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1.
Small ; 20(11): e2304088, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37939310

RESUMO

The use of natural cartilage extracellular matrix (ECM) has gained widespread attention in the field of cartilage tissue engineering. However, current approaches for delivering functional scaffolds for osteoarthritis (OA) therapy rely on knee surgery, which is limited by the narrow and complex structure of the articular cavity and carries the risk of injuring surrounding tissues. This work introduces a novel cell microcarrier, magnetized cartilage ECM-derived scaffolds (M-CEDSs), which are derived from decellularized natural porcine cartilage ECM. Human bone marrow mesenchymal stem cells are selected for their therapeutic potential in OA treatments. Owing to their natural composition, M-CEDSs have a biomechanical environment similar to that of human cartilage and can efficiently load functional cells while maintaining high mobility. The cells are released spontaneously at a target location for at least 20 days. Furthermore, cell-seeded M-CEDSs show better knee joint function recovery than control groups 3 weeks after surgery in preclinical experiments, and ex vivo experiments reveal that M-CEDSs can rapidly aggregate inside tissue samples. This work demonstrates the use of decellularized microrobots for cell delivery and their in vivo therapeutic effects in preclinical tests.


Assuntos
Cartilagem Articular , Células-Tronco Mesenquimais , Osteoartrite , Animais , Suínos , Humanos , Cartilagem Articular/fisiologia , Engenharia Tecidual , Matriz Extracelular/química , Fenômenos Magnéticos , Alicerces Teciduais/química
2.
Pediatr Allergy Immunol ; 35(6): e14166, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38822736

RESUMO

BACKGROUND: There is increasing interest in elucidating the relationship between adenoid hypertrophy (AH) and allergic rhinitis (AR). However, the impact of aeroallergen sensitization patterns on children with AH and AR remains unclear. METHODS: Patients aged 2-8 years (recruited from January 2019 to December 2022) with nasal symptoms were assessed for allergies, adenoid size, and respiratory viral infection history. The serum total immunoglobulin E (IgE) and specific IgE levels were measured, and flexible nasal endoscopy was performed. The relationship between AH, aeroallergen sensitization patterns, and lymphocyte subpopulations in adenoid samples was analyzed using flow cytometry. RESULTS: In total, 5281 children were enrolled (56.5% with AR; and 48.6% with AH). AH was more prevalent in children with AR. Compared to nonsensitized individuals, those polysensitized to molds had a higher prevalence of AH (adjusted OR 1.61, 95% CI 1.32-1.96) and a greater occurrence of two or more respiratory viral infections, particularly in adenoidectomy patients. The percentages and corrected absolute counts of regulatory T (Treg) cells, activated Tregs, class-switched memory B cells (CSMBs), natural killer (NK) T cells, and NK cell subpopulations were reduced in the adenoid tissues of children with both AH and AR (AH-AR) compared to AH-nAR children. Polysensitization in AH-AR children correlated with lower CSMB percentages. CONCLUSION: Polysensitivity to molds is associated with an increased risk of AH in children with AR. Fewer B cells, NK cells, and Treg cells with an effector/memory phenotype were detected in the adenoids of AR children, and these lower percentages of immune cells, particularly CSMBs, were closely linked to aeroallergen sensitization models and respiratory viral infection.


Assuntos
Tonsila Faríngea , Hipertrofia , Imunoglobulina E , Rinite Alérgica , Humanos , Tonsila Faríngea/imunologia , Tonsila Faríngea/patologia , Criança , Masculino , Feminino , Hipertrofia/imunologia , Pré-Escolar , Rinite Alérgica/imunologia , Rinite Alérgica/epidemiologia , Imunoglobulina E/sangue , Fenótipo , Alérgenos/imunologia , Linfócitos T Reguladores/imunologia , Prevalência , Adenoidectomia
3.
Small ; 19(44): e2301889, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37423966

RESUMO

Multidrug combination therapy provides an effective strategy for malignant tumor treatment. This paper presents the development of a biodegradable microrobot for on-demand multidrug delivery. By combining magnetic targeting transportation with tumor therapy, it is hypothesized that loading multiple drugs on different regions of a single magnetic microrobot can enhance a synergistic effect for cancer treatment. The synergistic effect of using two drugs together is greater than that of using each drug separately. Here, a 3D-printed microrobot inspired by the fish structure with three hydrogel components: skeleton, head, and body structures is demonstrated. Made of iron oxide (Fe3 O4 ) nanoparticles embedded in poly(ethylene glycol) diacrylate (PEGDA), the skeleton can respond to magnetic fields for microrobot actuation and drug-targeted delivery. The drug storage structures, head, and body, made by biodegradable gelatin methacryloyl (GelMA) exhibit enzyme-responsive cargo release. The multidrug delivery microrobots carrying acetylsalicylic acid (ASA) and doxorubicin (DOX) in drug storage structures, respectively, exhibit the excellent synergistic effects of ASA and DOX by accelerating HeLa cell apoptosis and inhibiting HeLa cell metastasis. In vivo studies indicate that the microrobots improve the efficiency of tumor inhibition and induce a response to anti-angiogenesis. The versatile multidrug delivery microrobot conceptualized here provides a way for developing effective combination therapy for cancer.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias , Humanos , Animais , Células HeLa , Polietilenoglicóis/química , Hidrogéis , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Doxorrubicina/química , Neoplasias/tratamento farmacológico
4.
Mol Biol Rep ; 50(9): 7437-7444, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37479877

RESUMO

BACKGROUND: We compared the bone microstructure and metabolism of the femoral heads in patients with osteoporosis (OP) and non-OP patients to investigate the pathologic mechanism of OP and guide clinical treatment. METHODS AND RESULTS: From January 2020 to June 2021, we obtained femoral head samples from 30 patients undergoing hip replacement due to femoral neck fracture. All patients were women aged approximately 67 to 80 years (mean age, 74 years). According to the dual-energy X-ray results, the femoral head samples were divided into the OP (T< - 2.5) and non-OP (T > - 1.5) groups. Microcomputed tomography scanning, bone metrology analysis, hematoxylin and eosin staining, and Masson's trichrome staining were used to compare the local bone trabecular microstructure changes. Quantitative reverse transcription PCR was performed to identify changes in the osteogenesis-related genes and the osteoclast-related genes in specific regions to reflect osteogenic and osteoclastic activities. Femoral heads with OP showed significant changes in the local bone microstructure. Bone density, bone volume fraction, and the number and thickness of the bone trabeculae decreased. Local bone metabolism was imbalanced in the areas with microstructural changes in femoral heads with OP, with increased osteoclast activity and decreased osteoblast activity. CONCLUSIONS: Deterioration of bone microstructure is closely related to abnormal bone metabolism associated with the activity of osteoblasts and osteoclasts in osteoporotic femoral heads. Promoting bone formation by improving local bone metabolism, enhancing osteogenic activity and inhibiting osteoclast activity may be a promising way of preventing local OP and osteoporotic fractures.


Assuntos
Cabeça do Fêmur , Osteoporose , Humanos , Feminino , Idoso , Masculino , Cabeça do Fêmur/diagnóstico por imagem , Microtomografia por Raio-X , Osteoclastos , Osteogênese
5.
J Transl Med ; 20(1): 496, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316782

RESUMO

BACKGROUND: Aberrant sialoglycans on the surface of tumor cells shield potential tumor antigen epitopes, escape recognition, and suppress activation of immunocytes. α2,3/α2,6Gal- and α2,6GalNAc (Gal/GalNAc)-linked sialic acid residues of sialoglycans could affect macrophage galactose-type lectins (MGL) mediated-antigen uptake and presentation and promote sialic acid-binding immunoglobulin-like lectins (Siglecs) mediated-immunosuppression. Desialylating sialoglycans on tumor cells could present tumor antigens with Gal/GalNAc residues and overcome glyco-immune checkpoints. Thus, we explored whether vaccination with desialylated whole-cell tumor vaccines (DWCTVs) triggers anti-tumor immunity in ovarian cancer (OC). METHODS: Sialic acid (Sia) and Gal/GalNAc residues on OC A2780, OVCAR3, and ID8 cells treated with α2-3 neuraminidase (α2-3NA) and α2-6NA, and Sigec-9 or Siglec-E and MGL on DCs pulsed with desialylated OC cells were identified using flow cytometry (FCM); RT-qPCR determined IFNG expression of T cells, TRBV was sequenced using Sanger sequencing and cytotoxicity of αß T cells was measured with LDH assay; Anti-tumor immunity in vivo was validated via vaccination with desialylated whole-cell ID8 vaccine (ID8 DWCTVs). RESULTS: Gal/GalNAc but not Sia residues were significantly increased in the desialylated OC cells. α2-3NA-modified DWCTV increased MGL but decreased Siglec-9 or Siglec E expression on DCs. MGLbright/Siglec-9dim DCs significantly up-regulated IFNG expression and CD4/CD8 ratio of T cells and diversified the TCR repertoire of αß T-cells that showed enhanced cytotoxic activity. Vaccination with α2-3NA-modified ID8 DWCTVs increased MGLbright/Siglec-Edim DCs in draining lymph nodes, limited tumor growth, and extended survival in tumor-challenged mice. CONCLUSION: Desialylated tumor cell vaccine could promote anti-tumor immunity and provide a strategy for OC immunotherapy in a clinical setting.


Assuntos
Vacinas Anticâncer , Neoplasias Ovarianas , Humanos , Camundongos , Animais , Feminino , Epitopos , Ácido N-Acetilneuramínico/metabolismo , Linhagem Celular Tumoral , Apoptose , Neoplasias Ovarianas/terapia , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Antígenos , Galactose/metabolismo
6.
Opt Express ; 30(13): 23463-23474, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-36225025

RESUMO

The modulation of structural color through various methods has attracted considerable attention. Herein, a new modulation method for the structural colors in all-dielectric photonic crystals (PCs) using energetic ion beams is proposed. One type of periodic PC and two different defective PCs were experimentally investigated. Under carbon-ion irradiation, the color variation primarily originated from the blue shift of the optical spectra. The varying degrees of both the reflection and transmission structural colors mainly depended on the carbon-ion fluences. Such nanostructures are promising for tunable color filters and double-sided chromatic displays based on PCs.

7.
Respir Res ; 23(1): 48, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248029

RESUMO

BACKGROUND: The prevalence of allergic respiratory disease (ARD) is increasing worldwide during the last few decades, causing a great disease burden especially for children. Air pollution has been increasingly considered as a potential contributor to this trend, but its role in ARD induced by house dust mite (HDM-ARD) remains unclear, especially in time-series study. METHODS: A positive reporting of respiratory allergy to named allergens was included by serum specific IgE testing. A time series Quasi-Poisson regression with distributed lag non-linear model, combined with generalized linear model was used to examine the effects of air pollutants on ARD, HDM-ARD and ARD induced by non-house dust mite (NHDM-ARD). RESULTS: A total of 16,249 cases of ARD, including 8,719 HDM-ARD and 8,070 NHDM-ARD from 1 Jan 2013 to 31 Dec 2017 were involved in this study. Air pollutants were significantly associated with clinical visits for childhood ARD and HDM-ARD. Exposure to higher O3 and interquartile range (IQR) increment in O3 (40.6 µg/m3) increased the risks of clinical visits for childhood HDM-ARD (RRlag0-5 for the 95th percentile of O3: 1.26, 95% confidence interval (CI): 1.03, 1.55; RRlag0-5 for IQR increment (40.6 µg/m3): 1.09, 95% CI: 1.01, 1.17) and ARD (RRlag0-5 for the 95th percentile of O3: 1.19, 95% CI: 1.03, 1.38; RRlag0-5 for IQR increment (40.6 µg/m3): 1.06, 95% CI: 1.01, 1.12). In addition, higher O3 was associated with increased RR of boys with ARD (RRlag0-5 for the 95th percentile: 1.26, 95% CI: 1.05, 1.51; RRlag0-5 for IQR increment (40.6 µg/m3): 1.09, 95% CI: 1.02, 1.16) and HDM-ARD (RRlag0-5 for the 95th percentile: 1.36, 95% CI: 1.06, 1.75; RRlag0-5 for IQR increment (40.6 µg/m3): 1.11, 95% CI: 1.02, 1.22), but not in girls. CONCLUSIONS: Exposure to O3 appeared to be a trigger of clinical visits for childhood ARD, especially for HDM-ARD and boys. These findings provide novel evidence on the impact of air pollution on HDM-ARD, which may have significant implications for designing effective intervention programs to control and prevent childhood ARD, especially HDM-ARD, in China and other similar developing countries.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poeira/imunologia , Visita a Consultório Médico/estatística & dados numéricos , Pyroglyphidae/imunologia , Transtornos Respiratórios/etiologia , Adolescente , Poluentes Atmosféricos/análise , Animais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Transtornos Respiratórios/epidemiologia , Transtornos Respiratórios/imunologia , Estudos Retrospectivos
8.
Langmuir ; 38(10): 3180-3188, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35240036

RESUMO

Wetting states for droplets have been extensively investigated in the past. As the counter phase of the droplets, bubbles' wetting states have rarely been systematically explored. The wetting state of a bubble is closely related to its departure diameter, which plays significant roles in bubble-generated processes in boiling heat transfer and gas-evolving reactions. Based on the principle of minimum surface energy, we explicitly define three equilibrium wetting states (hemi-wicking state, Wenzel state, and Cassie-Baxter state) for bubbles on micro-/nanostructured surfaces in this paper. We analyze the three-phase contact line profiles for bubbles under these wetting states and propose theoretical models for predicting departure diameters of hemi-wicking-state bubble and Wenzel-state bubble on micro-/nanostructured surfaces. We identify competing effects of bubble departure in Wenzel state: the augmentation of contact line length due to the roughness, which would delay bubble departure, and the decrease of contact line length due to the reduced apparent contact angle, which would facilitate bubble departure. We demonstrate that hemi-wicking-state bubble exhibits a much smaller departure diameter on the textured surfaces. These findings are supported by numerical simulations by the three-dimensional (3D) multiple-relaxation-time lattice Boltzmann method. It is found that the length of the outermost contact lines instead of all contact lines determines the departure diameter of hemi-wicking-state bubble based on bubble detachment processes captured by our 3D numerical simulations. This work offers an avenue for the accurate prediction and control of bubble departure behaviors from micro-/nanostructured surfaces, and therefore can guide optimal designs of micro-/nanostructured surfaces in a variety of applications in boiling, desalination, and hydrogen production by electrolysis.

9.
Int J Mol Sci ; 23(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36292932

RESUMO

In recent years, cyclic peptides have attracted much attention due to their chemical and enzymatic stability, low toxicity, and easy modification. In general, the self-assembled nanostructures of cyclic peptides tend to form nanotubes in a cyclic stacking manner through hydrogen bonding. However, studies exploring other assembly strategies are scarce. In this context, we proposed a new assembly strategy based on cyclic peptides with covalent self-assembly. Here, cyclic peptide-(DPDPDP) was rationally designed and used as a building block to construct new assemblies. With cyclo-(DP)3 as the structural unit and 2,2'-diamino-N-methyldiethylamine as the linker, positively charged nanospheres ((CP)6NS) based on cyclo-(DP)3 were successfully constructed by covalent self-assembly. We assessed their size and morphology by scanning electron microscopy (SEM), TEM, and DLS. (CP)6NS were found to have a strong positive charge, so they could bind to siRNA through electrostatic interactions. Confocal microscopy analysis and cell viability assays showed that (CP)6NS had high cellular internalization efficiency and low cytotoxicity. More importantly, real-time polymerase chain reaction (PCR) and flow cytometry analyses indicated that (CP)6NS-siRNA complexes potently inhibited gene expression and promoted tumor cell apoptosis. These results suggest that (CP)6NS may be a potential siRNA carrier for gene therapy.


Assuntos
Nanosferas , Nanoestruturas , Nanotubos , RNA Interferente Pequeno/farmacologia , Peptídeos Cíclicos/química , Nanosferas/química , Nanotubos/química , Nanoestruturas/química
10.
Opt Express ; 29(20): 31915-31923, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34615273

RESUMO

We theoretically and experimentally investigate the angle-dependent omnidirectional photonic bandgap (PBG) in one-dimensional photonic crystals (PCs) comprising hyperbolic metamaterials (HMMs) for TM polarization, which is different from blue-shifted PBG in conventional all-dielectric photonic crystals. The frequency range of PBG increases when the incident angles increase, owing to the red-shift and blue-shift of the long-wavelength and short-wavelength band edges, respectively. The red-shifted band edge originates from the phase-variation compensation mechanism between the HMMs and dielectric material. The experimental values are in good agreement with the simulation results. These nanostructures are ideal for fabricating photonic devices such as omnidirectional reflectors.

11.
Small ; 16(41): e1906908, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32954642

RESUMO

Precise delivery of therapeutic cells to the desired site in vivo is an emerging and promising cellular therapy in precision medicine. This paper presents the development of a magnet-driven and image-guided degradable microrobot that can precisely deliver engineered stem cells for orthotopic liver tumor treatment. The microrobot employs a burr-like porous sphere structure and is made with a synthesized composite to fulfill degradability, mechanical strength, and magnetic actuation capability simultaneously. The cells can be spontaneously released from the microrobots on the basis of the optimized microrobot structure. The microrobot is actuated by a gradient magnetic field and guided by a unique photoacoustic imaging technology. In preclinical experiments on nude mice, microrobots carrying cells are injected via the portal vein and the released cells from the microrobots can inhibit the tumor growth greatly. This paper reveals for the first time of using degradable microrobots for precise delivery of therapeutic cells in vascular tissue and demonstrates its therapeutic effect in preclinical test.


Assuntos
Imãs , Neoplasias , Animais , Magnetismo , Camundongos , Camundongos Nus , Neoplasias/terapia , Células-Tronco
12.
Brain Behav Immun ; 87: 645-659, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32097763

RESUMO

Glioblastoma is a kind of malignant tumour and originates from the central nervous system. In the last century, some researchers and clinician have noticed that the psychosocial and neurocognitive functioning of patients with malignant gliomas can be impaired. Many clinical studies have demonstrated that part of patients, adults or children, diagnosed with glioblastoma will suffer from cognitive deficiency during their clinical course, especially in long-term survivors. Many nanoparticles (NPs) can inhibit the biological functions of tumours by modulating tumour-associated inflammation, which provokes angiogenesis and tumour growth. As one of the best antiviral nanoparticles (AVNPs), AVNP2 is the 2nd generation of AVNP2 that have been conjugated to graphite-graphene for improving physiochemical performance and reducing toxicity. AVNP2 inactivates viruses, such as the H1N1 and H5N1influenza viruses and even the SARS coronavirus, while it inhibits bacteria, such as MRSA and E. coli. As antimicrobials, nanoparticles are considered to be one of the vectors for the administration of therapeutic compounds. Yet, little is known about their potential functionalities and toxicities to the neurotoxic effects of cancer. Herein, we explored the functionality of AVNP2 on inhibiting C6 in glioma-bearing rats. The novel object-recognition test and open-field test showed that AVNP2 significantly improved the neuro-behaviour affected by C6 glioma. AVNP2 also alleviated the decline of long-term potentiation (LTP) and the decreased density of dendritic spines in the CA1 region induced by C6. Western blot assay and immunofluorescence staining showed that the expressions of synaptic-related proteins (PSD-95 and SYP) were increased, and these findings were in accordance with the results mentioned above. It revealed that the sizes of tumours in C6 glioma-bearing rats were smaller after treatment with AVNP2. The decreased expression of inflammatory factors (IL-1ß, IL-6 and TNF-α) by Western blotting assay and ELISA, angiogenesis protein (VEGF) by Western blotting assay and other related proteins (BDNF, NF-ĸB, iNOS and COX-2) by Western blotting assay in peri-tumour tissue indicated that AVNP2 could control tumour-associated inflammation, thus efficiently ameliorating the local inflammatory condition and, to some extent, inhibiting angiogenesis in C6-bearing rats. In conclusion, our results suggested that AVNP2 could have an effect on the peri-tumor environment, obviously restraining the growth progress of gliomas, and eventually improving cognitive levels in C6-bearing rats.


Assuntos
Antivirais/uso terapêutico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/psicologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Encefalite/etiologia , Encefalite/prevenção & controle , Glioma/complicações , Glioma/psicologia , Nanopartículas/uso terapêutico , Animais , Comportamento Animal , Peso Corporal/efeitos dos fármacos , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Disfunção Cognitiva/psicologia , Citocinas/biossíntese , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/patologia , Humanos , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Transplante de Neoplasias , Ratos , Ratos Sprague-Dawley , Reconhecimento Psicológico/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
13.
Invest New Drugs ; 37(6): 1146-1157, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30790151

RESUMO

The aim of this study was to explore the synergistic anti-tumor effects of cytarabine hyaluronic acid-tyramine (Ara-HA-Tyr) hydrogel conjugates and radiotherapy (RT) in the Lewis lung cancer (LLC) xenograft model, and the mechanisms involved. The radiotherapy sensitization ratio (SER) of 0.5 µg cytarabine (Ara-C) was 1.619 in the LLC cells. Ara-HA-Tyr was prepared by encapsulating Ara-C into hyaluronic acid-tyramine (HA-Tyr) conjugates. The hydrogels were formed through the oxidative coupling of tyramines by hydrogen peroxide (H2O2) and horseradish peroxidase (HRP). Mice engrafted with the LLC cells were given intra-tumoral injections of saline, Ara-C or Ara-HA-Tyr, with or without RT. The combination of Ara-HA-Tyr and RT increased survival compared to free Ara-C and RT (p < 0.05), and prolonged tumor growth delay (TGD). Furthermore, the RT + Ara-HA-Tyr combination therapy significantly reduced 18F-FDG uptake, induced cell cycle arrest at G2/M-phase, increased apoptosis and histone H2AX phosphorylation (γ-H2AX), and decreased the proliferation index (Ki67) in tumor cells compared to either monotherapy. Taken together, Ara-C encapsulated with HA-Tyr effectively sensitized tumor xenografts to RT and showed significantly less systemic toxicity. Graphical abstract In this work, Ara-C encapsulated with hyaluronic acid-tyramine conjugates (HA-Tyr) was prepared and used to investigate its synergistic anti-tumor efficacy by combination with radiotherapy in the Lewis lung cancer xenograft model. The synergistic mechanism may be related to tumor cell cycle redistribution, apoptosis and expression of histone H2AX phosphorylation.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/radioterapia , Citarabina/administração & dosagem , Ácido Hialurônico/administração & dosagem , Hidrogéis/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Animais , Apoptose , Carcinoma Pulmonar de Lewis/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Terapia Combinada , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Feminino , Histonas/metabolismo , Injeções Intralesionais , Neoplasias Pulmonares/metabolismo , Camundongos Endogâmicos C57BL
14.
J Neurooncol ; 129(1): 39-45, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27174198

RESUMO

We previously demonstrated that the acquired resistance because of Hsp27 activation weakens the cytotoxic effect of t-AUCB on glioblastoma cells. Since autophagy is regarded as a survival mechanism for cells exposed to cytotoxic agents, the aim of this study is to investigate whether t-AUCB induces autophagy and whether Hsp27 and autophagy are interacted with each other. Our data demonstrated that t-AUCB induces autophagy in glioblastoma cells and regulates multiple autophagy related-gene expression. t-AUCB induces overexpression of Atg7, which is downstream of Hsp27 and participates in the resistance of glioblastoma cells to t-AUCB treatment. Hsp27 inhibitor quercetin suppresses Atg7 expression and strengthens t-AUCB-induced cell death by autophagy blockage. We concluded that combination of quercetin and t-AUCB might be a potential strategy for glioblastoma treatment.


Assuntos
Antineoplásicos/administração & dosagem , Proteína 7 Relacionada à Autofagia/metabolismo , Autofagia/efeitos dos fármacos , Benzoatos/administração & dosagem , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Quercetina/administração & dosagem , Ureia/análogos & derivados , Antineoplásicos/uso terapêutico , Benzoatos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Expressão Gênica/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Proteínas de Choque Térmico , Humanos , Técnicas In Vitro , Chaperonas Moleculares , Quercetina/uso terapêutico , Ureia/administração & dosagem , Ureia/uso terapêutico
15.
Toxicol Appl Pharmacol ; 283(2): 83-91, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25596431

RESUMO

Benzo(a)pyrene is a common environmental and foodborne pollutant that has been identified as a human carcinogen. Although the carcinogenicity of benzo(a)pyrene has been extensively reported, its precise molecular mechanisms and the influence on system-level protein networks are not well understood. To investigate the system-level influence of benzo(a)pyrene on protein interactions and regulatory networks, a benzo(a)pyrene-rewired protein interaction network was constructed based on 769 key proteins derived from more than 500 literature reports. The protein interaction network rewired by benzo(a)pyrene was a scale-free, highly-connected biological system. Ten modules were identified, and 25 signaling pathways were enriched, most of which belong to the human diseases category, especially cancer and infectious disease. In addition, two lung-specific and two liver-specific pathways were identified. Three pathways were specific in short and medium-term networks (<48h), and five pathways were enriched only in the medium-term network (6h-48h). Finally, the expression of linker genes in the network was validated by Western blotting. These findings establish the overall, tissue- and time-specific benzo(a)pyrene-rewired protein interaction networks and provide insights into the biological effects and molecular mechanisms of action of benzo(a)pyrene.


Assuntos
Benzo(a)pireno/toxicidade , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/fisiologia , Linhagem Celular Tumoral , Humanos
16.
J Neurooncol ; 121(1): 83-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25200832

RESUMO

The aim of this study is to determine whether phosphorylation of AKT could be effected by t-AUCB-induced p-Hsp27 and whether p-AKT inhibition sensitizes glioblastoma cells to t-AUCB, and to evaluate the effects of simultaneous inhibition of p-Hsp27 and p-AKT on t-AUCB treated glioblastoma cells. Cell growth was detected using CCK-8 assay; Caspase-3 activity assay kits and flow cytometry were used in apoptosis analysis; Western blot analysis was used to detect p-Hsp27 and p-AKT levels; RNA interference using the siRNA oligos of Hsp27 was performed to knockdown gene expression of Hsp27. All data were analyzed by the Student-Newman-Keul's test. We demonstrated that t-AUCB treatment induces AKT phosphorylation by activating Hsp27 in U251 and LN443 cell lines. Inhibition of AKT phosphorylation by AKT inhibitor IV sensitizes glioblastoma cells to t-AUCB, strengthens t-AUCB suppressing cell growth and inducing cell apoptosis. We also found inhibiting both p-Hsp27 and p-AKT synergistically strengthen t-AUCB suppressing cell growth. Thus, p-AKT induced by p-Hsp27 confers the apoptosis-resistance in t-AUCB-treated glioblastoma cells. Targeting p-Hsp27 and/or p-AKT may be a potential effective strategy for the treatment of glioblastoma.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzoatos/farmacologia , Glioblastoma/tratamento farmacológico , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ureia/análogos & derivados , Apoptose/fisiologia , Western Blotting , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Citometria de Fluxo , Glioblastoma/fisiopatologia , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico , Humanos , Chaperonas Moleculares , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Interferência de RNA , Ureia/farmacologia
17.
Acta Pharmacol Sin ; 35(6): 825-31, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24793313

RESUMO

AIM: Trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) is a soluble epoxide hydrolase inhibitor that suppresses glioblastoma cell growth in vitro. The aim of this study was to examine whether the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) could sensitize glioma cells to t-AUCB-induced apoptosis. METHODS: Both U251 and U87 human glioblastoma cell lines were tested. Cell growth was assessed using the cell counting kit-8. Cell apoptosis was detected with caspase-3 activity assay kits and flow cytometry. The protein levels in the p38 MAPK/MAPKAPK2/Hsp27 pathway in the cells were analyzed using Western blots. RESULTS: Pretreatment with DAPT (2 µmol/L) substantially potentiated the growth inhibition caused by t-AUCB (200 µmol/L) in U251 and U87 cells. Furthermore, pretreatment with DAPT markedly increased t-AUCB-induced apoptosis of U251 and U87 cells. T-AUCB alone did not significant affect caspase-3 activity in the cells, but t-AUCB plus DAPT pretreatment caused significant increase of caspase-3 activity. Furthermore, pretreatment with DAPT completely blocked t-AUCB-induced phosphorylation of p38 MAPK, MAPKAPK2 and Hsp27 in the cells. CONCLUSION: The γ-secretase inhibitor DAPT sensitizes t-AUCB-induced apoptosis of human glioblastoma cells in vitro via blocking the p38 MAPK/MAPKAPK2/Hsp27 pathway, suggesting that the combination of t-AUCB and DAPT may be a potentially effective strategy for the treatment of glioblastoma.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Benzoatos/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Dipeptídeos/farmacologia , Glioblastoma/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Ureia/análogos & derivados , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glioblastoma/metabolismo , Proteínas de Choque Térmico HSP27/antagonistas & inibidores , Proteínas de Choque Térmico HSP27/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Ureia/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Zhongguo Yi Liao Qi Xie Za Zhi ; 38(1): 36-9, 2014 Jan.
Artigo em Zh | MEDLINE | ID: mdl-24839846

RESUMO

The free care smart infusion system which has the function of liquid end alarm and automatic stopping has been designed. In addition, the system can send the alarm to the health care staff by Zigbee wireless network. Besides, the database of infusion information has been set up, it can be used for inquiry afterwards.


Assuntos
Inteligência Artificial , Infusões Parenterais/instrumentação , Desenho de Equipamento , Tecnologia sem Fio
19.
World Neurosurg ; 185: e1280-e1286, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38514035

RESUMO

BACKGROUND: Intramedullary schwannoma is a relatively rare tumor with only a few literature reports. This study was aimed to report the clinical characteristics of intramedullary schwannoma and discuss imaging findings and treatment strategies. METHODS: The inclusion criterion was consecutive patients with intramedullary schwannomas who were surgically treated in our institution between 2017 and 2022. Data included clinical characteristics, radiologic features, surgical management, and prognosis. Clinical and follow-up details of all cases were collected and reviewed. RESULTS: This study included 3 male and 8 female patients. The mean age was 45 years (range 26-77 years). Cervical spine (4 cases, 36.4%), thoracic spine (4 cases, 36.4%), and lumbosacral spine (3 cases, 27.3%) involvement was found. Weakness, numbness and pain of limbs were the main symptoms at administration. Preoperative magnetic resonance imaging demonstrated lesion with spinal cord medullary invasion and well demarcated margins. The postoperative histologic examination showed benign lesions and confirmed the schwannoma. CONCLUSIONS: This article presented a series of 11 cases of intramedullary schwannoma with sharp margins and well-enhanced features. Prognosis and functional recovery were good after gross total resection.


Assuntos
Neurilemoma , Neoplasias da Medula Espinal , Neurilemoma/diagnóstico , Neurilemoma/patologia , Neurilemoma/cirurgia , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/cirurgia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Medula Cervical/patologia , Região Lombossacral , Tórax , Imageamento por Ressonância Magnética , Prognóstico , Margens de Excisão , Procedimentos Neurocirúrgicos
20.
ISA Trans ; 148: 212-223, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580576

RESUMO

This paper proposes an adaptive neural control strategy for stochastic microelectromechanical system (MEMS) gyroscopes, aiming to achieve a prescribed performance in a finite time. The radial basis function neural network is introduced to address the system's unknown nonlinear dynamics and stochastic disturbances. Then, the technology of finite-time prescribed performance function, along with the method of command-filtered backstepping design, is utilized to ensure both transient and steady-state performance and simultaneously solve the problem of "explosion of complexity." Moreover, a switching threshold event-triggered control law is proposed to cut down on communication resources and eliminate corresponding parametric inequality restrictions. The proposed adaptive state feedback control strategy is able to guarantee that the output tracking error converges to a prescribed, arbitrarily small residual set. Additionally, the closed-loop system's signals can be semi-globally ultimately uniformly bounded in probability. Finally, numerical simulations demonstrate the effectiveness and superiority of the proposed strategy.

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