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1.
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.

2.
J Sep Sci ; 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32246888

RESUMO

In this study, a novel photo-stimulated molecularly imprinted polymers based on magnetic mesoporous carrier surface, were developed for selective identification and intelligent separation of sulfamerazine in complex samples. The photosensitive monomer of the stimulated molecularly imprinted polymers was azobenzene derivative 5-[(4-(methacryloyloxy)phenyl) diazenyl] isophthalic acid with stimulus reaction mechanisms, which has photoisomerization between trans and cis for N = N bonds. Further, the properties of the photo-stimulated molecularly imprinted polymers were further evaluated through several sets of adsorption experiments. It illustrated that the maximum adsorption amount is 0.45 mmol/L. By ultraviolet spectrophotometer, the material reaches typical characteristic peaks of photo sensitivity, and the cycle time is 16 min. Three adsorption and desorption processes were repeated, the adsorption rate reached 34.4%. Overall, the photo-stimulated molecularly imprinted polymers can enrich and separate determine sulfamerazine with high selectivity, which have good recovery for real samples. This article is protected by copyright. All rights reserved.

3.
Clin Exp Immunol ; 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32222072

RESUMO

Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disease leading to visual impairment. Its pathogenic mechanisms remain poorly understood. Our purpose was to investigate the distinctive protein and metabolic profiles of sweat in patients with VKH disease. In the present study, proteomics and metabolomics analysis was performed on 60 sweat samples (30 VKH patients and 30 normal controls) using liquid chromatography tandem mass spectrometry. Parallel reaction monitoring (PRM) analysis was used to validate the results of our omics analysis. In total, we were able to detect 716 proteins and 175 metabolites. Among them, 116 proteins (99 decreased and 17 increased) were observed to be significantly different in VKH patients when compared to controls. Twenty-one differentially expressed metabolites were identified in VKH patients, of which eighteen included Choline, L-Tryptophan, Betaine and L-Serine were reduced, while the rest were increased. Our multi-omics strategy reveals an important role for the amino acid metabolic pathway in the pathogenesis of VKH disease. Significant differences in proteins and metabolites were identified in the sweat of VKH patients, and to some extent, an aberrant amino acid metabolism pathway may be a pathogenic factor in the pathogenesis of VKH disease.

4.
Int J Biol Macromol ; 154: 855-865, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32198034

RESUMO

Gene vectors are important for successful siRNA delivery. Four types of hyperbranched cationic polysaccharide derivatives (HCP) were synthesized by conjuncting 1,2-ethylenediamine (EDA) and diethylenetriamine (DETA) with glycogen or amylopectin respectively and named as G-EDA, G-DETA, A-EDA and A-DETA. The efficiency and safety of these HCPs to deliver siRNA were explored in vitro and in vivo. Our results showed that HCPs could form complexes with siRNA. All HCP/siRNA exhibited negligible cytotoxicity. Compared with A-EDA and A-DETA, G-EDA and G-DETA could carry much more siRNA into cells and then escape from endosomes. The delivery of MMP-9 siRNA (siMMP-9) by G-EDA and G-DETA significantly inhibited MMP-9 in HaCaT cells. Wound models in diabetic rats demonstrated that treatment of G-EDA/siMMP-9 could potently knock down MMP-9 of skin wound tissues and then enhanced wound healing. In summary, this study provided an effective and safe approach for siRNA delivery in vitro and in vivo.

5.
Inflammation ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32130574

RESUMO

Injurious mechanical ventilation has been shown to directly affect pulmonary and systemic immune responses. How these responses propagate or attenuate remains unknown. The goal of this study was to further determine whether toll-like receptor (TLR) 4 and WNT1-inducible signaling pathway protein 1 (WISP1) could contribute to injurious mechanical ventilation, especially focusing on the role of macrophages during experimental ventilator-induced lung injury. A prospective, randomized, and controlled animal study was designed, and male, wild-type (WT) C57BL/6 mice, TLR4 knockout (TLR4-/-), and lyzTLR4 knockout (lyzTLR4-/-) mice aging 8~12 weeks were used. Animals were anesthetized and randomized to spontaneous breathing (SB) group or to high tidal volume (VT, 20 ml/kg) mechanical ventilation (HTV) group. Histological evaluation, alveolar-capillary permeability of Evan's blue albumin (EBA), WISP1 protein levels, macrophage inflammatory protein-2 (MIP-2), and interleukin-6 (IL-6) in plasma and bronchoalveolar lavage fluid (BALF) concentrations were analyzed. HTV group was associated with a significant increase of WISP1 and EBA ratio in C57BL/6 mice, a significant decrease of WISP1 protein levels, and a significant decrease of IL-6, MIP-2 in plasma, and BALF concentrations of pro-inflammatory cytokines in TLR4-/- and lyzTLR4-/- knockout mice. In TLR4-/- mice and lyzTLR4-/- mice, there were also significant differences between SB group and HTV group in terms of H&E score and EBA ratio and level of pro-inflammation cytokines. The entire TLR4-targeted mice could further improve various inflammatory changes and damages when compared with lyzTLR4-targeted mice. What is more, TLR4-/- mice and lyzTLR4-/- mice reacted differently to rWISP1 and/or BMMC treated. TLR4-/- mice had no response to rWISP1, while lyzTLR4-/- mice still showed drastic response to both treatments. TLR4 and WISP1, especially the former one, on macrophages could contribute to releasing of pro-inflammatory cytokines during ventilator-induced lung injury. Injurious mechanical ventilation may result in an immune response which is similar to that of infection.

6.
Gene ; 738: 144482, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32087271

RESUMO

Arteriovenous malformations (AVMs) are congenital vascular lesions with a high tendency for aggravation and recurrence after treatment, and their genesis remains enigmatic. In this study, we investigated exosomal long non-coding RNA (lncRNA) and mRNA expression and constructed a competitive endogenous RNA regulatory network in AVMs. Ethics approval was provided, and informed written consent was given prior to the inclusion of all participants. Blood samples were obtained from patients with AVMs and healthy controls at Shanghai Ninth People's Hospital, China, from May to November 2018, and total exosomes were isolated and validated. Differentially expressed exosomal lncRNAs and mRNAs were detected by RNA-seq, analysed by bioinformatic methods and validated by qRT-PCR. A competitive endogenous RNA regulatory network was constructed. The characteristics of the captured extracellular vesicles conformed to the features of exosomes. A total of 117 dysregulated exosomal lncRNAs and 1159 dysregulated exosomal mRNAs were identified in AVMs. qRT-PCR demonstrated that the exosomal lncRNAs MIR4435-1HG, LINC00657, LOC101927854 and SEPT5-GP1BB were upregulated in AVM exosomes. The Gene Ontology (GO) terms haemopoiesis and negative regulation of neuron projection development were significantly enriched in relation to dysregulated exosomal cis lncRNAs. A total of 199 GO terms and 80 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched for the dysregulated exosomal mRNAs. In the exosomal lncRNA-miRNA-mRNA-related ceRNA regulatory network, the top 3 significant modules involved 31 dysregulated exosomal lncRNAs and 114 dysregulated exosomal mRNAs, which were enriched in the Rap 1, Ras, MAPK signalling pathways and platelet activation KEGG pathway. This study comprehensively identified dysregulated exosomal lncRNAs and mRNAs in AVMs, demonstrated the involvement of dysregulated lncRNA and mRNA patterns in AVMs and constructed an exosomal competitive endogenous RNA regulatory network.

7.
Nanomedicine (Lond) ; 15(6): 625-641, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32098564

RESUMO

Cell membranes have been continuously imitated and used for the modification of nanoparticles (NPs) to improve NP biological properties. Cell membrane-coated NPs, where core NPs are wrapped with plasma membrane vesicles, show high biocompatibility, targeting specificity and low side effects. Compared with conventional strategies, this novel approach directly leverages intact and natural functions of cell membranes, instead of replicating these features via synthetic techniques. This top-down technique bestows NPs with enhanced biointerfacing capabilities with potential in the diagnosis and treatment of cancer, infection and other diseases. Herein, we report on the advances in cell membrane-coated NPs, including the preparation process, source cell membranes for wrapping and potential applications of these cell membrane-coated NPs.

8.
World Neurosurg ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028008

RESUMO

BACKGROUND: Percutaneous transforaminal endoscopic diskectomy has been a major treatment for lumbar disk herniation. However, damage to exiting nerve roots is one of the most severe complications in this surgery. In this paper, the relationship of the exiting nerve root and the superior articular process in Kambin's triangle of the lumbar intervertebral foramen was assessed using cadavers and computed tomography (CT) imaging. METHODS: The anatomic relationship between the exiting nerve root and the superior articular process in Kambin's triangle of the intervertebral foramen was investigated on 6 cadavers. The distance between the exiting nerve and the superior articular process of the L1-2 to L5-S1 intervertebral foramina was measured using multiplane reconstruction. RESULTS: The bone-nerve space between the exiting nerve root and the superior articular process in Kambin's triangle was quite narrow both in cadaver and CT imaging study. The distance of the L5-S1 intervertebral foramen was the greatest, which was no more than 5.77 ± 0.56 mm. The distances increased gradually from the tip to the root, and the distances between the root and the tip were 0.91 ± 0.31 to 1.86 ± 0.57 mm, which took on a trapezoid shape that was relatively narrow at the proximal end and wider at the distal end. CONCLUSIONS: The bone-nerve space between the exiting nerve root and the superior articular process in Kambin's triangle of the lumbar intervertebral foramen was exceedingly narrow. It is necessary to perform a foraminoplasty to enlarge the working space and decrease the possibility of injury to the exiting nerve root.

9.
J Psychopharmacol ; 34(4): 441-451, 2020 Apr.
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.

10.
Int J Biol Macromol ; 148: 483-492, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31926232

RESUMO

Redox-responsive theranostic nanoparticles based on poly-(N-ε-carbobenzyloxy-l-lysine) (PZLL) grafted hyaluronan (HA) (HA-g-SS-PZLL) copolymers were constructed for hepatocellular carcinoma diagnosis and therapy. These hyaluronan derivatives formed nanoparticles via a self-assembly process in aqueous solution at low concentration. Theranostic nanoparticles were obtained after loading hydrophobic doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) into the core of the nanoparticles via a dialysis method. Theranostic nanoparticles exhibited redox triggered DOX release behavior, and faster DOX released from theranostic nanoparticles was detected under a reducing environment compared with slow DOX release under a normal physiological environment. Confocal laser scanning microscopy (CLSM), flow cytometry and Prussian blue staining against HepG2 cells demonstrated that HA-g-SS-PZLL theranostic nanoparticles were capable of delivering DOX and SPIO into the cells. The analysis of the anticancer effect revealed that the HA-g-SS-PZLL theranostic nanoparticles shown higher cytotoxicity against HepG2 cells than DOX-loaded HA-g-PZLL nanoparticles. In vitro T2 magnetic resonance imaging (MRI) results exhibited that theranostic nanoparticles showed a good contrast enhancement effect, and the r2 relaxivity value was approximately 231 Fe mM-1 s-1. Finally, the theranostic nanoparticles acted as nanoprobes for HepG2 tumor-bearing BALB/c mice for in vivo MRI. Therefore, HA-g-SS-PZLL copolymers have great potential as theranostic nanoparticles for tumor-targeted diagnosis and treatment.

11.
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.

12.
Blood Purif ; 49(1-2): 85-92, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31722330

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage renal disease (ESRD). Little is known about outcomes after in-center nocturnal hemodialysis (NHD) treatment in ADPKD patients with ESRD. OBJECTIVES: This study aimed to evaluate the effects of in-center NHD compared with conventional hemodialysis (CHD) and peritoneal dialysis (PD) in ADPKD. METHODS: We used data of ADPKD adult patients with ESRD in the hospital database from 2000 to 2016. Propensity score matching, competing-risk regression, and Cox regression models were used for analysis. RESULTS: A total of 170 ADPKD patients were included. The median follow-up time was 5.5 years. In the overall multivariate-adjusted analysis, no significant difference of mortality risk was found in NHD vs. CHD (hazard ratio [HR] 1.33, 95% CI 0.26-6.73, p = 0.31) and PD (HR 1.06, 95% CI 0.14-7.71, p = 0.55), respectively. The overall survival rate also was not significantly different among the 3 groups (p = 0.88). Based on the propensity score, 26 patients on CHD and 26 patients on PD were successfully matched to 13 NHD patients. In the matched analysis, NHD was not associated with a lower risk of mortality compared with CHD (HR 2.14, 95% CI 0.33-14.00, p = 0.31) and PD (HR 0.68, 95% CI 0.52-8.94, p = 0.55). The result was similar when treating renal transplantation as a competing event. However, NHD was associated with a lower rate of complications (38.5 vs. 84.6%, p = 0.003) and a higher level of serum albumin (p < 0.001) compared with PD. CONCLUSIONS: NHD may not be a better choice in survival compared with conventional dialysis modalities for ADPKD patients in this pilot study. Patients in NHD have fewer complications than PD. Future studies with large sample sizes and longer follow-up are required.

13.
Org Lett ; 22(4): 1233-1238, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31789039

RESUMO

A gold-catalyzed dearomatization reaction of indole derivatives was realized in the presence of JohnPhosAuCl/AgOMs to afford a series of spiroindolenines in excellent yields (≤99%). In addition, when the Hantzsch ester was used as the hydrogen transfer reagent, various spiroindolines were obtained in a cascade fashion starting from readily available indole derivatives in modest to good yields (≤79%). Both reactions feature readily available substrates, mild conditions, and good functional group tolerance.

14.
Acta Biomater ; 102: 298-314, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31751808

RESUMO

The anomalous high expression of matrix metalloproteinase 9 (MMP-9) is one important factor that impedes diabetic wound healing. Therefore, inhibition of MMP-9 expression in a diabetic wound could be a feasible method to promote wound healing. In this study, we studied the possibility of self-therapy using wound dressings that contain bacterial cellulose-hyperbranched cationic polysaccharide (BC-HCP) derivatives that encapsulate siRNA (BC-HCP/siMMP-9) and have controlled release properties. Herein, we used four HCPs (Gly-DMAPA, Gly-D4, Amyp-DMAPA, Amyp-D4) as gene carriers. Our results showed that all HCP derivatives were minimally toxic to cells in vitro, while the cationic properties of HCP could be used as a complexation agent for MMP-9 siRNA (siMMP-9). Upon exposure to bacterial cellulose (BC), the BC slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein levels of MMP-9 in a human immortalized epithelial cell line (HaCAT) and in diabetic rat wounds. Inhibition of MMP-9 in the wounds of diabetic rats resulted in a significant enhancement of wound healing, suggesting that the BC-HCP/siMMP-9 composite dressing could be used as a safe and effective dressing to promote wound healing in diabetic rats. STATEMENT OF SIGNIFICANCE: In this work, we evaluated the possibility of using bacterial cellulose-hyperbranched cationic polysaccharide derivatives (BC-HCP) as a self-therapeutic wound dressing with siRNA encapsulated and controlled release properties. Our results showed that the BC-HCP/siMMP-9 composite dressing slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein level of MMP-9 in human immortalized epithelial cell line and in the wound of diabetic rats. The BC-HCP/siMMP-9 composite dressing promoted diabetic wound healing by the unique nanostructure of BC and by releasing siMMP-9 for specific MMP-9 inhibition. Therefore, it could be used as a safe and effective dressing to promote wound healing in diabetic rats. This is the first evidence on the study of using BC as a dressing composite by encapsulating HCP/siRNA complexes for efficient RNAi gene silencing for better wound healing in diabetic rats.

15.
Int J Biol Macromol ; 143: 334-340, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31812748

RESUMO

The purpose of this study was to evaluate the effect of plasticizer type (glycerol, PEG-400, and sorbitol) and concentration (0%, 15%, 30% and 45%, w/w dry polymer weight) on rheological and physico-mechanical and structural properties of chitosan/zein blend film. Based on the analysis of rheological properties of chitosan/zein film-forming solutions, all film-forming solutions exhibited non-Newtonian behavior. The flow index of film-forming solution increased and apparent viscosity decreased with the increase of plasticizer concentration. The storage modulus (G') and the loss modulus (G″) decreased when plasticizer was added. The permeability of films increased significantly with the increase of plasticizer concentration, but the C/Z-P film (plasticized chitosan/zein film with PEG-400) had better barrier performance compared with the other two. The C/Z-P film had better mechanical properties and light transmission. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) revealed chitosan and zein had good compatibility due to the addition of the plasticizer, and crystallinity decreased with the increase of plasticizer concentration.

16.
Chem Commun (Camb) ; 56(3): 387-390, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31815265

RESUMO

Phase-pure all-inorganic zero-dimensional (0D) tin halide Cs4SnX6 (X = Br, I) nanocrystals (NCs) are successfully prepared for the first time. The as-prepared Cs4SnBr6 NCs exhibit a strongly Stokes-shifted broadband emission with a high photoluminescence quantum yield (PLQY) of 21% at room temperature.

17.
Small ; 16(3): e1905226, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31833672

RESUMO

0D lead-free metal halide nanocrystals (NCs) are an emerging class of materials with intriguing optical properties. Herein, colloidal synthetic routes are presented for the production of 0D Cs3 Cu2 X5 (X = I, Br, and Cl) NCs with orthorhombic structure and well-defined morphologies. All these Cs3 Cu2 X5 NCs exhibit broadband blue-green photoluminescence (PL) emissions in the range of 445-527 nm with large Stokes shifts, which are attributed to their intrinsic self-trapped exciton (STE) emission characteristics. The high PL quantum yield of 48.7% is obtained from Cs3 Cu2 Cl5 NCs, while Cs3 Cu2 I5 NCs exhibit considerable air stability over 45 days. Intriguingly, as X is changed from I to Br and Cl, Cs3 Cu2 X5 NCs exhibit a continuous redshift of emission peaks, which is contrary to the blueshift in CsPbX3 perovskite NCs.

18.
Int J Biol Macromol ; 144: 1-8, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31836391

RESUMO

We identified and characterized a novel superoxide dismutase (SOD), designated as CcSOD1, from the cDNA library from the tentacle tissue of the jellyfish Cyanea capillata. The full-length cDNA sequence of CcSOD1 consists of 745 nucleotides with an open reading frame encoding a mature protein of 154 amino acids, sharing a predicted structure similar to the typical Cu/Zn-SODs. The CcSOD1 coding sequence was cloned into the expression vector pET-24a and successfully expressed in Escherichia coli Rosetta (DE3) pLysS. The recombinant protein rCcSOD1 was purified by HisTrap High Performance chelating column chromatography and analyzed for its biological function. Our results showed that the purified rCcSOD1 could inhibit superoxide anion and keep active in a pH interval of 4.5-9 and a temperature interval of 10-70°C. Even when heated at 70°C for 60 min, rCcSOD1 retained 100% activity, indicating a relatively high thermostability. These results suggest that CcSOD1 protein may play an important role in protecting jellyfish from oxidative damage and can serve as a new resource for antioxidant products.

19.
Behav Brain Res ; 379: 112320, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31669345

RESUMO

There is a serious need for fast-acting drugs to treat post-traumatic stress disorder (PTSD). Our previous studies revealed that YL-IPA08, a novel small-molecule TSPO agonist, exerted significant anti-PTSD effects in various animal models. However, the onset time of YL-IPA08 and its underlying mechanisms remain unclear. In the present study, we first investigated the time course of YL-IPA08 compared to selective serotonin reuptake inhibitors (SSRIs) in the well-known time-dependent sensitization model of PTSD. YL-IPA08 required only 2-4 days of treatment to take effect in behavioural models of PTSD, whereas sertraline required 7-8 days. Furthermore, the mechanism study revealed that YL-IPA08 elicited anti-PTSD-like effects associated with increased GABA levels and allopregnanolone efflux in the hippocampus and prefrontal cortex and increased corticosterone levels in the serum after only 5 days of treatment, whereas sertraline required 9 days. Our results demonstrate that YL-IPA08 can exert fast-onset anti-PTSD-like effects, and its mechanisms may be related to the increased GABA levels, allopregnanolone efflux and the hypothalamic-pituitary-adrenal (HPA) axis function.

20.
Int J Nanomedicine ; 14: 9497-9512, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819446

RESUMO

Background: Critical-sized bone defects raise great challenges. Zein is of interest for bone regeneration, but it has limited ability to stimulate cell proliferation. In this regard, a poly (aspartic acid) (PAsp)-zein hybrid is promising, as PAsp can promote rat bone marrow stromal cell (rBMSCs) proliferation and osteogenic differentiation. This research aimed to develop electrospun PAsp-modified zein nanofibers to realize critical-sized bone defects repair. Methods: Three groups of PAsp-modified zein nanofibers were prepared, they were PAsp grafting percentages of 0% (zein), 5.32% (ZPAA-1), and 7.63% (ZPAA-2). Using rBMSCs as in vitro cell model and SD rats as in vivo animal model, fluorescence staining, SEM, CCK-8, ALP, ARS staining, µCT and histological analysis were performed to verify the biological and osteogenic activities for PAsp-modified zein nanofibers. Results: As the Asp content increased from 0% to 7.63%, the water contact angle decreased from 129.8 ± 2.3° to 105.5 ± 2.5°. SEM, fluorescence staining and CCK-8 assay showed that ZPAA-2 nanofibers had a superior effect on rBMSCs spreading and proliferation than did zein and ZPAA-1 nanofibers, ALP activity and ARS staining showed that ZPAA-2 can improve rBMSCs osteogenic differentiation. In vivo osteogenic activities was evaluated by µCT analysis, HE, Masson and immunohistochemical staining, indicating accelerated bone formation in ZPAA-2 SD rats after 4 and 8 weeks treatment, with a rank order of ZPAA-2 > ZPAA-1 > zein group. Moreover, the semiquantitative results of the Masson staining revealed that the maturity of the new bone was higher in the ZPAA-2 group than in the other groups. Conclusion: Electrospun PAsp-modified zein can provide a suitable microenvironment for osteogenic differentiation of rBMSCs, as well as for bone regeneration; the optimal membrane appears to have a PAsp grafting percentage of 7.63%.


Assuntos
Regeneração Óssea/fisiologia , Nanofibras/química , Peptídeos/química , Zeína/química , Fosfatase Alcalina/metabolismo , Animais , Diferenciação Celular , Proliferação de Células , Forma Celular , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Crânio/diagnóstico por imagem , Microtomografia por Raio-X
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