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2.
Artigo em Inglês | MEDLINE | ID: mdl-33355461

RESUMO

4D printing allows 3D printed structures to change their shapes overtime under external stimuli, finding a wide range of potential applications in actuators, soft robotics, active metamaterials, flexible electronics, and biomedical devices. However, most 4D printing uses soft polymers to accommodate large strain shape-changing capability at the price of low stiffness, which impedes their engineering applications. Here, we demonstrate an approach to design and manufacture self-morphing structures with large deformation and high modulus (∼4.8 GPa). The structures are printed by multimaterial direct ink writing (DIW) using composite inks that contain a high volume fraction of solvent, photocurable polymer resin, and short glass fibers as well as fumed silica. During printing, the glass fibers undergo shear-induced alignment through the nozzle, leading to highly anisotropic mechanical properties. The solvent is then evaporated, during which the aligned glass fibers enable anisotropic shrinkage in the parallel and perpendicular directions to the fiber alignment for shape shifting. A final postphotocuring step is applied to further increase the stiffness of the composite from ∼300 MPa to ∼4.8 GPa. A finite element analysis (FEA) model is developed to predict the influence of the solvent, fiber contents, and fiber orientation on the shape shifting. We demonstrate the anisotropic volume shrinkage of the structures can be used as active hinges to transform printed two-dimensional structures into complex three-dimensional structures with large shape-shifting and outstanding mechanical properties. This strategy for fabricating composite structures with programmable architectures and excellent mechanical properties shows potential applications in morphing lightweight structures with load-bearing capabilities.

3.
Front Cell Dev Biol ; 8: 563316, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33102474

RESUMO

Octamer-binding transcription factor 4 (Oct4) has been recently implicated as a proangiogenic regulator in several induced pluripotent stem cells (iPSCs), however, its role in cancer stem-like cells (CSCs) remain unclear. We report here that Oct4 participates in tumor vasculogenesis in liver CSCs (LCSCs). We identify that LCSCs possess the potential of endothelial trans-differentiation under endothelial induction, present endothelial specific markers and their functions in vitro, and participate in neovasculogenesis in vivo. The knockdown of the Oct4A by short hairpin RNA (shRNA) in LCSCs represses endothelial trans-differentiation potential, but induces endothelial lineage-restricted differentiation, the latter is positively regulated by Oct4B1. Furthermore, Oct4 regulates vasculogenesis in LCSCs may be via the AKT-NF-κB-p65 signaling pathway. This work reveals Oct4, which is a crucial regulator, plays a critical role in tumor endothelial-like cells transition of LCSCs through Oct4A and Oct4B1 by different ways. The simultaneous inhibition of both the isoforms of Oct4 is hence expected to help regress neovascularization derived from CSCs. Our findings may provide insights to the possible new mechanisms of tumor vasculogenesis for primary liver cancer.

4.
Shanghai Kou Qiang Yi Xue ; 29(4): 427-430, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-33089296

RESUMO

PURPOSE: To investigate the effect of Bio-Oss bone powder combined with platelet-rich fibrin on bone mass after implantation-guided bone regeneration in alveolar bone defects. METHODS: One hundred and six patients with single anterior tooth loss and labial alveolar bone defect were selected for implant implantation and guided bone regeneration at the same time. Patients in the experimental group (n=53) were treated with Bio-Oss bone powder combined with platelet-rich fibrin and biofilm to guide bone regeneration, while patients in the control group(n=53) were treated with Bio-Oss bone powder combined with biofilm to guide bone regeneration. The success rate of implantation, complication rate, the thickness of labial bone wall and the regeneration of bone defect were observed. Statistical analysis was performed on the data using SPSS 25.0 software package. RESULTS: There was no significant difference in the success rate of implants between the two groups(96.23% vs 88.68%, P>0.05). The thickness of the labial bone wall of the experimental group 12 months after implantation was significantly higher than that of the control group[(2.72±0.43) mm vs(2.51±0.36) mm], and the thickness of the labial wall of the implant at different sites was significantly greater than that of the control group(P<0.05). Bleeding index [(0.32±0.02) vs (0.42±0.03)], depth of probing [(3.31±0.69) mm vs (4.32±0.95) mm], loss of attachment [(3.06±0.52) mm vs (5.24±1.35) mm] was significantly smaller in the experimental group than in the control group (P<0.05); bone graft height [(2.61±0.52) mm vs (2.31±0.35) mm], osteogenesis height [(2.59±0.32) mm vs (2.01±0.16) mm] was significantly greater in the experimental group than in the control group(P<0.05). There was no significant difference in the incidence of complications between the two groups(1.89% vs 5.66%, P>0.05). CONCLUSIONS: Bio-Oss bone powder combined with platelet-rich fibrin can reduce bone loss and promote bone defect regeneration after guided bone regeneration.


Assuntos
Substitutos Ósseos , Fibrina Rica em Plaquetas , Regeneração Óssea , Humanos , Minerais
5.
Dalton Trans ; 49(42): 14941-14950, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33079106

RESUMO

The synthesis of four heteroleptic dinuclear Cu(i) complexes bearing tetraphosphine and diimine ligands was reported. Complexes 1-3 were successfully obtained through microwave synthesis while complex 4 was synthesized through traditionally stirring at room temperature. These complexes are listed as follows: [Cu2(Dpq)2(dppeda)](ClO4)2·1.5CH2Cl2 (1), [Cu2(neo)2(dppeda)](ClO4)2·1.3CH2Cl2·1.7C4H10O (2), [Cu2(batho)2(dppeda)](ClO4)2·C4H10O (3), and [Cu2(batho)2(dpppda)](ClO4)2·3CH2Cl2 (4) {(Dpq = pyrazino[2,3-f][1,10]phenanthroline, batho = 4,7-diphenyl-1,10-phenanthroline, neo = 2,9-dimethyl-1,10-phenanthroline, dppeda = N1,N1,N2,N2-tetrakis[(diphenylphosphino)methyl]-1,2-ethanediamine, and dpppda = N1,N1,N4,N4-tetrakis[(diphenylphosphino)methyl]-1,4-benzenediamine}. Their crystal structures have been elucidated by X-ray crystallography and their photophysical properties have been investigated in detail. Photophysical studies and time domain density functional theory (TD-DFT) calculations show that the luminescence performance of these four complexes is ascribed to metal-to-ligand charge transfer (MLCT) mixed with ligand-to-ligand charge transfer (LLCT), and complex 2 shows green emission at 574 nm with the highest quantum yield of up to 52.80%. In addition, the research of photoluminescence properties under the guidance of terahertz spectroscopy technology leads to the preliminary discovery of a correlation between crystal packing and luminescence. It is found that the terahertz spectrum and absorption peak are strongly interdependent on C-Hπ and ππ interactions, and the external weak interactions have negative effects on the luminescence performance. Herein, we predict that the terahertz spectroscopy analysis establishes a bridge between weak interactions (C-Hπ and ππ interactions) and the photoluminescence properties, and puts forward a problem that should be noticed in designing Cu(i) complexes.

6.
Brain Res ; 1748: 147082, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32866544

RESUMO

Neovascularization is a histological feature of glioma, especially of glioblastoma (GBM), being associated with tumor invasiveness and poor prognosis. However, current anti-angiogenic therapies targeting vascular endothelial cells (ECs), has exhibited poor efficacy in some GBM cases. This may be at least partially attributed to the potential of glioblastoma cells to construct blood supply chain via vasculogenic mimicry or endothelial differentiation. This study aims to explore differences in vasculogenic activity and sensitivity to angiogenic stimulants between normal human ECs and glioma cells of different grades. We found that grade IV U87 GBM cells showed highly inducible vasculogenic activity either in the orthotopic xenograft model or under in vitro angiogenic stimulants as compared with grade II CHG5 glioma cells. The hypoxia mimetic more strongly induced in vitro vasculogenic capacity and endothelial marker expression of U87 GBM cells than the stimulation with multiple proangiogenic growth factors (vascular endothelial growth factor, basic fibroblast growth factor and epidermal growth factor). In contrast, proangiogenic effect of hypoxia on human umbilical vein endothelial cells (HUVECs) was weaker than on U87 GBM cells. In addition, it was also observed that the in vitro vasculogenic process of U87 cells started later but lasted longer than that of HUVECs. These results demonstrate that when compared with normal ECs, high-grade glioma cells basically possess weaker vasculogenic activity, but exhibit higher sensitivity and longer-lasting response to angiogenic stimulants, especially to hypoxia. This may be helpful to develop novel anti-angiogenic strategies targeting both vascular ECs and vasculogenic glioma cells.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32897697

RESUMO

Magnetic soft materials (MSMs) have shown potential in soft robotics, actuators, metamaterials, and biomedical devices because they are capable of untethered, fast, and reversible shape reconfigurations as well as controllable dynamic motions under applied magnetic fields. Recently, magnetic shape memory polymers (M-SMPs) that incorporate hard magnetic particles in shape memory polymers demonstrated superior shape manipulation performance by realizing reprogrammable, untethered, fast, and reversible shape transformation and shape locking in one material system. In this work, we develop a multimaterial printing technology for the complex structural integration of MSMs and M-SMPs to explore their enhanced multimodal shape transformation and tunable properties. By cooperative thermal and magnetic actuation, we demonstrate multiple deformation modes with distinct shape configurations, which further enable active metamaterials with tunable physical properties such as sign-change Poisson's ratio. Because of the multiphysics response of the M-MSP/MSM metamaterials, one distinct feature is their capability of shifting between various global mechanical behaviors such as expansion, contraction, shear, and bending. We anticipate that the multimaterial printing technique opens new avenues for the fabrication of multifunctional magnetic materials.

8.
Curr Pharm Des ; 26(39): 5002-5011, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32418519

RESUMO

BACKGROUND AND OBJECTIVE: The benefits of physical activity (PA) for children and adolescents with disabilities are well documented, and children and adolescents with visual impairments (VI) engage in less PA than their sighted peers. Two reviews have summarized studies on PA of children and adolescents with VI, but no systematic review with semi-quantitative assessment has been conducted to specifically identify the correlates of their PA. This review aims to systematically summarize the existing literature, which investigated the correlates of PA of children and adolescents with VI until 2019 and identify variables that contribute to their PA participation. METHODS: A systematic search using Academic Search Premier (ASP), Education Resources Information Center (ERIC), Education Source (ES), PsycINFO, Psychology and Behavioral Sciences Collection (PBSC), MEDLINE, Scopus, and Web of Science (WOS) was conducted in September 2019 to identify studies examining the correlates of PA in children and adolescents with VI aged 5 to 17 years. Two researchers independently screened studies, assessed their methodological quality and extracted relevant data. The correlates of PA among children and adolescents with VI were synthesized and further assessed semi-quantitatively. RESULTS: A total of 17 articles identified correlates of PA in children and adolescents with VI. Out of 21 variables identified from the reviewed studies, 3 were consistently associated with PA of children and adolescents with VI. Body mass index (BMI)/obesity, percent of body fat, and visual impairment level were consistently and negatively associated with PA of children and adolescents with VI. Gender and age were identified as having inconsistent relationships with PA in children and adolescents with VI. The level of parental education was identified to have "no association" with children and adolescents with VI. CONCLUSION: This review can aid in developing effective interventions to improve the PA of children and adolescents with VI and propose directions for future research.

9.
ACS Appl Mater Interfaces ; 12(15): 17979-17987, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32196302

RESUMO

Inspired by diverse shape-shifting phenomena in nature, various man-made shape programmable materials have been developed for applications in actuators, deployable devices, and soft robots. However, fabricating mechanically robust shape-morphing structures with on-demand, rapid shape-transformation capability, and high load-bearing capacity is still a great challenge. Herein, we report a mechanically robust and rapid shape-shifting material system enabled by the volatilization of a non-fully-reacted, volatile component in a partially cured cross-linking network obtained from photopolymerization. Volume shrinkage induced by the loss of the volatile component is exploited to drive complex shape transformations. After shape transformation, the residual monomers, cross-linkers, and photoinitiators that cannot volatilize still exist in the network, which is ready for a further photopolymerization to significantly stiffen the initial material. Guided by analytic models and finite element analysis, we experimentally demonstrate that a variety of shape transformations can be achieved, including both 2D-to-3D and 3D-to-3D' transformations, such as a buckyball self-folding from a 2D hexagonal lattice sheet and multiple pop-up structures transforming from their initial compact configurations. Moreover, we show that an ultra-low-weight 3D Miura-ori structure transformed from a 2D sheet can hold more than 1600 times its weight after stiffness improvement via postcuring. This work provides a versatile and low-cost method to fabricate rapid and robust shape-morphing structures for potential applications in soft robots, deployable antennas, and optical devices.

10.
Clin Respir J ; 14(7): 667-674, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32162441

RESUMO

BACKGROUND: To examine the effects of Keratin 6A (KRT6A) protein on the proliferation, migration and invasion abilities of lung adenocarcinoma cells, and to analyse the relationship between the expression level of KRT6A protein and the survival prognosis of lung adenocarcinoma patients. METHODS: Western Blot was used to detect the expression of KRT6A protein in lung adenocarcinoma cell lines. CCK-8 experiment and colony formation assays were performed to detect the proliferation ability. Wound healing assay and transwell migration assay were conducted to detect the migration ability. Transwell invasion assay was conducted to detect the invasion ability. Immunohistochemistry was used to detect the expression of KRT6A protein in lung adenocarcinoma tissues. RESULTS: We first found that the expression of KRT6A protein in lung adenocarcinoma cell lines was low. After overexpressed KRT6A protein in lung adenocarcinoma cells, we then found that KRT6A protein could not only inhibit the proliferation ability of lung adenocarcinoma cells but also inhibit them migration and invasion abilities. In addition, we also found that there had obvious difference in the expression of KRT6A protein in between patients. And through further analysis, we finally discovered that high expression of KRT6A protein was related to favourable prognosis in lung adenocarcinoma patients. CONCLUSIONS: KRT6A protein inhibits the proliferation, migration and invasion abilities of lung adenocarcinoma cells, and high expression of KRT6A protein is a predictor of good prognosis in patients with lung adenocarcinoma.

11.
Adv Mater ; 32(4): e1906657, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31814185

RESUMO

Shape-programmable soft materials that exhibit integrated multifunctional shape manipulations, including reprogrammable, untethered, fast, and reversible shape transformation and locking, are highly desirable for a plethora of applications, including soft robotics, morphing structures, and biomedical devices. Despite recent progress, it remains challenging to achieve multiple shape manipulations in one material system. Here, a novel magnetic shape memory polymer composite is reported to achieve this. The composite consists of two types of magnetic particles in an amorphous shape memory polymer matrix. The matrix softens via magnetic inductive heating of low-coercivity particles, and high-remanence particles with reprogrammable magnetization profiles drive the rapid and reversible shape change under actuation magnetic fields. Once cooled, the actuated shape can be locked. Additionally, varying the particle loadings for heating enables sequential actuation. The integrated multifunctional shape manipulations are further exploited for applications including soft magnetic grippers with large grabbing force, reconfigurable antennas, and sequential logic for computing.

12.
Sci Rep ; 9(1): 17902, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784554

RESUMO

With the increasing amount of electronic waste (e-waste) generated globally, it is an enormous challenge to recycle printed circuit boards (PCBs) efficiently and environmentally friendly. However, conventional recycling technologies have low efficiency and require tough treatment such as high temperature (>200 °C) and high pressure. In this paper, a small-molecule assisted approach based on dynamic reaction was proposed to dissolve thermosetting polymers containing ester groups and recycle electronic components from PCBs. This effective approach operates below 200 °C and the polymer could be dissolved in a short time. It has a remarkable ability to recycle a wide range of commercial PCBs, including boards made of typical anhydride epoxy or polyester substrate. Besides, it is environmentally friendly as even the recycling solution could be reused multiple times. In addition, the wasted solution after recycling could be used for board bonding and damage repair. This work also demonstrates the advantage of using polymers containing ester groups as the PCB substrate in consideration of eco-friendly and efficient recycling.

13.
J Phys Condens Matter ; 31(50): 505406, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31491779

RESUMO

We perform the first-principles calculations combined with the particle swarm optimization algorithm to investigate the high-pressure phase diagrams of Na[Formula: see text]F3 ([Formula: see text] = Mn, Ni, Zn). Two reconstructive phase transitions are predicted from Pv-[Formula: see text] to pPv-[Formula: see text] at about 9 GPa and pPv-[Formula: see text] to ppPv-[Formula: see text] at around 26 GPa for NaZnF3. That is not the case for NaMnF3-a direct transition (reconstructive transition in nature but with the same Pnma space group) from Pv-[Formula: see text] to ppPv-[Formula: see text] phase around 12 GPa. Strikingly, our simulated results manifest that a disproportionation phase of NaZnF3 post-perovskite is uncovered along the way, which provides a successful explanation for the observed results in experiment. Additionally, the mechanical and thermal properties, especially the dynamical property, of the four NaZnF3 phases have also been studied. Here, we reveal the obvious softening of [Formula: see text]-wave velocity and bulk sound speed in pPv-[Formula: see text]-to-ppPv-[Formula: see text] transition, which may result in the discontinuity of seismic waves propagation through the Earth's interior.

14.
Sci Adv ; 5(5): eaav5790, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31058222

RESUMO

Three-dimensional (3D) printing or additive manufacturing, as a revolutionary technology for future advanced manufacturing, usually prints parts with poor control of complex gradients for functional applications. We present a single-vat grayscale digital light processing (g-DLP) 3D printing method using grayscale light patterns and a two-stage curing ink to obtain functionally graded materials with the mechanical gradient up to three orders of magnitude and high resolution. To demonstrate the g-DLP, we show the direct fabrication of complex 2D/3D lattices with controlled buckling and deformation sequence, negative Poisson's ratio metamaterial, presurgical models with stiffness variations, composites for 4D printing, and anti-counterfeiting 3D printing.

15.
ACS Appl Mater Interfaces ; 11(21): 19514-19521, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31062572

RESUMO

A method for fabricating long, soft, and reversibly actuatable liquid crystal elastomer (LCE) fibers by using direct ink write (DIW) printing was developed. Here, the LCE was produced based on a two-stage thermal-photo curing reaction between a difunctional acrylate monomer and thiol. The LCE ink, mixed with nanoclay to increase the viscosity, was extruded through a nozzle onto a rotating mandrel to obtain a long fiber. After printing, the fiber was first thermally cured on the mandrel, then mechanically stretched, and photocured to achieve liquid crystal chain alignment for stress-free reversible activation. Upon optimizing the ink viscosity and DIW printing parameters, long fibers (up to 1.5 m long from the laboratory) were obtained. The resulting fiber had a modulus of 2 MPa, 51% actuation strain, and a failure strain of well over 100%. The potential of these fibers for applications was demonstrated. The LCE fibers were knit, sewn, and woven to form a variety of smart textiles. The fiber was also used to mimic bicep muscles with both large activation force and activation strain. By incorporating further intelligent characteristics, such as conductivity and biosensing into a single fiber, the LCE fibers could be potentially used for smart clothing, soft robotics, and biomedical devices.


Assuntos
Elastômeros/química , Cristais Líquidos/química , Músculo Esquelético/fisiologia , Têxteis , Dispositivos Eletrônicos Vestíveis , Impressão
16.
Asian J Pharm Sci ; 14(5): 569-580, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32104484

RESUMO

Mitochondria are currently known as novel targets for treating cancer, especially for tumors displaying multidrug resistance (MDR). This present study aimed to develop a mitochondria-targeted delivery system by using triphenylphosphonium cation (TPP+)-conjugated Brij 98 as the functional stabilizer to modify paclitaxel (PTX) nanocrystals (NCs) against drug-resistant cancer cells. Evaluations were performed on 2D monolayer and 3D multicellular spheroids (MCs) of MCF-7 cells and MCF-7/ADR cells. In comparison with free PTX and the non-targeted PTX NCs, the targeted PTX NCs showed the strongest cytotoxicity against both 2D MCF-7 and MCF-7/ADR cells, which was correlated with decreased mitochondrial membrane potential. The targeted PTX NCs exhibited deeper penetration on MCF-7 MCs and more significant growth inhibition on both MCF-7 and MCF-7/ADR MCs. The proposed strategy indicated that the TPP+-modified NCs represent a potentially viable approach for targeted chemotherapeutic molecules to mitochondria. This strategy might provide promising therapeutic outcomes to overcome MDR.

17.
Zhonghua Nan Ke Xue ; 25(8): 675-680, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32227708

RESUMO

Objective: To search for a method of establishing a reliable mouse model of orchitis and investigate the association of orchitis with the activation of the inflammasome. METHODS: We equally randomized 40 adult male KM mice into groups A (sham operation), B (intraperitoneal injection of lipopolysaccharide ï¼»LPSï¼½), C (unilateral testicular injection of glacial acetic acid ï¼»GAAï¼½), and D (unilateral testicular injection of LPS). At 3 weeks after modeling, we measured the sperm concentration and percentage of progressively motile sperm (PMS) in the epididymis by computer-assisted semen analysis, observed the pathological changes in the testis tissue by HE staining, and determined the expressions of the Caspase-1 and interleukin (IL)-1ß proteins by Western blot. RESULTS: The sperm concentration in the epididymis was significantly decreased in groups B (ï¼»25.74 ± 3.19ï¼½ ×106/ml), C (ï¼»17.16 ± 4.41ï¼½ ×106/ml) and D (ï¼»16.92 ± 7.13ï¼½ ×106/ml) as compared with that in group A (ï¼»28.20 ± 1.63ï¼½ ×106/ml) (all P < 0.05), even more significantly in B than in C and D (P < 0.01), and so was PMS in groups B (ï¼»29.57 ± 2.16ï¼½%), C (ï¼»18.10 ± 2.38ï¼½%) and D (ï¼»7.34 ± 1.63ï¼½%) in comparison with group A (ï¼»59.34 ± 1.10ï¼½%) (P < 0.01), even more significantly in B and C than in D (P < 0.01). Light microscopy revealed different degrees of pathological changes in the testis tissue, most significant in group D, followed by C and B. Both the expressions of Caspase-1 and IL-1ß were remarkably up-regulated in groups B, C and D compared with those in group A (P < 0.01), even more markedly in D than in B and C (P < 0.05). CONCLUSIONS: Unilateral testicular injection of LPS is a more efficient method than either unilateral testicular injection of GAA or intraperitoneal injection of LPS for establishing the mouse model of orchitis. Orchitis may be pathologically associated with the activation of the NLRP3 inflammasome.


Assuntos
Modelos Animais de Doenças , Orquite/induzido quimicamente , Testículo/efeitos dos fármacos , Animais , Caspase 1/metabolismo , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos , Masculino , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Contagem de Espermatozoides , Testículo/patologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-30412790

RESUMO

BACKGROUND: The renin angiotensin-aldosterone system (RAAS) and lipoxins (LXs) have similar roles in many processes. We previously reported that BML-111, a Lipoxin receptor agonist, inhibited chronic injury hepatic fibrosis by regulating RAAS, but whether LXs are involved in BML-111-mediated protection from acute injury is unclear still. METHODS: We established models of acute liver/lung injury and confirmed them with histopathology and myeloperoxidase (MPO) measurements. BML-111, a lipoxin receptor agonist, was applied to mimic the effects of LXs. The contents and activities of angiotensin converting enzyme(ACE) and angiotensinconverting enzyme 2 (ACE2) were measured through ELISA and activity assay kits respectively. Angiotensin II (AngII), angiotensin-(1-7) (Ang-1-7), AngII type 1 receptor (AT1R), and Mas receptor were quantified with ELISA and Western blot. RESULTS: Models of acute injury were established successfully and BML-111 protected LPS-induced acute lung injury and LPS/D-GalN-induced acute liver injury. BML-111 repressed the activity of ACE, but increased the activity of ACE2. BML-111 decreased the expression levels of ACE, AngII, and AT1R, meanwhile increased the levels of ACE2, Ang-(1-7), and Mas. Furthermore, BOC-2, an inhibitor of lipoxin receptor, reversed all the effects. CONCLUSION: BML-111 could protect against acute injury via regulation RAAS.


Assuntos
Ácidos Heptanoicos/farmacologia , Receptores de Lipoxinas/agonistas , Sistema Renina-Angiotensina/efeitos dos fármacos , Angiotensina I/metabolismo , Angiotensina II/metabolismo , Animais , Citoproteção/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/lesões , Fígado/metabolismo , Fígado/patologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/prevenção & controle , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Regulação para Cima/efeitos dos fármacos
19.
Eur J Pharm Sci ; 126: 59-68, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29684426

RESUMO

We report a proof-of-concept for the development of mitochondria-targeting nanoparticles (NPs) loaded with geranylgeranylacetone (GGA) to protect against a wide range of gentamicin-induced ototoxicity symptoms in a zebrafish model. The polymeric NPs were functionalized with a mitochondrial-homing peptide (d­Arg­Dmt­Orn­Phe­NH2) and exhibited greater mitochondrial uptake and lower gentamicin uptake in hair cells via mechanotransduction (MET) channels and tuned machinery in the hair bundle than the ordinary NPs did. Blockade of MET channels rapidly reversed this effect, indicating the reversible responses of hair cells to the targeting NPs were mediated by MET channels. Pretreatment of hair cells with mitochondria-targeting GGA-loaded NPs exhibited a superior acute or chronic protective efficacy against subsequent exposure to gentamicin compared with unmodified formulations. Mitochondrial delivery regulating the death pathway of hair cells appeared to cause the therapeutic failure of untargeted NPs. Thus, peptide-directed mitochondria-targeting NPs may represent a novel therapeutic strategy for mitochondrial dysfunction-linked diseases.


Assuntos
Antibacterianos/toxicidade , Diterpenos/administração & dosagem , Gentamicinas/toxicidade , Mitocôndrias/metabolismo , Nanopartículas/química , Oligopeptídeos/química , Animais , Morte Celular , Portadores de Fármacos , Liberação Controlada de Fármacos , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/patologia , Mecanotransdução Celular , Nanomedicina , Polietilenoglicóis/química , Poliglactina 910/química , Estudo de Prova de Conceito , Peixe-Zebra
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