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1.
Environ Sci Ecotechnol ; 21: 100417, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38638605

RESUMEN

Zero Valent Iron (ZVI), an ideal reductant treating persistent pollutants, is hampered by issues like corrosion, passivation, and suboptimal utilization. Recent advancements in nonmetallic modified ZVI (NM-ZVI) show promising potential in circumventing these challenges by modifying ZVI's surface and internal physicochemical properties. Despite its promise, a thorough synthesis of research advancements in this domain remains elusive. Here we review the innovative methodologies, regulatory principles, and reduction-centric mechanisms underpinning NM-ZVI's effectiveness against two prevalent persistent pollutants: halogenated organic compounds and heavy metals. We start by evaluating different nonmetallic modification techniques, such as liquid-phase reduction, mechanical ball milling, and pyrolysis, and their respective advantages. The discussion progresses towards a critical analysis of current strategies and mechanisms used for NM-ZVI to enhance its reactivity, electron selectivity, and electron utilization efficiency. This is achieved by optimizing the elemental compositions, content ratios, lattice constants, hydrophobicity, and conductivity. Furthermore, we propose novel approaches for augmenting NM-ZVI's capability to address complex pollution challenges. This review highlights NM-ZVI's potential as an alternative to remediate water environments contaminated with halogenated organic compounds or heavy metals, contributing to the broader discourse on green remediation technologies.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38290454

RESUMEN

Objective: This study investigates the efficacy of DWI combined with intraoperative ultrasound for deep brain glioma treatment, analyzing changes in Karnofsky performance status (KPS) scores and imaging signs. Objectives include elucidating the approach's advantages, addressing knowledge gaps, and contributing insights into its effectiveness for enhancing deep brain glioma management. Methods: In this retrospective study, we analyzed a total of 346 patients with deep brain glioma who underwent surgical treatment at our hospital from July 2015 to January 2022. After applying inclusion and exclusion criteria, 310 patients were selected and categorized into a control group (n = 150) and an observation group (n = 160) based on different auxiliary techniques of surgical treatment. The degree of resection and Karnofsky performance status (KPS) scores were assessed at 1 day preoperatively, 1 week, and 1 month postoperatively for both groups. Additionally, we conducted a comprehensive analysis of DWI and ultrasound imaging signs among patients with different grades of deep brain glioma. The study duration covered the specified period, and statistical analyses were performed to evaluate the outcomes. Results: In our study, the observation group demonstrated significantly improved resection degrees, with a total resection rate of 82.50% compared to the control group's 65.33%. Preoperative Karnofsky performance status scores showed no significant difference between groups (P > .05), but postoperative scores at 1 week and 1 month were significantly higher in the observation group (P < .05). Intraoperative ultrasound and DWI revealed distinct imaging signs differentiating low-grade and high-grade patients. These results highlight the efficacy of DWI combined with intraoperative ultrasound resection in enhancing resection outcomes and influencing postoperative Karnofsky performance status. Conclusions: DWI combined with intraoperative ultrasonic resection in deep brain glioma has a significant effect, with specific imaging signs, which can effectively improve the total resection rate and KPS score, and is worthy of clinical promotion. DWI combined with intraoperative ultrasound has important clinical significance in the resection of deep brain gliomas. The better resection results and improved postoperative Karnofsky performance-status score that we observed suggest a possible benefit in patient outcomes, which could influence treatment strategies. The precise imaging signs identified by this method provide valuable guidance for targeted and effective tumor resection.

3.
World J Clin Cases ; 11(27): 6327-6343, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37900230

RESUMEN

BACKGROUND: Wuzhuyu decoction, a traditional Chinese medicinal formula, is effective in treating hepatocellular carcinoma (HCC). AIM: To explore the potential mechanism of action of Wuzhuyu decoction against HCC. METHODS: The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform. HCC was used as a search query in GeneCards, Online Mendelian Inheritance in Man, Malacards, DisGeNET, Therapeutic Target Database, and Comparative Toxicogenomics Database. The overlapping targets of the Wuzhuyu decoction and HCC were defined, and then protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. CytoHubba was used to select hub genes, and their binding activities and key active components were verified using molecular docking. RESULTS: A total of 764 compounds, 77 active compounds, and 204 potential target genes were identified in Wuzhuyu decoction. For HCC, 9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates. A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined, including 10 hub genes (tumor necrosis factor, interleukin-6, AKT1, TP53, caspase-3, mitogen-activated protein kinase 1, epidermal growth factor receptor, MYC, mitogen-activated protein kinase 8, and JUN). There were six main active components (quercetin, kaempferol, ginsenoside Rh2, rutaecarpine, ß-carotene, and ß-sitosterol) that may act on hub genes to treat HCC in Wuzhuyu decoction. Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase, p53, phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt, Janus kinase-signal transducer of activators of transcription, and Hippo signaling pathways. Further verification based on molecular docking results showed that the small molecule compounds (quercetin, kaempferol, ginsenoside Rh2, rutaecarpine, ß-carotene, and ß-sitosterol) contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes. CONCLUSION: This study revealed that Wuzhuyu decoction may be a latent multicomponent, multitarget, and multipathway treatment for HCC. It provided novel insights for verifying the mechanism of Wuzhuyu decoction in the treatment of HCC.

4.
Org Lett ; 25(41): 7491-7496, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37816042

RESUMEN

Using the robust N-heterocyclic carbene-palladium complex (SIPr)Ph2Pd(cin)Cl, a highly efficient and easy-to-operate method has been developed at room temperature for the solvent-free Buchwald-Hartwig amination of heteroaryl chlorides with various amines. The amount of catalyst can be as low as 0.05 wt %. The system was demonstrated on 47 substrates and successfully applied to the synthesis of commercial pharmaceuticals and candidate drugs with high yields. Furthermore, the protocol can be used to prepare aniline derivatives on a multigram scale without yield loss.

5.
Eur J Pharmacol ; 958: 176074, 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37742812

RESUMEN

BACKGROUND: Platycodin D (PD) is a potent bioactive constituent in the medicinal herb Platycodon grandiflorum. It has shown anticancer properties, particularly against glioblastoma (GB) and other human malignancies. DEPDC1B (DEP domain-containing protein 1B) is an oncogene associated with epithelial-mesenchymal transition (EMT). It is highly expressed in GB and correlated with tumor grade and patient prognosis. In this study, we investigated whether the antiglioma effect of PD was associated with downregulation of DEPDC1B. METHODS: Gene expression and clinical data were obtained from the China Glioma Genome Atlas and The Cancer Genome Atlas databases for glioma samples. In vitro experiments were conducted using Cell Counting Kit-8 and Transwell assays to assess the impact of PD on the proliferation, migration, and invasion of GB cells. mRNA and protein expression was evaluated using real-time polymerase chain reaction and western blotting, respectively. RESULTS: PD exerted inhibitory effects on the proliferation and motility of GB cells. PD downregulated DEPDC1B protein as well as several markers associated with EMT, namely N-cadherin, vimentin, and Snail. The suppressive effects of PD were enhanced when DEPDC1B was knocked down in GB cells, while overexpression of DEPDC1B in cells reversed the inhibitory effects of PD. CONCLUSION: PD exerts an antiglioma effect by regulating DEPDC1B-mediated EMT.

6.
Eur J Pharmacol ; 948: 175697, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-36997048

RESUMEN

BACKGROUND: Platycodin D (PD) is a major bioactive component of Platycodon grandiflorum, a medicinal herb that is widely used in China, and is effective against various human cancers, including glioblastoma multiforme (GBM). S phase kinase-related protein 2 (Skp2) is oncogenic and overexpressed in various human tumors. It is highly expressed in GBM and its expression is correlated with tumor growth, drug resistance and poor prognosis. In this study, we investigated whether inhibition of glioma progression by PD is mediated by decreasing expression of Skp2. METHODS: Cell Counting Kit-8 (CCK-8) and Transwell assays were used to determine the effects of PD on GBM cell proliferation, migration, and invasion in vitro. mRNA and protein expression were determined by real time polymerase chain reaction (RT-PCR) and western blotting, respectively. The U87 xenograft model was used to verify the anti-glioma effect of PD in vivo. Expression levels of Skp2 protein were analyzed by immunofluorescence staining. RESULTS: PD suppressed proliferation and motility of GBM cells in vitro. The expression of Skp2 in U87 and U251 cells was significantly reduced by PD. PD mainly decreased the cytoplasmic expression of Skp2 in glioma cells. Skp2 protein expression was downregulated by PD, resulting in upregulation of its downstream targets, p21and p27. The inhibitory effect of PD was enhanced by Skp2 knockdown in GBM cells and reversed in cells with Skp2 overexpression. CONCLUSION: PD suppresses glioma development by regulation of Skp2 in GBM cells.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/genética , Proteínas Quinasas Asociadas a Fase-S/genética , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Neoplasias Encefálicas/genética , Glioma/patología , Proliferación Celular , Línea Celular Tumoral , Movimiento Celular , Regulación Neoplásica de la Expresión Génica
7.
Sci Rep ; 12(1): 19980, 2022 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-36411289

RESUMEN

To analyse the microlesion effect (MLE) in the globus pallidus interna (GPi) of deep brain stimulation (DBS) in patients with Meige syndrome. Thirty-two patients with primary Meige syndrome who underwent GPi-DBS in this study. Burke-Fahn-Marsden Dystonia Rating Scale scores (BFMDRS-M) were obtained for the evaluation of clinical symptoms at 3 days before DBS (baseline), 24 h after DBS surgery, once weekly for 1 month until electrical stimulation, 6 months postoperatively and 12 months after surgery. Twenty-seven patients had MLE after GPi-DBS. The mean time of BFMDRS-M scores maximal improvement from MLE was 35.9 h postoperatively (range, 24-48 h), and the mean scores improved by 49.35 ± 18.16%. At 12 months after surgery, the mean BFMDRS-M scores improved by 50.28 ± 29.70%. There was a positive correlation between the magnitude of MLE and the motor score at 12 months after GPi-DBS (R2 = 0.335, p < 0.05). However, there was no correlation between the duration of MLE and DBS improvement. Most Meige syndrome patients who underwent GPi-DBS and had MLE benefited from MLE. For Meige syndrome, MLE might be a predictive factor for patient clinical symptom improvement from DBS.


Asunto(s)
Estimulación Encefálica Profunda , Distonía , Síndrome de Meige , Humanos , Síndrome de Meige/terapia , Globo Pálido/cirugía , Globo Pálido/fisiología , Estimulación Encefálica Profunda/efectos adversos , Resultado del Tratamiento
8.
Front Plant Sci ; 13: 963269, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36119592

RESUMEN

The tea plant is a kind of ammonium-preferring crop, but the mechanism whereby ammonium (NH4 +) regulate its growth is not well understood. The current study focused on the effects of NH4 + on tea plants. Transcriptomic analysis was performed to investigate the early- and late-stage NH4 + deprivation and resupply in tea plants shoots. Through short- and long-term NH4 + deficiency, the dynamic response to NH4 + stress was investigated. The most significant effects of NH4 + deficiency were found to be on photosynthesis and gene ontology (GO) enrichment varied with the length of NH4 + deprivation. Enriched KEGG pathways were also different when NH4 + was resupplied at different concentrations which may indicate reasons for tolerance of high NH4 + concentration. Using weighted gene co-expression network analysis (WGCNA), modules related to significant tea components, tea polyphenols and free amino acids, were identified. Hence, NH4 + could be regarded as a signaling molecule with the response of catechins shown to be higher than that of amino acids. The current work represents a comprehensive transcriptomic analysis of plant responses to NH4 + and reveals many potential genes regulated by NH4 + in tea plants. Such findings may lead to improvements in nitrogen efficiency of tea plants.

9.
Nat Prod Res ; : 1-9, 2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-35983797

RESUMEN

Phytochemical investigations on the fruits of Cascabela thevetia (L.) Lippold led to obtain three new cardenolides (1-3) and five known analogues (4-7). Their structures were elucidated by means of UV, IR, HR-ESI-MS, 1D and 2D NMR spectroscopic data analysis. Compounds 1 and 2 represent the first examples of naturally occurring cardenolides with 19-nor-5(10)-ene group and α-l-3-demethyl-thevetose, respectively. Compound 3 is a rare C-nor-D-homocardenolide in nature. All isolated cardenolides (1-7) were evaluated for their cytotoxic activities against four human cancer cell lines (MCF-7, HCT-116, HeLa and HepG2), and the results indicated the compounds with sugar units (1, 2, 4, and 5) exhibited stronger cytotoxic activities with IC50 values ranging between 0.022 and 0.308 µM.

10.
Int J Nanomedicine ; 16: 4105-4115, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34163162

RESUMEN

PURPOSE: Glioblastoma multiforme (GBM) poorly responds to chemotherapy owing to the existence of blood-brain barriers (BBB). It has been a long desire to develop BBB-permeable vehicles to facilitate drug targeting to GBM. METHOD AND RESULTS: Here, we report that doxorubicin hydrochloride loaded in ApoE peptide-functionalized reduction-sensitive polymersomes (ApoE-PS-DOX) induces potent therapy of orthotopic U-87 MG model in nude mice. ApoE-PS-DOX with varying amount of ApoE (10~30 mol%) all had stable DOX loading and small sizes (< 90 nm). As revealed by flow cytometry, confocal microscopy, apoptosis and MTT assays, ApoE-PS-DOX with 20 mol.% ApoE induced the best cellular uptake and inhibitory effect to U-87 MG cells, which were much better than the non-targeted PS-DOX and liposomal doxorubicin (Lipo-DOX) used in the clinic. ApoE-PS-DOX revealed a pharmacokinetic profile comparable to PS-DOX but induced considerably better growth inhibition of orthotopically xenografted U-87 MG tumors in nude mice than PS-DOX and Lipo-DOX, leading to significant survival benefits with a median survival time of 44 days, which was almost doubled relative to the phosphate-buffered saline (PBS) group. Moreover, in contrast to mice treated with Lipo-DOX and PS-DOX, ApoE-PS-DOX group exhibited little body weight loss, signifying that ApoE-PS-DOX not only has low side effects but also can effectively inhibit glioblastoma invasion. CONCLUSION: This ApoE-docked multifunctional polymersomal doxorubicin induces potent and safe chemotherapy of orthotopic U-87 MG model in nude mice offering an alternative treatment modality for GBM.


Asunto(s)
Apolipoproteínas E/metabolismo , Transformación Celular Neoplásica , Doxorrubicina/química , Doxorrubicina/farmacología , Portadores de Fármacos/química , Glioblastoma/patología , Polímeros/química , Animales , Barrera Hematoencefálica/efectos de los fármacos , Línea Celular Tumoral , Doxorrubicina/metabolismo , Glioblastoma/tratamiento farmacológico , Humanos , Ratones , Ratones Desnudos , Oxidación-Reducción
11.
Sci Rep ; 11(1): 8742, 2021 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-33888857

RESUMEN

Deep-brain stimulation (DBS) is an effective treatment for patients with Meige syndrome. The globus pallidus interna (GPi) and the subthalamic nucleus (STN) are accepted targets for this treatment. We compared 12-month outcomes for patients who had undergone bilateral stimulation of the GPi or STN. Forty-two Asian patients with primary Meige syndrome who underwent GPi or STN neurostimulation were recruited between September 2017 and September 2019 at the Department of Neurosurgery, Peking University People's Hospital. The primary outcome was the change in motor function, including the Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) and disability subscale (BFMDRS-D) at 3 days before DBS (baseline) surgery and 1, 3, 6, and 12 months after surgery. Secondary outcomes included health-related quality of life, sleep quality status, depression severity, and anxiety severity at 3 days before and 12 months after DBS surgery. Adverse events during the 12 months were also recorded. Changes in BFMDRS-M and BFMDRS-D scores at 1, 3, 6, and 12 months with DBS and without medication did not significantly differ based on the stimulation target. There were also no significant differences in the changes in health-related quality of life (36-Item Short-Form General Health Survey) and sleep quality status (Pittsburgh Sleep Quality Index) at 12 months. However, there were larger improvements in the STN than the GPi group in mean score changes on the 17-item Hamilton depression rating scale (- 3.38 vs. - 0.33 points; P = 0.014) and 14-item Hamilton anxiety rating scale (- 3.43 vs. - 0.19 points; P < 0.001). There were no significant between-group differences in the frequency or type of serious adverse events. Patients with Meige syndrome had similar improvements in motor function, quality of life and sleep after either pallidal or subthalamic stimulation. Depression and anxiety factors may reasonably be included during the selection of DBS targets for Meige syndrome.


Asunto(s)
Estimulación Encefálica Profunda , Globo Pálido/fisiopatología , Núcleo Subtalámico/fisiopatología , Anciano , Femenino , Humanos , Masculino , Síndrome de Meige/fisiopatología , Persona de Mediana Edad , Estudios Retrospectivos
12.
Br J Neurosurg ; 35(4): 486-491, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33650924

RESUMEN

OBJECTIVE: To assess the efficacy of microvascular decompression (MVD) for hemifacial spasm with an enhanced recovery after surgery (ERAS) protocol. METHODS: 984 hemifacial spasm patients who underwent MVD from Jan 2017 to Dec 2017 were analyzed. They were divided into the conventional treatment group (control; n = 453) and the later ERAS group (n = 531). The multimodal ERAS protocol consists of 23 perioperative elements. Time to feeding, mobilization, and urinary catheter removal, wound pain, postoperative nausea and vomiting (PONV), and total, preoperative, and perioperative hospital length of stay (LOS), along with outcomes and complications, were analyzed. RESULTS: The patients in both groups had similar clinical characteristics. Patients in the ERAS group had significantly higher rates of early feeding (469 [88.5%], ERAS, vs. 183 [40.6%], control; p < 0.05), early mobilization (497 [93.7%], ERAS, vs. 215 [47.7%], control; p < 0.05), and early removal of urinary catheter (458 [86.4%], ERAS, vs. 175 [38.8%], control; p < 0.05). The ERAS group also had a significantly lower incidence of wound pain (135 [25.5%], ERAS, vs. 348 [77.2%], control) and PONV (173 [32.6%], ERAS, vs. 251 (55.7%), control) (p < 0.05) and significantly shorter preoperative (0.9 ± 0.3 d, ERAS, vs. 2.3 ± 0.6 d, control), postoperative (4.1 ± 0.4 d, ERAS, vs. 5.8 ± 0.7 d, control), and total LOS (5.2 ± 0.3 d, ERAS, vs. 8.8 ± 0.6 d, control) (p < 0.05). There was no significant difference in outcomes or surgical complication rates between two groups. CONCLUSIONS: Implementation of the ERAS protocol for patients undergoing MVD procedures for the treatment of HFS improved the quality of perioperative care without an increase in adverse events.


Asunto(s)
Recuperación Mejorada Después de la Cirugía , Espasmo Hemifacial , Cirugía para Descompresión Microvascular , Espasmo Hemifacial/cirugía , Humanos , Tiempo de Internación , Atención Perioperativa , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento
14.
Neuromodulation ; 24(2): 293-299, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32476223

RESUMEN

OBJECTIVE: To investigate the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Meige syndrome. MATERIALS AND METHODS: Fifteen consecutive patients who underwent STN-DBS at the Peking University People's Hospital between September 2017 and June 2018 were included in this study. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score and the BFMDRS disability score were obtained prior to surgery, and at specific time points after surgery. Patients' sleep status was also assessed before and after surgery. RESULTS: The BFMDRS movement scores decreased from 15.3 ± 4.6 to 5.2 ± 6.2 after STN-DBS, with a mean improvement of 68.6% (p < 0.05). The BFMDRS disability scores were also significantly decreased, from 6.9 ± 3.3 to 3.5 ± 2.9, with a mean improvement of 51.7% (p < 0.05). The eye, mouth, speech, and swallowing movement scores also decreased significantly after STN-DBS compared to baseline (p < 0.05). The sleep quality of the patients was also improved after surgery. CONCLUSIONS: These findings demonstrate that the STN is an effective brain target for the treatment of patients with Meige syndrome. STN-DBS was not only able to improve patients' motor symptoms, but also their sleep status.


Asunto(s)
Estimulación Encefálica Profunda , Síndrome de Meige , Núcleo Subtalámico , Estudios de Seguimiento , Globo Pálido , Humanos , Síndrome de Meige/terapia , Resultado del Tratamiento
15.
J Neurol Neurosurg Psychiatry ; 91(12): 1343-1348, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33028603

RESUMEN

OBJECTIVES: To study the efficacy and safety of bilateral globus pallidus internus deep brain stimulation (GPi-DBS) in refractory Meige syndrome (MS) and evaluate the psychiatric disorders before and after surgery. METHODS: Twenty-two patients with MS treated with bilateral GPi-DBS were retrospectively analysed before surgery and after continuous neurostimulation. Before surgery, patients were assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Self-Rating Depression Scale, Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) and Pittsburgh Sleep Quality Index (PQSI), which corresponded to motor symptoms, depressive state, quality of life and sleep quality, respectively. The implantable pulse generator of each patient was activated at 1 month after surgery. At 1 month, 3 months, 6 months and 12 months after continuous neurostimulation, all patients were evaluated by the same scales above. RESULTS: The BFMDRS movement scores decreased from 15.0±5.3 before surgery to 3.5±4.5 at 12 months after neurostimulation, with a mean improvement of 78% (p<0.001). The BFMDRS disability scores improved from 7.4±4.9 before surgery to 4.0±4.6 at 12 months after neurostimulation, with a mean improvement of 56% (p<0.001). The postoperative SF-36 scores had the remarkable improvement compared with baseline scores. Impaired sleep quality was found in 82% of patients and depression in 64% before surgery, which didn't neither obtained amelioration after continuous neurostimulation. CONCLUSIONS: Bilateral pallidal neurostimulation is a beneficial therapeutic option for refractory MS, which could improve the motor symptoms except for depression and sleep quality.


Asunto(s)
Estimulación Encefálica Profunda/métodos , Depresión/psicología , Globo Pálido , Síndrome de Meige/terapia , Calidad de Vida , Sueño , Anciano , Trastornos de la Articulación/epidemiología , Trastornos de Deglución/epidemiología , Mareo/epidemiología , Femenino , Trastornos Neurológicos de la Marcha/epidemiología , Humanos , Hipoestesia/epidemiología , Neuroestimuladores Implantables , Masculino , Síndrome de Meige/fisiopatología , Síndrome de Meige/psicología , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento
16.
Adv Healthc Mater ; 8(16): e1900500, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31231966

RESUMEN

Small interfering RNA (siRNA) is considered a highly specific and potent biotherapeutic that holds tremendous potential for the treatment of various diseases. The clinical translation of siRNA is, however, greatly impeded by the lack of safe and efficient delivery vehicles in vivo. Here, the development of selective cell penetrating peptide (CPP33)-functionalized chimeric lipopepsomes (CPP33-CLP) for efficient encapsulation and selective delivery of polo-like kinase 1 specific siRNA (siPLK1) to orthotopic A549 human lung tumor in vivo is reported. Interestingly, siRNA is tightly encapsulated into CPP33-CLP with a superb encapsulation efficiency of over 95% owing to the thick strong electrostatic interactions. Notably, siPLK1-loaded CPP33-CLP (siPLK1-CPP33-CLP) is selectively internalized by A549 human lung cancer cells, efficiently escapes from endosomes, and swiftly releases siRNA into the cytoplasm, affording a significant sequence-specific gene silencing in vitro. Moreover, siPLK1-CPP33-CLP exhibits prolonged blood circulation, enhanced tumor accumulation, effective suppression of tumor growth, and considerably elevated survival time of orthotopic A549 human lung tumor-bearing nude mice. These chimeric lipopepsomes appear as an attractive and potent nanoplatform for safe and targeted siRNA delivery.


Asunto(s)
Péptidos de Penetración Celular/química , Neoplasias Pulmonares/terapia , Interferencia de ARN/fisiología , Células A549 , Animales , Citoplasma/metabolismo , Endosomas/metabolismo , Silenciador del Gen/fisiología , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , ARN Interferente Pequeño/genética
17.
Biochem Biophys Res Commun ; 514(4): 1270-1277, 2019 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-31113618

RESUMEN

Verbascoside (VB), a glycosylated phenylpropanoid compound, is derived from the plant Syringa vulgaris (Oleaceae) and has been shown to have antitumor effects in multiple human cancers, including glioblastoma (GBM); however, the underlying mechanism has not been completely elucidated. Epithelial-to-mesenchymal transition (EMT) is the pivotal event in tumor progression. c-Met, a receptor tyrosine kinase, plays an important role in GBM aggressiveness via promoting EMT. The current study aimed to explore whether VB suppresses c-Met-induced EMT and investigated the mechanism of c-Met degradation. We found that VB inhibited GBM cell growth and downregulated c-Met and the EMT markers (snail, vimentin, and zeb1) in vitro and in an orthotopic xenograft mouse model. In addition, overexpressing c-Met in glioblastoma cells abolished the effects of VB on EMT. We also used a microscale thermophoresis (MST) assay to show that VB could directly bind to the c-Met protein, and we showed that VB degraded the c-Met protein via the ubiquitination-proteasome pathway. Our study is the first to identify a new mechanism for the anticancer effects of VB, namely, the inhibition of EMT by directly targeting c-Met; the inhibition of EMT results in c-Met protein degradation through the ubiquitination-proteasome pathway. Our current research indicates that VB is a potential agent to treat GBM via the ubiquitin-mediated degradation of c-Met.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Glioblastoma/tratamiento farmacológico , Glucósidos/farmacología , Fenoles/farmacología , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Proteínas Proto-Oncogénicas c-met/metabolismo , Relación Estructura-Actividad , Células Tumorales Cultivadas
18.
Oncotarget ; 9(12): 10483-10496, 2018 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-29535821

RESUMEN

Osteosarcoma(OS) remains a major health concern in childhood and adolescence, although cisplatin is one of the gold standard chemotherapeutic drugs in the treatment of OS, chemoresistant to cisplatin is common. Phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin inhibitor (mTOR) pathway and autophagy regulates chemosensitivity incancer cells. In this study, we hypothesized that NVP-BEZ235, a dual inhibitor of PI3K/mTOR, could synergize cisplatin sensitivity in OS. In vitro, NVP-BEZ235 plus cisplatinexerted a synergistic effect on cell proliferation inhibition and apoptosis induction. Cisplatin could activate PI3K-Akt-mTOR pathway activity in early times, whereas, NVP-BEZ235 could inhibit PI3K-Akt -mTOR pathway activity all the times alone or combined with cisplatin. What's more, NVP-BEZ235 could switch function of autophagy induced by cisplatin to synergize cisplatin sensitivity. In vivo, pronounced decrease in tumor cell proliferation and increase in apoptosisin combination-treated mouse xenograft models compared with cisplatin or NVP-BEZ235 treated models. All these results suggest NVP-BEZ235 could synergize cisplatin sensitivity in OS, combination of NVP-BEZ235 with cisplatin could represent a novel therapeutic strategy for treatment of OS.

19.
World Neurosurg ; 111: e335-e339, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29258938

RESUMEN

OBJECTIVE: To compare the efficacy and complications of microvascular decompression (MVD) by complete neuroendoscopy versus microscopy for 213 cases of trigeminal neuralgia (TN). METHODS: Between January 2014 and January 2016, 213 patients with TN were randomly assigned to the neuroendoscopy (n = 105) or microscopy (n = 114) group for MVD via the suboccipital retrosigmoid approach. All procedures were performed by the same neurosurgeon. Follow-up was conducted by telephone interview. Statistical data were analyzed with the chi-square test, and a probability (P) value of ≤0.05 was considered statistically significant. Chi-square test was conducted using SAS 9.4 software (SAS Institute, Cary, North Carolina, USA). RESULTS: There were no statistical differences between the 2 groups in pain-free condition immediately post procedure, pain-free condition 1 year post procedure, hearing loss, facial hypoesthesia, transient ataxia, aseptic meningitis, intracranial infections, and herpetic lesions of the lips. There were no instances of death, facial paralysis, cerebral hemorrhage, or cerebrospinal fluid leakage in either group. CONCLUSIONS: There were no significant differences in the cure rates or incidences of surgical complications between neuroendoscopic and microscopic MVD.


Asunto(s)
Microcirugia/métodos , Cirugía para Descompresión Microvascular/métodos , Neuroendoscopía/métodos , Procedimientos Neuroquirúrgicos/métodos , Neuralgia del Trigémino/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neurocirujanos , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos
20.
Oncol Rep ; 39(3): 1052-1062, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29286139

RESUMEN

Paeoniflorin (PF), a natural compound isolated from Paeoniae radix, has been shown to exert antitumor effects in various types of human cancers including glioma. However, the mechanism of action is not well understood. S-phase kinase-associated protein (Skp)2 functions as an oncogene in many cancers. In the present study, we investigated whether Skp2 mediates the anti-glioma activity of PF. We found that PF inhibited glioma cell proliferation, migration and invasion, and induced G2/M arrest and apoptosis. Skp2 expression was downregulated in glioma cells treated with PF. PF-induced antitumor effects in glioma cells were abolished by Skp2 overexpression but were enhanced by RNA interference of Skp2. Moreover, PF treatment inhibited U87 cell-derived tumor growth in a xenograft mouse model. These results demonstrate that PF exerts its antitumor effects in part by inhibiting Skp2 expression in glioma cells and could be a promising therapeutic agent for glioma therapy.


Asunto(s)
Apoptosis/efectos de los fármacos , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/patología , Ciclo Celular/efectos de los fármacos , Glioma/patología , Glucósidos/farmacología , Monoterpenos/farmacología , Proteínas Quinasas Asociadas a Fase-S/antagonistas & inhibidores , Animales , Antiinflamatorios no Esteroideos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/enzimología , Proliferación Celular/efectos de los fármacos , Femenino , Glioma/tratamiento farmacológico , Glioma/enzimología , Humanos , Ratones , Ratones Desnudos , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
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