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1.
Artif Cells Nanomed Biotechnol ; 47(1): 1888-1897, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31072140

RESUMO

Storage lesions in red blood cells (RBCs) hinder efficient circulation and tissue oxygenation. The absence of flow mechanics and gas exchange may contribute to this problem. To test if in vitro compensation of flow mechanics and gas exchange helps RBC recovery, three-dimensional polydimethylsiloxane (PDMS) porous structures were fabricated with a sugar mould, simulating lung alveoli. RBC suspensions were passed through the porous structure cyclically, simulating in vivo blood circulation. Acid-base indices, partial gas pressures, ions, glucose and RBC indices were analyzed. An atomic force microscope was used to investigate local mechanical properties of intact RBCs. RBCs suspensions that passed through the porous structures had a higher pH and oxygen partial pressure, and a lower potassium concentration and carbon dioxide partial pressure. Meantime they had better biochemical properties relative to static samples, namely, they exhibited a more homogenous distribution of Young's Modulus. RBCs that passed through a PDMS porous structure were healthier than static ones, giving hints to prevent RBC storage lesions.


Assuntos
Preservação de Sangue , Dimetilpolisiloxanos/química , Dimetilpolisiloxanos/farmacologia , Eritrócitos/efeitos dos fármacos , Gases/metabolismo , Hemorreologia/efeitos dos fármacos , Nylons/química , Nylons/farmacologia , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Módulo de Elasticidade/efeitos dos fármacos , Eritrócitos/citologia , Eritrócitos/metabolismo , Glucose/metabolismo , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Masculino , Porosidade , Ratos , Ratos Wistar
2.
Lab Chip ; 19(9): 1579-1588, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30924490

RESUMO

Collective cellular migration plays a central role in development, regeneration, and metastasis. In these processes, mechanical interactions between cells are fundamental but measurement of these interactions is often hampered by technical limitations. To overcome some of these limitations, here we describe a system that integrates microfluidics with traction microscopy (TM). Using this system we can measure simultaneously, and in real time, migration speeds, tractions, and intercellular tension throughout an island of confluent Madin-Darby canine kidney (MDCK) cells. The cell island is exposed to hepatocyte growth factor (HGF) at a controlled gradient of concentrations; HGF is known to elicit epithelial-to-mesenchymal transition (EMT) and cell scattering. As expected, the rate of expansion of the cell island was dependent on the concentration of HGF. Higher concentrations of HGF reduced intercellular tensions, as expected during EMT. A novel finding, however, is that the effects of HGF concentration and its gradient were seen within an island. This integrated experimental system thus provides an integrated tool to better understand cellular forces during collective cellular migration under chemical gradients.


Assuntos
Fator de Crescimento de Hepatócito/farmacologia , Dispositivos Lab-On-A-Chip , Microscopia/instrumentação , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Cães , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Células Madin Darby de Rim Canino , Integração de Sistemas
3.
Kaohsiung J Med Sci ; 35(3): 175-182, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30887723

RESUMO

Bone tendon junction injury is hard to cure because of its special anatomical structure, and the treatment applied for bone-tendon junction injury cannot result in the perfect vascular regeneration and restoration of the fibrocartilage zone. In this article, we aim to explore the effect of caveolin-1 as a slow-release material on bone-tendon junction healing. Seventy-two New Zealand rabbits were randomly selected and assigned into the experimental, sham-operated and control groups (n = 24). Caveolin-1 microspheres and microcapsule were developed as drug delivery system. At the 4th, 8th, and 12th weeks after surgery, quadriceps muscle patella-patellar tendon (QMPPT) was obtained from each rabbit to observe the tendon-to-bone tunnel healing, and X-ray examination, histological examination and biomechanical testing were applied for evaluating new bone formation. As the X-ray showed, caveolin-1 increased the new bone area at each time point. At the 4th and 8th weeks after surgery, the rabbit treated with caveolin-1 slow release material showed repair of fibrocartilage. According to the biomechanical results, the cross-sectional area, breaking load and ultimate tensile strength were increased along with time. At the same time point, caveolin-1 increased the ultimate tensile strength. Our study demonstrates that caveolin-1 as a slow-release material could accelerate bone-tendon junction healing by promoting the formation of the transition zone.


Assuntos
Osso e Ossos/metabolismo , Osso e Ossos/patologia , Caveolina 1/farmacologia , Tendões/metabolismo , Tendões/patologia , Cicatrização , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Quitosana/química , Preparações de Ação Retardada/farmacologia , Feminino , Fibrocartilagem/efeitos dos fármacos , Cinética , Masculino , Microesferas , Músculos/efeitos dos fármacos , Tamanho da Partícula , Patela/efeitos dos fármacos , Coelhos , Tendões/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
4.
Carbohydr Polym ; 212: 277-288, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30832858

RESUMO

In order to better utilize and combine the advantages of poly(d,l-lactide) (PDLLA) matrix and natural polysaccharide chitin whiskers (CHWs), needle-like CHWs with chiral nematic liquid crystal characteristics and remarkable moduli were chosen to surface modify PDLLA film. By a vertical coating method, a stable and well-ordered CHWs coating was formed on the surface of the PDLLA film through a polydopamine (PDA) interlayer. The high stability of the well-ordered CHWs coating on the surface of the PDLLA film was confirmed by PBS soaking experiment in terms of the changes of weight and surface morphology of the film. The surface microstructure and composition of the resulting PDLLA-PDA-CHWs film were characterized by field emission scanning electron microscopy (FESEM), atomic force microscope (AFM) and X-ray photoelectron spectroscopy (XPS), and the thickness of the PDLLA, PDA and CHWs layers was determined using FESEM, too. Comparing with traditional PDLLA/CHWs film, prepared by solution blending with optimal content of 5 wt% CHWs, the hydrophilicity and mechanical properties of the PDLLA-PDA-CHWs film were significantly improved owing to the immobilization of a highly ordered CHWs coating. Furthermore, in vitro cell culture showed that the well-ordered CHWs coating had a more significant effect on promoting the adhesion, spreading, proliferation and osteogenic differentiation of MC3T3-E1 cells. All these results showed that the resulting PDLLA-PDA-CHWs film with well-ordered CHWs coating designed through simple and effective approach has promising application in bone repair material field.


Assuntos
Quitina/química , Quitina/farmacologia , Osteogênese/efeitos dos fármacos , Poliésteres/química , Poliésteres/farmacologia , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Fenômenos Biomecânicos/fisiologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular , Estabilidade de Medicamentos , Camundongos , Osteogênese/fisiologia
5.
Biomed Pharmacother ; 112: 108598, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30784908

RESUMO

Anisomeles malabarica (AM) is an aromatic plant traditionally used for the treatment of diabetes mellitus in India. Following bioassay guided fractionation, we recently identified an active fraction of AM (AMAF, with potential mix of active principles) that showed significant antihyperglycemic and antihyperlipidemic activities. In addition, AMAF treatment improved insulin levels. However, the biochemical mechanism/s through which AMAF demonstrates the antidiabetic effects is largely unknown. Based on its beneficial effects we investigated the biochemical mechanism of the anti-diabetic activity of A.malabarica active fraction (AMAF) in streptozotocin (STZ) induced diabetic rats. Streptozotocin induced diabetic rats were treated with AMAF (50 mg AMAF/kg/day) for 30 days and alterations in the body weights, glycogen and protein content of tissues, functional markers of hepatic and renal tissues, carbohydrate metabolic enzymes and their genes expression were evaluated. Lipid peroxides levels and activities of antioxidant enzymes of hepatic and renal tissues were also measured. The AMAF treatment resulted in increase in body weights, hepatic and renal protein and tissue glycogen levels in diabetic treated rats compared to diabetic rats. In addition, the treatment improved activities of carbohydrate metabolic enzymes, antioxidant enzymes and, liver and renal functional markers in the AMAF treated diabetic rats. Gene expressions of key carbohydrate metabolic enzymes/factors glucokinase, glucose transporter protein (GLUT-2) and phosphoenolpyruvate carboxykinase (PEPCK) were also normalized up on AMAF treatment in diabetic rats. Our studies indicate that the isolated active fraction of AM (AMAF) from the leaves of A.malabarica positively regulated the glucose homeostasis and oxidative stress through carbohydrate metabolism and antioxidant enzyme activities respectively in hepatic and renal tissues.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Lamiaceae , Extratos Vegetais/uso terapêutico , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Fenômenos Biomecânicos/fisiologia , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Avaliação Pré-Clínica de Medicamentos/métodos , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Estreptozocina/toxicidade
6.
Carbohydr Polym ; 209: 338-349, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30732816

RESUMO

The effect of wheat straw arabinoxylan (AX) and ß-glucan stearic acid ester (SABG) composite coating on the quality and storage life of apple (Royal Delicious) was studied at 22 °C (±2) with relative humidity of 65% and 85% for 60 days. Fresh fruits were coated with surface coatings of AX-SABG, shellac in the concentration range of 1-4%. Application of both AX-SABG (1-4%) and shellac (1-4%) coatings was found to significantly reduce weight loss, respiration rate, fruit softening process, ripening index, color degradation and polyphenol oxidase activity compared to control during the storage period of more than 30 days. However, an AX-SABG coating was more effective in reducing fruit decay and loss of aroma volatiles followed by shellac coated apples; the un-coated apples being showing maximum quality deterioration. These findings confirmed the potential benefits of applying AX-SABG coating to extend the shelf life and quality of apples especially during transportation and storage.


Assuntos
Ésteres/química , Qualidade dos Alimentos , Malus/efeitos dos fármacos , Ácidos Esteáricos/química , Xilanos/farmacologia , beta-Glucanas/química , beta-Glucanas/farmacologia , Fenômenos Biomecânicos/efeitos dos fármacos , Catecol Oxidase/metabolismo , Respiração Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cor , Conservação de Alimentos , Frutas/efeitos dos fármacos , Frutas/metabolismo , Malus/citologia , Malus/enzimologia , Malus/metabolismo , Odorantes/análise , Peroxidase/metabolismo
7.
Can J Physiol Pharmacol ; 97(5): 429-435, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30661369

RESUMO

The amount of calcium released from the sarcoplasmic reticulum in skeletal muscle rapidly declines during repeated twitch contractions. In this study, we test the hypothesis that caffeine can mitigate these contraction-induced declines in calcium release. Lumbrical muscles were isolated from male C57BL/6 mice and loaded with the calcium-sensitive indicator, AM-furaptra. Muscles were then stimulated at 8 Hz for 2.0 s in the presence or absence of 0.5 mM caffeine, at either 30 °C or 37 °C. The amplitude and area of the furaptra-based intracellular calcium transients and force produced during twitch contractions were calculated. For each of these measures, the values for twitch 16 relative to twitch 1 were higher in the presence of caffeine than in the absence of caffeine at both temperatures. We conclude that caffeine can attenuate contraction-induced diminutions of calcium release during repeated twitch contractions, thereby contributing to the inotropic effects of caffeine.


Assuntos
Cafeína/farmacologia , Cálcio/metabolismo , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Contração Muscular/efeitos dos fármacos , Músculos/efeitos dos fármacos , Músculos/fisiologia , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extremidade Superior
8.
J Fr Ophtalmol ; 42(2): 166-169, 2019 Feb.
Artigo em Francês | MEDLINE | ID: mdl-30679128

RESUMO

Cross-linking (CXL) is a technique whose design aims to achieve a specific goal: to harden the corneal tissue of eyes with a progressive form of keratoconus. Other indications are being investigated, such as treatment of infectious keratitis and prevention of corneal ectasia post corneal ablative refractive surgery. Hardening the cornea means changing its biomechanical properties. The existence of true corneal hardening after CXL would inevitably result in an increase in measured intraocular pressure (IOP). This would have a considerable impact in the screening and follow-up of glaucoma patients who have undergone cross-linking because of the central role of IOP measurement in glaucomatous pathology.


Assuntos
Córnea/efeitos dos fármacos , Reagentes para Ligações Cruzadas/farmacologia , Pressão Intraocular/efeitos dos fármacos , Ceratocone/tratamento farmacológico , Adolescente , Adulto , Fenômenos Biomecânicos/efeitos dos fármacos , Córnea/diagnóstico por imagem , Córnea/fisiologia , Topografia da Córnea , Reagentes para Ligações Cruzadas/uso terapêutico , Feminino , Seguimentos , Glaucoma/diagnóstico , Glaucoma/tratamento farmacológico , Glaucoma/fisiopatologia , Humanos , Ceratocone/diagnóstico , Ceratocone/fisiopatologia , Masculino , Tonometria Ocular , Adulto Jovem
9.
Expert Rev Med Devices ; 16(2): 135-144, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30588868

RESUMO

INTRODUCTION: Intestinal segments are currently used in reconstructive urology to create urinary diversion after cystectomy. Ileal conduit (IC) is the dominant type of urinary diversion. Nevertheless, IC is not an ideal solution as the procedure still requires entero-enterostomy to restore the bowel continuity. This step is a source of relevant complications that might prolong recovery time. Fabrication of artificial urinary conduit is a tempting idea to introduce an alternative form of urinary diversion which might improve cystectomy outcomes. AREAS COVERED: The aim of this review is to discuss available research data about artificial urinary conduit and identify major challenges for future studies. EXPERT OPINION: Fabrication of artificial urinary conduit is in range of current tissue engineering technology but there are still many challenges to overcome. There is an urgent need for studies to be conducted on large animal models with long follow up to expose the limitation of experimental strategies and to gather data for translational research.


Assuntos
Engenharia Tecidual/métodos , Derivação Urinária/tendências , Animais , Materiais Biocompatíveis/farmacologia , Fenômenos Biomecânicos/efeitos dos fármacos , Cistectomia , Humanos , Próteses e Implantes
10.
Lab Chip ; 19(3): 464-474, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30570636

RESUMO

On-chip high-throughput phenotyping of single cells has gained a lot of interest recently due to the discrimination capability of label-free biomarkers such as whole-cell deformability and refractive index. Here we present on-chip refractive index cytometry (RIC) for whole-cell deformability at a high measurement rate. We have further exploited a previously published on-chip optical characterization method which enhances cellular discrimination through the refractive index measurement of single cells. The proposed on-chip RIC can simultaneously probe the cellular refractive index, effective volume and whole-cell deformability while reaching a measurement rate up to 5000 cells per second. Additionally, the relative position of the nucleus inside the cell is reflected by the asymmetry of the measured curve. This particular finding is confirmed by our numerical simulation model and emphasized by a modified cytoskeleton HL-60 cells model. Furthermore, the proposed device discriminated HL-60 derived myeloid cells such as neutrophils, basophils and promyelocytes, which are indistinguishable using flow cytometry. To our knowledge, this is the first integrated device to simultaneously characterize the cellular refractive index and whole-cell deformability, yielding enhanced discrimination of large myeloid cell populations.


Assuntos
Citometria de Fluxo/instrumentação , Dispositivos Lab-On-A-Chip , Fenômenos Mecânicos , Refratometria/instrumentação , Análise de Célula Única/instrumentação , Fenômenos Biomecânicos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Citocalasina B/farmacologia , Células HL-60 , Humanos , Fenômenos Mecânicos/efeitos dos fármacos
11.
J Biomech ; 83: 315-318, 2019 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-30527389

RESUMO

INTRODUCTION: Application of lipopolysaccharide (LPS) is a widely employed model to mimic acute respiratory distress syndrome (ARDS). Available data regarding LPS-induced biomechanical changes on pulmonary epithelial cells are limited only to P. aeruginosa LPS. Considering that LPS from different bacteria could promote a specific mechanical response in epithelial cells, we aim to assess the effect of E. coli LPS, widely employed as a model of ARDS, in the biomechanics of alveolar epithelial cells. METHODS: Young's modulus (E) of alveolar epithelial cells (A549) was measured by atomic force microscopy every 5 min throughout 60 min of experiment after treatment with LPS from E. coli (100 µg/mL). The percentage of cells presenting actin stress fibers (F-actin staining) was also evaluated. Control cells were treated with culture medium and the values obtained were compared with LPS-treated cells for each time-point. RESULTS: Application of LPS induced significant increase in E after 20 min (77%) till 60 min (104%) in comparison to controls. Increase in lung epithelial cell stiffness induced by LPS was associated with a higher number of cells presenting cytoskeletal remodeling. CONCLUSIONS: The observed effects of E. coli LPS on alveolar epithelial cells suggest that this widely-used LPS is able to promote a quick formation of actin stress fibers and stiffening cells, thereby facilitating the disruption of the pulmonary epithelial barrier.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Escherichia coli/química , Lipopolissacarídeos/farmacologia , Fenômenos Mecânicos/efeitos dos fármacos , Células A549 , Células Epiteliais Alveolares/metabolismo , Fenômenos Biomecânicos/efeitos dos fármacos , Humanos
12.
Int J Nanomedicine ; 13: 3609-3623, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29983557

RESUMO

Purpose: This study was designed to evaluate the biocompatibility and osseointegration of polyethylene terephthalate ligament after coating with hydroxyapatite (PET/HA) by using the plasma spraying technique in vitro and in vivo. Methods: In this study, PET/HA sheets were prepared by using the plasma spraying technique. The characterization, the viability of bone marrow stromal cells (BMSCs), and the mRNA expression of bone formation-related genes were evaluated in vitro. The osseointegration in vivo was investigated in the rabbit anterior cruciate ligament (ACL) reconstruction model by micro-computed tomography (micro-CT) analysis, histological evaluation, and biomechanical tests. Results: Scanning electron microscopy (SEM) results showed that the surface of polyethylene terephthalate (PET) becomes rough after spraying with hydroxyapatite (HA) nanoparticles, and the water contact angle was 75.4°±10.4° in the PET/HA-plasma group compared to 105.3°±10.9° in the control group (p<0.05). The cell counting kit-8 counting results showed that the number of BMSCs significantly increased in the PET/HA-plasma group (p<0.05). Reverse transcription polymerase chain reaction (RT-PCR) results showed that there was an upregulated mRNA expression of bone formation-related genes in the PET/HA-plasma group (p<0.05). Micro-CT results showed that the transactional area of tibial tunnels and femoral tunnels was smaller in the PET/HA-plasma group (p<0.05). The histological evaluation scores of the PET/HA-plasma group were significantly superior to those of the PET control group at 8 and 12 weeks (p<0.05). The biomechanical tests showed an increased maximum load to failure and stiffness in the PET/HA-plasma group compared to those in the control group at 8 and 12 weeks. Conclusion: Both in vitro and in vivo results demonstrated in this study suggest that the biocompatibility and osseointegration of PET/HA ligament were significantly improved by increasing the proliferation of cells and upregulating the expression of bone formation-related genes. In a word, the PET/HA-plasma ligament is a promising candidate for ACL reconstruction in future.


Assuntos
Ligamento Cruzado Anterior/efeitos dos fármacos , Materiais Biocompatíveis/farmacologia , Durapatita/farmacologia , Osseointegração/efeitos dos fármacos , Gases em Plasma/química , Polietilenotereftalatos/química , Animais , Ligamento Cruzado Anterior/diagnóstico por imagem , Fenômenos Biomecânicos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Fêmur/cirurgia , Regulação da Expressão Gênica/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Coelhos , Espectrometria por Raios X , Tíbia/efeitos dos fármacos , Tíbia/cirurgia , Água/química , Microtomografia por Raio-X
13.
J Colloid Interface Sci ; 531: 410-420, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30048889

RESUMO

We investigated the biophysical effects (cell elasticity and spring constant) caused on Saos-2 human osteoblast-like cells by nanosized metal (Co and Ti) wear debris, as well as the adhesive characteristics of cells after exposure to the metal nanoparticles. Cell mitochondrial activity was investigated using the MTT assays; along with LDH assay, metal uptake, cell apoptosis and mineralisation output (alizarin red assay) of the cells. Osteoblasts mitochondrial activity was not affected by Ti nanoparticles at concentrations up to 1 mg/ml and by Cobalt nanoparticles at concentrations < 0.5 mg/ml; however elasticity and spring constant were significantly modified by the exposure to nanoparticles of these metals in agreement with the alteration of cell conformation (shape), as result of the exposure to simulated wear debris, demonstrated by fluorescence images after actin staining.


Assuntos
Cobalto/efeitos adversos , Citoesqueleto/efeitos dos fármacos , Nanopartículas Metálicas/efeitos adversos , Mitocôndrias/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Titânio/efeitos adversos , Apoptose/efeitos dos fármacos , Fenômenos Biomecânicos/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Citoesqueleto/metabolismo , Elasticidade/efeitos dos fármacos , Humanos , Prótese Articular/efeitos adversos , Mitocôndrias/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Tamanho da Partícula
14.
J Colloid Interface Sci ; 529: 53-64, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29883930

RESUMO

Despite great innovative and technological promises, nanoparticles (NPs) can ultimately exert an antibacterial activity by affecting the cell envelope integrity. This envelope, by conferring the cell its rigidity and protection, is intimately related to the mechanical behavior of the bacterial surface. Depending on their size, surface chemistry, shape, NPs can induce damages to the cell morphology and structure among others, and are therefore expected to alter the overall mechanical properties of bacteria. Although Atomic Force Microscopy (AFM) stands as a powerful tool to study biological systems, with high resolution and in near physiological environment, it has rarely been applied to investigate at the same time both morphological and mechanical degradations of bacteria upon NPs treatment. Consequently, this study aims at quantifying the impact of the silica NPs (SiO2-NPs) on the mechanical properties of E. coli cells after their exposure, and relating it to their toxic activity under a critical diameter. Cell elasticity was calculated by fitting the force curves with the Hertz model, and was correlated with the morphological study. SiO2-NPs of 100 nm diameter did not trigger any significant change in the Young modulus of E. coli, in agreement with the bacterial intact morphology and membrane structure. On the opposite, the 4 nm diameter SiO2-NPs did induce a significant decrease in E. coli Young modulus, mainly associated with the disorganization of lipopolysaccharides in the outer membrane and the permeation of the underlying peptidoglycan layer. The subsequent toxic behavior of these NPs is finally confirmed by the presence of membrane residues, due to cell lysis, exhibiting typical adhesion features.


Assuntos
Antibacterianos/farmacologia , Elasticidade/efeitos dos fármacos , Escherichia coli/citologia , Escherichia coli/efeitos dos fármacos , Nanopartículas , Dióxido de Silício/farmacologia , Fenômenos Biomecânicos/efeitos dos fármacos , Escherichia coli/ultraestrutura , Infecções por Escherichia coli/microbiologia , Humanos , Microscopia de Força Atômica , Nanopartículas/química , Dióxido de Silício/química
15.
J Chem Phys ; 148(21): 215105, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29884039

RESUMO

DNA intra-strand cross-link (ICL) agents are widely used in the treatment of cancer. ICLs are thought to form a link between the same strand (intra-strand) or complimentary strand (inter-strand) and thereby increase the stability of DNA, which forbids the processes like replication and transcription. As a result, cell death occurs. In this work, we have studied the enhanced stability of a double stranded DNA in the presence of ICLs and compared our findings with the results obtained in the absence of these links. Using atomistic simulations with explicit solvent, a force is applied along and perpendicular to the direction of the helix and we measured the rupture force and the unzipping force of DNA-ICL complexes. Our results show that the rupture and the unzipping forces increase significantly in the presence of these links. The ICLs bind to the minor groove of DNA, which enhance the DNA stabilisation. Such information may be used to design alternative drugs that can stall replication and transcription that are critical to a growing number of anticancer drug discovery efforts.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , DNA/química , Fenômenos Mecânicos , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico/efeitos dos fármacos , Fenômenos Biomecânicos/efeitos dos fármacos
16.
PLoS One ; 13(5): e0196766, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29734349

RESUMO

BACKGROUND: Titanium (Ti)-6Al-4V alloy, which is widely used in spinal instrumentation with a pedicle screw (PS) system. However, significant clinical problems, including loosening and back-out of PSs, persist. During the last decade, a novel technology that produces bioactive Ti from chemical and heat treatments has been reported that induces the spontaneous formation of a hydroxyapatite (HA) layer on the surface of Ti materials. The purpose of this study was to study the effect of bioactivation of Ti-6Al-4V PSs on the ability of HA formation in vitro and its biocompatibility and bone-bonding ability in vivo. METHODS: Ti-6V-4Al alloy PSs were prepared and bioactivated by NaOH-CaCl2-heat-water treatments. The HA-forming ability of bioactive PSs in simulated body fluid (SBF) was evaluated by field emission scanning electron microscopy (FE-SEM) and energy dispersive X-ray analysis (EDX). Six 11-month-old female beagle dogs were used for the in vivo study. Bioactive and control (without bioactivation) PSs were left and right randomly placed from L1 to L6. One and three months after surgery, lumbar spines were removed for biomechanical and histological analyses. RESULTS: In vitro: The surface analysis of bioactive PSs by FE-SEM and EDX showed substantial HA deposits over the entire surface. In vivo: The mean extraction torque was significantly higher for bioactive PSs compared to controls PSs (P<0.01); there was no significant difference in pull-out strength between control and bioactive PSs. Histologically, the contact area between bone tissue and screw surface showed no significant trend to be greater in bioactive PSs compared to control PSs (P = 0.06). CONCLUSIONS: Bioactive PSs prepared by chemical and heat treatments formed layers of HA on the surface of screws in vitro that improved biocompatibility and bonding ability with bone in vivo. Bioactive PSs may reduce screw loosening to overcome the obstacles confronted in spinal instrumentation surgery.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Vértebras Lombares/fisiopatologia , Vértebras Lombares/cirurgia , Ligas/química , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Osso e Ossos/cirurgia , Cães , Durapatita/química , Feminino , Temperatura Alta , Parafusos Pediculares , Estresse Mecânico , Propriedades de Superfície , Titânio/química
17.
Biomed Pharmacother ; 102: 1015-1024, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29710518

RESUMO

Prenylation of bioactive natural compounds has been postulated to be able to enhance the utilization rate and affinity of the compounds with cell membranes, thus promote their bioactivities. Coumestrol, isolated from Medicago sativa, has been known as a phytoestrogen which has bone health benefits. In our previous work, psoralidin, a prenylated coumestrol, was proved to have a higher ability than coumestrol to promote bone formation and to attenuate resorption in vitro. However, it remains to be investigated whether psoralidin will have stronger bone health benefits than coumestrol. In the current study, psoralidin was isolated from Psoralea corylifolia L. and the osteotropic activities of coumestrol and psoralidin were compared in ovariectomized (OVX) rats. Both coumestrol and psoralidin were found to suppress OVX-induced bone loss in vivo, as shown by improved total bone mineral content (t-BMC) or density (t-BMD) and mineral apposition rate, bone biomechanical properties, microstructure and trabecular bone formation, enhanced osteogenic differentiation but suppressed adipogenic differentiation of bone marrow stromal cells (BMSCs), and activation of PI3K/Akt axis and downstream factors such as GSK3ß/ß-catenin and Nrf-2/HO-1. However, psoralidin was shown to have higher activities than coumestrol in the above measurements/indices. Our findings demonstrate that psoralidin, as a novel anti-osteoporosis candidate, could suppress bone loss in OVX rats and have better osteoprotective effects than coumestrol, which may be related to the presence of the isopentenyl group in psoralidin.


Assuntos
Benzofuranos/farmacologia , Cumarínicos/farmacologia , Cumestrol/química , Cumestrol/farmacologia , Osteogênese/efeitos dos fármacos , Pentanos/química , Fosfatidilinositol 3-Quinases/metabolismo , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adipogenia/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Benzofuranos/química , Biomarcadores/sangue , Biomarcadores/urina , Fenômenos Biomecânicos/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Calcificação Fisiológica , Cumarínicos/química , Estradiol/farmacologia , Feminino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Minerais/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/enzimologia , Ovariectomia , Oxirredução , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fosfatase Ácida Resistente a Tartarato/metabolismo , Útero/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos
18.
Ophthalmic Res ; 60(2): 100-108, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29804113

RESUMO

PURPOSE: Studying genipin variable concentrations, treatment durations, and delivery methods as a substance to increase corneal stiffness by inducing corneal collagen cross-linking (CXL). MATERIALS AND METHODS: 100 bovine corneas treated with different genipin concentrations (0.1, 0.5, and 1%) and treatment durations (15 min, 40 min, 2 h, and 3 days) through different delivery methods compared to 10 controls treated with riboflavin/UV. Histology examination, enzymatic digestion with collagenase and thermal differential scanning calorimetry were performed on the different samples. RESULTS: Bovine corneas soaked in 0.5% genipin morphologically showed 4.7% CXL in comparison to 5.6% in controls (p < 0.05). Corneas treated with topical 0.5% genipin, by a 140-µL drop applied hourly for 2 h, showed 7% corneal CXL. Corneas treated with topical genipin 0.5% for 30 min, 1 and 2 h showed 54 ± 6, 40 ± 7, and 39 ± 9% enzymatic degradation, respectively, in comparison to controls (74%). Corneas treated with 0.5% genipin for 1, 2, and 8 h showed higher thermal denaturation resistance (Td values of 64.9 ± 0.3, 64.7 ± 0.0 and 67.3 ± 0.9), respectively, in comparison to the control group (64.6 ± 0.5) (p < 0.05). CONCLUSIONS: Genipin 0.5%, in a 140-µL drop applied hourly for 2 h, showed better potential to enhance corneal stiffness and stability through inducing CXL.


Assuntos
Córnea/efeitos dos fármacos , Reagentes para Ligações Cruzadas/farmacologia , Iridoides/farmacologia , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Bovinos , Colágeno/metabolismo , Reagentes para Ligações Cruzadas/administração & dosagem , Iridoides/administração & dosagem , Modelos Animais , Fatores de Tempo , Raios Ultravioleta
19.
PLoS One ; 13(4): e0195261, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29634740

RESUMO

Bone-to-bone integration can be obtained by osteoconductive ceramics such as hydroxyapatite (HAp) and beta-tricalcium phosphate (ß-TCP), but cartilage-to-cartilage integration is notoriously difficult. Many cartilage repair therapies, including microfracture and mosaicplasty, capitalize on the reparative aspects of subchondral bone due to its resident population of stem cells and vascularity. A strategy of incorporating tissue engineered neocartilage into a ceramic to form an osteochondral construct may serve as a suitable alternative to achieve cartilage graft fixation. The use of a tissue engineered osteochondral construct to repair cartilage defects may also benefit from the ceramic's proximity to underlying bone and abundant supply of progenitor cells and nutrients. The objective of the first study was to compare HAp and ß-TCP ceramics, two widely used ceramics in bone regeneration, in terms of their ability to influence neocartilage interdigitation at an engineered osteochondral interface. Additional assays quantified ceramic pore size, porosity, and compressive strength. The compressive strength of HAp was six times higher than that of ß-TCP due to differences in porosity and pore size, and HAp was thus carried forward in the second study as the composition with which to engineer an osteochondral construct. Importantly, it was shown that incorporation of the HAp ceramic in conjunction with the self-assembling process resulted in functionally viable neocartilage. For example, only collagen/dry weight and ultimate tensile strength of the chondral control constructs remained significantly greater than the neocartilage cut off the osteochondral constructs. By demonstrating that the functional properties of engineered neocartilage are not negatively affected by the inclusion of an HAp ceramic in culture, neocartilage engineering strategies may be directly applied to the formation of an osteochondral construct.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Fosfatos de Cálcio/farmacologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/fisiologia , Durapatita/farmacologia , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Cartilagem Articular/citologia , Ovinos
20.
J Drugs Dermatol ; 17(4): 442-450, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29601621

RESUMO

BACKGROUND: This split-face, controlled study investigated the ability of a topical crosslinked hyaluronic acid formulation (RHA serum) to enhance clinical results from fillers, microneedling, or chemical peeling of aging skin. Previous comparative skin explant studies demonstrated greater efficacy of RHA serum than topical non-crosslinked high or low molecular weight hyaluronic acid in decreasing trans-epidermal water loss, increasing epidermal hydration, and improving corneocyte microstructure. METHODS: 24 female subjects aged 35 to 55 were enrolled. 8 received intradermal hyaluronic acid filler injection, 8 received microneedling, and 8 received superficial mandelic acid chemical peeling. Subjects initiated twice-daily, standardized application of RHA serum to one side of the face 2 days after the procedure. Topographical imaging, bioinstrumental, and blinded clinical evaluations were performed at days 0, 14, and 28. RESULTS: Areas treated with RHA serum showed statistically significant improvements in skin surface topography and hydration compared to untreated areas. Blinded investigator scoring showed greater improvement of RHA serum-treated skin in moisture, tone/complexion, radiance, texture, uniformity, and global appearance. Subjects' questionnaire responses correlated with these findings. Subjects expressed greater satisfaction with appearance of the treated hemiface. No adverse events were observed during the study. CONCLUSIONS: When initiated post-procedurally, topical RHA serum was well-tolerated and enhanced biomechanical properties, quality, and clinical appearance of the skin. Based on these data, RHA serum may be of value in improving patient outcomes and satisfaction following minimally invasive aesthetic procedures. The availability of the same hyaluronic acid technology also as a cohesive, tissue-integrating injectable filler enables synergistic, multi-level treatment plans to be devised.

J Drugs Dermatol. 2018;17(4):442-450.

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Assuntos
Reagentes para Ligações Cruzadas/administração & dosagem , Elasticidade/efeitos dos fármacos , Ácido Hialurônico/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/patologia , Creme para a Pele/administração & dosagem , Administração Cutânea , Adulto , Fenômenos Biomecânicos/efeitos dos fármacos , Abrasão Química/métodos , Reagentes para Ligações Cruzadas/química , Feminino , Humanos , Ácido Hialurônico/química , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Creme para a Pele/química
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