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1.
J Colloid Interface Sci ; 664: 916-927, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38503077

RESUMO

As a typical perovskite material, NaTaO3 has been regarded as a potential catalyst for photocatalytic hydrogen evolution (PHE) process, due to its excellent photoelectric property and superior chemical stability. However, the photocatalytic activity of pure NaTaO3 was largely restricted by its poor visible-light absorption ability and rapid recombination of photogenerated charge carriers. Therefore, a covalently bonded TpBpy covalent organic framework (COF)/NaTaO3 (TpBpy/NaTaO3) heterostructure was designed and synthesized by the post modification strategy with (3-aminopropyl) triethoxysilane (APTES) and the in situ solvothermal process. Benefiting from the enhanced built-in electric field by the interfacial covalent bonds and the formation of S-scheme heterostructure between TpBpy and NaTaO3, which were proved by the Ar+-cluster depth profile and X-ray photoelectron spectroscopy (XPS), as well as density functional theory (DFT) calculation results, both the charge transfer efficiency and the PHE performance of the TpBpy/NaTaO3 composites were significantly improved. Additionally, the composites exhibited an excellent absorption performance in the visible region, which was also beneficial for the photocatalytic process. As expected, the optimal TpBpy/20%NaTaO3 composite achieved a remarkable hydrogen evolution rate of 17.3 mmol·g-1·h-1 (10 mg of catalyst) under simulated sunlight irradiation, which was about 173 and 2.4 times higher than that of pure NaTaO3 and TpBpy, respectively. This work provided a novel strategy for constructing highly effective and stable semiconductor/COFs heterostructures with strong interfacial interaction for photocatalytic hydrogen evolution.

2.
Signal Transduct Target Ther ; 8(1): 402, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37816755

RESUMO

The interleukin-17 (IL-17) family comprises six members (IL-17A-17F), and recently, all of its related receptors have been discovered. IL-17 was first discovered approximately 30 years ago. Members of this family have various biological functions, including driving an inflammatory cascade during infections and autoimmune diseases, as well as boosting protective immunity against various pathogens. IL-17 is a highly versatile proinflammatory cytokine necessary for vital processes including host immune defenses, tissue repair, inflammatory disease pathogenesis, and cancer progression. However, how IL-17 performs these functions remains controversial. The multifunctional properties of IL-17 have attracted research interest, and emerging data have gradually improved our understanding of the IL-17 signaling pathway. However, a comprehensive review is required to understand its role in both host defense functions and pathogenesis in the body. This review can aid researchers in better understanding the mechanisms underlying IL-17's roles in vivo and provide a theoretical basis for future studies aiming to regulate IL-17 expression and function. This review discusses recent progress in understanding the IL-17 signaling pathway and its physiological roles. In addition, we present the mechanism underlying IL-17's role in various pathologies, particularly, in IL-17-induced systemic lupus erythematosus and IL-17-related tumor cell transformation and metastasis. In addition, we have briefly discussed promising developments in the diagnosis and treatment of autoimmune diseases and tumors.


Assuntos
Doenças Autoimunes , Interleucina-17 , Humanos , Interleucina-17/genética , Inflamação , Citocinas , Transdução de Sinais/genética , Doenças Autoimunes/genética
3.
J Gastroenterol ; 58(9): 908-924, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37433897

RESUMO

BACKGROUND: Therapies for cholangiocarcinoma are largely limited and ineffective. Herein, we examined the role of the FGF and VEGF pathways in regulating lymphangiogenesis and PD-L1 expression in intrahepatic cholangiocarcinoma (iCCA). METHODS: The lymphangiogenic functions of FGF and VEGF were evaluated in lymphatic endothelial cells (LECs) and iCCA xenograft mouse models. The relationship between VEGF and hexokinase 2 (HK2) was validated in LECs by western blot, immunofluorescence, ChIP and luciferase reporter assays. The efficacy of the combination therapy was assessed in LECs and xenograft models. Microarray analysis was used to evaluate the pathological relationships of FGFR1 and VEGFR3 with HK2 in human lymphatic vessels. RESULTS: FGF promoted lymphangiogenesis through c-MYC-dependent modulation of HK2 expression. VEGFC also upregulated HK2 expression. Mechanistically, VEGFC phosphorylated components of the PI3K/Akt/mTOR axis to upregulate HIF-1α expression at the translational level, and HIF-1α then bound to the HK2 promoter region to activate its transcription. More importantly, dual FGFR and VEGFR inhibition with infigratinib and SAR131675 almost completely inhibited lymphangiogenesis, and significantly suppressed iCCA tumor growth and progression by reducing PD-L1 expression in LECs. CONCLUSIONS: Dual FGFR and VEGFR inhibition inhibits lymphangiogenesis through suppression of c-MYC-dependent and HIF-1α-mediated HK2 expression, respectively. HK2 downregulation decreased glycolytic activity and further attenuated PD-L1 expression. Our findings suggest that dual FGFR and VEGFR blockade is an effective novel combination strategy to inhibit lymphangiogenesis and improve immunocompetence in iCCA.


Assuntos
Colangiocarcinoma , Linfangiogênese , Humanos , Camundongos , Animais , Antígeno B7-H1/metabolismo , Hexoquinase/metabolismo , Hexoquinase/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia
4.
Front Public Health ; 10: 1015861, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452945

RESUMO

Background: Leukemia caused by occupational risk is a problem that needs more attention and remains to be solved urgently, especially for acute lymphoid leukemia (ALL), acute myeloid leukemia (AML), and chronic lymphoid leukemia (CLL). However, there is a paucity of literature on this issue. We aimed to assess the global burden and trends of leukemia attributable to occupational risk from 1990 to 2019. Methods: This observational trend study was based on the Global Burden of Disease (GBD) 2019 database, the global deaths, and disability-adjusted life years (DALYs), which were calculated to quantify the changing trend of leukemia attributable to occupational risk, were analyzed by age, year, geographical location, and socio-demographic index (SDI), and the corresponding estimated annual percentage change (EAPC) values were calculated. Results: Global age-standardized DALYs and death rates of leukemia attributable to occupational risk presented significantly decline trends with EAPC [-0.38% (95% CI: -0.58 to -0.18%) for DALYs and -0.30% (95% CI: -0.45 to -0.146%) for death]. However, it was significantly increased in people aged 65-69 years [0.42% (95% CI: 0.30-0.55%) for DALYs and 0.38% (95% CI: 0.26-0.51%) for death]. At the same time, the age-standardized DALYs and death rates of ALL, AML, and CLL were presented a significantly increased trend with EAPCs [0.78% (95% CI: 0.65-0.91%), 0.87% (95% CI: 0.81-0.93%), and 0.66% (95% CI: 0.51-0.81%) for DALYs, respectively, and 0.75% (95% CI: 0.68-0.82%), 0.96% (95% CI: 0.91-1.01%), and 0.55% (95% CI: 0.43-0.68%) for death], respectively. The ALL, AML, and CLL were shown an upward trend in almost all age groups. Conclusion: We observed a substantial reduction in leukemia due to occupational risks between 1990 and 2019. However, the people aged 65-69 years and burdens of ALL, AML, and CLL had a significantly increased trend in almost all age groups. Thus, there remains an urgent need to accelerate efforts to reduce leukemia attributable to occupational risk-related death burden in this population and specific causes.


Assuntos
Leucemia Linfocítica Crônica de Células B , Leucemia , Humanos , Carga Global da Doença , Leucemia Linfocítica Crônica de Células B/epidemiologia , Leucemia/epidemiologia , Bases de Dados Factuais , Anos de Vida Ajustados por Deficiência
5.
J Colloid Interface Sci ; 597: 206-214, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33872877

RESUMO

Photocatalysis utilizing solar energy is a promising strategy for mitigating energy crisis and environmental pollution. Exploring a cost-effective, stable, eco-friendly, and efficient photocatalytic system is extremely urgent. Herein, copper encapsulated within nitrogen-doped carbon nanosphere (Cu@NC) possessing a unique core-shell structure with high catalytic activity was prepared by ion-exchange and pyrolysis using resin as support. The protective carbon shell can prevent the leaching of metal ions and deactivation of the catalyst. Benefiting from the special structure, Cu@NC exhibited excellent activity and durability toward the degradation of tetracycline by the activation of peroxymonosulfate (PMS). The radical trapping experiments and electron spin resonance analyses were applied to elucidate the main reactive species. This work highlights the great potential of Cu@NC core-shell nanosphere as photocatalyst, which provides a new opportunity for the remediation of environmental pollution.

6.
Nanoscale ; 13(11): 5765-5779, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33704300

RESUMO

The synergism of combination chemotherapy can only be achieved under specific drug ratios. Herein, hyaluronic acid (HA)-functionalized regenerated silk fibroin-based nanoparticles (NPs) were used to concurrently deliver curcumin (CUR) and 5-fluorouracil (5-FU) at various weight ratios (3.3 : 1, 1.6 : 1, 1.1 : 1, 1 : 1, and 1 : 1.2) to breast tumor cells. The generated HA-CUR/5-FU-NPs were found to have desirable particle sizes (around 200 nm), narrow size distributions, and negative zeta potentials (about -26.0 mV). Interestingly, these NPs showed accelerated drug release rates when they were exposed to buffers that mimicked the multi-hallmarks in the tumor microenvironment (pH/hydrogen peroxide/glutathione/hyaluronidase). The surface functionalization of NPs with HA endowed them with in vitro and in vivo breast tumor-targeting properties. Furthermore, we found that the co-loading of CUR and 5-FU in HA-functionalized NPs exhibited obvious synergistic anti-cancer, pro-apoptotic, and anti-migration effects, and the strongest synergism was found at the CUR/5-FU weight ratio of 1 : 1.2. Most importantly, mice experiments revealed that HA-CUR/5-FU-NPs (1 : 1.2) showed a superior anti-cancer activity against metastatic breast cancer compared to the single drug-loaded NPs and non-functionalized CUR/5-FU-NPs (1 : 1.2). Collectively, these results demonstrate that HA-CUR/5-FU-NPs (1 : 1.2) can be exploited as a robust nanococktail for the treatment of breast cancer and its lung metastasis.


Assuntos
Neoplasias da Mama , Curcumina , Nanopartículas , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Curcumina/uso terapêutico , Sistemas de Liberação de Medicamentos , Quimioterapia Combinada , Humanos , Camundongos , Microambiente Tumoral
7.
J Mater Chem B ; 9(6): 1604-1615, 2021 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-33471012

RESUMO

The therapeutic efficacies of oral nanotherapeutics for ulcerative colitis (UC) are seriously hindered by the lack of mucus-penetrating capacity and uncontrolled drug release. To overcome these limitations, the surface of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) was functionalized with pluronic F127 (PF127), and catalase (CAT)/curcumin (CUR) was co-encapsulated into these NPs. The obtained P-CUR/CAT-NPs had a hydrodynamic particle size of approximately 274.1 nm, narrow size distribution, negative zeta potential (-14.0 mV), and smooth surface morphology. Moreover, the introduction of PF127 to the surface of NPs not only facilitated their mucus penetration, but also improved their cellular uptake efficiency by the target cells (macrophages). We further found that the encapsulation of CAT could remarkably increase the release rate of CUR from NPs in the presence of an H2O2-rich environment. Additionally, P-CUR/CAT-NPs showed the strongest capacity to suppress the secretion of the main pro-inflammatory cytokines, in comparison with their counterparts (CUR-NPs and P-CUR-NPs). Importantly, oral administration of P-CAT/CUR-NPs showed the best therapeutic outcomes than the other NPs. Collectively, these results clearly demonstrate that these mucus-penetrating NPs loaded with CAT and CUR can be exploited as an efficient nanotherapeutic for UC therapy.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Curcumina/uso terapêutico , Sistemas de Liberação de Medicamentos , Nanopartículas/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Células Cultivadas , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Curcumina/administração & dosagem , Curcumina/química , Liberação Controlada de Fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície
8.
J Control Release ; 328: 454-469, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-32890553

RESUMO

Lung metastasis of breast cancer is a leading cause of cancer-related death in women. Herein, we attempted to simultaneously inhibit the growth and lung metastasis of breast cancer by delivering quercetin (QU) using LyP-1-functionalized regenerated silk fibroin-based nanoparticles (NPs). The generated LyP-1-QU-NPs had a desirable diameter (203.2 nm) and a negatively charged surface (-12.7 mV). Interestingly, these NPs exhibited intrinsic responsibilities when triggered by various stimulating factors in the tumor microenvironment (acidic pH, reactive oxygen species, and glutathione). In vitro experiments revealed that the introduction of LyP-1 to the NP surface could significantly increase their cellular uptake efficiencies by 4 T1 cells, and facilitate their accumulation in mitochondria. Moreover, LyP-1-QU-NPs showed the strongest mitochondrial damage effect among all the treatment groups. We also found that LyP-1-QU-NPs not only exhibited excellent pro-apoptotic activities but also presented strong inhibitory effects on cell mobility (migration and invasion) through anti-glycolysis and pro-autophagy. Mice experiments confirmed that LyP-1-QU-NPs could efficiently inhibit the in situ growth of breast tumors and further restrict their lung metastasis. Collectively, our results demonstrate that LyP-1-QU-NPs, which integrates the functions of tumor cell targeting, mitochondria targeting, bioresponsive drug release, pro-apoptosis, and anti-mobility, can be developed as a promising nanotherapeutic for the effective treatment of breast cancer and its lung metastasis.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Nanopartículas , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Quercetina , Microambiente Tumoral
9.
Front Psychol ; 11: 28, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32047461

RESUMO

This study examines the underlying mechanism that connects career social support with employability through a survey of 392 Chinese college students. The results showed that career social support had a positive effect on career adaptation and employability of college students, and career adaptation mediated the association between career social support and employability. Furthermore, proactive personality was found to play a moderating role in linking career adaptation and employability. More specifically, higher levels of a proactive personality strengthen the enhancing effect of career adaptation on the employability of college students. Therefore, there was a moderated mediation effect between career social support and employability of college students.

10.
ACS Biomater Sci Eng ; 6(2): 1052-1063, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33464840

RESUMO

Combinational cancer therapy offers a promising strategy to overcome the limitations of single-drug treatment, including limited therapeutic efficacy, serious side effects, and low survival rate. Injectable silk fibroin (SF) hydrogel has emerged as an effective platform for localized treatment. Herein, hydrophilic SF (HSF) was extracted from regenerated SF and self-assembled into hydrogel within 2-6 h. The obtained HSF hydrogel showed obvious viscoelasticity, thixotropic behavior, and self-healing performance. Interestingly, this hydrogel also exhibited excellent stimuli-responsive drug release profiles when triggered by multiple factors (acidity, reactive oxygen species, glutathione, hyperthermia, and near-infrared (NIR)), suggesting that it could achieve spatially and temporally on-demand drug release in response to tumor microenvironment and extra-tumor NIR irradiation. Importantly, intratumoral injection of doxorubicin (DOX)/Cy7-loaded HSF-based hydrogel (DOX/Cy7-hydrogel) plus NIR irradiation exerted the best antitumor effect among all the treatment groups, revealing the strong synergistic effects of chemo/photothermal/photodynamic therapy. It is worth noting that this DOX/Cy7-hydrogel could almost eliminate the entire tumor masses, significantly prolonging the survival time of tumor-bearing mice over 60 days without detectable adverse effects. Collectively, our findings suggest that this injectable DOX/Cy7-hydrogel with thixotropic and multistimuli responsive properties could be developed as a promising platform for localized and synergistic treatment of cancer.


Assuntos
Fibroínas , Hipertermia Induzida , Neoplasias , Animais , Doxorrubicina , Hidrogéis , Camundongos , Neoplasias/tratamento farmacológico , Microambiente Tumoral
11.
Nanomedicine (Lond) ; 14(17): 2373-2378, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31290366

RESUMO

The incidence of colonic diseases (e.g., inflammatory bowel diseases and colon cancer) is rapidly rising. Nanotherapeutic has been considered as a promising strategy in the treatment of colonic diseases. Silk fibroin (SF) has been widely used as a drug-carrier matrix. Interestingly, SF-based nanoparticles (SFNPs) have intrinsic anti-inflammatory activity, wound healing capacity and lysosomal environment-responsive drug-release property. With further investigations, the sequences of SF molecules could be precisely modified through chemical reactions or transgenic techniques to greatly improve the properties of SFNPs. Here, we review recent advances in the application of SFNPs toward the treatment of colonic diseases. We also discuss future developments that might improve the anti-inflammatory and anti-colon cancer activities of SF-based nanotherapeutics.


Assuntos
Neoplasias do Colo/terapia , Fibroínas/uso terapêutico , Doenças Inflamatórias Intestinais/terapia , Nanopartículas/uso terapêutico , Animais , Humanos , Nanomedicina
12.
Stress ; 22(6): 640-646, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31057066

RESUMO

Previous studies have revealed stress-induced dysregulation of hypothalamic-pituitary-adrenal (HPA) axis in women with premenstrual syndrome (PMS). So far, however, the results about the relationship between HPA axis dysregulation and PMS are mixed. To this end, it is necessary to investigate the basal activity of the HPA axis in women with PMS instead of only assessing a certain stressor. Therefore, this study evaluated the relationship between the cortisol awakening response (CAR) and PMS. Thirty-two women with PMS (mean age 22.47 ± 2.20 years) and 36 healthy controls (mean age 22.28 ± 2.43 years) were included in this study. Saliva samples of our participants were collected successively at 0, 30, 45, and 60 min after awakening to assess CAR during each of two phases of the menstrual cycle (the mid-follicular phase and the late luteal phase). The results showed a significantly attenuated CAR in women with PMS compared with the healthy controls, especially at 45 and 60 min after awakening, regardless of the menstrual cycle phases. Furthermore, there was a significant negative correlation between PMS severity as measured by PMS scale and AUCi (i.e. the Area Under the Curve with respect to increase) in the mid-follicular phase. Our findings suggested that an attenuated CAR activity profile may be an important risk factor for the development of PMS.


Assuntos
Hidrocortisona/metabolismo , Síndrome Pré-Menstrual/metabolismo , Adulto , Feminino , Fase Folicular/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Fase Luteal/metabolismo , Ciclo Menstrual/metabolismo , Sistema Hipófise-Suprarrenal/fisiologia , Síndrome Pré-Menstrual/fisiopatologia , Síndrome Pré-Menstrual/psicologia , Saliva/metabolismo , Estresse Psicológico/metabolismo , Adulto Jovem
13.
Biomaterials ; 212: 39-54, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31103945

RESUMO

The requirement for the favorable therapeutics against ulcerative colitis (UC) is that anti-inflammatory drugs can be specifically internalized by macrophages and subsequently be on-demand released to suppress inflammation. Herein, we developed a type of multi-bioresponsive anti-inflammatory drug (curcumin, CUR)-loaded nanoparticles (NPs) that were derived from natural silk fibroin and followed by surface functionalization with chondroitin sulfate (CS). The generated CS-CUR-NPs had a desired average particle size (175.4 nm), a uniform size distribution and negative surface charge (-35.5 mV). Strikingly, these NPs exhibited excellent bioresponsibility when triggered with the intrinsic stimuli (acidity, glutathione and reactive oxygen species) within activated macrophages, indicating that they could conceivably confer the on-demand intracellular drug release. Furthermore, we found that CS functionalization yielded notably targeted drug delivery to macrophages, and thereby enhanced the anti-inflammatory activities of NPs. Most importantly, animal experiments revealed that these nanotherapeutics could remarkably alleviate the symptoms of UC, maintain the homeostasis of intestinal microbiota and improve the survival rate of mice with UC through the route of oral administration or intravenous injection. Our results suggest that these facilely fabricated CS-CUR-NPs, which exhibit excellent biocompatibility, multi-bioresponsive drug release and macrophage-targeted capacity, could be exploited as a promising therapeutic platform for clinical UC treatment.


Assuntos
Materiais Biocompatíveis/química , Colite Ulcerativa/tratamento farmacológico , Citoplasma/metabolismo , Liberação Controlada de Fármacos , Fibroínas/química , Receptores de Hialuronatos/metabolismo , Nanopartículas/química , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Sulfatos de Condroitina/química , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , Curcumina/farmacologia , Curcumina/uso terapêutico , Endocitose/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Nanopartículas/ultraestrutura , Células RAW 264.7 , Distribuição Tecidual/efeitos dos fármacos
14.
J Pharm Sci ; 108(7): 2238-2242, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30779888

RESUMO

Porous microparticles (MPs) have been regarded as a promising vehicle for drug delivery. Herein, porous MPs and their counterparts (nonporous MPs) were produced by a conventional emulsion-solvent evaporation method in the presence and absence of ammonium bicarbonate, and curcumin was encapsulated into these MPs during the preparation process. The obtained MPs possessed desirable diameters of around 1.2 µm and negative zeta potentials of approximately -28 mV. It was found that the release rate of curcumin was remarkably increased with the introduction of pores in MPs. Furthermore, orally administered porous MPs achieved statistically significantly better therapeutic outcomes against ulcerative colitis mouse model induced by dextran sulfate sodium, in comparison to nonporous MPs. These findings confirmed that porous MPs could be served as a promising platform for the treatment of ulcerative colitis via oral route.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Curcumina/química , Curcumina/farmacologia , Nanopartículas/química , Polímeros/química , Administração Oral , Animais , Bicarbonatos/química , Sulfato de Dextrana/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Feminino , Camundongos , Tamanho da Partícula , Porosidade
15.
Mol Pharm ; 16(1): 49-59, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30485109

RESUMO

Reactive oxygen species (ROS) are highly overproduced in cancerous tissues, and thus oxidation-responsive nanoparticles (NPs) have emerged as a promising drug carrier for cancer-targeted drug delivery. In this study, we successfully synthesized poly(vanillyl alcohol- co-oxalate) (PVAX) polymer with an excellent ROS-responsive capacity. A well-established emulsion-solvent evaporation method was used to fabricate PVAX-based curcumin (CUR)-loaded NPs (PVAX-NPs) and their counterparts (poly(lactic- co-glycolic acid)-based CUR-loaded NPs, PLGA-NPs). It was found that these NPs had a hydrodynamic particle size of approximately 245 nm, narrow size distribution (polydispersity index less than 0.1), negative zeta potential (around -18 mV), smooth surface appearance, and high drug encapsulation efficiency. Moreover, we found that the CUR release rate of PVAX-NPs was greatly increased in the presence of a hydrogen peroxide-rich environment due to the cleavage of polyoxalate ester bonds in PVAX polymer, resulting in the evenly distribution of CUR within the whole cancer cells. More importantly, PVAX-NPs exhibited much stronger anticancer activities and pro-apoptotic capacities than PLGA-NPs both in vitro and in vivo. These results clearly demonstrate that these ROS-responsive PVAX-NPs can be exploited as a robust anticancer drug delivery platform in chemotherapy.


Assuntos
Antineoplásicos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Polímeros/química , Curcumina/química , Portadores de Fármacos/química , Humanos , Células MCF-7 , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo
16.
Int J Pharm ; 557: 135-144, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30594685

RESUMO

To improve the penetration and accumulation of anti-inflammatory drugs in colitis tissue, we functionalized the surface of porous poly(lactic-co-glycolic acid) nanoparticles (NPs) using pluronic F127 (PF127) and loaded curcumin (CUR) into the resulting NPs to obtain porous PF127-functionalized CUR-loaded NPs (porous PF127-NPs). These NPs had an average hydrodynamic diameter of about 270 nm with a highly monodisperse size distribution, slightly negative surface charge and controllable CUR release profile. It was found that they had good biocompatibility and yielded a much higher cellular uptake rate of CUR than porous CUR-loaded NPs without PF127 modification (porous NPs). In addition, porous PF127-NPs showed a greater capacity to inhibit the major pro-inflammatory cytokines (IL-6, IL-12 and TNF-α) secreted from lipopolysaccharide-activated macrophages than porous NPs and non-porous PF127-NPs. In vivo experiments suggested that porous PF127-NPs achieved the best therapeutic outcomes against ulcerative colitis (UC) in mice compared with porous NPs and non-porous PF127-NPs. Our results clearly demonstrate that these fabricated porous PF127-NPs show a great promise as an efficient CUR nanocarrier for UC therapy.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Curcumina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , Poloxâmero/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Administração Oral , Animais , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana , Feminino , Lipopolissacarídeos/farmacologia , Camundongos , Células RAW 264.7
17.
ACS Biomater Sci Eng ; 5(11): 6231-6242, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33405530

RESUMO

Silk sericin (SS) is abundant in silk industry wastewater, and it has emerged as a promising natural protein for biomedical research. However, its therapeutic potential against ulcerative colitis (UC) has not been exploited. The objective of this study is to investigate the therapeutic effects of SS in a dextran sulfate sodium-induced UC mouse model, and further discover its underlying mechanisms. The purified SS molecules showed negative cytotoxicity, and could be efficiently internalized by colonic epithelial cells and macrophages. In vitro experiments revealed that it could accelerate the mucosal healing, down-regulate the production of pro-inflammatory factors, increase the secretion of anti-inflammatory cytokines, and eliminate the intracellular reactive oxygen species. Finally, animal experiments confirmed that oral administration of hydrogel (chitosan/alginate)-embedding SS molecules attenuated UC-induced symptoms (e.g., body weight loss, colon shortening, increase of spleen weight, and histopathological appearance), which was supported by signs of mucosal healing, anti-inflammation, and elevation of the amounts of tight junction proteins (occludin and zonula occludens-1) and mucin protein (MUC2). Taken together, our results demonstrate that SS can be exploited as a promising oral natural therapeutic for UC treatment with the aid of hydrogel.

18.
Colloids Surf B Biointerfaces ; 169: 92-98, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29751345

RESUMO

Oral microparticles (MPs) have been considered as promising drug carriers in the treatment of ulcerative colitis (UC). Here, a facile strategy based on a conventional emulsion-solvent evaporation technique was used to fabricate bowl-shaped MPs (BMPs), and these MPs loaded with anti-inflammatory drug (curcumin, CUR) during the fabrication process. The physicochemical properties of the resultant BMPs were characterized by dynamic light scattering, scanning electron microscope, confocal laser scanning microscope and X-ray diffraction as well as contact angle goniometer. Results indicated that BMPs had a desirable hydrodynamic diameter (1.84 ±â€¯0.20 µm), a negative zeta potential (-26.5 ±â€¯1.13 mV), smooth surface morphology, high CUR encapsulation efficiency and controlled drug release profile. It was found that CUR molecules were dispersed in an amorphous state within the polymeric matrixes. In addition, BMPs showed excellent hydrophilicity due to the presence of Pluronic F127 and poly(vinyl alcohol) on their surface. More importantly, orally administered BMPs could efficiently alleviate UC based on a dextran sulfate sodium-induced mouse model. These results collectively suggest that BMP can be exploited as a readily scalable oral drug delivery system for UC therapy.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Curcumina/uso terapêutico , Sistemas de Liberação de Medicamentos , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Colite Ulcerativa/induzido quimicamente , Curcumina/administração & dosagem , Curcumina/química , Sulfato de Dextrana , Modelos Animais de Doenças , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Feminino , Hidrodinâmica , Camundongos , Camundongos Endogâmicos , Tamanho da Partícula , Propriedades de Superfície , Molhabilidade
19.
Psychophysiology ; 52(2): 182-91, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25154679

RESUMO

Resting frontal alpha asymmetry measures the relative activation intensity across the left and right frontal regions that represent emotional experience. Here, the focus is on levels of alpha asymmetry between high- and low-neuroticism females across the menstrual cycle. Resting alpha asymmetry in healthy females who scored high or low on neuroticism was assessed during the menstrual phase, the late follicular phase, and the midlate luteal phase. High-neuroticism females exhibited lower relative left prefrontal activity than did low-neuroticism females during the midlate luteal phase, as indexed by alpha1 and alphaTotal asymmetry scores at the prefrontal electrode positions (FP1/2 ). EEG results demonstrate that the resting frontal alpha asymmetry of high- and low-neuroticism females was moderated by the menstrual cycle, and high-neuroticism females should pay particular attention to their emotional experience during the midlate luteal phase.


Assuntos
Transtornos de Ansiedade/psicologia , Lobo Frontal/fisiologia , Ciclo Menstrual/fisiologia , Personalidade/fisiologia , Adolescente , Adulto , Eletroencefalografia , Emoções/fisiologia , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Ciclo Menstrual/psicologia , Neuroticismo , Determinação da Personalidade , Progesterona/sangue , Adulto Jovem
20.
Stress ; 18(2): 160-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25518868

RESUMO

This study assessed the effects of premenstrual syndrome (PMS) and menstrual phases on the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system axis and psychological responses to the Trier Social Stress Test (TSST). Thirty-six PMS women (mean age 21.69 ± 2.16 years) and 36 control women (mean age 22.03 ± 2.48 years) participated in the TSST task, either in the follicular phase or in the late luteal phase (each group N = 18). Saliva samples, heart rate and subjective stress levels were collected for seven time points throughout the test (10, 20, 30, 40, 55, 70 and 100 min). The results indicated that in comparison with control women, PMS women displayed blunted cortisol stress responses to the TSST irrespective of the menstrual phases, as indexed by the cortisol levels across time, area under the curve with respect to ground (AUCg) and peak change scores of cortisol. The results also demonstrated that the measurements indexed by cortisol levels across time, AUCg and peak change scores of heart rate were smaller in women tested during the late luteal phase than during the follicular phase. Correlation results indicated that AUCg was negatively correlated with PMS scores. These results suggest that measures of cortisol, rather than heart rate or subjective responses to stress, may be most closely associated with PMS. Furthermore, hypo-reactivity of the HPA axis may be pathologically relevant to PMS because it predicts heightened PMS severity.


Assuntos
Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Síndrome Pré-Menstrual/metabolismo , Estresse Psicológico/metabolismo , Feminino , Fase Folicular/metabolismo , Frequência Cardíaca/fisiologia , Humanos , Fase Luteal/metabolismo , Fase Luteal/psicologia , Síndrome Pré-Menstrual/fisiopatologia , Síndrome Pré-Menstrual/psicologia , Saliva/química , Comportamento Social , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Sistema Nervoso Simpático/fisiopatologia , Adulto Jovem
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