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1.
Acta Neurochir (Wien) ; 166(1): 210, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38735896

RESUMEN

PURPOSE: To evaluate the safety and efficacy of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) for drug-resistant focal epilepsy and investigate the relationship between post-RFTC remission duration and delayed excision surgery effectiveness. METHODS: We conducted a retrospective analysis of 43 patients with drug-resistant focal epilepsy who underwent RFTC via SEEG electrodes. After excluding three, the remaining 40 were classified into subgroups based on procedures and outcomes. Twenty-four patients (60%) underwent a secondary excision surgery. We determined the predictive value of RFTC outcome upon subsequent surgical outcome by categorizing the delayed secondary surgery outcome as success (Engel I/II) versus failure (Engel III/IV). Demographic information, epilepsy characteristics, and the duration of seizure freedom after RFTC were assessed. RESULTS: Among 40 patients, 20% achieved Engel class I with RFTC alone, while 24 underwent delayed secondary excision surgery. Overall, 41.7% attained Engel class I, with a 66.7% success rate combining RFTC with delayed surgery. Seizure freedom duration was significantly longer in the success group (mean 4.9 months, SD = 2.7) versus the failure group (mean 1.9 months, SD = 1.1; P = 0.007). A higher proportion of RFTC-only and delayed surgical success group patients had preoperative lesional findings (p = 0.01), correlating with a longer time to seizure recurrence (p < 0.05). Transient postoperative complications occurred in 10%, resolving within a year. CONCLUSION: This study demonstrates that SEEG-guided RFTC is a safe and potential treatment option for patients with drug-resistant focal epilepsy. A prolonged duration of seizure freedom following RFTC may serve as a predictive marker for the success of subsequent excision surgery.


Asunto(s)
Epilepsia Refractaria , Electrocoagulación , Electroencefalografía , Epilepsias Parciales , Humanos , Masculino , Femenino , Adulto , Electrocoagulación/métodos , Electroencefalografía/métodos , Estudios Retrospectivos , Epilepsia Refractaria/cirugía , Resultado del Tratamiento , Epilepsias Parciales/cirugía , Epilepsias Parciales/fisiopatología , Adulto Joven , Persona de Mediana Edad , Adolescente , Pronóstico , Técnicas Estereotáxicas , Niño
2.
Acta Pharm Sin B ; 14(2): 579-601, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38322344

RESUMEN

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.

3.
Bioact Mater ; 35: 1-16, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38298451

RESUMEN

Segmental bone defects, stemming from trauma, infection, and tumors, pose formidable clinical challenges. Traditional bone repair materials, such as autologous and allogeneic bone grafts, grapple with limitations including source scarcity and immune rejection risks. The advent of nucleic acid nanotechnology, particularly the use of DNA hydrogels in tissue engineering, presents a promising solution, attributed to their biocompatibility, biodegradability, and programmability. However, these hydrogels, typically hindered by high gelation temperatures (∼46 °C) and high construction costs, limit cell encapsulation and broader application. Our research introduces a novel polymer-modified DNA hydrogel, developed using nucleic acid nanotechnology, which gels at a more biocompatible temperature of 37 °C and is cost-effective. This hydrogel then incorporates tetrahedral Framework Nucleic Acid (tFNA) to enhance osteogenic mineralization. Furthermore, considering the modifiability of tFNA, we modified its chains with Aptamer02 (Apt02), an aptamer known to foster angiogenesis. This dual approach significantly accelerates osteogenic differentiation in bone marrow stromal cells (BMSCs) and angiogenesis in human umbilical vein endothelial cells (HUVECs), with cell sequencing confirming their targeting efficacy, respectively. In vivo experiments in rats with critical-size cranial bone defects demonstrate their effectiveness in enhancing new bone formation. This innovation not only offers a viable solution for repairing segmental bone defects but also opens avenues for future advancements in bone organoids construction, marking a significant advancement in tissue engineering and regenerative medicine.

4.
Cell Prolif ; 56(12): e13518, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37309689

RESUMEN

The mechanism of the balance between subchondral angiogenesis and articular damage within osteoarthritis (OA) progression remains a mystery. However, the lack of specific drugs leads to limited clinical treatment options for OA, frequently failing to prevent eventual joint destruction in patients. Increasing evidence suggests that subchondral bone angiogenesis precedes cartilage injury, while proliferating endothelial cells (ECs) induce abnormal bone formation. Signal transducer and activator of transcription 3 (Stat3) is triggered by multiple cytokines in the OA microenvironment. Here, we observed elevated Stat3 activation in subchondral bone H-type vessels. Endothelial Stat3 activation will lead to stronger cell proliferation, migration and angiogenesis by simulating ECs in OA. In contrast, either Stat3 activation inhibition or knockdown of Stat3 expression could relieve such alterations. More interestingly, blocking Stat3 in ECs alleviated angiogenesis-mediated osteogenic differentiation and chondrocyte lesions. Stat3 inhibitor reversed surgically induced subchondral bone H-type vessel hyperplasia in vivo, significantly downregulating vessel volume and vessel number. Due to the reduced angiogenesis, subchondral bone deterioration and cartilage loss were alleviated. Overall, our data suggest that endothelial Stat3 activation is an essential trigger for OA development. Therefore, targeted Stat3 blockade is a novel promising therapeutic regimen for OA.


Asunto(s)
Cartílago Articular , Osteoartritis , Factor de Transcripción STAT3 , Humanos , Cartílago Articular/metabolismo , Células Endoteliales/metabolismo , Osteoartritis/metabolismo , Osteogénesis , Factor de Transcripción STAT3/metabolismo
5.
J Funct Biomater ; 14(4)2023 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-37103311

RESUMEN

Gluten is a natural byproduct derived from wheat starch, possessing ideal biocompatibility. However, its poor mechanical properties and heterogeneous structure are not suitable for cell adhesion in biomedical applications. To resolve the issues, we prepare novel gluten (G)/sodium lauryl sulfate (SDS)/chitosan (CS) composite hydrogels by electrostatic and hydrophobic interactions. Specifically, gluten is modified by SDS to give it a negatively charged surface, and then it conjugates with positively charged chitosan to form the hydrogel. In addition, the composite formative process, surface morphology, secondary network structure, rheological property, thermal stability, and cytotoxicity are investigated. Moreover, this work demonstrates that the change can occur in surface hydrophobicity caused by the pH-eading influence of hydrogen bonds and polypeptide chains. Meanwhile, the reversible non-covalent bonding in the networks is beneficial to improving the stability of the hydrogels, which shows a prominent prospect in biomedical engineering.

6.
Medicine (Baltimore) ; 102(11): e32860, 2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36930074

RESUMEN

BACKGROUND: This study aimed to evaluate the clinical efficacy of minimally invasive puncture and drainage (MIPD) versus trepanation and drainage in the treatment of chronic subdural hematoma (CSDH). METHODS: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang database were searched for studies on the treatment of CSDH by MIPD and trepanation and drainage. By reading the title, abstract and full text, and screening according to the inclusion and exclusion criteria, the qualified articles were confirmed. Subsequently, the literature quality was evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions, and the data of the research subjects and the primary outcome measures were extracted for meta-analysis with RevMan 5.1 software. RESULTS: Ten articles were included, with a total of 1000 patients. According to the meta-analysis, the 2 groups showed no statistical difference in CSDH recurrence rate (P > .05). The operation time, intraoperative blood loss, and incidence of postoperative adverse reactions were lower and the cure rate was higher in the MIPD group compared with trepanation and drainage group (all P < .05). By drawing the funnel plot of the outcome measures with heterogeneity, it can be seen that the distribution on both sides of the funnel was basically symmetrical, suggesting a low deviation possibility of the analysis results and reliable reference significance of our findings. CONCLUSION: Compared with trepanation and drainage, MIPD has better clinical effects and higher safety in treating CSDH and can effectively reduce surgery-induced damage, which is worth popularizing in clinical practice.


Asunto(s)
Hematoma Subdural Crónico , Trepanación , Humanos , Trepanación/métodos , Hematoma Subdural Crónico/cirugía , Paracentesis , Drenaje/métodos , Resultado del Tratamiento , Recurrencia
7.
Am J Transl Res ; 13(4): 3254-3261, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34017496

RESUMEN

OBJECTIVE: To explore the correlation between uric acid (UA), cystatin C (Cys-C), homocysteine (Hcy), and chronic heart failure (CHF). METHODS: 45 patients with CHF were selected as the research group; 45 healthy people were selected as the control group. The levels of serum UA, Cys-C and Hcy were detected. RESULTS: The in The research group had much higher levels of serum UA, Cys-C and Hcy than the control group (all P<0.05). The levels of above indexes also increased with an increase in cardiac function classification. Patients with major adverse cardiovascular events (MACE) had much higher levels of serum UA, Cys-C, and Hcy than those without MACE in the research group (all P<0.05). In addition, the levels of these above indexes in the research group were all positively correlated with the left ventricular end diastolic diameter (LVEDD) (all P<0.05), and all negatively correlated with the f left ventricular ejection fraction (LVEF) (P<0.05). What is more, the levels of these above indexes in the research group were all positively correlated with New York Heart Association (NYHA) grade (all P<0.05). The diagnostic sensitivity of serum UA level, Cys-C level, and Hcy level in joint diagnosis of CHF patients was higher than that of any single index diagnosis (P<0.05), and the specificity of combined diagnosis was lower than that of single index diagnosis (P<0.05). CONCLUSION: The levels of serum UA, Cys-C, and Hcy in CHF patients may be used as reference indexes for clinical screening of early CHF patients and could provide a certain reference for clinical evaluation.

8.
Oncol Lett ; 19(4): 3349-3355, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32256828

RESUMEN

Breast cancer is the second leading primary cause for cancer-related mortality among women and metastasis to the brain is a disastrous event for patients with increasing incidence. A previous study confirmed the critical function of RRM2 in breast cancer cell growth. Unfortunately, the role and fundamental molecular mechanism of RRM2 in breast cancer metastasis remains elusive. In the current study, higher RRM2 expression was validated in breast cancer tissues, especially in the brain metastasis group. Simultaneously, the expression of RRM2 was increased in breast cancer cells relative to the normal breast epithelial cell line MCF-10A, concomitant with higher levels of RRM2 in the highly metastatic MDA-MB-231 cell line relative to the weakly metastatic MCF-7 cell line. Knockdown of RRM2 by small interfering-RRM2 transfection notably suppressed the malignant metastatic behavior of breast cancer cells, including invasion and migration. Simultaneously, RRM2 downregulation also restrained the transcription and release of vascular endothelial growth factor (VEGF) in breast cancer cells. Moreover, inhibition of RRM2 dampened the activation of phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling by decreasing phosphorylated-AKT and downstream matrix metalloproteinases-2 expression. Intriguingly, reactivation of the PI3K/AKT pathway with its agonist insulin-like growth factor-1 reversed the adverse effects of RRM2 suppression on cancer cell invasion, migration and VEGF expression. Together, these findings suggest that RRM2 may act as a pro-metastatic factor to facilitate breast cancer metastasis by evoking cell invasion, migration and VEGF expression through the PI3K/AKT signaling pathway. This study may provide an attractive target for metastatic intervention in breast cancer.

9.
J Am Chem Soc ; 142(4): 2051-2058, 2020 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-31905287

RESUMEN

Supramolecular polymers based on host-guest molecular recognition have emerged as promising platforms for the development of smart materials. However, the studies on them are primarily conducted in solution and/or in the gel state. In contrast, little is known about dynamic properties and applications of supramolecular polymers in bulk. Herein, we present a self-cross-linking supramolecular polymer network (SPN) as a model system to understand the bulk properties controlled by noncovalent interactions. Specifically, the SPN monomer is composed of two benzo-21-crown-7 (B21C7) host units and two dialkylammonium salt guest moieties on a four-arm core, wherein complementary host-guest complexation drives the formation of the SPN with [2]pseudorotaxane linkages between B21C7 and ammonium motifs. The dynamic and reversible behaviors of the linkages are evaluated by measurement of viscoelasticity. The results indicate that the host-guest molecular recognition becomes highly dynamic at elevated temperature. Moreover, the relatively high activation energy of the SPN manifests itself as a new type of thermoplastic material with network topology freezing glass transition. Finally, we demonstrate how these findings provide insights into the malleability and processability of the SPN by simple demos. The fundamental understanding gained from the research on this SPN in bulk will facilitate the advancement and application of supramolecular materials.

10.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(6): 666-670, 2019 Jun 15.
Artículo en Chino | MEDLINE | ID: mdl-31197990

RESUMEN

OBJECTIVE: To explore the effectiveness of proximal femoral nail antirotation (PFNA) assisted by mesh locator in treatment of intertrochanteric fracture in the elderly. METHODS: Ninety-four elderly patients with intertrochanteric fractures admitted between August 2014 and July 2017 were selected as the study subjects. They were randomly divided into trial group (48 cases) and control group (46 cases). In trial group, PFNA was implanted assisted by mesh locator after closed reduction; while in control group, PFNA was implanted by conventional method. There was no significant difference between the two groups in terms of gender, age, cause of injury, time from injury to admission, fracture side and classification, and medical complications ( P>0.05). The operation time, intraoperative blood loss, fluoroscopy times, hospital stay, incision length, and complications were recorded. Visual analogue scale (VAS) was used to evaluate the degree of pain at 3 days after operation, and Harris score was used to evaluate hip function before operation and at 3, 6, and 9 months after operation. RESULTS: Compared with control group, the operation time and incision length of trial group shortened, the blood loss and fluoroscopy times reduced, the pain after operation alleviated obviously; the differences between the two groups were significant ( P<0.05). There was no significant difference in hospital stay between the two groups ( P>0.05). The patients in both groups were followed up 9-12 months, with an average of 10.6 months. X-ray films showed that the fractures healed in both groups, and the healing time in control group was (11.2±3.2) weeks, while that in trial group was (11.6±2.9) weeks, showing no significant difference between the two groups ( t=1.262, P=0.120). There was no significant difference in Harris score between the two groups before operation and at 3, 6, and 9 months after operation ( P>0.05). There was 1 case of incision infection, 2 cases of coxa vara, and 1 case of pressure ulcer in trial group, and the incidence of complications was 8.3%. There was 1 case of coxa vara, 2 cases of pressure ulcer, and 1 case of internal fixation loss in control group, and the incidence of complications was 8.7%. There was no significant difference in the incidence of complications between the two groups (χ 2=0.783, P=0.112). CONCLUSION: It is feasible to implant PFNA assisted by mesh locator in treatment of intertrochanteric fracture in the elderly. Compared with the traditional operation, it can shorten the operation time, shorten the incision, and relieve the pain after operation.


Asunto(s)
Fijación Intramedular de Fracturas , Fracturas de Cadera , Anciano , Clavos Ortopédicos , Fémur , Fracturas de Cadera/cirugía , Humanos , Mallas Quirúrgicas , Resultado del Tratamiento
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(6): 1610-1615, 2018 Dec.
Artículo en Chino | MEDLINE | ID: mdl-30501692

RESUMEN

OBJECTIVE: To investigate whether the down-regulation of miR-125b can reverse the drug-resistence of doxorubicine-resistant leukemia cell lines or not, so as to explore a new method for treatment of drug-resistant leukemia patients. METHODS: The expression levels of miR125b in doxorubicine drug-sensitive and doxorubicine drug-resistant leukemia cell lines.HL-60, K562 and HL-60/Dox, the K562/Dox were detected by using RT-qPCR; the up-regulation or inhibition of miR-1256 expression in HL-60/Dox were performed by electroporation transfection, then the viability of cells treated with doxorubicine of different concentration was detected by CCK-8 method, the proliferation inhibition curve of cells was drawed, and the IC50 was calculated. RESULTS: The miR-125b expression was obviously up-regulated in drug-resistant cell lines HL-60/DOX and K562/DOX, as compared with HL-60 and K562 cell lines. The miR-125b expression level in HL-60/DOX and K562/DOX cells was 15 times and 5 times higher than that in HL-60 and K562 cells, respectively. The up-regulating or inhibiting expression of miR-125b in HL-60/DOX cells found that the proliferation inhibition rate in cells transfected with miR-125b mimic significantly decreased, compared with control group (P<0.01), while the proliferation inhibition rate in cells transfected with miR-125b inhibitor significantly increased, compared with control group(P<0.01). CONCLUSION: The miR-125b expression in HL-60/Dox and K562/Dox cells has been up-regulated, down-regulation of miR-125b expression can reverse the drug resistance of leukemia cells to doxorubicine.


Asunto(s)
Regulación hacia Abajo , Leucemia , Doxorrubicina , Resistencia a Antineoplásicos , Humanos , Células K562 , MicroARNs
12.
Exp Ther Med ; 16(3): 2665-2669, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30186499

RESUMEN

The present study aimed to verify the expression and investigate the role of microRNA (miR)-148a in intervertebral disc degeneration (IDD) and explore the associated underlying mechanisms. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to investigate levels of miR-148a in the peripheral blood mononuclear cells (PBMCs) of patients with IDD. To investigate the role of miR-148a in IDD, a stable miR-148a-overexpression/underexpression human nucleus pulposus (NP) cell line was generated by transfection with miR-148a mimic/inhibitor. Then, NP cells were treated with LPS (10 µM) to induce inflammation. The mRNA expression level of miR-148a in NP cells was determined by RT-qPCR and the expression levels of p38 and p-p38 were measured using western blotting. The mRNA expression and supernatant level of pro-inflammatory cytokines, tumor necrosis factor (TNF-α), interleukin (IL)-1ß and IL-6, was evaluated by RT-qPCR and ELISA, respectively. The results indicated that miR-148a was significantly downregulated in the PBMCs of IDD patients compared with healthy controls. In vitro upregulation of miR-148a in LPS-stimulated NP cells, by transfection with miR-148a mimic, resulted in inhibition of p-p38 expression; however, inhibition of miR-148a led to overexpression of p-p38. Meanwhile, the production of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) was significantly reduced in miR-148a-overexpressing LPS-stimulated NP cells and significantly increased in miR-148a-underexpressing NP cells. In conclusion, miR-148a inhibits pro-inflammatory cytokines released by intervertebral disc cells via regulation of the p38/mitogen-activated protein kinase pathway.

13.
Biochem Biophys Res Commun ; 499(4): 765-771, 2018 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-29605301

RESUMEN

Increasing evidences demonstrate the essential roles of circular RNAs (circRNAs) in human cancers. However, the study about the functions of circRNAs in glioma remains very limited. In the present study, we found that circRNA hsa_circ_0007534 was highly expressed in glioma tissues compared to normal brain tissues. Furthermore, we found that knockdown of hsa_circ_0007534 significantly inhibited the proliferation and migration of glioma cells. In mechanism, we showed that hsa_circ_0007534 could sponge miR-761 to repress its availability in glioma cells. We found that inhibition of miR-761 could rescue the suppressed proliferation and migration of glioma cells by hsa_circ_0007534 knockdown. Moreover, we explored the downstream mechanism and found that ZIC5 was a target of miR-761. We showed that hsa_circ_0007534 promoted the expression of ZIC5 by inhibiting miR-761 in glioma cells. And restoration of ZIC5 expression significantly reversed the effects of hsa_circ_0007534 knockdown on glioma cell proliferation and migration. In summary, our results demonstrated that hsa_circ_0007534 serves as an oncogene in glioma via promoting ZIC5 expression by repressing miR-761 availability. Our results suggested that hsa_circ_0007534/miR-761/ZIC5 regulatory loop might be a promising therapeutic target for glioma treatment.


Asunto(s)
Movimiento Celular/genética , Glioma/genética , Glioma/patología , MicroARNs/metabolismo , ARN/metabolismo , Transducción de Señal , Factores de Transcripción/metabolismo , Secuencia de Bases , Línea Celular Tumoral , Proliferación Celular/genética , Proteínas de Unión al ADN , Técnicas de Silenciamiento del Gen , Humanos , MicroARNs/genética , ARN/genética , ARN Circular , Regulación hacia Arriba/genética
14.
World Neurosurg ; 109: e778-e782, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29074421

RESUMEN

OBJECTIVE: Hemifacial spasm (HFS) is a disorder characterized by intermittent, involuntary facial muscle contractions. Microvascular decompression (MVD) is the gold treatment for HFS. The aim of this research was to discuss whether patients undergoing MVD as their initial surgical intervention experience greater spasm control than patients experiencing an MVD performed as a subsequent surgical intervention. METHODS: The study included 976 patients with HFS, 452 of whom (group A) underwent MVD as their initial surgical intervention and 524 of whom (group B) underwent subsequent MVD. Relevant clinical data including outcome of MVD, operative findings, complications, and so on were collected immediately after MVD operation and at follow-up. RESULTS: The follow-up period was 7-9 years (mean, 7.96 ± 0.87 years). The mean age at intervention was 53.14 years and 55.43 years in the 2 groups, respectively. The long-term postoperative relief rate of patients in the 2 groups was 98.23% and 87.21%, respectively. There was a significant difference in long-term postoperative relief rate of patients between the 2 groups (P < 0.05). CONCLUSIONS: Patients undergoing MVD for HFS as the primary treatment experience better long-term efficacy than patients first treated with botulinum neurotoxin type A.


Asunto(s)
Espasmo Hemifacial/diagnóstico , Espasmo Hemifacial/cirugía , Cirugía para Descompresión Microvascular/métodos , Cirugía para Descompresión Microvascular/tendencias , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
15.
Appl Biochem Biotechnol ; 175(7): 3244-57, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25686559

RESUMEN

The aim of this study was to synthesize a chitosan (CS) derivative, a quaternary ammonium salt crystal called N-2-hydroxypropyl trimethyl ammonium chloride chitosan (HACC), and test a series of HACC and pEGFP-DNA complexes at different weight ratios for their efficiency of gene delivery into human cells. CS was modified with cationic etherifying agent to obtain the CS derivative. Fourier transform infrared spectra were recorded on KBr pellets with a spectrometer. (1)H nuclear magnetic resonance (NMR) spectra of HACC were obtained using a spectrometer. HACC was subsequently used to prepare HACC/DNA complexes at different weight ratios by coacervation method. The resulting particle size and surface charge were assessed by laser light scattering using a zeta potential analyzer. The HACC/DNA complex formation and DNA protection in the nanoparticle complex was investigated by gel mobility shift assay and DNase I protection assay, respectively. The cytotoxicity of HACC and HACC/DNA nanoparticles was evaluated by MTT assay using (mesenchymal stem cell) MSC lines. The nanoscale structure of the particles was obtained by transmission electron microscope (TEM). The FTIR spectrum of HACC showed the characteristic quaternary ammonium group absorption band at 1475 cm(-1), which indicated the presence of quaternary ammonium group. The successful synthesis of HACC was also confirmed by (1)H NMR spectrum. HACC showed good solubility in water and was electropositive. HACC efficiently packed and protected pEGFP-DNA at a weight ratio of 10. With increased weight ratios, the surface charge of the composite particle increased from negative to positive, the average particle size increased, and HACC nanoparticle had a higher carrying efficiency. The nanoparticles released DNA in two distinct phases, and 55 % was released within the first 20 h of solubilization. The nanoparticles under TEM showed circular or oval shapes. The particles exhibited no cytotoxicity against human cells. No significant difference in gene delivery efficiency was detected between HACC/pEGFP-GDNF and liposome/pEGFP-GDNF complexes (33.8 vs. 34 %, P = 0.363). In this study, HACC was successfully synthesized, and HACC/DNA complex assembled efficiently. HACC showed strong DNA binding affinity and high protection of DNA and was non-cytotoxic to human cells. The particles had appropriate nanostructure, mean diameter, and DNA release time. The results suggest that HACC nanoparticles are a novel tool for efficient and safe gene delivery.


Asunto(s)
ADN/genética , Técnicas de Transferencia de Gen , Terapia Genética , Nanopartículas/química , Línea Celular Tumoral , Quitosano/análogos & derivados , ADN/administración & dosificación , ADN/química , Proteínas Fluorescentes Verdes/administración & dosificación , Proteínas Fluorescentes Verdes/química , Proteínas Fluorescentes Verdes/genética , Humanos , Espectroscopía de Resonancia Magnética , Nanopartículas/administración & dosificación , Transfección
16.
Neurochem Int ; 61(7): 1011-20, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22841891

RESUMEN

Apoptosis of cholinergic neurons is one of the core hallmarks of Alzheimer's disease. SH-SY5Y neuroblastoma cells differentiated to the cholinergic phenotype were exposed to 100nM staurosporine. Over a treatment period of 24h, the pro- and anti-apoptotic factors, caspase-3 and Bcl-2, as well as LDH release as a measure of cell viability, were assessed in conjunction with the number of apoptotic cells by means of fluorescence-activated cell sorting. Caspase-3 activity and LDH release increased by 30% and 20% over controls, respectively, while Bcl-2 levels rose by 200% over controls. Furthermore, staurosporine treatment resulted in decreased acetylcholinesterase (AChE) enzymatic activity and decreased protein levels of the AChE splice variant tailed AChE (AChE-T). Only a slight increase in levels of readthrough AChE (AChE-R) was observed. Likewise, staurosporine reduced levels and activity of the cholinergic players choline acetyltransferase and high affinity choline uptake. The present study demonstrates that treatment with staurosporine leads to apoptotic events, which, however, are not reflected in the increased AChE activity and the alterations of AChE isoforms expression that are usually seen in apoptotic conditions. The effects of various additional phosphorylation inhibitors on AChE activity suggest that these unexpected cholinergic effects, firstly, are linked to the impact of staurosporine on phosphorylation and, secondly, reveal themselves in a first phase of cellular adaption that precedes neurotoxicity and subsequent cell death.


Asunto(s)
Apoptosis/efectos de los fármacos , Diferenciación Celular , Inhibidores Enzimáticos/farmacología , Neuroblastoma/patología , Receptores Colinérgicos/metabolismo , Estaurosporina/farmacología , Acetilcolinesterasa/metabolismo , Western Blotting , Caspasa 3/metabolismo , Línea Celular Tumoral , Electroforesis en Gel de Poliacrilamida , Humanos , L-Lactato Deshidrogenasa/metabolismo , Neuroblastoma/enzimología , Neuroblastoma/metabolismo , Fosforilación
17.
J Hazard Mater ; 186(1): 911-20, 2011 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-21177019

RESUMEN

Ce(0.67)Zr(0.33)O(2) doped with iron oxide was prepared and the corresponding Pd-only three-way catalysts were examined and characterized. Pd/CZFe(1%) catalyst exhibits the best catalytic performance for CO, HC, NO and NO(2) elimination and the widest operation window. The doping of iron oxide with 1% loading suggests the formation of more homogeneous Ce-Zr-Fe-O ternary solid solution, which seems to facilitate the reduction of Ce(4+)→Ce(3+) or the formation of oxygen vacancy and to promote the interaction between Ce-Zr and Fe. Moreover, the Ce redox behaviour for surface reduction suggests depending not only on the formation of homogeneous Ce-Zr-Fe-O but also on the surface property of the sample. The increase in the concentration of oxygen vacancies under all atmospheres for CZFe(1%) sample also results in the enhancement of oxygen storage complete capacity.


Asunto(s)
Cerio/química , Hierro/química , Emisiones de Vehículos , Circonio/química , Catálisis , Espectrometría Raman , Difracción de Rayos X
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