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1.
Cell Mol Neurobiol ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31828466

RESUMO

Neurodegenerative diseases all share several common features such as involvement of oxidative damage and mitochondrial dysfunction in pathogenesis. Oxidative stress induced by overproduction of mitochondrial reactive oxygen species (ROS) or impairment of the antioxidant deficiency results in mitochondrial dysfunction and initiation of the cell death cascade. Berberine (BBR), a traditional Chinese medicine, has been reported to exert anti-oxidative stress and anti-apoptosis effect in CNS diseases. However, the mechanism of BBR on regulating mitophagy and protecting mitochondrial function under oxidative stress remains unclear. In present study, we evaluated the beneficial effects of BBR on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity. Furthermore, we explored the protective role of BBR in mitochondrial function and mitophagy under oxidative stress in PC-12 cells. Our results demonstrated that BBR effectively inhibited t-BHP-induced apoptosis which is associated with the decreased leakage of lactate dehydrogenase (LDH) and ROS overproduction. Moreover, BBR significantly suppressed cytochrome c expression, upregulated the ratio of Bcl-2/Bax, and ameliorated mitochondrial dysfunction by optimizing mitochondria membrane potential (ΔΨm) status and ATP production. In addition, BBR reduced the expression of autophagy-specific marker LC3, SQTM1/p62, and maintained lysosome normal function which involved the restoration of upstream signaling pathway AKT and mTOR phosphorylation level. Collectively, these findings suggested that BBR protects PC-12 cells from oxidative injury through inhibiting ROS level, mitochondria dysfunction, and mitophagy via PI3K/AKT/mTOR signaling pathways, which suggest a potential therapeutic strategy for oxidative stress and neurotoxic damages.

2.
Nanoscale ; 11(35): 16515-16522, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31453606

RESUMO

An electrochemical functionalization method is developed to fabricate N- and O-rich graphene films (F-RGO-60) with an expanded interlayer distance. In particular, the functionalization process could be completed within 60 seconds at room temperature, which is conducive to large-scale commercial applications. Electrochemical synthesis of F-RGO-60 leads to two synergetic effects simultaneously: (1) the expansion of the interlayer distance caused by a bubble effect, which leads to more exposure of the active surface area and (2) the introduction of N-doped sites and oxygen-containing functional groups, which not only improves the hydrophilicity of F-RGO-60 but also provides extra pseudocapacitance. It is worth mentioning that after electrochemical functionalization, F-RGO-60 can still maintain a high density of 1.47 g cm-3. Due to their optimal surface area, good electrolyte wettability and massive redox-active sites, the specific capacitance of F-RGO-60 films can reach up to 319.4 F cm-3 (217.3 F g-1) at 1 A g-1 in a three-electrode system, which is about 3.6 times larger than that of RGO films (60 F g-1). The integration of the low-cost preparation method and outstanding performance suggests that F-RGO-60 has great development prospects as supercapacitor electrode materials.

3.
ChemSusChem ; 12(17): 4046-4053, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31257701

RESUMO

Metallic-state 2D SnS2 nanosheets with expanded lattice spacing and a defect-rich structure were synthesized by the intercalation of Ni into the van der Waals gap of SnS2 . The expanded lattice spacing efficiently enhanced the electrochemical performance of the SnS2 for sodium-ion batteries owing to the change electron state density and energy band structure. In operando synchrotron XRD and theoretical calculations were used to gain insight into the influence of foreign metal-ion doping and its location. The optimized architecture obtained by in situ uniform growth of nanosheets on carbon fibers significantly enhanced the electrochemical performance. The inherent advantages of this architecture are shorter paths for ion insertion and extraction, larger contact area for more sodium diffusion pathways, and superior electrolyte penetration. Benefiting from the Ni intercalated SnS2 bilayer, the internal adjustment of the electronic state and the enlarged interlayer spacing significantly enhanced the electron transport kinetics, which can be explained by the metallic-state properties. The integrated electrode exhibited an initial high reversible capacity of 795 mAh g-1 at 0.1 A g-1 , with a stable capacity retention of 666 mAh g-1 after 100 cycles. Good rate capability was also exhibited with specific capacities of 691, 564, 437 mAh g-1 at current densities of 200, 500, and 1000 mA g-1 , respectively.

4.
Front Pharmacol ; 10: 406, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31105562

RESUMO

Traumatic brain injury (TBI) is one of the most common causes of neurological damage in young human populations. Vitamin B12 has been reported to promote axon growth of neuronal cells after peripheral nerve injury, which is currently used for the treatment of peripheral nerve damage in the clinical trial. Thus, we hypothesized that TBI can be attenuated by vitaminB12 treatment through its beneficial role on axon regeneration after nerve injury. To confirm it, the biological function of vitaminB12 was characterized using hematoxylin and eosin (H&E) staining, Luxol fast blue (LFB) staining, western blot analysis, and immunohistochemistry staining. The results showed that the neurological functional recovery was improved in the VitaminB12-treated group after TBI, which may be due to downregulation of the endoplasmic reticulum stress-related apoptosis signaling pathway. Moreover, the microtubule stabilization, remyelination and myelin reparation were rescued by vitamin B12, which was consistent with the treatment of 4-phenylbutyric acid (4-PBA), an endoplasmic reticulum stress inhibitor. The study suggests that vitamin B12 may be useful as a novel neuroprotective drug for TBI.

5.
ACS Appl Mater Interfaces ; 10(10): 8955-8964, 2018 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-29469567

RESUMO

A novel strategy is proposed to construct a compact-nanobox (CNB) structure composed of irregular nanograins (average diameter ≈ 10 nm), aiming to confine the electrode-electrolyte contact area and enhance initial Coulombic efficiency (ICE) of transition metal oxide (TMO) anodes. To demonstrate the validity of this attempt, CoO-CNB is taken as an example which is synthesized via a carbothermic reduction method. Benefiting from the compact configuration, electrolyte can only contact the outer surface of the nanobox, keeping the inner CoO nanograins untouched. Therefore, the solid electrolyte interphase (SEI) formation is reduced. Furthermore, the internal cavity leaves enough room for volume variation upon lithiation and delithiation, resulting in superior mechanical stability of the CNB structure and less generation of fresh SEI. Consequently, the SEI remains stable and spatially confined without degradation, and hence, the CoO-CNB electrode delivers an enhanced ICE of 82.2%, which is among the highest values reported for TMO-based anodes in lithium-ion batteries. In addition, the CoO-CNB electrode also demonstrates excellent cyclability with a reversible capacity of 811.6 mA h g-1 (90.4% capacity retention after 100 cycles). These findings open up a new way to design high-ICE electrodes and boost the practical application of TMO anodes.

6.
J Neurotrauma ; 35(12): 1329-1344, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29316847

RESUMO

Spinal cord injury (SCI) is a severe nervous system disease that may lead to lifelong disability. Studies have shown that autophagy plays a key role in various diseases; however, the mechanisms regulating cross-talk between autophagy, inflammation, and endoplasmic reticulum (ER) stress during SCI recovery remain unclear. This study was designed to investigate the mechanism by which chloroquine (CQ) inhibits autophagy-associated inflammation and ER stress in rats during their recovery from acute SCI. We evaluated the locomotor function, level of autophagy, and levels of inflammatory cytokines and ER-stress-associated proteins and examined the degradation of the key regulator of inflammation inhibitor of kappa B alpha (I-κBα) through autophagy by analyzing the colocalization of I-κBα, p62, and microtubule-associated protein 1 light chain 3-II. In addition, overexpression of the p62 and activating transcription factor 4 (ATF4) silencing plasmids was used to verify the important roles for autophagic degradation and ER stress. In this study, locomotor function is improved, and autophagy and inflammation are significantly inhibited by, CQ treatment in the model rats. In addition, CQ significantly inhibits the degradation of ubiquitinated I-κBα and blocks the nuclear translocation of nuclear factor kappa B p65 and expression of inflammatory factors. Overexpression of p62 increases I-κBα degradation and improves inflammatory responses. Moreover, CQ treatment also inhibits the activation of ER stress in the rat SCI model, and the ATF4 signaling pathway is required for ER-stress-induced activation of autophagy. These findings reveal a novel mechanism underlying the beneficial effects of CQ on the recovery of SCI, particularly the mechanisms regulating cross-talk between autophagy, inflammation, and ER stress.


Assuntos
Cloroquina/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Inflamação/patologia , Fármacos Neuroprotetores/farmacologia , Traumatismos da Medula Espinal/patologia , Animais , Autofagia/efeitos dos fármacos , Feminino , Inflamação/metabolismo , Inflamação/fisiopatologia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia
7.
Oncotarget ; 8(49): 85949-85968, 2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-29156769

RESUMO

Therapeutics used to treat central nervous system (CNS) injury are designed to promote axonal regeneration and inhibit cell death. Previous studies have shown that liraglutide exerts potent neuroprotective effects after brain injury. However, little is known if liraglutide treatment has neuroprotective effects after spinal cord injury (SCI). This study explores the neuroprotective effects of liraglutide and associated underlying mechanisms. Our results showed that liraglutide could improve recovery after injury by decreasing apoptosis as well as increasing microtubulin acetylation, and autophagy. Autophagy inhibition with 3-methyladenine (3-MA) partially reversed the preservation of spinal cord tissue and decreased microtubule acetylation and polymerization. Additionally, siRNA knockdown of GLP-1R suppressed autophagy and reversed mTOR inhibition induced by liraglutide in vitro, indicating that GLP-1R regulates autophagic flux. GLP-1R knockdown ameliorated the mTOR inhibition and autophagy induction seen with liraglutide treatment in PC12 cells under H2O2 stimulation. Taken together, our study demonstrated that liraglutide could reduce apoptosis, improve functional recovery, and increase microtubule acetylation via autophagy stimulation after SCI. GLP-1R was associated with both the induction of autophagy and suppression of apoptosis in neuronal cultures.

8.
J Nanosci Nanotechnol ; 17(1): 341-7, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-29620833

RESUMO

LiFePO4 (LFP) microparticles coated homogeneously with three-dimensional (3D) carbon nanotube (CNT) conductive networks were successfully prepared via a simple and effective ball milling method by controlling Polyvinylidene fluoride (PVDF) content in cathode electrode slurry. Scanning electron microscopy (SEM) demonstrated that the electrical bridge between the LFP could be well modulated by varying the amount of the CNTs and PVDF. The LFP/CNTs composite with 3 wt% CNTs and 5 wt% PVDF, in which CNTs are embedded in the microspheres homogeneously, possesses the best 3D CNT conductive networks and exhibits the best electrochemical property with high capacity retention of 95.72% at 0.25 C after 50 cycles. Essentially, in comparison with those samples without CNT networks, this CNT network structure can greatly enhance the electrical conductivity, thus markedly improving the electrochemical performance. (LFP) microparticles coated homogeneously with three-dimensional (3D) carbon nanotube (CNT) conductive networks were successfully prepared via a simple and effective ball milling method by controlling Polyvinylidene fluoride (PVDF) content in cathode electrode slurry. Scanning electron microscopy (SEM) demonstrated that the electrical bridge between the LFP could be well modulated by varying the amount of the CNTs and PVDF. The LFP/CNTs composite with 3 wt% CNTs and 5 wt% PVDF, in which CNTs are embedded in the microspheres homogeneously, possesses the best 3D CNT conductive networks and exhibits the best electrochemical property with high capacity retention of 95.72% at 0.25 C after 50 cycles. Essentially, in comparison with those samples without CNT networks, this CNT network structure can greatly enhance the electrical conductivity, thus markedly improving the electrochemical performance.

9.
Shanghai Kou Qiang Yi Xue ; 25(4): 481-483, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-27858075

RESUMO

PURPOSE: To investigate the clinical effect of Nd:YAG laser combined with total glucosides of paeony (TGP) taken orally for the treatment of erosive oral lichen planus (OLP). METHODS: Sixty patients who were diagnosed as erosive OLP with clinical symptoms were divided into experimental group (n=28) and control group (n=32) using a random number table. All patients received TGP while the patients in the experimental group were given Nd:YAG laser irradiation. The clinical effects were evaluated 3 months after treatment. The data were analyzed using SPSS 17.0 software package. RESULTS: Three months later, the average VAS score and sign score had improved significantly to (1.36±1.39) and (2.32±1.56) in the experimental group. The same tendency was observed in the control group and at the time point no significant difference was observed between the experimental group and the control group. The effectiveness of the experimental group was significantly higher than the control group (82.1% vs 53.1%). CONCLUSIONS: Nd: YAG laser combined with TGP can improve the efficacy of erosive OLP. The regime is safe and effective, which is worth of wide clinical application.


Assuntos
Glucosídeos/uso terapêutico , Terapia a Laser , Líquen Plano Bucal/terapia , Paeonia , Terapia Combinada , Humanos , Lasers de Estado Sólido
10.
Chem Asian J ; 11(20): 2911-2917, 2016 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-27468952

RESUMO

Lithium-sulfur (Li-S) batteries are attractive owing to their higher energy density and lower cost compared with the universally used lithium-ion batteries (LIBs), but there are some problems that stop their practical use, such as low utilization and rapid capacity-fading of the sulfur cathode, which is mainly caused by the shuttle effect, and the uncontrollable deposition of lithium sulfide species. Herein, we report the design and fabrication of dual-confined sulfur nanoparticles that were encapsulated inside hollow TiO2 spheres; the encapsulated nanoparticles were prepared by a facile hydrolysis process combined with acid etching, followed by "wrapping" with graphene (G-TiO2 @S). In this unique composite architecture, the hollow TiO2 spheres acted as effective sulfur carriers by confining the polysulfides and buffering volume changes during the charge-discharge processes by means of physical force from the hollow spheres and chemical binding between TiO2 and the polysulfides. Moreover, the graphene-wrapped skin provided an effective 3D conductive network to improve the electronic conductivity of the sulfur cathode and, at the same time, to further suppress the dissolution of the polysulfides. As results, the G-TiO2 @S hybrids exhibited a high and stable discharge capacity of up to 853.4 mA h g-1 over 200 cycles at 0.5 C (1 C=1675 mA g-1 ) and an excellent rate capability of 675 mA h g-1 at a current rate of 2 C; thus, G-TiO2 @S holds great promise as a cathode material for Li-S batteries.

11.
BMC Cancer ; 15: 917, 2015 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-26582454

RESUMO

BACKGROUND: Standardized chemotherapy used in cancer patients with severe kidney insufficiency is ineffective. Although there are some pharmacokinetic studies on cyclophosphamide in kidney insufficiency patients, to the best of our knowledge, the pharmacokinetics and safety of combination of cyclophosphamide and docetaxel as postoperative chemotherapy in a patient with early stage breast cancer undergoing hemodialysis is unclear thus far. CASE PRESENTATION: The patient received regular TC regimen (cyclophosphamide 600 mg/m2, docetaxel 75 mg/m2). She underwent hemodialysis 48 h after chemotherapy. Blood samples at multiple time-points were collected for determination of plasma levels of cyclophosphamide and docetaxel. Pharmacokinetic analyses indicated that compared with the reference data, the in vivo half-life (66.96 h) and drug exposure (150%) of cyclophosphamide significantly increased; however, pharmacokinetic parameters of docetaxel was unaffected. Patient developed grade I thrombocytopenia and grade III leukopenia without any other severe adverse reactions. In total, four cycles of treatment were completed. After the chemotherapy, the patient received tamoxifen as endocrine therapy for one and a half years. No recurrence was reported. CONCLUSION: These results suggest that the standard TC regimen is mostly safe and could be used as postoperative adjuvant chemotherapy for hemodialysis patients with early stage breast cancer.


Assuntos
Antineoplásicos/farmacocinética , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/farmacocinética , Diálise Renal , Insuficiência Renal Crônica/metabolismo , Taxoides/farmacocinética , Antineoplásicos/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Ciclofosfamida/efeitos adversos , Docetaxel , Feminino , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Insuficiência Renal Crônica/terapia , Taxoides/efeitos adversos
12.
Int J Biol Sci ; 11(7): 845-59, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26078726

RESUMO

Fibroblasts play a pivotal role in the process of cutaneous wound repair, whereas their migratory ability under diabetic conditions is markedly reduced. In this study, we investigated the effect of basic fibroblast growth factor (bFGF) on human dermal fibroblast migration in a high-glucose environment. bFGF significantly increased dermal fibroblast migration by increasing the percentage of fibroblasts with a high polarity index and reorganizing F-actin. A significant increase in intracellular reactive oxygen species (ROS) was observed in dermal fibroblasts under diabetic conditions following bFGF treatment. The blockage of bFGF-induced ROS production by either the ROS scavenger N-acetyl-L-cysteine (NAC) or the NADPH oxidase inhibitor diphenylene iodonium chloride (DPI) almost completely neutralized the increased migration rate of dermal fibroblasts promoted by bFGF. Akt, Rac1 and JNK were rapidly activated by bFGF in dermal fibroblasts, and bFGF-induced ROS production and promoted dermal fibroblast migration were significantly attenuated when suppressed respectively. In addition, bFGF-induced increase in ROS production was indispensable for the activation of focal adhesion kinase (FAK) and paxillin. Therefore, our data suggested that bFGF promotes the migration of human dermal fibroblasts under diabetic conditions through increased ROS production via the PI3K/Akt-Rac1-JNK pathways.


Assuntos
Movimento Celular/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fibroblastos/fisiologia , Glucose/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Pele/citologia , Análise de Variância , Western Blotting , Polaridade Celular/fisiologia , Proliferação de Células/fisiologia , Fibroblastos/efeitos dos fármacos , Humanos , Microscopia de Fluorescência , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , Cicatrização/fisiologia , Proteínas rac1 de Ligação ao GTP/metabolismo
13.
Asian Pac J Cancer Prev ; 16(6): 2397-402, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25824771

RESUMO

Previous studies have shown that miR-454 plays an important role in a variety of biological processes in various human cancer cells. However, the underlying mechanisms of this microRNA in colorectal cancer (CRC) cells remain largely unknown. In the present study, we investigated the miR-454 role in CRC cell proliferation. We found that miR-454 expression is markedly upregulated in CRC tissues and CRC cells compared with the matched tumor adjacent tissues and the FHC normal colonic cell line. Ectopic expression of miR-454 promoted the proliferation and anchorage-independent growth of CRC cells, whereas inhibition of miR-454 reduced this effect. Bioinformatics analysis further revealed cylindromatosis (CYLD), a putative tumor suppressor as a potential target of miR-454. Data from luciferase reporter assays showed that miR-454 directly binds to the 3'-untranslated region (3'-UTR) of CYLD mRNA and repressed expression at both transcriptional and translational levels. In functional assays, CYLD-silenced in miR-454-in-transfected SW480 cells have positive effect to promote cell proliferation, suggesting that direct CYLD downregulation is required for miR-454-induced CRC cell proliferation. In sum, our data provide compelling evidence that miR-454 functions as an onco-miRNA, playing a crucial role in the promoting cell proliferation in CRC, and its oncogenic effect is mediated chiefly through direct suppression of CYLD expression.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas Supressoras de Tumor/antagonistas & inibidores , Regiões 3' não Traduzidas , Apoptose , Western Blotting , Adesão Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Enzima Desubiquitinante CYLD , Humanos , Técnicas Imunoenzimáticas , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
14.
Nanotechnology ; 25(47): 475601, 2014 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-25369800

RESUMO

Nitrogen-doped carbon nanotubes (NCNTs) were prepared using a simple ultrasonic spray pyrolysis method. The precursor concentration effect was examined to effectively control alignment, open tip and diameter of the NCNTs by changing xylene/cyclohexylamine ratio. The structure and morphology of the resultant NCNTs were characterized by scanning electron microscopy, transmission electron microscopy and x-ray photoelectron spectroscopy. The degree of alignment and the diameter of the NCNTs increased as the xylene/cyclohexylamine precursor mixture was changed from 0 to 35% cyclohexylamine. This precursor composition also caused a large number of open-ended nanotubes to form with graphite layers inside the cavities of the NCNTs. However, further increase cyclohexylamine content in the precursor reduced the degree of alignment and diameter of the NCNTs. We demonstrate control over the NCNT alignment and diameter, along with the formation of open-ended nanotube tips, and propose a growth mechanism to understand how these properties are interlinked.

15.
Med Oncol ; 31(6): 976, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24793617

RESUMO

Bevacizumab and panitumumab are human monoclonal antibodies with different targeting antigens, vascular endothelial growth factor, and epidermal growth factor receptor. This study examined the efficacy and safety of combining bevacizumab and panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) as the second-line therapy for patients with metastatic colorectal cancer (mCRC). Patients with mCRC, and previously failed with oxaliplatin-based chemotherapy, were given bevacizumab (3 mg/kg) and panitumumab (3 mg/kg) plus FOLFIRI every other week. From September 2008 to July 2012, 173 patients were included in the study. The response rate was 42.3 %, and the disease-controlled rate was 65.7 %. The median progression-free survival was 6.5 months, and the median overall survival was 15.4 months. Various adverse events (AE) including those known toxicities associated with antibody therapy were recorded. The overall AE rate was 64.5 % for grade 3-4. The treatment of combining bevacizumab and panitumumab plus FOLFIRI is effective and safe as a second-line therapy for patients with mCRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Panitumumabe , Resultado do Tratamento , Adulto Jovem
16.
Am J Nephrol ; 31(4): 363-74, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20332614

RESUMO

BACKGROUND: Recent studies suggest the involvement of the adenosine monophosphate-activated serine/threonine protein kinase (AMPK) pathway in the pathogenesis of diabetic nephropathy (DN). Resveratrol, an agent that activates AMPK, may have the potential to protect against the development of DN. This study was designed to investigate the therapeutic effects of resveratrol on renal hypertrophy in early-stage diabetes and the underlying mechanisms. METHOD: Molecular and structural changes involved in the pathogenesis of DN were tested in a rat model of early-stage diabetes. Renal mesangial cells (RMCs) were cultured in media containing different concentrations of glucose with or without resveratrol. Cellular DNA synthesis was assayed by measuring (3)H-thymidine incorporation. The phosphorylation status of AMPK, eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), and phospho- ribosomal protein S6 (S6) was analyzed by Western blot. RESULTS: Resveratrol reduced plasma creatinine and urinary albumin excretion and attenuated renal hypertrophy without affecting blood glucose levels. Moreover, resveratrol activated AMPK and inhibited phosphorylation of 4E-BP1 and S6 in diabetic rat kidneys. In vitro, resveratrol blocked high glucose-induced dephosphorylation of AMPK and phosphorylation of 4E-BP1 and S6 and strongly inhibited both the DNA synthesis and proliferation of RMCs. CONCLUSION: These findings suggest the possibility that resveratrol exerts antiproliferative, antihypertrophic effects by activating AMPK and reducing 4E-BP1 and S6 phosphorylation, thus suppressing the development and progression of DN.


Assuntos
Nefropatias Diabéticas/prevenção & controle , Rim/patologia , Proteínas Quinases/fisiologia , Estilbenos/uso terapêutico , Animais , Hipertrofia/prevenção & controle , Masculino , Fosforilação/efeitos dos fármacos , Proteínas Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Resveratrol , Estilbenos/farmacologia
17.
Breast ; 18(3): 197-203, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19482475

RESUMO

PURPOSE: The NOEY2 gene mutations and protein expression in human breast cancers, adjacent breast tissues and breast benign lesions were analysed to explore the potential correlation between the mutation spectrum and breast cancer development and progression. EXPERIMENTAL DESIGN: The promoter, exon and intron regions of NOEY2 gene were amplified by polymerase chain reaction (PCR) with DNA extracted from 50 human breast cancer and corresponding adjacent breast tissues as well as 50 breast benign lesions, respectively. The PCR products were then sequenced and analysed. The effect of mutations on the expression of NOEY2 protein by immunohistochemistry were proven as well. RESULTS: Twenty-one of 50 (42%) breast cancer mutations were identified in promoter (11 cases) and exon 2 (seven cases on untranslation region and three on coding region) and 17 of 50 (34%) adjacent breast tissues (all were atypical hyperplasia lesions) occurred mutations, including six promoter mutations and 11 exon 2 changes (10 cases on untranslation region and one on coding region). Interestingly, the mutations were identified in both breast cancers and the corresponding adjacent breast tissues collected from the same patient in seven of them. No mutation was identified in all benign breast tissues. Immunohistochemical analysis showed that two of 17 mutational adjacent breast tissue samples were NOEY2 immunoreaction negative, and in all 21 mutations of breast cancers five cases were of loss of NOEY2 expression. All mutations with immunoreaction negative factor were located at promoter and/or exon 2 coding region. NOEY2 gene mutations were not correlated with patient ages, histological types, tumour sizes, histological grades, clinical stages, axillary lymph node metastases or with the condition of hormone receptor (ER, PR) expression and HER2 amplification. CONCLUSIONS: The mutations of human NOEY2 were identified in human breast cancers and the corresponding adjacent breast tissues. The hot mutation spots were its promoter and exon 2 regions, and those occurring at the exon2 coding region and part of the promoter may alter the expression of NOEY2. The presence of NOEY2 mutations in human breast cancer and early-stage lesions indicates that NOEY2 mutations may be partly associated with breast tumourigenesis.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteínas rho de Ligação ao GTP/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Análise Mutacional de DNA/métodos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hiperplasia/genética , Hiperplasia/patologia , Imuno-Histoquímica , Pessoa de Meia-Idade , Mutação , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Reação em Cadeia da Polimerase/métodos
18.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 33(6): 519-23, 2004 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-15586410

RESUMO

OBJECTIVE: To determine the effects of lactose inducing on the expression of recombinant Helicobacter pylori rUreB and rhpaA, and Escherichia coli rLTB and rLTKA63. METHODS: BIO-RAD gel image analysis system was applied to detect the outputs of the recombinant proteins. SDS-PAGE was performed to measure the target protein expression of recombinant genes at various periods of growth, different lactose concentrations, various inducing temperatures and times. The results of the target protein expression induced by lactose were compared to those by isopropyl-beta-D-thiogalactoside (IPTG). RESULTS: Lactose showed higher efficiency to induce the expression of rHpaA, rUreB, rLTB and rLTKA63 than IPTG. The expression outputs of target recombinant proteins induced at 37 degrees C were remarkably higher than those at 28 degrees C. The optimal expression parameters were 0.8 of OD600 value, 50 g/L of lactose, 4 hours of inducing time for rHpaA, and 1.2 of OD600 value, 100 g/L of lactose, 5 hours of inducing time for both the rUreB and rLtB,and 0.8 of OD600 value, 100 g/L of lactose, 4 hours for rLTKA63. CONCLUSION: Lactose, a sugar with non-toxicity and low cost, is able to induce the recombinant genes to express the target proteins with higher efficiency than IPTG.


Assuntos
Adesinas Bacterianas/biossíntese , Toxinas Bacterianas/biossíntese , Enterotoxinas/biossíntese , Proteínas de Escherichia coli/biossíntese , Lactose/farmacologia , Urease/genética , Adesinas Bacterianas/genética , Toxinas Bacterianas/genética , Vacinas Bacterianas/biossíntese , Vacinas Bacterianas/genética , Enterotoxinas/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Engenharia Genética , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Humanos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Vacinas Sintéticas/biossíntese , Vacinas Sintéticas/genética
19.
Zhongguo Zhong Yao Za Zhi ; 29(4): 326-30, 2004 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-15706869

RESUMO

OBJECTIVE: To identify Tongren Dahuoluo pills and Tongren Niuhuangqingxin pills respectively by analysis of IR fingerprint. METHOD: Both drugs were extracted with hexane, ethylether and butanone respectively and then the obtained extracts were measured with the ET-IR spectrometer. RESULT: By analyzing IR fingerprint of 25 batches of Tongren Dahuoluo pills and 27 batches of Tongren Niuhuangqingxin pills, we found that different batches of the same drug hadstabile and repeatable fingerprint. CONCLUSION: By using IR fingerprint, either Tongren Dahuoluo pills or Tongren Niuhuangqingxin pills can be exactly identified. It provides a rapid method for drug identification and quality control.


Assuntos
Medicamentos de Ervas Chinesas/química , Plantas Medicinais , Combinação de Medicamentos , Contaminação de Medicamentos/prevenção & controle , Medicamentos de Ervas Chinesas/administração & dosagem , Plantas Medicinais/química , Controle de Qualidade , Espectrofotometria Infravermelho
20.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 32(3): 192-6, 2003 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-12881861

RESUMO

OBJECTIVE: To investigate the cardiac effect of interleukin-2 (IL-2) and to explore the underlying mechanism. METHODS: The video tracking system and spectrofluorometric method were used to measure the cell contraction and intracellular calcium. Fura-2/AM was used as a calcium fluorescence probe. Langendorff perfusion technique was used to determine the effect of IL-2 on the intact heart. RESULTS: Compared with the control group, IL-2 5 U/ml, 50 U/ml significantly decreased cell contraction amplitude [(74.95+/-4.79) vs (98.09+/-5.02)%, (64.30+/-5.24) vs (97.38+/-4.05)%], peak velocity of cell shortening [(70.23+/-4.85)% vs (98.09+/-5.46)%, (61.15+/-5.20)% vs (97.38+/-6.85)%], peak velocity of cell relengthening [(71.22+/-4.79)% vs (98.32+/-6.08)%, (68.16+/-5.24)% vs (97.55+/-5.00)%] and end- diastolic cell length [(88.28+/-5.84)% vs (97.95+/-5.52)%, (84.18+/-6.52)% vs (98.94+/-6.76)%]. IL-2 (5 U/ml, 50 U/ml) also markedly inhibited intracellular calcium transient [(74.94+/-4.90)% vs (98.09+/-3.74)%,(71.00+/-5.28)% vs (97.38+/-5.52)%], and elevated end-diastolic calcium level of ventricular myocytes [(113.91+/-5.93)% vs (100.10+/-3.02)%, (119.09+/-7.12)% vs (100.52+/-6.00)%], which were attenuated by the opioid receptor antagonist naloxone (Nal,10 nmol/L). In the isolated perfused rat heart,when compared with the control group, IL-2 50 U/ml markedly decreased left ventricular developed pressure [(79.91+/-2.18) vs (93.84+/-2.94)mmHg], maximal rate of rise of left ventricular pressure [(2370.7358.29) vs (2591.50+/-62.81)mmHg] maximal rate of fall of left ventricular [-(1460.95+/-38.6) vs -(1634.24+/-54.05) mmHg/s] and heart rate [(217.35+/-10.56) vs (244.52+/-11.23) beats/min], but increased left ventricular end-diastolic pressure (11.44+/-1.02 vs 9.23+/-0.46). Pretreatment with Nal (10 nmol/L) antagonized the cardiac depression and left ventricular end-diastolic pressure elevation induced by IL-2. CONCLUSION: The cardiac effect of IL-2 is mediated by opioid receptors on the membrane of cardiomyocytes.


Assuntos
Interleucina-2/farmacologia , Contração Miocárdica/efeitos dos fármacos , Naloxona/farmacologia , Receptores Opioides kappa/efeitos dos fármacos , Animais , Cálcio/metabolismo , Depressão Química , Técnicas In Vitro , Masculino , Ratos , Ratos Sprague-Dawley , Receptores Opioides kappa/fisiologia
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