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1.
ACS Catal ; 13(22): 15074-15086, 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-38026819

RESUMEN

As a critical component of the OX-ZEO composite catalysts toward syngas conversion, the Cr-doped ZnO ternary system can be considered as a model system for understanding oxide catalysts. However, due to the complexity of its structures, traditional approaches, both experimental and theoretical, encounter significant challenges. Herein, we employ machine learning-accelerated methods, including grand canonical Monte Carlo and genetic algorithm, to explore the ZnO(1010) surface with various Cr and oxygen vacancy (OV) concentrations. Stable surfaces with varied Cr and OV concentrations were then systematically investigated to examine their influence on the CO activation via density functional theory calculations. We observe that Cr tends to preferentially appear on the surface of ZnO(1010) rather than in its interior regions and Cr-doped structures incline to form rectangular islands along the [0001] direction at high Cr and OV concentrations. Additionally, detailed calculations of CO reactivity unveil an inverse relationship between the reaction barrier (Ea) for C-O bond dissociation and the Cr and OV concentrations, and a linear relationship is observed between OV formation energy and Ea for CO activation. Further analyses indicate that the C-O bond dissociation is much more favored when the adjacent OVs are geometrically aligned in the [1210] direction, and Cr is doped around the reactive sites. These findings provide a deeper insight into CO activation over the Cr-doped ZnO surface and offer valuable guidance for the rational design of effective catalysts for syngas conversion.

2.
Nutrients ; 15(18)2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37764862

RESUMEN

We aimed to examine the association of milk intake with sleep disorders and their specific indicators. The current study included 768 adults aged 28-95 from Wenling, China. Milk intake was assessed using a food frequency questionnaire with ten food items, while sleep disorders were measured using the Pittsburgh Sleep Quality Index (PSQI), with higher scores indicating poorer sleep. The participants were divided into two groups according to the average intake of milk per week: rare intake (≤62.5 mL/week) and regular intake (>62.5 mL/week). Primary measurements were multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the prevalence of sleep disorders concerning regular milk intake compared with rare intake. In secondary analyses, linear regression analyses were performed to assess the effects of milk intake on sleep disorders and their specific dimensions. Regular intake of milk did not have a significant association with sleep disorders compared with rare intake (adjusted OR: 0.72, 95%; CI: 0.51, 1.03), but this association was found to be pronounced with sleep disturbances (OR: 0.49, 95%; CI: 0.28, 0.87). Increased intake of milk was significantly associated with the lower scores of PSQI for sleep quality (ß: -0.045, 95%; CI: -0.083, -0.007) and sleep disturbances (ß: -0.059, 95%; CI: -0.090, -0.029), respectively. When stratified by age and gender, the benefits of milk intake for sleep disorders and sleep disturbances were more significant in older adults (≥65) and men than in younger persons and women. In summary, regular milk intake benefits sleep quality, which may contribute to nutritional psychiatric support for prevention against sleep disorders.


Asunto(s)
Leche , Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos del Sueño-Vigilia , Anciano , Animales , Femenino , Humanos , Masculino , Estudios Transversales , Pueblos del Este de Asia , Sueño , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/etiología , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años
3.
Dig Dis Sci ; 68(8): 3283-3292, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37335414

RESUMEN

BACKGROUND/AIMS: To explore the protective effects and therapeutic mechanism of Esomeprazole (PPI), polaprezinc granule (PZ), and PPI + PZ on reflux esophagitis (RE) in the rat model. METHODS: Wistar rats were randomly divided into 9 groups, which contain the control group, the acid cessation group (0.7% HCl, Q3D × 4), and the acid persistence group (0.7% HCl, Q3D × 11). PPI was administered by gavage at 8 mg·kg-1 body weight and PZ was administered by gavage at 120 mg·kg-1 body weight once a day for 15 days. The gastric cardia tissue of the feeding tube was observed under the light microscope, and the levels of interleukin-8 (IL-8) and prostaglandin E2 (PGE2) were measured by ELISA. The expression of EGFR, Akt, p-Akt, and p-mTOR was detected by Western blot. RESULTS: The ELISA results showed that the levels of IL-8 and PGE2 were significantly increased in the model group, but decreased in all groups after treatment. In the acid cessation group, PZ treatment had the most significant effect on reducing IL-8 levels and PPI + PZ treatment had the most significant effect on reducing PGE2 levels. In the acid persistence group, the PPI treatment had the most significant effect on reducing the levels of IL-8 and PGE2, and the PZ treatment could also significantly reduce their levels, close to the normal value. Western blot results showed that the expression of PI3K/Akt/mTOR pathway protein was increased in the model group, while its expression was decreased after treatment. CONCLUSIONS: Polaprezinc has a significant therapeutic effect on RE in rats, which can reduce the levels of IL-8 and PGE2 and downregulate the expression of PI3K/Akt/mTOR signal pathway protein. The efficacy of polaprezinc in the treatment of reflux esophagitis is comparable to that of PPI, and the combination of them is more effective in the reflux esophagitis treatment.


Asunto(s)
Esofagitis Péptica , Ratas , Animales , Esofagitis Péptica/tratamiento farmacológico , Interleucina-8 , Ratas Wistar , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Dinoprostona/uso terapéutico , Serina-Treonina Quinasas TOR
4.
ACS Catal ; 13(8): 5104-5113, 2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37123602

RESUMEN

Oxygen vacancies (OVs) play important roles on any oxide catalysts. In this work, using an investigation of the OV effects on ZnO(101̅0) for CO and H2 activation as an example, we demonstrate, via machine learning potentials (MLPs), genetic algorithm (GA)-based global optimization, and density functional theory (DFT) validations, that the ZnO(101̅0) surface with 0.33 ML OVs is the most likely surface configuration under experimental conditions (673 K and 2.5 MPa syngas (H2:CO = 1.5)). It is found that a surface reconstruction from the wurtzite structure to a body-centered-tetragonal one would occur in the presence of OVs. We show that the OVs create a Zn3 cluster site, allowing H2 homolysis and C-O bond cleavage to occur. Furthermore, the activity of intrinsic sites (Zn3c and O3c sites) is almost invariable, while the activity of the generated OV sites is strongly dependent on the concentration of the OVs. It is also found that OV distributions on the surface can considerably affect the reactions; the barrier of C-O bond dissociation is significantly reduced when the OVs are aligned along the [12̅10] direction. These findings may be general in the systems with metal oxides in heterogeneous catalysis and may have significant impacts on the field of catalyst design by regulating the concentration and distribution of the OVs.

5.
J Chromatogr A ; 1689: 463747, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36621106

RESUMEN

As green, less toxic, and abundant ligands with rich functional groups, natural products are widely used in synthesis of chromatographic stationary phases. In this work, dodecyl imide maleopimaric acid glycidyl methacrylate ester (C12-MPAGN) was prepared from maleopimaric acid through the imidization and ring-opening based esterification reaction. By using "thiol-ene" click chemistry, it was chemically bonded to the silica and (3-mercaptopropyl) trimethoxysilane (γ-MPS) was used as the coupling agent to obtain dodecyl imide maleopimaric acid glycidyl methacrylate ester bonded silica stationary phase (Sil-C12-MPAGN). Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopies (SEM), and elemental analysis (EA) were utilized to verify that the Sil-C12-MPAGN stationary phase was successfully prepared with C12-MPAGN immobilized on the silica surface. In order to evaluate the chromatographic performance and retention mechanisms of the Sil-C12-MPAGN column and compared with C18 column, a variety of compounds were used, including stander mixture of Tanaka, alkylbenzenes, polycyclic aromatic hydrocarbons (PAHs), phenols and flavonoids. Based on these multiple interactions, including hydrophobic, hydrogen-bonding, and π-π interactions, high selectivity and superior separation performance were demonstrated by the Sil-C12-MPAGN column for probe molecules what had previously been mentioned. In addition, the quantitative determination of paclitaxel content in Yew bark extract was conducted with this column, which was found that the concentration was 83.67 mg/L, respectively. In short, the present study proposes a new strategy for introducing rosin to liquid chromatography with high selectivity and separation performance.


Asunto(s)
Cromatografía de Fase Inversa , Ésteres , Cromatografía de Fase Inversa/métodos , Espectroscopía Infrarroja por Transformada de Fourier , Imidas , Dióxido de Silicio/química , Interacciones Hidrofóbicas e Hidrofílicas , Cromatografía Líquida de Alta Presión/métodos
6.
Anal Chim Acta ; 1239: 340661, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36628701

RESUMEN

A column prepared using a unique three-membered phenanthrene skeleton of rosin has complementary selectivity to a C18 column for some separation tasks. In this study, propylene pimaric acid (16-hydroxyethyl acrylate-34-n-butyl) ester (BRB) and propylene pimaric acid (16-hydroxyethyl acrylate-34-dodecyl) ester (BRLA) were used as functional ligands to prepare two novel stationary phases, namely BRB@SiO2 and BRLA@SiO2, through a "thiol-ene" click chemistry reaction. The characterization results of Fourier transform infrared spectroscopy, thermogravimetric analysis, nitrogen adsorption-desorption measurements, and contact angle tests showed that the BRB@SiO2 and BRLA@SiO2 stationary phases were successfully prepared. In addition, the performance of the columns was evaluated using the Tanaka test and hydrophobic subtraction model, which showed that the stationary phases exhibited typical reversed-phase chromatography performance and good hydrophobicity, hydrophobic selectivity, and steric selectivity. The changes in the retention of Panax notoginseng saponins on a column under different chromatographic conditions (acetonitrile content, flow rate, and column temperature) were investigated. The separation effect of BRB@SiO2 and BRLA@SiO2 columns on P. notoginseng saponins was better than that of the C18 column and the BRLA@SiO2 column could replace the C18 column for the detection of P. notoginseng saponins.


Asunto(s)
Panax notoginseng , Saponinas , Dióxido de Silicio/química , Panax notoginseng/química , Ésteres , Interacciones Hidrofóbicas e Hidrofílicas
7.
J Clin Med ; 11(23)2022 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-36498624

RESUMEN

Background: Quadruple therapy with polaprezinc provided an alternative to Helicobacter pylori eradication; however, the effect on gut microbiota remains uncertain. This study aims to identify whether polaprezinc-containing quadruple therapy causes adverse microbiota effects among asymptomatic adults, compared with bismuth therapy. Methods: This was a randomized control trial. One hundred asymptomatic H. pylori-infected adults were randomly (1:1) assigned to two treatment groups (polaprezinc-containing therapy, PQT; or bismuth-containing therapy, BQT). Fecal samples were collected from subjects before and 4−8 weeks after therapy. Samples were sequenced for the V4 regions of the 16S rRNA gene. Results: The relative abundance of the three dominant bacterial phyla (Bacteroidota, Firmicutes, and Proteobacteria) accounted for more than 95% of each treatment group. The alpha diversity between eradications that succeeded and those that failed had no significant difference (p > 0.05). After successful eradication, the alpha diversity in the BQT group decreased in comparison with the baseline (p < 0.05). Subjects who were successfully eradicated by BQT showed considerably lower alpha diversity indices than those of the PQT at follow-up (p < 0.05). The abundance of Parasutterella in subjects who were successfully eradicated by PQT was four times greater than that of BQT (q < 0.05). Conclusion: A 14-day PQT may be superior to BQT in maintaining short-term gut microbiota homeostasis after H. pylori treatment. Our findings preliminarily provide evidence of the short-term impacts of the gut microbiota after PQT treatment of H. pylori infection.

8.
Polymers (Basel) ; 14(23)2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36501475

RESUMEN

In order to understand the ablation behaviors of CFRP laminates in an atmospheric environment irradiated by continuous wave laser, CFRP laminates were subjected to a 1080-nm continuous wave laser (6-mm laser spot diameter), with different laser power densities carried out in this paper. The internal delamination damage in CFRP laminates was investigated by C-Scan. The rear- and front-face temperature of CFRP laminates were monitored using the FLIR A 655 sc infrared camera, and the rear-face temperature was monitored by K type thermocouples. The morphology of ablation damage, the area size of the damaged heat affected zone (HAZ), crater depth, thermal ablation rate, mass ablation rate, line ablation rate, etc., of CFRP laminates were determined and correlated to the irradiation parameters. It is found that the area size of the damage HAZ, mass ablation rate, line ablation rate, etc., increased as the laser power densities. The dimensionless area size of the damaged HAZ decreased gradually along the thickness direction of the laser irradiation surface.

9.
Contrast Media Mol Imaging ; 2022: 1649904, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36101805

RESUMEN

In order to explore the clinical treatment of severe acne, this paper proposed the effect of CT technology combined with modified qinfan decoction on improving sores and promoting angiogenesis. From October 2016 to November 2017, 69 patients with severe acne treated in the first traditional Chinese medicine hospital of a city were selected for retrospective analysis. The 69 patients were randomly divided into control group and treatment group. There were 34 patients in the control group and 35 patients in the treatment group. Patients in the control group were treated with VSD. Patients in the treatment group were treated with qinfan decoction combined with VSD. Then, the total effective rate, the time of clinical symptom improvement, the time when the new granulation began to grow, and the time when the sore surface area was reduced by 1/2 were compared between the two groups. The results showed that after treatment, the total effective rate of the treatment group was higher than that of the control group. The time for the improvement of clinical symptoms, the time for the growth of new granulation, and the time for the reduction of the sore surface area by 1/2 were shorter than those of the control group, and the healing rate of the sore surface was higher than that of the control group (P < 0.05). Qinfan decoction combined with negative pressure sealing drainage technology has a significant effect on the treatment of severe acne and can promote its rehabilitation.


Asunto(s)
Acné Vulgar , Acné Vulgar/diagnóstico por imagen , Acné Vulgar/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
10.
Acc Chem Res ; 55(9): 1237-1248, 2022 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-35442027

RESUMEN

ConspectusMicrokinetic modeling based on density functional theory (DFT) energies plays an essential role in heterogeneous catalysis because it reveals the fundamental chemistry for catalytic reactions and bridges the microscopic understanding from theoretical calculations and experimental observations. Microkinetic modeling requires building a set of ordinary differential equations (ODEs) based on the calculation results of thermodynamic properties of adsorbates and kinetic parameters for the reaction elementary steps. Solving a microkinetic model can extract information on catalytic chemistry, including critical reaction intermediates, reaction pathways, the surface species distribution, activity, and selectivity, thus providing vital guidelines for altering catalysts.However, the quantitative reliability of traditional microkinetic models is often insufficient to conclusively extrapolate the mechanistic details of complex reaction systems. This can be attributed to several factors, the most important of which is the limitation of obtaining an accurate estimation of the energy inputs via traditional calculation methods. These limitations include the difficulty of using static DFT methods to calculate reaction energies of adsorption/desorption processes, often rate-controlling or selectivity-determining steps, and the inadequate consideration of surface coverage effects. In addition, the robust microkinetic software is rare, which also complicates the resolution of complex catalytic systems.In this Account, we review our recent works toward refining the predictions of microkinetic modeling in heterogeneous catalysis and achieving theory-experiment parity for activity and selectivity. First, we introduce CATKINAS, a microkinetic software developed in our group, and show how it disentangles the problem that traditional microkinetic software has and how it can now be applied to obtain kinetic results for more sophisticated reaction systems. Second, we describe a molecular dynamics method developed recently to obtain the free-energy changes for the adsorption/desorption process to fill in the missing energy inputs. Third, we show that a rigorous consideration of surface coverage effects is pivotal for building more realistic models and obtaining accurate kinetic results. Following a series of studies on acetylene hydrogenation reactions on Pd catalysts, we demonstrate how this new approach can provide an improved quantitative understanding of the mechanism, active site, and intrinsic structural sensitivity. Finally, we conclude with a brief outlook and the remaining challenges in this field.

11.
Se Pu ; 40(3): 234-241, 2022 Mar 08.
Artículo en Chino | MEDLINE | ID: mdl-35243833

RESUMEN

The sanqi is the dried root of Panax notoginseng (Burk.) F. H. Chen. The main components responsible for the drug actions of sanqi are notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, and ginsenoside Rd, which account for about 80% of the saponin content in sanqi. It is widely used in the treatment of anemia, coronary heart disease, hypertension, stroke sequelae, and other diseases. However, sanqi has many chemical components with complex and similar structures, which are difficult to separate. In this study, alkylated silica gel bonded with hydrogenated rosin hydroxyethyl acrylate (HRHA) was prepared via mercapto-ene click chemistry. A new type of modified rosin-bonded silica stationary phase (SiO2@HRHA) for high performance liquid chromatography was prepared for the separation of five saponins (R1, Rg1, Re, Rb1, and Rd). It was characterized by thermogravimetric analysis, Fourier-transform infrared spectroscopy, specific surface area and microporous physical adsorption and elemental analysis. The results showed that SiO2@HRHA had a regular spherical shape with porous surfaces, along with a specific surface area of 308.55 m2/g and an average pore diameter of 6.78 nm. Performance evaluation of the column revealed that the SiO2@HRHA column showed typical reversed-phase chromatographic behavior with better flowability and reproducibility. Results of the Tanaka test showed that SiO2@HRHA column had good stereoselectivity and hydrogen bond capacity. Compared to other stationary phases, e. g. silica modified with acrylopimaric acid (16-hydroxyethyl-34-hydroxyethyl acrylate) ester (AAE) and dihydroterpineol (DTP), which were prepared in our laboratory at the same time, the SiO2@HRHA column demonstrated better resolution (Rs) for the separation of the five saponins under optimal chromatographic conditions. The Rs values for R1, Rg1, Re, Rb1, and Rd were 3.33, 3.54, 20.17 and 9.72, respectively on the SiO2@HRHA column. Rs between Rg1 and Re was also better than that obtained on a C18 column. Panax notoginseng saponins were separated on the SiO2@HRHA column using acetonitrile and water as the mobile phases at the flow rate of 1.0 mL/min at 25 ℃. The optimal UV detection wavelength was 203 nm. It was found that the five saponins could be separated better using the SiO2@HRHA column than the SiO2@AAE and SiO2@DTP columns. Because the ternary phenanthrene skeleton of the rosin group in SiO2@HRHA had structural similarity and good stereoselectivity to the polycyclic compounds (Panax notoginseng saponins). In addition, according to the hydrophobicity evaluation, the SiO2@HRHA column showed the best hydrophobicity among the three columns, which may be conducive to the separation of the five saponins. Thus, this study can provide a new avenue for the separation and purification of Panax notoginseng saponins from actual samples.


Asunto(s)
Ginsenósidos , Panax notoginseng , Saponinas , Cromatografía Líquida de Alta Presión , Ginsenósidos/análisis , Panax notoginseng/química , Reproducibilidad de los Resultados , Resinas de Plantas , Saponinas/análisis , Saponinas/química , Dióxido de Silicio
12.
JACS Au ; 2(2): 328-334, 2022 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35252983

RESUMEN

Heterogenous hydrogenation reactions are essential in a wide range of chemical industries. In this work, we find that the hydrogenation of acetaldehyde on birnessite cannot occur through the traditional mechanisms due to the strong adsorption of the aldehyde and hydrogen on the surface, using first-principles calculations. We discover that this reaction can occur feasibly via a solvent-cocatalyzed mechanism with molecular hydrogen in the liquid phase: a methanol solvent or a similar solvent is required for the reaction. Free energy calculations shows that the methanol solvent preferentially fills the oxygen vacancies of the catalyst surface and spontaneously dissociates on the surface, in which the resulting hydroxyl group then acts as the coordination site for the carbonyl bond and allows the reaction to proceed without adsorption of the reactants on the surface. The reasons this new mechanism is more favorable over the traditional mechanisms in the literature are scrutinized and discussed. The new mechanism may be followed in many other systems.

13.
ISA Trans ; 129(Pt B): 192-203, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35221091

RESUMEN

To solve the state feedback stabilization problem for a class of T-S fuzzy systems, a new stability synthesis method is raised to further relax the conservatism existing in the analysis process. First, a series of nonlinear polynomials are used to approximate the system membership functions. And satisfied approximation results can be obtained. Then a polynomials transformation method is raised to change the polynomial membership functions into linear form. This method can facilitate the synthesis process and achieve better approximation precision. Therefore, by a membership function involving stability analysis approach, linear matrix inequality form stability conditions are given. Finally, by presenting and analyzing a numerical and a practical examples, the conservatism reduction effects of the proposed methods are verified.

14.
J Chromatogr A ; 1665: 462815, 2022 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-35038614

RESUMEN

Paclitaxel (PTX) is a complex diterpenoid anticancer drug whose separation from yew biomass poses a significant challenge. In this study, a new stationary phase comprising hydrogenated rosin (ß-acryloxyl ethyl) ester (HRE)-bonded silica (HRE@SiO2) is developed to separate and purify PTX from crude yew-bark extract using high-performance liquid chromatography. In HRE@SiO2, HRE molecules, which are functional ligands, are bonded to the surface of a silica gel matrix using a coupling agent, (3-mercaptopropyl)trimethoxysilane. The proposed HRE@SiO2 stationary phase was characterized by Fourier-transform infrared spectroscopy, elemental analysis, thermogravimetric analysis, scanning electron microscopy, laser diffraction granulometry, and nitrogen gas adsorption. The HRE@SiO2 column exhibited excellent chromatographic performance, satisfactory performance reproducibility, and typical reversed-phase chromatographic behavior. An HRE@SiO2 column was used to separate PTX and its analogs, achieving resolutions exceeding 7.43 for consecutively eluted species. Stoichiometric displacement theory for retention (SDT-R), the van Deemter equation, and van 't Hoff plots were used to analyze the separation mechanism and properties of the HRE@SiO2 column. The results showed that hydrophobic interactions determine the analyte retention and the separation of PTX and its analogs on an HRE@SiO2 column is an exothermic process driven by enthalpy. Furthermore, an HRE@SiO2 column was employed to separate and purify PTX from crude yew-bark extract, increasing PTX purity from 6% to 82%. The findings of this study provide insights for developing rosin-based stationary phases for the separation of natural products.


Asunto(s)
Paclitaxel , Dióxido de Silicio , Cromatografía Líquida de Alta Presión , Ésteres , Interacciones Hidrofóbicas e Hidrofílicas , Corteza de la Planta , Reproducibilidad de los Resultados , Resinas de Plantas
15.
IEEE Trans Cybern ; 52(8): 7906-7912, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33417579

RESUMEN

In this text, a membership function derivatives (MFDs) extrema-based method is proposed to relax the conservatism both in stability analysis and synthesis problems of Takagi-Sugeno fuzzy systems. By the designed algorithm, the nonpositiveness of the MFDs extrema is conquered. For an open-loop system, based on certain information of the MFs and derivatives, a series of convex stability conditions is derived. Then, an extremum-based construction method is adopted to involve the MF information. For the shape of MFDs, a coordinate transformation algorithm is proposed to involve it in the stability conditions to achieve local stable effects. For a state-feedback control system, conditions guaranteeing the stability and robustness are listed. Finally, simulation examples and comparisons are carried out to clarify the conservatism reduction results of the raised method.

16.
Biochem Biophys Res Commun ; 559: 176-182, 2021 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-33945995

RESUMEN

Oncolytic virus can selectively recognize cancer cells, target tumors, and stimulate an oncolytic and immune response. Recombinant armed oncolytic vaccinia virus has emerged as an attractive tool in oncolytic virotherapy because it has tumor-specific cytotoxicity and serves as a vector to express immune genes. A novel thymidine kinase (TK) gene-deleted oncolytic vaccinia virus (named ΔTK-Armed-VACV) armed with anti-human-programed cell death-1 protein (PD-1) antibody and anti-human-tumor necrosis factor receptor superfamily, member 9 (4-1BB) antibody genes was constructed based on Western Reserve in our previous study. The present study evaluated the ability of this virus for cancer-targeted therapy both in vitro and in vivo. A complete morphological structure of ΔTK-Armed-VACV was verified using transmission electron microscopy. The antibody was co-expressed with the replication of ΔTK-Armed-VACV in vitro assessed by Western blot analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-rboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay showed that the ΔTK-Armed-VACV exhibited significant tumor-specific cytotoxicity in vitro. The ΔTK-Armed-VACV inhibited the tumor growth in a 4T1 or A549 tumor-bearing mouse model. ELISpot assay showed that ΔTK-Armed-VACV-treated mice induced the expression of interferon-gamma, and lactate dehydrogenase-dependent cytotoxicity assay revealed that the ΔTK-Armed-VACV treatment activated tumor-specific cytotoxic T lymphocytes. The results indicated that oncolytic VACV with Western Reserve-mediated anti-human-PD-1 and anti-human-4-1BB antibody co-expression exerted a significant antitumor effect, indicating that the combination of oncolytic virotherapy and immunotherapy by the oncolytic VACV expressing one or more immune checkpoint genes might have satisfactory clinical expectations.


Asunto(s)
Anticuerpos/genética , Neoplasias/terapia , Virus Oncolíticos/genética , Receptor de Muerte Celular Programada 1/inmunología , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Virus Vaccinia/genética , Células A549 , Animales , Anticuerpos/inmunología , Femenino , Expresión Génica , Humanos , Inmunoterapia/métodos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias/genética , Neoplasias/inmunología , Viroterapia Oncolítica/métodos , Virus Oncolíticos/inmunología , Virus Vaccinia/inmunología
17.
J Cell Mol Med ; 25(3): 1554-1567, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33410606

RESUMEN

Hypertrophic scar (HS) is a severe fibrotic skin disease. It has always been a major problem in clinical treatment, mainly because its pathogenesis has not been well understood. The roles of bacterial contamination and prolonged wound inflammation were considered significant. IL-10 is a potent anti-inflammatory cytokine and plays a pivotal role in wound healing and scar formation. Here, we investigate whether IL-10 alleviates lipopolysaccharide (LPS)-induced inflammatory response and skin scarring and explore the possible mechanism of scar formation. Our results showed that the expression of TLR4 and pp65 was higher in HS and HS-derived fibroblasts (HSFs) than their counterpart normal skin (NS) and NS-derived fibroblasts (NSFs). LPS could up-regulate the expression of TLR4, pp65, Col I, Col III and α-SMA in NSFs, but IL-10 could down-regulate their expression in both HSFs and LPS-induced NSFs. Blocking IL-10 receptor (IL-10R) or the phosphorylation of STAT3, their expression was up-regulated. In addition, in vitro and in vivo models results showed that IL-10 could alleviate LPS-induced fibroblast-populated collagen lattice (FPCL) contraction and scar formation. Therefore, IL-10 alleviates LPS-induced skin scarring via IL-10R/STAT3 axis regulating TLR4/NF-κB pathway in dermal fibroblasts by reducing ECM proteins deposition and the conversion of fibroblasts to myofibroblasts. Our results indicate that IL-10 can alleviate the LPS-induced harmful effect on wound healing, reduce scar contracture, scar formation and skin fibrosis. Therefore, the down-regulation of inflammation may lead to a suitable scar outcome and be a better option for improving scar quality.


Asunto(s)
Fibroblastos/metabolismo , Interleucina-10/metabolismo , Lipopolisacáridos/administración & dosificación , FN-kappa B/metabolismo , Receptores de Interleucina-10/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Receptor Toll-Like 4/metabolismo , Animales , Biopsia , Cicatriz Hipertrófica/etiología , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patología , Citocinas/metabolismo , Susceptibilidad a Enfermedades , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Modelos Biológicos , Conejos , Piel/metabolismo , Piel/patología
18.
Front Genet ; 11: 597508, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33329742

RESUMEN

The lack of a useful biomarker partly contributes to the increased mortality of non-small cell lung cancer (NSCLC). MiRNAs have become increasingly appreciated in diagnosis of NSCLC. In the present study, we used microarray to screen 2,549 miRNAs in serum samples from the training cohort (NSCLC, n = 10; the healthy, n = 10) to discover differentially expressed miRNAs (DEMs). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was applied to validate the expression level of selected overexpressed DEMs of NSCLC in a validation cohort (NSCLC, n = 30; the healthy, n = 30). Area under the receiver operating characteristic curve (AUC) was performed to evaluate diagnostic capability of the DEMs. The expression of the miRNAs in tissues was analyzed based on the TCGA database. Subsequently, the target genes of the miR-4687-3p were predicted by TargetScan. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were tested by R software (ClusterProfiler package). NSCLC cells were transfected with inhibitor or mimic to down-regulate or up-regulate the miR-4687-3p level. The function of miR-4687-3p on proliferation, invasion, and migration of lung cancer cells were investigated through CCK-8 and Transwell assays, respectively. In the results, we identified serum miR-4687-3p that provided a high diagnostic accuracy of NSCLC (AUC = 0.679, 95%CI: 0.543-0.815) in the validation cohort. According to the TCGA database, we found that the miR-4687-3p level was significantly higher in NSCLC tissues than in normal lung tissues (p < 0.05). GO and KEGG pathway enrichment analysis showed that postsynaptic specialization and TGF-ß signaling pathway were significantly enriched. Down-regulation of miR-4687-3p could suppress the proliferation, invasion, and migration of the NSCLC cells, compared with inhibitor negative control (NC). Meanwhile, overexpression of miR-4687-3p could promote the proliferation, invasion, and migration of the NSCLC cells compared with mimic NC. As a conclusion, our study first discovered that serum miR-4687-3p might have clinical potential as a non-invasive diagnostic biomarker for NSCLC and play an important role in the development of NSCLC.

19.
Environ Pollut ; 256: 113416, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31677871

RESUMEN

Marine oil spill often causes contamination of drinking water sources in coastal areas. As the use of oil dispersants has become one of the main practices in remediation of oil spill, the effect of oil dispersants on the treatment effectiveness remains unexplored. Specifically, little is known on the removal of dispersed oil from contaminated water using conventional adsorbents. This study investigated sorption behavior of three prototype activated charcoals (ACs) of different particle sizes (4-12, 12-20 and 100 mesh) for removal of dispersed oil hydrocarbons, and effects of two model oil dispersants (Corexit EC9500A and Corexit EC9527A). The oil content was measured as n-alkanes, polycyclic aromatic hydrocarbons (PAHs), and total petroleum hydrocarbons (TPHs). Characterization results showed that the smallest AC (PAC100) offered the highest BET surface area of 889 m2/g and pore volume of 0.95 cm3/g (pHPZC = 6.1). Sorption kinetic data revealed that all three ACs can efficiently adsorb Corexit EC9500A and oil dispersed by the two dispersants (DWAO-I and DWAO-II), and the adsorption capacity followed the trend: PAC100 > GAC12 × 20 > GAC4 × 12. Sorption isotherms confirmed PAC100 showed the highest adsorption capacity for dispersed oil in DWAO-I with a Freundlich KF value of 10.90 mg/g∙(L/mg)1/n (n = 1.38). Furthermore, the presence of Corexit EC9500A showed two contrasting effects on the oil sorption, i.e., adsolubilization and solubilization depending on the dispersant concentration. Increasing solution pH from 6.0 to 9.0 and salinity from 2 to 8 wt% showed only modest effect on the sorption. The results are useful for effective treatment of dispersed oil in contaminated water and for understanding roles of oil dispersants.


Asunto(s)
Hidrocarburos/química , Contaminación por Petróleo , Contaminantes Químicos del Agua/química , Adsorción , Alcanos , Carbón Orgánico/química , Cinética , Petróleo/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Hidrocarburos Policíclicos Aromáticos/química , Salinidad , Agua de Mar/química , Tensoactivos/química , Contaminantes Químicos del Agua/análisis
20.
Exp Ther Med ; 18(6): 4927-4934, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31798714

RESUMEN

Polaprezinc (PZ), a chelate of zinc and L-carnosine, has been widely used in the treatment of gastric ulcers since 1994. In recent years, researchers have found PZ to have a beneficial effect on various experimentally induced models of colitis in mice. In the present study, 6% dextran sodium sulfate (DSS) was used to induce a model of ulcerative colitis (UC) in Institute of Cancer Research mice. The therapeutic effect and mechanism of PZ action in a model of UC was studied in order to provide an experimental basis for the clinical application of PZ in UC treatment. The effect of PZ on UC was evaluated in five groups of mice: A vehicle control only group, a DSS model control group (DSS, 6%), a validated treatment control group (DSS 6% + Mesalamine), a low-dose PZ treatment group (DSS 6% + PZ 60 mg/kg) and a high-dose PZ group (DSS 6% + PZ 120 mg/kg). After the animals were sacrificed, blood was collected and the serum levels of NF-κB and tumor necrosis factor-α (TNF-α) were measured. Changes in histology were observed by light microscopy. The protein levels of AKT, phosphorylated AKT and heat shock protein 70 (HSP70) were determined by western blot analysis. The results suggested that PZ reduced the DSS-induced increase in the inflammatory proteins TNF-α and NF-κB in the UC model. The high-dose of PZ also increased the HSP70 protein level, inhibited AKT phosphorylation in a DSS-induced UC animal model, and decreased white blood cell and neutrophil % counts compared to levels in an untreated DSS control group. Histopathology indicated that the mice of the DSS model group had irregular colonic villi, a large number of inflammatory cells and mucosal damage, whereas mice of the group treated with PZ had small intestinal villus morphology and their villi showed signs of recovery from the damage of UC. The results of the present study indicated that PZ significantly alleviates DSS-induced UC in mice, relieves diarrhea, and inhibits the phosphorylation of inflammatory factors and the inflammatory AKT signaling pathway.

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