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1.
Oral Oncol ; 125: 105718, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35063882

RESUMO

OBJECTIVE: Induction chemotherapy followed by concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, survival benefits from additional induction chemotherapy varied significantly among patients. This study aimed to determine the predictive value of body mass index (BMI) in induction chemotherapy in NPC. MATERIALS AND METHODS: This post-hoc analysis included patients from two multicenter, randomized, phase 3 trials (NCT01245959 and NCT01872962), in which patients were randomized to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone. RESULTS: Among 960 patients participated, 957 were included in this analysis. 82 (8.6%) patients had baseline BMI < 18.5 kg/m2 (underweight) and 875 (91.4%) had BMI ≥ 18.5 kg/m2 (normal /overweight). Higher proportion of normal/overweight patients completed ≥2 cycles of induction chemotherapy than underweight patients (96.5% vs. 88.4%, p = 0.042). A strong trend for interaction was observed between BMI and induction chemotherapy regarding failure-free survival (FFS) and overall survival (OS, both pinteraction < 0.001). Normal/overweight patients benefited from induction chemotherapy regarding FFS (83.8% vs. 72.9%, p < 0.001) or OS (93.1% vs. 86.9%, p < 0.001), while underweight patients did not (p = 0.24 and p = 0.65, respectively). These results were confirmed in multivariate analysis and multiple sensitivity analyses. CONCLUSION: Using pooled data from two landmark phase III trials, we found that underweight patients might not benefit from additional induction chemotherapy in locoregionally advanced NPC. If confirmed in prospective studies, this could help guide individual treatment in the clinic.

2.
Nat Commun ; 13(1): 501, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35079021

RESUMO

Radiotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC), and approximately 20% of patients experience treatment failure due to tumour radioresistance. However, the exact regulatory mechanism remains poorly understood. Here, we show that the deubiquitinase USP44 is hypermethylated in NPC, which results in its downregulation. USP44 enhances the sensitivity of NPC cells to radiotherapy in vitro and in vivo. USP44 recruits and stabilizes the E3 ubiquitin ligase TRIM25 by removing its K48-linked polyubiquitin chains at Lys439, which further facilitates the degradation of Ku80 and inhibits its recruitment to DNA double-strand breaks (DSBs), thus enhancing DNA damage and inhibiting DNA repair via non-homologous end joining (NHEJ). Knockout of TRIM25 reverses the radiotherapy sensitization effect of USP44. Clinically, low expression of USP44 indicates a poor prognosis and facilitates tumour relapse in NPC patients. This study suggests the USP44-TRIM25-Ku80 axis provides potential therapeutic targets for NPC patients.

3.
Sci Rep ; 12(1): 912, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042891

RESUMO

The 15# coal seam of Yangmei No.5 Mine, which produces anthracite, which is the least prone to spontaneous combustion, has a serious hidden danger of spontaneous combustion due to the high sulfur content in the coal. Based on the better conductivity of anthracite, we designed an electrolysis experiment to accelerate the electrochemical oxidation of pyrite in coal. Through experiments and analysis of thermodynamic characteristic parameters, it is obtained that the electrochemical oxidation of pyrite and its main products Fe3+ and Fe2+ have a coupled catalytic effect on the spontaneous combustion of high-sulfur coal in Yangquan. Combined with the FTIR test and analysis, it is found that the electrochemical process causes spatial polarization in the coal, so that polar groups such as -OH undergo spatial diversion and increase the activity. Due to the high content of -OH in Yangquan anthracite, the electrochemical process has the greatest effect on promoting -OH oxidation. Fe3+ and Fe2+ act as strong oxidants and free radicals to promote the -CH2- reaction to generate C=O and promote the generation of CO. This research provides a new direction for the exploration of the spontaneous combustion mechanism of high-sulfur anthracite.

4.
ACS Omega ; 6(43): 29091-29099, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34746598

RESUMO

The hydrated salt disodium hydrogen phosphate dodecahydrate (DHPD, Na2HPO4·12H2O) has a suitable phase transition temperature and high latent heat of phase transition. Still there are problems such as supercooling, phase separation, and low thermal conductivity. In this paper, DHPD, sodium carboxymethyl cellulose (CMC), aluminum oxide (Al2O3), and poly(vinylpyrrolidone) (PVP) are used to configure DHPD-CAP to suppress supercooling and phase separation successfully. Multiwalled carbon nanotubes (MWCNTs) are used to stabilize DHPD-CAP phase-change materials and improve the thermal conductivity of pure DHPD. Further studies show only a physical interaction between MWCNTs and DHPD, and no new phases are generated. The addition of MWCNTs can also promote the nucleation of the DHPD-CAP composite, and the corresponding latent heat of phase change shows a trend of increasing and then decreasing with the increase of MWCNT content. Compared with DHPD after one cycle, the latent heat of DHPD-CAP/MWCNT4 increases by 36.19%. With the addition of MWCNTs, the thermal stability of the composites is improved compared to pure DHPD. The DHPD-CAP/MWCNT4 composite has good stability after many cycles.

5.
Ann Transl Med ; 9(10): 845, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34164479

RESUMO

Background: Methotrexate (MTX) is an important anticancer agent and immunosuppressant with a narrow therapeutic window. Wuzhi capsule (WZC) is an extract of Schisandra which is widely used to treat liver diseases. Co-administration of MTX and WZC is common in the clinical setting, but research on the interaction between WZC and MTX is limited. This study aimed to investigate the effects of WZC on the pharmacokinetics of MTX in rats and to explore the role of membrane transport proteins OAT1/3 and P-gp in the interaction of these drugs. Methods: Plasma MTX concentration was detected by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS), and the messenger RNA (mRNA) and protein expression of OAT1/3 and P-gp was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting analyses, respectively. Results: The study results revealed that co-administration of WZC decreased the CLz/F and Vz/F of MTX, increased the Cmax and area under the curve [(AUC)0-24 h] of MTX, and inhibited OAT1/3 expression in the kidney and P-gp expression in the small intestine. Conclusions: The findings suggested that there is a drug interaction between WZC and MTX and that OAT1/3 in the kidney and P-gp in the small intestine may be the main targets mediating the drug interaction, and attention should be paid when they are used in combination.

6.
J Cancer ; 12(15): 4542-4551, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149918

RESUMO

Tumor distant metastasis is the primary cause of death in colorectal cancer (CRC) patients. GL-V9 is a newly synthesized flavonoid derivative with several beneficial biological functions including anti-tumor and anti-inflammation. However, the anti-metastatic effect of GL-V9 and related mechanisms in CRC remains unknown. In this study, the anti-invasive and anti-migratory activities of GL-V9 were investigated in CRC cells. Using MTT assay, cell wound healing assay, and transwell migration assay, we showed that GL-V9 suppressed CRC cell viability, migration, and invasion in a concentration-dependent manner. In addition, the protein expression levels as well as activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were significantly reduced after GL-V9 treatment. Further analysis of the underlying mechanism revealed that GL-V9 inhibited PI3K/Akt signaling pathway upstream of MMP-2 and MMP-9. In conclusion, our study demonstrated that GL-V9 could suppress CRC cell invasion and migration through PI3K/Ak and MMP-2/9 axis. Therefore, GL-V9 might be a potential novel therapeutic agent against CRC metastasis.

7.
Immunopharmacol Immunotoxicol ; 43(3): 380-385, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34028330

RESUMO

BACKGROUND: Allergic dermatitis (AD) is a chronic inflammatory skin disease that a variety of immune cells are involved in the progression of AD. Among them, T cells are one of major players of AD pathogenesis. The V-domain Ig suppressor of T cell activation (VISTA) has been reported that it has a potential immunomodulatory for T cell response. OBJECTIVE: This study aimed to investigate immunomodulatory of recombinant VISTA-Ig fusion protein in AD mice model. METHODS: The model of AD was built with oxazolone (OXA) in BALB/c mice, then VISTA-Ig was used to treat AD by intraperitoneal (IP) injection. The ear thickness was measured by a digital thickness gauge. The ears tissues were collected and subjected to hematoxylin-eosin (H&E) and toluidine blue (TB) staining. The secretion levels of IL-4 and IgE in the serum were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of inflammatory cytokines (IL-1ß, IL-6, IL-12, and INF-γ) in ear tissues were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Treatment with VISTA-Ig successfully alleviated the symptoms of AD, such as erythema, horny substance, and swelling. The infiltration of inflammatory cells was significantly reduced following VISTA-Ig therapy. The secretion levels of IL-4 and IgE in the serum were significantly attenuated following treatment with VISTA-Ig. Additionally, VISTA-Ig observably down-regulated inflammatory cytokines expression in ear tissues. CONCLUSIONS & CLINICAL RELEVANCE: Taken together, our results showed that VISTA-Ig possessed the potential to be a novel immunomodulatory candidate drug against AD.

8.
Biomed Res Int ; 2021: 6686167, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954197

RESUMO

Whether the use of endovascular embolization could provide additional benefits in patients treated with stereotactic radiosurgery (SRS) for intracranial arteriovenous malformations (IAVMs) remains controversial. The current meta-analysis was conducted to assess the efficacy and safety of SRS with and without prior endovascular embolization in patients with IAVMs. The electronic databases of PubMed, EmBase, and Cochrane Library were systematically searched for eligible studies published from inception to August 12, 2020. The pooled results for obliteration rate, rehemorrhage rate, and permanent neurological deficits were calculated by odds ratios (ORs) with 95% confidence intervals (CIs) using the random-effects model. The sensitivity analysis, subgroup analysis, and publication bias for investigated outcomes were also evaluated. Nineteen studies (two prospective and 17 retrospective studies) involving a total of 3,454 patients with IAVMs were selected for the final meta-analysis. We noted that prior embolization and SRS were associated with a lower obliteration rate compared with SRS alone (OR, 0.57; 95% CI, 0.44-0.74; P < 0.001). However, prior embolization and SRS were not associated with the risk of rehemorrhage (OR, 1.05; 95% CI, 0.81-1.34; P = 0.729) and permanent neurological deficits (OR, 0.80; 95% CI, 0.48-1.33; P = 0.385) compared with SRS alone. The sensitivity analysis suggested that prior embolization might reduce the risk of permanent neurological deficits in patients with IAVMs treated with SRS. The treatment effects of prior embolization in patients with IAVMs could be affected by nidus volume, margin dose, intervention, and follow-up duration. This study found that prior embolization was associated with a reduced risk of obliteration in patients with IAVMs treated with SRS. Moreover, prior embolization might reduce the risk of permanent neurological deficits in patients with IAVMs.


Assuntos
Embolização Terapêutica/efeitos adversos , Malformações Arteriovenosas Intracranianas/cirurgia , Radiocirurgia/efeitos adversos , Adolescente , Adulto , Criança , Terapia Combinada , Feminino , Humanos , Hemorragias Intracranianas/etiologia , Masculino , Fatores de Risco , Resultado do Tratamento
9.
Ann Palliat Med ; 10(3): 3086-3096, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33752434

RESUMO

BACKGROUND: Canagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, is widely used for the treatment of type 2 diabetes mellitus. However, drug interactions with canagliflozin can affect its glucoselowering therapeutic effects or exacerbate its adverse effects. Telmisartan, an angiotensin receptor blocker (ARB), has been approved for the treatment of diabetic kidney disease. This study aimed to investigate the effects of telmisartan on the pharmacokinetics and tissue distribution of canagliflozin. METHODS: An ultra-performance liquid chromatography-tandem mass spectrometry method was successfully validated to determine the levels of canagliflozin in the plasma and tissues. The main pharmacokinetic parameters were calculated using the non-compartmental model. RESULTS: Compared with animals administered canagliflozin alone, the area under the receiver operating characteristic curve of animals co-administered telmisartan and canagliflozin was significantly increased after a single-day administration, but significantly decreased after a seven-day treatment regimen (both P<0.05). The highest concentrations of canagliflozin were detected in the kidneys, followed by the intestine, liver, heart, lung, spleen, and brain tissues. Furthermore, the concentration of canagliflozin in the heart, liver, lung, and kidney tissues at 2 hours post-administration was significantly higher in the telmisartan and canagliflozin group compared to the group treated with canagliflozin alone (P<0.05). CONCLUSIONS: A pharmacokinetic drug-drug interaction between telmisartan and canagliflozin might occur during drug co-administration.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Animais , Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Camundongos , Ratos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Telmisartan , Distribuição Tecidual
10.
Exp Cell Res ; 398(2): 112403, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33271128

RESUMO

The proliferation of mast cells (MCs) plays a crucial role in either physiological or pathological progression of human physical. C-Kit-mediated signaling pathway has been confirmed to play a key role in MCs proliferation, and the regulatory mechanisms of C-Kit-mediated MCs proliferation need to be further explored. Our previous study found that protein 4.1R could negatively regulate T cell receptor (TCR) mediated signal pathways in CD4+ T cells. Little is known about the function of 4.1R in C-Kit-mediated proliferation of MCs. In this study, P815-4.1R-/- cells were constructed by using CRISPR/Cas9 technique. Lack of 4.1R significantly enhanced P815 cells proliferation by accelerating the progression of cell cycle. 4.1R could also significantly alleviate the clinical symptoms of systemic mastocytosis (SM) and improve the overall survival of SM mice. Further study showed that 4.1R could interact directly with C-Kit to inhibit the activation of C-Kit-mediated Ras-Raf-MAPKs and PI3K-AKT signal pathways. Taken together, our findings demonstrate that protein 4.1R, a novel negative regulator, negatively regulates MCs proliferation by inhibiting C-Kit-mediated signal transduction, which maybe provide a potential target to the prevention and treatment of abnormal MCs proliferation-related diseases.


Assuntos
Proteínas do Citoesqueleto/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Transdução de Sinais , Animais , Proliferação de Células , Células Cultivadas , Humanos , Camundongos Endogâmicos DBA
11.
Sci Rep ; 10(1): 21882, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33318555

RESUMO

In order to study the adsorption characteristics of H2S, CH4 and N2 by coal under different conditions, the new macromolecular structure model of Dongqu No. 2 was constructed, and the grand canonical Monte Carlo (GCMC) method was used to simulate the adsorption process of three types of gases in coal. The dependence of adsorption capacity of coal on its temperature, pressure and moisture content was analyzed. The results show that with the increase of pressure and temperature, adsorption isotherms of all the three gases follow Langmuir model. For pressure greater than 2 MPa, the influence of temperature on adsorption capacity was greater than that of pressure. With rise in temperature, the decrease in rate of H2S adsorption was least and drops in the heat of adsorption of H2S most. This indicates that the adsorption of H2S on coal is more stable than those of CH4 and N2. As the water content of coal increased, its adsorption capacity for the present three gases decreased linearly, and the capacity for H2S (1.77 mmol/g) changed the most. The reduction of free volume linearly and preferential occupation of adsorption sites by water molecules are the main reasons for the highest change in the adsorbed amount of H2S gas.

12.
Immunopharmacol Immunotoxicol ; 42(5): 416-422, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32762390

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic skin inflammatory disease characterized by disequilibrium between Th1/Th2 lymphocytes. Helicobacter pylori neutrophil-activating protein (HP-NAP) has been reported that it has the potential immunomodulatory effect able to regulate the Th1/Th2 balance. OBJECTIVE: This study aimed to investigate the therapeutic effect of HP-NAP in AD mice model. METHODS: The model of AD was built with oxazolone (OXA) in BALB/c mice, then HP-NAP was used to treat AD by intraperitoneal injection. Ear thickness was measured by a digital thickness gauge. The ears tissues were collected and subjected to hematoxylin-eosin (H&E) and toluidine blue (TB) staining. The mRNA expression levels of inflammatory cytokines (IL-1ß, IL-5, IL-6, and TNF-α) in ear tissue were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The secretion of IgE, IL-4, and IFN-γ was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Treatment with HP-NAP successfully alleviated the symptoms of AD, such as erythema, horny substance, and swelling. The infiltration of lymphocytes and mast cells were significantly reduced following HP-NAP therapy. The secretion of IgE and IL-4 was significantly attenuated following treatment with HP-NAP. Additionally, HP-NAP observably downregulated inflammatory cytokine expression (e.g. IL-1ß, IL-5, IL-6, and TNF-α) in ear tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Taken together, our results showed that HP-NAP possessed the potential to be a novel immunomodulatory candidate drug against AD.


Assuntos
Proteínas de Bactérias/farmacologia , Dermatite Atópica/prevenção & controle , Fatores Imunológicos/farmacologia , Pele/efeitos dos fármacos , Animais , Quimiotaxia de Leucócito/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Modelos Animais de Doenças , Feminino , Imunoglobulina E/metabolismo , Mediadores da Inflamação/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos Endogâmicos BALB C , Oxazolona , Pele/imunologia , Pele/metabolismo , Equilíbrio Th1-Th2/efeitos dos fármacos
13.
Immunology ; 161(4): 314-324, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32852059

RESUMO

During the immune response, B cells can enter the memory pathway, which is characterized by class switch recombination (CSR), or they may undergo plasma cell differentiation (PCD) to secrete immunoglobulin. Both of these processes occur in activated B cells, which are reported to relate to membrane-association proteins and adaptors. Protein 4.1R acts as an adaptor, linking membrane proteins to the cytoskeleton, and is involved in many cell events such as cell activation and differentiation, and cytokine secretion. However, the effect of 4.1R on regulating B-cell fate is unclear. Here, we show an important association between B-cell fate and 4.1R. In vitro, primary B cells were stimulated with lipopolysaccharide combined with interleukin-4; results showed that 4.1R-deficient (4.1R-/- ) cells compared with wild-type (4.1R+/+ ) B cells augmented expression of activation-induced cytidine deaminase and germline, resulting in increased IgG1+ B cells, whereas the secretion of IgG1 and IgM was reduced, and CD138+ B cells were also decreased. Throughout the process, 4.1R regulated canonical nuclear factor (NF-κB) rather than non-canonical NF-κB to promote the expression of CSR complex components, leading to up-regulation of B-cell CSR. In contrast, 4.1R-deficient B cells showed reduced expression of Blimp-1, which caused B cells to down-regulate PCD. Furthermore, over-activation of canonical NF-κB may induce apoptosis signaling to cause PCD apoptosis to reduce PCD number. In summary, our results suggest that 4.1R acts as a B-cell fate regulator by inhibiting the canonical NF-κB signaling pathway.


Assuntos
Linfócitos B/imunologia , Citoesqueleto/metabolismo , Proteínas dos Microfilamentos/metabolismo , NF-kappa B/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , Switching de Imunoglobulina , Imunoglobulina G/metabolismo , Memória Imunológica , Imunomodulação , Interleucina-4/metabolismo , Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos/genética , Transdução de Sinais
14.
Environ Sci Pollut Res Int ; 27(25): 31872-31883, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32504431

RESUMO

Natural colloids (NCs) are ubiquities in aquatic environments, which play an important role in the fate and transport of metal elements. Combined with a multi-method analytical approach, this study investigates the spectral characteristics and the contamination of metals of NCs from the five tributaries of Poyang Lake and the lakes in Nanchang City. Results showed that NCs in river samples were characteristic by the smaller molecular weight, lower chromophoric dissolved organic matter (CDOM) concentration, higher aromaticity, and higher CDOM contribution to the organic carbon than those in lake samples. Based on the parallel factor analysis model, three fluorophores were identified, including two humic-like components (C1 and C2) and a protein-like component (C3). NCs in river and lake waters were dominant by the humic-like substance (C1) and the protein-like substance (C3), respectively, with the relatively high fluorescence intensity for all the fluorophores in lake samples. Furthermore, NCs from the river samples were primarily terrestrial NCs with a high degree of humification. The average detection frequency of metal elements was nearly 50% for both river and lake samples, whereas the concentrations of the metal elements were higher in lake samples. Principal component analysis (PCA) results showed that the contamination of the detected metals could divide into three categories, with relatively high concentrations of Ba, Pb, Zn, Al, Sr, and Fe in lake samples. Moreover, PCA results showed that NCs in lakes with higher values of the absorbance and fluorescence parameters were associated with the higher concentration of metal elements, revealing that the spectral characteristic could be the proxy indicator of the contamination of metal elements of NCs.


Assuntos
Lagos , Rios , China , Coloides , Análise Fatorial , Metais , Espectrometria de Fluorescência
15.
Iran J Immunol ; 17(1): 14-25, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32224538

RESUMO

BACKGROUND: Melanoma is a common and malignant cutaneous tumor, which is responsible for a large proportion of skin cancer deaths. Dendritic cell (DC)-based vaccines have achieved positive results in the treatment of melanoma because of their ability to induce cytotoxic response to facilitate tumor elimination. OBJECTIVE: To improve the efficacy of dendritic cell-based vaccines by the adjuvant activity of Helicobacter pylori neutrophil activating protein (HP-NAP). METHODS: The recombinant HP-NAP (rHP-NAP) was expressed by using prokaryotic expression system. DCs were cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. After treating with rHP-NAP, the maturation of DCs and dendritic cell-based vaccine were assayed by using flow cytometry and qRT-PCR. The activation and proliferation of T cells were measured by FCM, ELISA and MTT methods. The tumor specific cytotoxic response to resistant B16F10 was detected by using lactate dehydrogenase-release assay and qRT-PCR. RESULTS: The rHP-NAP, prepared from E. coli prokaryotic expression system, was able to significantly promote the maturation of dendritic cell-based vaccine loaded with tumor cell lysate (TCL) of B16F10 (DC-B16F10-TCL). Furthermore, it effectively induced the activation and proliferation of T cells and tumor specific cytotoxic response to resistant B16F10 melanoma tumor cells. CONCLUSION: These results suggested that rHP-NAP possesses the potential for use as an adjuvant of dendritic cell-based vaccine in anti-melanoma treatment.


Assuntos
Adjuvantes Imunológicos/farmacologia , Proteínas de Bactérias/farmacologia , Vacinas Anticâncer/farmacologia , Células Dendríticas/transplante , Melanoma Experimental , Animais , Proteínas de Bactérias/imunologia , Vacinas Anticâncer/imunologia , Humanos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia , Receptores Toll-Like/agonistas
16.
Front Neurol ; 11: 609384, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33424758

RESUMO

Objective: Heparinization is applied to prevent ischemic complications in the endovascular treatment of intracranial aneurysms, but there is no unified heparinization scheme. Diffusion-weighted imaging (DWI) can be used to evaluate ischemia after endovascular therapy for intracranial aneurysms. The goal of this study is to apply DWI to evaluate the effects of different heparinization schemes on intracranial aneurysms treated with endovascular therapy. Methods: We retrospectively reviewed 141 patients with 149 aneurysms treated with endovascular interventions from July 2019 to April 2020 at our center, including 96 aneurysms treated with local heparinization and 53 aneurysms treated with systemic heparinization. We collected the basic information of the patients, including age, sex, comorbidities, and aneurysm characteristics, and associated treatment data. New ischemic lesions detected by DWI were categorized belonging to four types. Multivariate logistic regression was used to compare the effects of different heparinization schemes on intracranial aneurysms treated with endovascular therapy. Results: There were no significant differences in age, sex, hypertension, diabetes, and aneurysm size or location between the two groups. The incidence and distribution types of DWI abnormalities in the local heparinization groups and systemic heparinization groups were not significantly different (P > 0.05). There was a correlation between the laser engraving stent and postoperative DWI abnormalities (P < 0.003). Multivariate logistic regression analysis showed that the laser engraving stent was significantly correlated with postoperative DWI abnormalities (odds ratio, 4.71; 95% CI: 1.51-14.58; P = 0.007). Conclusion: Compared with systemic heparinization, local heparinization does not increase the incidence of DWI abnormalities after endovascular treatment, and its application in this group of patients is safe and effective.

17.
Neurol Res ; 42(1): 8-16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31878844

RESUMO

Objectives: Long noncoding RNAs (lncRNAs) play substantial roles in cerebral ischemia. Growth arrest-specific 5 (GAS5) was reported to be involved in stroke. In the present study, we aimed to investigate the roles of GAS5 in cerebral condition and unveil the underlying mechanism.Method: Transient focal ischemia was induced by intraluminal occlusion of the right Middle cerebral artery occlusion (MCAO) and 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to evaluate the volume of cerebral infarction. RT-qPCR was applied to evaluate the level of GAS5 and miR-221. Fluorescence activated Cell Sorting (FACS) and Terminal deoxynucleotidyl transferased (TUNEL)  were used for detection of apoptosis. Western blotting was applied for protein level. Luciferase assay was applied to reveal the underlying relationship between GAS5 and miR-221 or p53-upregulated modulator of apoptosis (PUMA) and miR-221.Results: The results indicated that GAS5 was up-regulated in MCAO rats and in vitro hypoxia cell model while miR-221 expression was decreased in vitro hypoxia cell model. GAS5 promoted cells apoptosis, while miR-221 inhibited cell apoptosis through regulation of PUMA and downstream JNK/H2AX signaling. Moreover, GAS5 and miR-221 have direct interaction and PUMA was the target of miR-221, indicating that GAS5 regulated PUMA through sponging miR-221.Conclusions: the present study revealed that GAS5 aggravated cell apoptosis in hypoxia condition via miR-221/PUMA axis, which may provide potential targets for the treatment of stroke.


Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Apoptose/fisiologia , Isquemia Encefálica/metabolismo , MicroRNAs/metabolismo , Neurônios/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Isquemia Encefálica/patologia , Hipóxia Celular/fisiologia , Células Cultivadas , Células HEK293 , Humanos , Masculino , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Regulação para Cima/fisiologia
18.
Int J Biol Macromol ; 144: 615-623, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31843600

RESUMO

The structural modification of polysaccharides directly affects their physicochemical properties and applications. Dextran, a chained polysaccharide, consists of multiple d-glucose molecules with repetitive structures. In this study, the physicochemical properties of oxidized dextran (DO) at different concentrations of NaClO/NaBr and H2O2 were compared. The results showed that NaClO/NaBr oxidation is more conducive to the formation of carboxyl groups. Oxidized dextran with NaClO/NaBr (DOB) showed good iron (III) chelating ability, and the DOB­iron (III) complex (DOBIC) had an iron content of 28.31%. According to structural analysis, NaClO/NaBr (2 g/100 g of active chlorine) and H2O2 (4 g/100 g), respectively, oxidize the C1 and C2 hydroxyl groups of dextran to carboxyl groups and open the ring when DO and iron have the strongest chelation ability. The complex is indeed a chelate iron complex, and iron core is composed of iron oxyhydroxide or the ß-FeOOH mineral polymorph. These results indicate that DOBIC is expected to be a good iron supplement or food additive to strengthen iron.


Assuntos
Brometos/química , Complexos de Coordenação/química , Dextranos/química , Peróxido de Hidrogênio/química , Quelantes de Ferro/química , Compostos de Sódio/química , Hipoclorito de Sódio/química , Compostos Férricos/química , Concentração de Íons de Hidrogênio , Ferro/química , Cinética , Minerais/química , Peso Molecular , Oxirredução , Relação Estrutura-Atividade
19.
J Asian Nat Prod Res ; 22(9): 839-849, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31364407

RESUMO

The synergistic anti-tumor effect of schisandrin B (Sch.B) and apatinib was investigated in vitro. The CCK-8 assay revealed that Sch.B enhanced the inhibition of apatinib on cell proliferation by arresting cell cycle in G0/G1 phase. Sch.B also potentiated the suppression of apatinib on cell migration and invasion, by means of wound-healing and transwell invasion assay. Flow cytometry results showed that Sch.B enhanced apoptosis induced by apatinib. The results were confirmed by western blot analysis of the proteins MMP-9, and Bax caspase-9, and -12. These results suggest that combining apatinib and Sch.B is an effective therapeutic strategy for preventing GC progression. [Formula: see text].


Assuntos
Apoptose , Ciclo-Octanos , Linhagem Celular Tumoral , Proliferação de Células , Lignanas , Estrutura Molecular , Compostos Policíclicos , Piridinas
20.
Exp Cell Res ; 384(2): 111648, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31562860

RESUMO

The correct functioning of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is required for normal skin development and homeostasis. Cellular hyperproliferation induced by dysregulation of EGFR is tightly associated with structural and functional defects of hair follicles, skin lesions, and tumorigenesis. However, a number of questions still remain regarding the mechanism of EGFR activation and signaling. Here, we report that 4.1R, a member of the membrane-cytoskeleton linker FERM family proteins, plays critical roles in EGFR activation and signaling in keratinocytes. We demonstrated that knockout of 4.1R augments the excessive proliferation potential of keratinocytes by immunohistochemical analysis using murine skin samples. 4.1R-/- keratinocytes display enhanced EGFR-mediated Akt/ERK signaling by upregulating EGFR expression and phosphorylation, which can be reversed by either EGFR or MEK phosphorylation inhibitors. Mechanistically, coimmunoprecipitation and immunofluorescent staining results confirmed that 4.1R can impair the activation of EGFR through direct binding to EGFR and reduce the downstream signaling. Taken together, a deficiency of 4.1R would therefore serve to sustain aberrant EGFR-mediated cellular signaling, leading to hyperproliferation. Our findings highlight the role of 4.1R in the regulation of EGFR signaling in keratinocytes and suggest that 4.1R acts as a novel regulator for EGFR activation.


Assuntos
Proliferação de Células/fisiologia , Receptores ErbB/metabolismo , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas dos Microfilamentos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Animais , Proliferação de Células/efeitos dos fármacos , Proteínas do Citoesqueleto/metabolismo , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia
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