 3D Smart mA modulation with the ASIR algorithm at NI values 26, 36, and 46 for A2/B2, A3/B3, and A4/B4, respectively. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of all images were calculated after CTPA. Images were then subjectively evaluated using a 5-point scale. The volume CT dose index and dose-length product (DLP) were recorded and their means calculated. The DLP was converted to the effective dose (ED). RESULTS: In group A, the SNR, CNR, and subjective image scores showed no statistical differences (P > 0.05). The ED in subgroup A4 was 67.12% and 31.53% lower than that in A1 and A2, respectively. In group B, the variables showed no significant differences between the subgroups B3, B1, and B2 (P > 0.05). The ED in subgroup B3 was 50.12% and 35.95% lower than that in B1 and B2, respectively. CONCLUSIONS: Setting different NI values according to BMIs and applying the ASIR algorithm can more effectively reduce the radiation dose in CTPA than in fast-kV switching dual energy CT, while maintaining image quality. Imaging may be performed at NI = 46 in patients with lower BMI (group A) and at NI = 36 in patients with higher BMI (group B).


Assuntos
Algoritmos , Índice de Massa Corporal , Angiografia por Tomografia Computadorizada/métodos , Interpretação de Imagem Assistida por Computador/métodos , Pulmão/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Pulmão/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico por imagem , Doses de Radiação , Razão Sinal-Ruído
4.
Biosci Biotechnol Biochem ; 80(8): 1451-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27098211

RESUMO

Curcumin is a potential natural anticancer drug with low oral bioavailability because of poor water solubility. The aqueous solubility of curcumin is enhanced by means of modification with the carbohydrate units. Polymerization of the curcumin-containing monomer with carbohydrate-containing monomer gives the water-soluble glycopolymer bearing curcumin pendant residues. The obtained copolymers (P1 and P2) having desirable water solubility were well-characterized by infrared spectroscopy (IR), nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), UV-Vis absorption spectroscopy, and photoluminescence spectroscopy. The copolymer P2 with a molar ratio of 1:6 (curcumin/carbohydrate) calculated from the proton NMR results exhibits a similar anticancer activity compared to original curcumin, which may serve as a potential chemotherapeutic agent in the field of anticancer medicine.


Assuntos
Antineoplásicos/química , Curcumina/análogos & derivados , Lipase/química , Metacrilatos/química , Metilglucosídeos/química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Metilaminas/química , Polimerização , Solubilidade , Soluções , Água/química
5.
DNA Cell Biol ; 35(1): 24-32, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26430912

RESUMO

Different domains of the multifunctional transcription factor Y-box binding protein 1 (YB1) regulate proliferation, differentiation, and apoptosis by transactivating or repressing the promoters of various genes. Here we report that the C-terminal domain of YB1 (YB1 CTD) is involved in endothelial cell proliferation, apoptosis, and tube formation. The oligo pull-down assays demonstrated that YB1 directly binds double-stranded GC box sequences in endothelial cells through the 125-220 amino acids. Adenovirus expression vectors harboring green fluorescent protein (GFP) or GFP-tagged YB1 CTD were constructed and used to infect EA.hy926 endothelial cells. Overexpression of the YB1 CTD significantly increased p21 expression, decreased cyclin B1 expression, and inhibited the proliferation of EA.hy926 cells. YB1 CTD overexpression also increased Bax and active caspase 3 expression, decreased Bcl-2 expression, and induced apoptosis in EA.hy926 cells. Furthermore, overexpression of the YB1 CTD significantly suppressed migration and tube formation in EA.hy926 cells. Finally, YB1 CTD decreased ERK1/2 phosphorylation in EA.hy926 cells. These findings demonstrated vital roles for YB1 in endothelial cell proliferation, apoptosis, and tube formation through transcriptional regulation of GC box-related genes.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Células Endoteliais/fisiologia , Neovascularização Fisiológica/genética , Proteína 1 de Ligação a Y-Box/fisiologia , Diferenciação Celular/genética , Movimento Celular/genética , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Humanos , Domínios e Motivos de Interação entre Proteínas/genética , Estrutura Terciária de Proteína/genética , Transativadores/genética , Transfecção , Proteína 1 de Ligação a Y-Box/química , Proteína 1 de Ligação a Y-Box/genética
6.
Cell Biosci ; 5: 63, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26579219

RESUMO

Nuclear factor κB (NF-κB) is a family of inducible transcription factors that plays a vital role in different aspects of immune responses. NF-κB is normally sequestered in the cytoplasm as inactive complexes via physical association with inhibitory proteins termed IκBs. In response to immune and stress stimuli, NF-κB members become activated via two major signaling pathways, the canonical and noncanonical pathways, and move to the nucleus to exert transcriptional functions. NF-κB is vital for normal immune responses against infections, but deregulated NF-κB activation is a major cause of inflammatory diseases. Accumulated studies suggest the involvement of NF-κB in the pathogenesis of renal inflammation caused by infection, injury, or autoimmune factors. In this review, we discuss the current understanding regarding the activation and function of NF-κB in different types of kidney diseases.

7.
Neurol Res ; 37(11): 974-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26217932

RESUMO

The study was aimed to observe the morphology of intraepidermal nerve fibre (IENF) and to explore the relationships between intraepidermal nerve fibre density (IENFD) and anatomic sites, age, genders and races. Intraepidermal nerve fibre was observed using immunohistochemistry. The relationships between IENFD and anatomic sites, ages, genders and races were analysed by quantitative analysis of IENFD. Five patterns of the IENFs were observed according to the morphological classification. A significant difference was observed in IENFD between different anatomic sites (P < 0.05). A linear negative correlation was observed between IENFD and age (r = - 0.2931, P < 0.01). No significant difference was found between IENFD and genders. Intraepidermal nerve fibre density at distal leg of Chinese (395.54 ± 166.92) was higher than that of Finnish (114.62 ± 32.32, P < 0.01). Skin biopsy may be an effective tool in quantitation of IENFD in healthy individuals. Intraepidermal nerve fibre density is independent of genders, and closely associated with anatomic sites, races and ages.


Assuntos
Fibras Nervosas , Pele/anatomia & histologia , Pele/inervação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Braço/inervação , Criança , Feminino , Pé/inervação , Mãos/inervação , Humanos , Perna (Membro)/inervação , Masculino , Pessoa de Meia-Idade , Coxa da Perna/inervação , Adulto Jovem
8.
Korean J Urol ; 56(7): 519-24, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26175871

RESUMO

PURPOSE: To assess the safety and efficacy of an ultramini nephrostomy tract, which we were using for the first time, combined with flexible ureterorenoscopy (URS) in the treatment of pediatric patients with multiple renal calculi. MATERIALS AND METHODS: Twenty pediatric patients (age, ≤ 6 years) underwent ultramini percutaneous nephrolithotomy (PCNL) combined with flexible URS. The group had multiple renal calculi, which were bilateral in 3 cases and were located in a total of 23 sites. The calculi were located in 2 calyces in 10 cases, scattered in more than 2 calyces in 7 cases, and limited to 1 calyx in 3 cases. The average patient age was 37.35 months (range, 14-68 months). The average stone diameter was 2.0 cm (range, 1-3.0 cm). In all patients, an ultramini nephrostomy tract was established under ultrasound guidance (dilated to F10) with simultaneous sheath placement. The flexible URS was placed into the collecting system during holmium laser lithotripsy. RESULTS: When ultramini PCNL was combined with flexible ureterorenoscopic holmium laser lithotripsy, the complete stone-free rate was 87% (20/23). The average level of hemoglobin decreased to 1.0 g/dL after the operation. No blood transfusions were needed. Levels of blood urea nitrogen, creatinine, and C-reactive protein were not significantly different before and after the operation. The average duration of hospitalization was approximately 4.85 days, and all cases were followed up for 6 to 12 months. No complications were found. CONCLUSIONS: Ultramini PCNL combined with flexible ureterorenoscopic holmium laser lithotripsy is a safe and effective treatment for children with multiple renal calculi.


Assuntos
Cálculos Renais/cirurgia , Nefrostomia Percutânea/métodos , Ureteroscopia/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Cálculos Renais/patologia , Cálculos Renais/ultraestrutura , Tempo de Internação/estatística & dados numéricos , Litotripsia a Laser/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos , Adulto Jovem
9.
J Gastroenterol Hepatol ; 30(3): 609-18, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25168399

RESUMO

BACKGROUND AND AIM: Hepatic cirrhosis is the final stage of liver dysfunction, characterized by diffuse fibrosis, which is the main response to the liver injury. This study is to investigate the effects of ursolic acid (UA) on liver functions and fibrosis in bile duct ligation (BDL) mice and to determine the underlying mechanisms. METHODS: Cultured hepatocytes were treated with lipopolysaccharide (LPS) in the presence or absence of UA. The reactive oxygen species (ROS) level, protein levels of IκBα, iNOS and Cox-2, and NF-κB activation were detected, respectively. C57/BL6 and AMP-activated protein kinase (AMPK)α2(-/-) mice were subjected to BDL for 14 days. UA was administered by gavage. The markers of liver function and oxidative stress, and liver histopathology were analyzed after treatment. RESULTS: Treatment of hepatocytes with UA dose-dependently activates AMPK, which is abolished by silence of liver kinase B1 (LKB1). LPS significantly increased ROS productions, apoptosis, NF-κB activation, and expressions of iNOS and Cox-2 in cultured hepatocytes. All these effects were blocked by co-incubation with UA. Importantly, silence of LKB1, AMPK, or iNOS/Cox-2 by small interference RNA transfection reversed UA-induced effects in cultured cells. In an animal study, 14-day BDL induced liver fibrosis and liver injury, accompanied with increased oxidative stress and protein expressions of iNOS and Cox-2 in liver. Treatment of UA significantly attenuated the BDL-induced detrimental effects in wild-type mice but not in AMPKα2(-/-) mice. CONCLUSION: UA via LKB1-AMPK signaling offers protective effects on BDL-induced liver injury in mice, which may be related to inhibition of oxidative stress.


Assuntos
Proteínas Quinases Ativadas por AMP/fisiologia , Cirrose Hepática/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Animais , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Depressão Química , Relação Dose-Resposta a Droga , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Lipopolissacarídeos/efeitos adversos , Lipopolissacarídeos/antagonistas & inibidores , Cirrose Hepática/etiologia , Hepatopatias/etiologia , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/genética
10.
Cell Biosci ; 4(1): 70, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25485089

RESUMO

BACKGROUND: Chemical crosslinking is the most straightforward method to produce bispecific antibodies (BsAb) for arming ex vivo activated cytotoxic T lymphocytes. However, heterogeneous polymers are produced by chemical crosslinking. Currently, it is not known under what circumstances or to what extent further purification is needed. RESULTS: In this study, we purified Traut's Reagent-Sulfo-SMCC crosslinked anti-CD3 × anti-HER2 by size-exclusion column chromatography and compared the capacity of the crude and the purified forms of the BsAb in enhancing cytokine-induced killer (CIK) cell-mediated cytotoxicity in vitro. We found that the purified BsAb assisted CIK cells more efficiently than the crude form only when the spontaneous cytotoxicity of the CIK cells was relatively low; otherwise, the two forms performed almost identically. CONCLUSIONS: For the CIK cells of low spontaneous cytotoxicity, purified BsAb is a more powerful substitute for crude BsAb in enhancing their killing efficacy. However, that purification of BsAb is not necessary for robust CIK cells. This phenomenon also corroborates that CIK-mediated cytotoxicity is highly dependent on cell contact.

11.
Biol Trace Elem Res ; 151(3): 415-23, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23292301

RESUMO

The effects of Mn(2+) on the proliferation, osteogenic and adipogenic differentiation of BMSCs were evaluated by employing MTT, ΔΨm, cell cycle, ALP activity, collagen production, ARS and oil red O stain assays. The results indicated that Mn(2+) decreased the viability at most concentrations for 24 h, but the viability was increased with prolonging incubation time. Mn(2+) at the concentrations of 1×10(-7) and 1×10(-6)mol/L decreased ΔΨm in the BMSCs for 48 h. Mn(2+) induced G2/M phase cell cycle arrest at tested concentrations. On day 7 and 10, the effect of Mn(2+) on the osteogenic differentiation depended on concentration, but it inhibited osteogenic differentiation at all tested concentrations for 14 d. The effect of Mn(2+) on the synthesis of collagen of BMSCs depended on concentration for 7 d, but Mn(2+) inhibited the synthesis of collagen at all tested concentrations for 10 d. On day 14, Mn(2+) inhibited the formation of mineralized matrix nodules of BMSCs at all tested concentrations, the inhibitory effect turned to be weaker with prolonging incubation time. Mn(2+) promoted the adipogenic differentiation of BMSCs at all tested concentrations for 10 d, but had no effect with prolonging incubation time. These findings suggested the effects of Mn(2+) on the proliferation, osteogenic differentiation and adipogenic differentiation of BMSCs are very complicated, concentration and incubation time are key factors for switching the biological effects of Mn(2+) from damage to protection.


Assuntos
Adipócitos/citologia , Adipogenia/efeitos dos fármacos , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Manganês/farmacologia , Osteogênese/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Camundongos , Camundongos Endogâmicos , Células Estromais/citologia , Células Estromais/efeitos dos fármacos , Relação Estrutura-Atividade
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