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1.
Front Immunol ; 12: 653356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796116

RESUMO

Background: Pemphigus is a rare but life-threatening autoimmune skin disease characterized by blistering on skin and/or mucous membranes. The physiological process of blister formation involves IgG antibodies against the desmogleins (Dsgs) and desmocollins (Dscs). Additional autoAbs have also been suggested to mediate the disease heterogeneity, such as anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies, the essential culprits of the immune system in autoimmune thyroid diseases. Purpose: To investigate the levels and antibody positivity of anti-TPO and anti-Tg antibodies in pemphigus patients. Methods: Antibody positivity and levels of anti-TPO and anti-Tg antibodies in pemphigus patients as compared to healthy controls were examined. A meta-analysis was conducted by reviewing six similar studies. Results: 98 Chinese pemphigus patients and 65 healthy controls were enrolled in the study. Our meta-analysis revealed a significant correlation between increased presence of positive anti-TPO and anti-Tg antibodies and pemphigus, particularly for pemphigus vulgaris (PV). Such correlation was also observed in our own hospitalized PV patients, but not in pemphigus foliaceus (PF) patients. In addition, the status of anti-TPO and anti-Tg antibodies were also compared between females and males within PV patients, PF patients or controls, as well as compared for females or males between pemphigus patients and controls. In the analysis of T cell counts, we found abnormal low CD3 + T cell counts (< 690 n/µl) were only detected in patients whose thyroid antibody levels were less than 20 IU/ml. Conclusion: Pemphigus patients showed higher levels and antibody positivity of anti-TPO and anti-Tg antibodies than healthy controls. Further investigations are needed to identify the pathogenic functions of these antibodies in pemphigus, as well as to identify the potential shared susceptibility genes.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33661622

RESUMO

Sodium-ion batteries (SIBs) are the appropriate alternatives to lithium-ion batteries (LIBs) for the large-scale energy storage applications because of the abundant resources and wide distribution of sodium on earth. O3-NaCrO2 is a promising cathode material for SIBs due to its stable structure and low-cost raw materials. In this paper, we design and synthesize a powder consisting of submicrometer-sized O3-NaCrO2 spheres (s-NaCrO2) self-assembled with nanoflakes, which exhibits faster ion migration ability and strong structure robustness. The galvanostatic intermittent titration technique test reveals the higher apparent Na+ diffusion coefficient of s-NaCrO2 when compared with a normal NaCrO2 powder with an irregular particle morphology. The s-NaCrO2 shows impressive electrochemical properties with a capacity of 90 mAh g-1 at 50 C. In addition, outstanding cycling stability is shown when tested at 20 C, where a capacity of 90 mAh g-1 is maintained with a retention of 87% after 1500 cycles. Also, s-NaCrO2 is advantageous at high (50 °C) and low (-10 °C) temperatures. The full cells assembled employing Sb/C as the anode exhibit good rate capability with 85 mAh g-1 obtained at 50 C.

3.
Carbohydr Polym ; 258: 117706, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33593576

RESUMO

Combination treatment through the co-delivery of drugs and genes by nanoformulations may achieve a synergistic effect. In our previous study, poly(amidoamine) dendronized chitosan derivative (PAMAM-Cs) showed good gene transfection efficiency and low cytotoxicity. Here, we incorporated hydrophobic deoxycholic acid (DCA) onto the chitosan backbone of PAMAM-Cs to obtain an amphiphilic derivative-PAMAM-Cs-DCA, which could self-assemble into cationic nanoparticles (NPs). The resulting NPs with diameters of 140-220 nm can encapsulate the hydrophobic anticancer drug doxorubicin (DOX) in the core while bind pDNA via the positively charged PAMAM shell. PAMAM-Cs-DCA NPs could completely complex with pDNA at a ratio of nitrogen to phosphorous (N/P) low as 1 and the complexes achieved a transfection efficiency up to 74 % at N/P 20. Moreover, low-dose co-delivered DOX could enhance the transgene expression, showing a synergistic effect. These results suggest that PAMAM-Cs-DCA NPs hold great promise to co-deliver chemotherapeutics and nucleic acid drugs.

4.
Cell Death Dis ; 12(1): 94, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462208

RESUMO

Circular RNAs (circRNAs) is one type of important non-coding RNAs that participate in tumorigenesis and cancer progression. In our previous study, we performed a microarray analysis of circRNAs between the tumor tissues and the adjacent normal tissues of hepatocellular carcinoma (HCC) patients, and found that the circRNA hsa_circ_0007456 is significantly downregulated in the tumor tissues and correlated with the prognosis of HCC. We further investigated the relationship between the expression levels of hsa_circ_0007456 in HCC and the susceptibility of NK cells, and found that the expression levels of hsa_circ_0007456 in HCC cell lines significantly influenced their susceptibility to NK cells. Through a series of screening and validation, we found that hsa_circ_0007456 mainly functioned through sponging miR-6852-3p and regulating the expression of intercellular adhesion molecule-1 (ICAM-1) in HCC. The miR-6852-3p/ICAM-1 axis is essential for the NK cytotoxicity toward HCC mediated by hsa_circ_0007456. In conclusion, we identify here hsa_circ_0007456 as a promising biomarker of HCC, and highlight hsa_circ_0007456/miR-6852-3p/ICAM-1 axis as an important signaling pathway in the process of tumor immune evasion and the tumorigenesis of HCC.

5.
J Food Biochem ; : e13550, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33150631

RESUMO

To elucidate the α-glucosidase (α-GC) inhibitory mechanism of theaflavin-3-gallate (TF-3-G), their interaction mechanism was investigated using spectroscopy and molecular docking analysis. The inhibition ratio of TF-3-G against α-GC was determined to be 92.3%. Steady fluorescence spectroscopy showed that TF-3-G effectively quenched the intrinsic fluorescence of α-GC through static quenching, forming a stable complex through hydrophobic interactions. Formation of the TF-3-G/α-GC complex was also confirmed by resonance light scattering spectroscopy. Synchronous fluorescence spectroscopy and circular dichroism spectroscopy indicated that the secondary structure of α-GC was changed by TF-3-G. Molecular docking was used to simulate TF-3-G/α-GC complex formation, showing that TF-3-G might be inserted into the hydrophobic region around the active site of ɑ-GC, and bind with the catalytic Asp215 and Asp352 residues. The ɑ-GC inhibitory mechanism of TF-3-G was mainly attributed to the change in ɑ-GC secondary structure caused by the complex formation. PRACTICAL APPLICATIONS: α-Glucosidase (α-GC) can hydrolyze the glycosidic bonds of starch and oligosaccharides in food and release glucose. Therefore, the inhibition of α-GC activity has been used to treat postprandial hyperglycemia and type 2 diabetes mellitus. Theaflavin-3-gallate (TF-3-G), a flavonoid found in the fermentation products of black tea, exhibits strong inhibition of α-GC activity. However, the α-GC inhibitory mechanism of TF-3-G is unclear. This study aids understanding of this mechanism, and proposed a possibly basic theory for improving the medicinal value of TF-3-G in diabetes therapy.

6.
Cell Death Dis ; 11(10): 838, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037177

RESUMO

An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in tumor development and progression. However, their involvement in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Epigenetic regulation is one major mechanism utilized by cancer cells to control lncRNA expression. We identified that lncRNA VENTXP1 was epigenetically silenced in multiple cancer types, and its lower expression was correlated with poorer survival in HNSCC patients. Through in silico analysis and experimental validation, we identified miR-205-5p and its direct interacting partner of VENTXP1, which regulates HNSCC cell proliferation and tumorigenicity. Using RNA-seq and differential gene expression analysis, we further identified ANKRD2 as a miR-205-5p target, which plays an essential role in modulating NF-kB signaling. These findings suggest that VENTXP1 inhibits tumor growth via suppressing miR-205-5p/ANKRD2-mediated NF-kB signaling in HNSCC. Thus, pharmaceutical targeting of DNA methylation to restore VENTXP1 expression might constitute a therapeutic strategy for HNSCC.

7.
Opt Express ; 28(20): 30015-30034, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33114888

RESUMO

As the reference radiometric calibration standard of sensors on the Haiyang-1C (HY-1C) satellite platform, the satellite calibration spectrometer (SCS) is equipped with an onboard calibration system composed of double solar diffusers and an erbium-doped diffuser to monitor the postlaunch radiometric response change. Herein, through onboard calibration data analysis, the calibration diffuser performance remains stable without degradation, and the Moderate Resolution Imaging Spectroradiometer (MODIS) on Terra is adopted as a reference to repeatedly verify onboard radiometric calibration results by selecting different dates and reflectance scenes. The SCS equivalent reflectance is obtained by combining the mean digital number (DN) of the SCS crossing area image with the radiometric calibration coefficient. The spectral reflectance is obtained via interpolation and iteration, which is adopted as the actual MODIS incident pupil spectral reflectance because the small imaging time interval can be ignored and almost vertically observed, and it is convoluted with the MODIS spectral response function to obtain the predicted equivalent reflectance. Validation is completed by comparing the predicted MODIS equivalent reflectance to the measured value based on the onboard calibration coefficient. The results show that (1) the difference between the measured and predicted MODIS band equivalent reflectance is between -0.00466 and 0.0039, and (2) the percentage difference between the measured and predicted MODIS band equivalent reflectance ranges from 4.17% and 1.24%, indicating that the calibration system carried on HY-1C can perform high-precision SCS radiometric calibration, meeting the cross-calibration accuracy requirements of other loads on the same platform.

8.
ACS Appl Mater Interfaces ; 12(40): 44671-44678, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32909427

RESUMO

Cr2O3 is generally considered as an impurity phase with negative effects on the electrochemical performance of NaCrO2 because it may cause a certain degree of capacity loss. In this study, however, we have found the bright side of Cr2O3 as a protective coating material, which greatly improves the Na+ storage capability, especially the cycling stability, of NaCrO2. After 1000 cycles at 10C, a capacity of 100.4 mAh g-1 with a high capacity retention of 84.8% can be achieved for a Cr2O3-coated NaCrO2 sample. The optimal sample exhibits a rate performance with 108.0 mAh g-1 at a high rate of 60C. Cyclic voltammetry analysis indicates that such an in situ-formed inactive Cr2O3 layer has little influence on Na+ diffusion in NaCrO2 electrodes, but it prevents the direct contact between the active material and the electrolyte, suppressing the side reactions effectively.

9.
Curr Med Sci ; 40(4): 597-601, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32767260

RESUMO

In late December 2019, COVID-19 was firstly recognized in Wuhan, China and spread rapidly to all of the provinces of China. The West Campus of Wuhan Union Hospital, the designated hospital to admit and treat the severe and critically ill COVID-19 cases, has treated a large number of such patients with great success and obtained lots of valuable experiences based on the Chinese guideline (V7.0). To standardize and share the treatment procedures of severe and critically ill cases, Wuhan Union Hospital has established a working group and formulated an operational recommendation, including the monitoring, early warning indicators, and several treatment principles for severe and critically ill cases. The treatment experiences may provide some constructive suggestions for treating the severe and critically ill COVID-19 cases all over the world.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , China/epidemiologia , Técnicas de Laboratório Clínico , Terapia Combinada , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Estado Terminal , Dexametasona/uso terapêutico , Hospitais , Humanos , Imunização Passiva , Medicina Tradicional Chinesa , Pandemias , Pneumonia Viral/epidemiologia , Terapia Respiratória/métodos
10.
Int J Biol Macromol ; 164: 1124-1132, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682045

RESUMO

An acidic tea polysaccharide (TPSA) isolated from green tea was fractionated using a precipitation-fractionation method into seven fractions with different molecular weights. TPSA was characterized as a hyperbranched polysaccharide with a globular homogeneous conformation by analysis of solution parameters of each fraction using static light scattering and viscosity analyses. Observation by transmission electron microscopy confirmed that TPSA occurred as globular homogeneous particles with size in the range of 20-40 nm. To simulate the branched chain segments of TPSA, four model molecules were designed based on chemical structure of TPSA. Molecular docking analysis indicated that the branched chain segments of TPSA similar to the TPSA-4 model molecule showed preferential binding to α-amylase to form the TPSA/α-amylase complex through hydrogen bonding interactions. Circular dichroism spectroscopy showed that the structure of α-amylase was not significantly affected by TPSA. The mechanism of α-amylase inhibitory activity of TPSA was simulated by molecular docking analysis. The branched chain segments of TPSA similar to the TPSA-4 model molecule likely act as a potential competitor to the starch substrate to inhibit the activity of α-amylase.

11.
Huan Jing Ke Xue ; 41(7): 3315-3325, 2020 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608905

RESUMO

Wheat straw biochar (BC) was modified by KOH and magnetics to generate composited modified biochar (FKC). Based on characterization by scanning electron microscopy-energy dispersive spectrometry (SEM-EDS), Brunauer-Emmett-Teller (BET), Fourier transform infrared (FT-IR), X-ray diffraction (XRD), and magnetic (VSM) techniques, the adsorption characteristics and mechanisms of Cd2+ in water and the effects of temperature, pH value, and dosage on the adsorption characteristics of FKC were studied. The results showed that the modified biochar was loose and porous. The specific surface area of FKC increased by 19.11 times, the number of aromatic and oxygen-containing functional groups such as O-H, C=O, and C=C increased, and a new functional group Fe-O formed compared to the BC. FKC is magnetic, and its magnetization is 8.43 emu·g-1, which can be recycled and reused. The adsorption of Cd2+ by FKC fitted well with the pseudo-second-order kinetic model and the Langmuir model, indicating that chemical adsorption is the main adsorption mechanism. The theoretical maximum equilibrium adsorption capacity of FKC is 23.44 mg·g-1, which is 1.47 times that of BC. The thermodynamic parameters suggested the adsorption of Cd2+ by FKC was a spontaneous and endothermic process. The adsorption capacity increased with an increase of pH in the region 2-8, and a biochar dosage of 10 g·L-1 was used. After three cycles of adsorption-desorption-adsorption, the adsorption capacity of Cd2+ by FKC still reached 17.71 mg·g-1, indicating that FKC has good reusability. These results can provide a theoretical basis for the application of KOH and magnet-modified biochar from wheat straw to remove heavy metals from contaminated wastewater.

12.
Neuropharmacology ; 178: 108230, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32693005

RESUMO

Anxiety disorders are the most prevalent group of mental disorders globally, leading to considerable losses in health, functioning and increase of medical costs. Till now, the search for novel pharmacological treatments is driven by the growing medical need to improve on the effectiveness and the side effect profile of existing drugs. In central nervous system, the mitochondrially located translocator protein (18 kDa, TSPO) serves as the rate-limiting step for neurosteroidogenesis and influences GABAergic transmission. Since 5-HT is one of the most comprehensively studied neurotransmitter systems in the anxiety field, in the present study, we want to investigate whether 5-HT system is involved in the anxiolytic-like effects of YL-IPA08, a novel TSPO ligand designed and synthesized at our institute. Our data showed that YL-IPA08 could potentiate the 5-HTP-induced head-twitch response, and the anxiolytic-like effect of YL-IPA08 was abolished by pCPA or 5,7-DHT pretreatment in mice. Furthermore, we found that YL-IPA08 increased the extracellular levels of 5-HT in the rat ventral hippocampus in freely moving rat using the rapid and validated HPLC coupled with microdialysis. In addition, 5-HT level was positively correlated with the level of allopregnanolone. The above results suggest that 5-HT neurotransmission may play a critical role in the anxiolytic-like effects of YL-IPA08.

13.
Colloids Surf B Biointerfaces ; 194: 111159, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32534367

RESUMO

As a soluble cellulose derivative, methylcellulose (MC), can be used to construct thermosensitive hydrogels. However, a pure MC gel is generally considered an inert material that is inadequate for cell survival. We adopted an environmentally friendly method to fabricate a nano-hydroxyapatite (nHA) hybrid MC hydrogel. Rheology results showed that the addition of nHA increased the gelation temperature. Furthermore, the live/dead assay confirmed that the addition of nHA improved the survival of bone marrow-derived mesenchymal stem cells (BMSCs) inside the gel. In addition, ARS staining indicated that the presence of nHA stimulated osteogenic differentiation. Finally, in vivo cranial defect experiments showed improved remediation efficiency when using the nHA hybrid MC hydrogel to carry BMSCs.

14.
Int J Nanomedicine ; 15: 3023-3038, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431499

RESUMO

Introduction: Advanced tumor-targeted theranostic nanoparticles play a key role in tumor diagnosis and treatment research. In this study, we developed a multifunctional theranostic platform based on an amphiphilic hyaluronan/poly-(N-ε-carbobenzyloxy-L-lysine) derivative (HA-g-PZLL), superparamagnetic iron oxide (SPIO) and aggregation-induced emission (AIE) nanoparticles for tumor-targeted magnetic resonance (MR) and fluorescence (FL) dual-modal image-guided photodynamic therapy (PDT). Materials and Methods: The amphiphilic hyaluronan acid (HA) derivative HA-g-PZLL was synthesized by grafting hydrophobic poly-(N-ε-carbobenzyloxy-L-lysine) (PZLL) blocks onto hyaluronic acid by a click conjugation reaction. The obtained HA-g-PZLLs self-assembled into nanoparticles in the presence of AIE molecules and SPIO nanoparticles to produce tumor-targeted theranostic nanoparticles (SPIO/AIE@HA-g-PZLLs) with MR/FL dual-modal imaging ability. Cellular uptake of the theranostic nanoparticles was traced by confocal laser scanning microscopy (CLSM), flow cytometry and Prussian blue staining. The intracellular reactive oxygen species (ROS) generation characteristics of the theranostic nanoparticles were evaluated with CLSM and flow cytometry. The effect of PDT was evaluated by cytotoxicity assay. The dual-mode imaging ability of the nanoparticles was evaluated by a real-time near-infrared fluorescence imaging system and magnetic resonance imaging scanning. Results: The resulting theranostic nanoparticles not only emit red fluorescence for high-quality intracellular tracing but also effectively produce singlet oxygen for photodynamic tumor therapy. In vitro cytotoxicity experiments showed that these theranostic nanoparticles can be efficiently taken up and are mainly present in the cytoplasm of HepG2 cells. After internalization, these theranostic nanoparticles showed serious cytotoxicity to the growth of HepG2 cells after white light irradiation. Discussion: This work provides a simple method for the preparation of theranostic nanoparticles with AIE characteristics and MR contrast enhancement, and serves as a dual-modal imaging platform for image-guided tumor PDT.


Assuntos
Meios de Contraste/química , Imagem por Ressonância Magnética , Nanopartículas/química , Imagem Óptica , Fotoquimioterapia , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Feminino , Fluorescência , Células Hep G2 , Humanos , Ácido Hialurônico/síntese química , Ácido Hialurônico/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Polilisina/síntese química , Polilisina/química , Espectroscopia de Prótons por Ressonância Magnética , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Br J Anaesth ; 125(1): e28-e37, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32312571

RESUMO

Tracheal intubation in coronavirus disease 2019 (COVID-19) patients creates a risk to physiologically compromised patients and to attending healthcare providers. Clinical information on airway management and expert recommendations in these patients are urgently needed. By analysing a two-centre retrospective observational case series from Wuhan, China, a panel of international airway management experts discussed the results and formulated consensus recommendations for the management of tracheal intubation in COVID-19 patients. Of 202 COVID-19 patients undergoing emergency tracheal intubation, most were males (n=136; 67.3%) and aged 65 yr or more (n=128; 63.4%). Most patients (n=152; 75.2%) were hypoxaemic (Sao2 <90%) before intubation. Personal protective equipment was worn by all intubating healthcare workers. Rapid sequence induction (RSI) or modified RSI was used with an intubation success rate of 89.1% on the first attempt and 100% overall. Hypoxaemia (Sao2 <90%) was common during intubation (n=148; 73.3%). Hypotension (arterial pressure <90/60 mm Hg) occurred in 36 (17.8%) patients during and 45 (22.3%) after intubation with cardiac arrest in four (2.0%). Pneumothorax occurred in 12 (5.9%) patients and death within 24 h in 21 (10.4%). Up to 14 days post-procedure, there was no evidence of cross infection in the anaesthesiologists who intubated the COVID-19 patients. Based on clinical information and expert recommendation, we propose detailed planning, strategy, and methods for tracheal intubation in COVID-19 patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Intubação Intratraqueal/métodos , Equipamento de Proteção Individual , Pneumonia Viral/terapia , Idoso , China , Infecções por Coronavirus/complicações , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Hipotensão/etiologia , Hipóxia/etiologia , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/complicações , Pneumonia Viral/prevenção & controle , Pneumotórax/etiologia , Guias de Prática Clínica como Assunto , Estudos Retrospectivos
16.
Curr Med Sci ; 40(2): 327-331, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32337693

RESUMO

This study compared Sheng Xue Ning (SXN) tablets with ferrous succinate (FS) tablets in terms of their efficacy for the treatment of iron-deficient renal anemia and safety in patients subject to maintenance hemodialysis (MHD). A total of 94 patients undergoing MHD were randomly assigned to an experiment group (receiving oral SXN tablets, SXN group) and a control group (orally given FS tablets, FS group) and followed up for 12 weeks. Erythropoietin (EPO) was used in both groups. The efficacy was assessed by detecting the subsequent changes in hemoglobin (Hb), serum iron (SI), SF and transferrin saturation (TSAT). At the 12th week, Hb and TSAT levels in both groups were significantly increased compared to those in the screening period (P<0.05). However, no significant difference in Hb and TSAT was found between the two groups. The average weekly EPO dosage used was lower in SXN group than in FS group (P<0.05) at the 10th week and the 12th week. Our study showed that SXN tablets can effectively ameliorate renal anemia and keep iron metabolism stable in MHD patients, and its efficacy is virtually close to that of FS tablets. Meanwhile, SXN tablets can reduce the dosage of EPO and have a good safety profile.

17.
Arch Biochem Biophys ; 687: 108369, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32335047

RESUMO

A neutral tea polysaccharide (TPSN) was isolated from green tea. Gas chromatography analysis showed that TPSN was composed of d-glucose, l-arabinose and d-galactose residues at a molar ratio of 90.0: 9.1: 0.9. The weight-averaged molecular weight of TPSN was determined as about 2.0 × 105 g mol-1 using static light scattering analysis. The result of nuclear magnetic resonance (NMR) spectroscopy indicated that TPSN and water-soluble starch had similar structures. TPSN exhibited inhibitory activity towards α-amylase through the noncompetitive inhibition mechanism, but the tertiary structure of α-amylase related to enzymatic activity, analyzed using circular dichroism spectroscopy, was not affected by TPSN. Meanwhile, TPSN exhibited hydrolysis properties catalyzed by α-amylase. Molecular docking analysis revealed that the various behaviors of TPSN to α-amylase could be attributed to that the different chain segments of TPSN combined with different amino acid residues of α-amylase.


Assuntos
Inibidores Enzimáticos/química , Polissacarídeos/química , Chá/química , alfa-Amilases/antagonistas & inibidores , Animais , Camellia sinensis/química , Ensaios Enzimáticos , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Hidrólise , Cinética , Simulação de Acoplamento Molecular , Peso Molecular , Polissacarídeos/isolamento & purificação , Polissacarídeos/metabolismo , Ligação Proteica , Suínos , alfa-Amilases/metabolismo
18.
Mater Sci Eng C Mater Biol Appl ; 109: 110636, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228909

RESUMO

Though curcumin has potential treatment value for most chronic diseases, it exerts little potency in the clinic because of its low aqueous solubility, high chemical instability and poor pharmacokinetics. To enhance its potency, we developed a zein-based micelle as a nanocarrier to encapsulate curcumin. Herein, superhydrophilic zwitterionic polymers, poly(sulfobetaine methacrylate) (PSBMA), were conjugated to zein to obtain an amphiphilic zein-PSBMA conjugate. These conjugates could self-assemble into micelles composed of antifouling PSBMA shells and zein cores. The results from the cytokine secretion assay showed that the micelles induced a low level of macrophage activation. Moreover, the results from the in vivo fluorescence imaging experiment confirmed their long-circulating property, exceeding 72 h in mice. In comparison with native curcumin, micelle-encapsulated curcumin had a 230-fold increase in stability in vitro, and its half-life was 22-fold longer, according to a pharmacokinetic study on mice. Overall, this work presents a zein-PSBMA micelle with a long circulation time as a useful nanocarrier for effective curcumin delivery.

19.
J Psychopharmacol ; 34(4): 441-451, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31913078

RESUMO

BACKGROUND: Fast-acting and cognitive-enhancing antidepressants are desperately needed. Activation of translocator protein (18 kDa, TSPO) is a novel strategy for developing potential antidepressants, but there are no data available on the onset time of TSPO ligands. This study aimed to investigate the fast-onset antidepressant actions of AC-5216, a selective TSPO ligand, in TSPO knock-out (KO) mice. METHODS: TSPO wild-type (WT) and KO mice were subjected to a six-week chronic unpredicted stress (CUS) paradigm. Then, the mice were treated with AC-5216 and tested with depressive and cognitive behaviours. RESULTS: A single dose of AC-5216 (0.3 mg/kg) exerted anxiolytic- and antidepressant-like actions in TSPO WT mice. Moreover, in chronically stressed WT mice, two to four days of AC-5216 treatment (0.3 mg/kg, once per day) produced fast-onset antidepressant-like effects in the novelty-suppressed feeding and sucrose preference tests, as well as memory-enhancing effects in the novel object recognition test. In addition, a rapid (with five days of treatment) restoration of serum corticosterone levels and prefrontal cortex (PFC) allopregnanolone levels was found. Further studies showed that in these stress-exposed WT mice, AC-5216 significantly increased the levels of mTOR signalling-related proteins (mBDNF, p-mTOR, PSD-95, synapsin-1, GluR1), as well as the total dendritic length and branching points of pyramidal neurons in the PFC. CONCLUSIONS: These results suggest that TSPO mediates the fast-onset antidepressant-like and memory-enhancing effects of AC-5216, possibly through the rapid activation of mTOR signalling and restoration of dendritic complexity in the PFC.

20.
ACS Appl Mater Interfaces ; 12(6): 7575-7585, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31958010

RESUMO

A simple and green layer-by-layer assembly strategy is developed for the preparation of a highly bioavailable nanocomposite photosensitizer by assembling near-infrared (NIR) light-sensitive porphyrin/G-quadruplex complexes on the surface of a highly biocompatible nanoparticle that is prepared via Zn2+-assisted coordination self-assembly of an amphiphilic amino acid. After being efficiently delivered to the target site and internalized into tumor cells via enhanced permeability and retention effect and interactions between aptamers and tumor markers, the as-prepared nanoassembly can be directly used as an NIR light-responsive photosensitizer for tumor photodynamic therapy (PDT) since the porphyrin/G-quadruplex complexes are exposed on the nanoassembly surface and kept in an active state. It can also disassemble under the synergistic stimuli of an acidic pH environment and overexpressed glutathione, leasing more efficient porphyrin/G-quadruplex composite photosensitizers while reducing the interference caused by glutathione-dependent 1O2 consumption. Since the nanoassembly can work no matter if it is disassembled or not, the compulsory requirement for in vivo photosensitizer release is eliminated, thus resulting in the great improvement of the bioavailability of the photosensitizer. The PDT applications of the nanoassembly were well demonstrated in both in vitro cell and in vivo animal experiments.

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