RESUMO
Proteins can self-assemble into a range of nanostructures as a result of molecular interactions. Amyloid nanofibrils, as one of them, were first discovered with regard to the relevance of neurodegenerative diseases but now have been exploited as building blocks to generate multiscale materials with designed functions for versatile applications. This review interconnects the mechanism of amyloid fibrillation, the current approaches to synthesizing amyloid protein-based materials, and the application in bioplastic development. We focus on the fundamental structures of self-assembled amyloid fibrils and how external factors can affect protein aggregation to optimize the process. Protein self-assembly is essentially the autonomous congregation of smaller protein units into larger, organized structures. Since the properties of the self-assembly can be manipulated by changing intrinsic factors and external conditions, protein self-assembly serves as an excellent building block for bioplastic development. Building on these principles, general processing methods and pathways from raw protein sources to mature state materials are proposed, providing a guide for the development of large-scale production. Additionally, this review discusses the diverse properties of protein-based amyloid nanofibrils and how they can be utilized as bioplastics. The economic feasibility of the protein bioplastics is also compared to conventional plastics in large-scale production scenarios, supporting their potential as sustainable bioplastics for future applications.
Assuntos
Proteínas Amiloidogênicas , Nanoestruturas , Amiloide/química , Nanoestruturas/química , BiopolímerosRESUMO
The emerging applications of hydrogel materials at different length scales, in areas ranging from sustainability to health, have driven the progress in the design and manufacturing of microgels. Microgels can provide miniaturized, monodisperse, and regulatable compartments, which can be spatially separated or interconnected. These microscopic materials provide novel opportunities for generating biomimetic cell culture environments and are thus key to the advances of modern biomedical research. The evolution of the physical and chemical properties has, furthermore, highlighted the potentials of microgels in the context of materials science and bioengineering. This review describes the recent research progress in the fabrication, characterization, and applications of microgels generated from biomolecular building blocks. A key enabling technology allowing the tailoring of the properties of microgels is their synthesis through microfluidic technologies, and this paper highlights recent advances in these areas and their impact on expanding the physicochemical parameter space accessible using microgels. This review finally discusses the emerging roles that microgels play in liquid-liquid phase separation, micromechanics, biosensors, and regenerative medicine.
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Microgéis , Materiais Biocompatíveis/química , Hidrogéis/química , Microfluídica , Medicina RegenerativaRESUMO
PURPOSE: We present our experience with transoral segmental mandibulectomy, in conjunction with vascularized osseous mandibular reconstruction, utilizing an intraoral anastomosis and free of extraoral incisions. Virtual surgical planning and intraoperative navigation were used to help achieve this minimally invasive and scar-free approach. METHODS: A retrospective study was performed on 9 patients who underwent transoral segmental mandibulectomy followed by vascularized osseous reconstruction using an intraoral anastomosis between January 2018 and October 2018. The anastomotic recipient vessels were the facial artery and vein. The outcome variable was defined as the flap survival. Postoperative panoramic radiographs and computed tomography images were obtained for assessment of the neo-mandible. In addition, we performed a cadaver dissection to highlight relevant anatomic details of the facial artery and vein. RESULTS: Successful transoral segmental mandibulectomy was achieved in 9 patients, with an intraoral anastomosis successfully achieved in 8 patients. In one patient, an extraoral anastomosis was required because of challenging facial vein anatomy. Both recipient and donor sites healed uneventfully with a 100% successful rate of flap survival. In all cases, a well-positioned neo-mandible with good occlusion was demonstrated on postoperative imaging and examination. A symmetric facial appearance with no restrictions in mouth opening was also achieved in each case. In our cadaver dissection, we describe the anatomical course of the facial artery and vein. An average angle of 30° between these vessels is identified. CONCLUSIONS: Transoral segmental mandibulectomy combined with intraoral microvascular mandibular reconstruction is a surgically achievable technique with the benefit of being scar free.
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Retalhos de Tecido Biológico , Neoplasias Mandibulares , Reconstrução Mandibular , Procedimentos de Cirurgia Plástica , Transplante Ósseo/métodos , Cadáver , Cicatriz , Retalhos de Tecido Biológico/cirurgia , Humanos , Neoplasias Mandibulares/cirurgia , Osteotomia Mandibular/métodos , Reconstrução Mandibular/métodos , Estudos RetrospectivosRESUMO
BACKGROUND: Uncontrollable bleeding after tooth extraction usually occurs in patients with coagulation diseases, including hemophilia, von Willebrand's disease, vitamin K deficiency, platelet deficiency, and taking anticoagulant drugs. Hemophilia A is an X-linked recessive disorder caused by insufficiency of coagulation factor VIII. Mild hemophilia, defined by factor level between 0.05 and 0.40 IU/mL, is characterized by uncontrollable hemorrhage after trauma or invasive operations. Some mild hemophiliacs may remain undiagnosed until late adulthood. Therefore, surgical management of these patients may be relatively neglected. These case reports describe two uncontrollable bleeding patients with unknown mild hemophilia A after tooth extraction. CASE PRESENTATION: This paper reports 2 cases of persistent bleeding after tooth extraction under local anesthesia which could not be completely stopped by routine treatments. Both of them denied prior illness and injury, allergies, anticoagulant medication history, systemic and family illness. The APTT and other coagulation screening tests of the two patients before surgery were normal. Finally, they were diagnosed with mild hemophilia A via coagulation factor assays. The patients acquired complete hemostasis by receiving coagulation factor supplement therapy in hematologic department. CONCLUSION: Mild hemophilia is marked by subclinical, asymptomatic and even normal coagulation test results. The purpose of these case reports is to bring dental professionals' attention that APTT test alone cannot be used to exclude mild hemophilia, and provide reasonable evaluation and treatment procedures of bleeding patients after tooth extraction.
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Hemofilia A , Doenças de von Willebrand , Adulto , Plaquetas , Hemofilia A/complicações , Hemofilia A/diagnóstico , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Extração Dentária/efeitos adversos , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/tratamento farmacológicoRESUMO
BACKGROUND: Fibular flaps have been widely used for mandibular and maxillary reconstructions. On occasion, anatomical variants of fibular arteries (FA) will be encountered. PURPOSE: Although anatomical variants of FA during fibular harvest have been reported, controversy exists regarding whether simple color Doppler ultrasonography (CDU) and physical examinations (PE) are sufficient for early preoperative detection. MATERIAL AND METHODS: A 10-year retrospective analysis in our department was performed to find the patients with various FA anomalies confirmed by computed tomography angiography (CTA) or intraoperative findings. RESULTS: A total number of 19 FA anomalies were found either pre- or intraoperatively in 16 patients, in whom three cases were with bilateral FA variants. Type IIIC variants, also called arteria peronea magna (great peroneal artery), were confirmed in two legs, while the majority (13 legs) had type IIIA hypoplastic/aplastic posterior tibialis arteries (PTA). Four legs had new type IIID (low FA and PTA bifurcations). Preoperative CDU and PE only suspected anomalies in two legs. Six cases proceeded with using the affected fibulas, within whom vascular grafts were used in half of them for lengthening the FA pedicle. Local ischemia, partial soleus muscle necrosis, and claudication were reported in one. CONCLUSIONS: Routine CTA before every fibular harvest, rather than simple PE and CDU, should be added for screening contraindications and ensuring safety for fibular flap harvest.
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Artérias/anormalidades , Angiografia por Tomografia Computadorizada , Fíbula/cirurgia , Perna (Membro)/irrigação sanguínea , Exame Físico , Ultrassonografia Doppler em Cores , Adulto , Idoso , Artérias/diagnóstico por imagem , Contraindicações de Procedimentos , Feminino , Fíbula/irrigação sanguínea , Humanos , Masculino , Reconstrução Mandibular , Maxila/cirurgia , Pessoa de Meia-Idade , Artéria Poplítea/anormalidades , Artéria Poplítea/diagnóstico por imagem , Cuidados Pré-Operatórios , Procedimentos de Cirurgia Plástica , Estudos Retrospectivos , Retalhos Cirúrgicos , Artérias da Tíbia/anormalidades , Artérias da Tíbia/diagnóstico por imagemRESUMO
3D scaffolds in the form of hydrogels and microgels have allowed for more native cell-culture systems to be developed relative to flat substrates. Native biological tissues are, however, usually spatially inhomogeneous and anisotropic, but regulating the spatial density of hydrogels at the microscale to mimic this inhomogeneity has been challenging to achieve. Moreover, the development of biocompatible synthesis approaches for protein-based microgels remains challenging, and typical gelation conditions include UV light, extreme pH, extreme temperature, or organic solvents, factors which can compromise the viability of cells. This study addresses these challenges by demonstrating an approach to fabricate protein microgels with controllable radial density through microfluidic mixing and physical and enzymatic crosslinking of gelatin precursor molecules. Microgels with a higher density in their cores and microgels with a higher density in their shells are demonstrated. The microgels have robust stability at 37 °C and different dissolution rates through enzymolysis, which can be further used for gradient scaffolds for 3D cell culture, enabling controlled degradability, and the release of biomolecules. The design principles of the microgels could also be exploited to generate other soft materials for applications ranging from novel protein-only micro reactors to soft robots.
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Microfluídica , Microgéis , Técnicas de Cultura de Células , Gelatina , HidrogéisRESUMO
Although homeoproteins Msx1 and Msx2, the cell-specific transcription regulators, have been proven to play multiple roles in the embryogenesis of bone, muscle and tooth, the functions and mechanisms of Msx1 and Msx2 in the development of the central nervous system of mice after birth are not clear because of the death of Msx1 and Msx1/2 germline-deleted embryo at late gestation of mouse. In current research, Nestin-Cre mice was introduced to generate the central nervous system-specific knockout mice (Nestin-Cre;Msx1,Msx2fl/fl). We found that besides the falling of the body mass and the brain volume, the cortical tissue sections and staining showed the decreasing thickness of layer II-IV and declining number of vertebral cells in layer V resulting from Msx1/2 deletion. In addition, electrophysiological tests revealed the aberrant action potential parameters of deep pyramidal neurons in Nestin-Cre;Msx1,2â¯fl/fl mice, which may be related with the ethology impairment displayed in further experiments. We discovered Nestin-Cre;Msx1,2â¯fl/fl mice had severe impairment in their athletic ability and kinematic learning ability in rotate test, and exhibited hyperactivity in open-field test. Above all, our results revealed that deletion of homeoproteins Msx1 and Msx2 could lead to behavioral disorders and suggested that Msx1 and Msx2 played a crucial role in regulating the development and function of the neocortex. In addition, our current research provided a new mouse model for understanding the pathogenesis of human central nervous system disease.
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Deleção de Genes , Proteínas de Homeodomínio/genética , Fator de Transcrição MSX1/genética , Neocórtex/patologia , Neurônios/patologia , Potenciais de Ação , Animais , Fenômenos Biomecânicos , Camundongos , Camundongos Knockout , Neocórtex/anormalidades , Neocórtex/metabolismo , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Neurônios/metabolismo , Condicionamento Físico AnimalRESUMO
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Efficient tumor accumulation and body clearance are two paralleled requirements for ideal nanomedicines. However, it is hard for both to be met simultaneously. The inefficient clearance often restrains the application of drug delivery systems (DDSs), especially for high-dosage administration. In this study, the star-like and block structures are combined to enhance the tumor specific targeting of the parent structures and obtain additional renal excretion property. The influences of polymer architectures and chemical compositions on the physicochemical and biological properties, particularly the simultaneous achievement of tumor accumulation and renal clearance, have been investigated. Among the tested conjugates, an eight-arm triblock star polymer based on poly(ethylene glycol) (PEG) and poly( N-(2-hydroxyl) methacrylamide) (PHPMA) is found to simultaneously fulfill the requirements of superior tumor accumulation and efficient renal clearance due to the appropriate micelle size and reversible aggregation process. On the basis of this conjugate, 60 mg/kg of Dox equivalent (much higher than the maximum tolerated dose (MTD) of Dox) can be administered to efficiently suppress tumor growth without causing any obvious toxicity. This work provides a new approach to design polymer-drug conjugates for tumor specific application, which can simultaneously address the efficacy and safety concerns.
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Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Nanoconjugados/química , Acrilamidas/química , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacocinética , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Nanoconjugados/efeitos adversos , Polietilenoglicóis/química , Eliminação Renal , Distribuição TecidualRESUMO
Poly(ethylene glycol) (PEG) shell-sheddable micelles are proved to be effective tools for rapid intracellular drug delivery. However, some adverse factors, such as the potential immunogenicity and the accelerated blood clearance, might be accompanied with the traditional PEG sheddable micelles. Here, a poly(N-2-hydroxypropyl methacrylamide) (PHPMA) sheddable block copolymer containing disulfide bonds on the main chain is prepared to form pH- and reduction-dual-responsive micelles. The most optimal synthetic route of the block copolymer is selected from three potential pathways. Doxorubicin is loaded via an acid-labile hydrazone bond to achieve high drug loading content and to prevent premature drug release. As expected, as-prepared shell-sheddable micelles exhibit faster intracellular drug release and more satisfactory in vitro anticancer efficacy than the nonsheddable counterpart did. This design provides a feasible guideline for the efficient synthesis of similar shell-sheddable micelles consisting of PHPMA coatings.
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Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Polímeros/síntese química , Sobrevivência Celular/efeitos dos fármacos , Dissulfetos/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Células HeLa/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Metacrilatos/síntese química , Metacrilatos/química , Metacrilatos/farmacologia , Micelas , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polímeros/química , Polímeros/farmacologiaRESUMO
The demand for complete dentures is expected to increase worldwide, but complete dentures are mainly designed and fabricated manually involving a broad series of clinical and laboratory procedures. Therefore, the quality of complete dentures largely depends on the skills of the dentist and technician, leading to difficulty in quality control. Computer-aided design and manufacturing (CAD/CAM) has been used to design and fabricate various dental restorations including dental inlays, veneers, crowns, partial crowns, and fixed partial dentures (FPDs). It has been envisioned that the application of CAD/CAM technology could reduce intensive clinical/laboratory work for the fabrication of complete dentures; however, CAD/CAM is seldom used to fabricate complete dentures due to the lack of suitable CAD software to design virtual complete dentures although the CAM techniques are in a much advanced stage. Here we report the successful design of virtual complete dentures using CAD software of 3Shape Dental System 2012, which was developed for designing fixed prostheses instead of complete dentures. Our results demonstrated that complete dentures could be successfully designed by the combination of two modeling processes, single coping and full anatomical FPD, available in the 3Shape Dental System 2012.
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Desenho Assistido por Computador , Planejamento de Dentadura/métodos , Prótese Total , Desenho Assistido por Computador/instrumentação , Técnica de Fundição Odontológica , Planejamento de Dentadura/instrumentação , Humanos , Ajuste Oclusal/métodos , SoftwareRESUMO
Biofilms are antibiotic-resistant, sessile bacterial communities that occupy most moist surfaces on Earth and cause chronic and medical device-associated infections. Despite their importance, basic information about biofilm dynamics in common ecological environments is lacking. Here, we demonstrate that flow through soil-like porous materials, industrial filters, and medical stents dramatically modifies the morphology of Pseudomonas aeruginosa biofilms to form 3D streamers, which, over time, bridge the spaces between obstacles and corners in nonuniform environments. We discovered that accumulation of surface-attached biofilm has little effect on flow through such environments, whereas biofilm streamers cause sudden and rapid clogging. We demonstrate that flow-induced shedding of extracellular matrix from surface-attached biofilms generates a sieve-like network that captures cells and other biomass, which add to the existing network, causing exponentially fast clogging independent of growth. These results suggest that biofilm streamers are ubiquitous in nature and strongly affect flow through porous materials in environmental, industrial, and medical systems.
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Biofilmes/crescimento & desenvolvimento , Contaminação de Equipamentos , Pseudomonas aeruginosa/fisiologia , Membranas Artificiais , PorosidadeRESUMO
OBJECTIVE: The aim of authors' study was to present their 10-year experience in the treatment of giant ossifying fibroma (GOF), and to prove if GOF can be totally excised preventing recurrence. The authors' secondary goal was to study the aesthetic and functional outcomes after radical resection of GOF followed by immediate reconstruction. METHODS: Eighteen patients who underwent radical ablative surgery of GOF of the jaw followed by immediate reconstruction with vascularized fibula flap or ilium flap between May 2003 and May 2013 were taken. Recurrence rate was statistically observed and 2-year postoperative aesthetic and functional outcomes were evaluated. RESULTS: The average length of follow-up was 4.5 years. There was no residual tumor or tumor recurrence observed in any patient during the mean follow-up of 4.5 years, and good cosmesis and functional outcome was noted after ablative surgery of GOF followed by computer-assisted reconstruction. CONCLUSIONS: For giant OF, if it is mainly located in the jaws without invasion of the skull base and/or pterygoid process, radical surgical treatment should be performed for prevention of tumor recurrence. And good aesthetic and functional results can be achieved by immediate computer-assisted reconstruction and dental rehabilitation.
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Fibroma Ossificante/cirurgia , Neoplasias Mandibulares/cirurgia , Osteotomia Mandibular , Neoplasias Maxilares/cirurgia , Osteotomia Maxilar/métodos , Adolescente , Adulto , Feminino , Fibroma Ossificante/diagnóstico por imagem , Seguimentos , Humanos , Imageamento Tridimensional , Masculino , Neoplasias Mandibulares/diagnóstico por imagem , Neoplasias Maxilares/diagnóstico por imagem , Pessoa de Meia-Idade , Cirurgia Assistida por Computador , Tomografia Computadorizada por Raios X , Interface Usuário-Computador , Adulto JovemRESUMO
PURPOSE: Posterior tibial slope that is created during proximal tibial resection in total knee arthroplasty has emerged as an important factor in the mechanics of the knee joint and the surgical outcome. But the ideal degree of posterior tibial slope for recovery of the knee joint function and preventions of complications remains controversial and should vary in different racial groups. The objective of this paper is to investigate the effects of posterior tibial slope on contact stresses in the tibial polyethylene component of total knee prostheses. METHODS: Three-dimensional finite element analysis was used to calculate contact stresses in tibial polyethylene component of total knee prostheses subjected to a compressive load. The 3D finite element model of total knee prosthesis was constructed from the images produced by 3D scanning technology. Stresses in tibial polyethylene component were calculated with four different posterior tibial slopes (0°, 3°, 6° and 9°). RESULTS: The 3D finite element model of total knee prosthesis we presented was well validated. We found that the stress distribution in the polythene as evaluated by the distributions of the von Mises stress, the maximum principle stress, the minimum principle stress and the Cpress were more uniform with 3° and 6° posterior tibial slopes than with 0° and 9° posterior tibial slopes. Moreover, the peaks of the above stresses and trends of changes with increasing degree of knee flexion were more ideal with 3° and 6° posterior slopes. CONCLUSIONS: The results suggested that the tibial component inclination might be favourable to 7°-10° so far as the stress distribution is concerned. The range of the tibial component inclination also can decrease the wear of polyethylene. Chinese posterior tibial slope is bigger than in the West, and the current domestic use of prostheses is imported from the West, so their demands to tilt back bone cutting can lead to shorten the service life of prostheses; this experiment result is of important clinical significance, guiding orthopaedic surgeon after the best angle to cut bone.
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Artroplastia do Joelho , Articulação do Joelho/cirurgia , Tíbia/cirurgia , Materiais Biocompatíveis , Análise de Elementos Finitos , Humanos , Imageamento Tridimensional , Articulação do Joelho/fisiopatologia , Prótese do Joelho , Polietileno , Falha de Prótese , Estresse Mecânico , Tíbia/fisiopatologiaRESUMO
BACKGROUND: Bone marrow cell profiles are variable after total hip arthroplasty (THA), including variable levels of Stro-1+ and bone morphogenetic protein receptor (BMPRs)+ cells. We investigated the impact of bone marrow cell profiles on changes in periprosthetic bone mineral density (BMD) in uncemented THA patients. MATERIAL AND METHODS: Bone marrow aspirates were collected from the metaphyseal region of discarded femoral heads from 24 consecutive THA patients (12 men and 12 women; mean age 66.7 ± 11.0 years; range 52-87 years) treated from March 2009 to March 2011 at a single facility. Perioperative proportions of Stro-1+ and BMPR+ cells in femoral heads were assessed by flow cytometry. Follow-up examined the proximal femur Gruen zones R1 and R7 at 1 week and at 3, 6, and 12 months after THA, using dual-energy X-ray absorptiometry. Associations between BMD loss and age, gender, BMPRs+, and Stro-1+ were analyzed. RESULTS: At 3 months, R1 and R7 BMD decreased by 4.4% and 6.4%, respectively (P<0.05). At 12 months, the overall BMD decreases in R1 and R7 were 10.2% and 1%, respectively (P<0.05). Higher Stro-1+ cells proportion predicted R7 BMD increases at all time points (P<0.05) and R1 BMD increases at 6 and 12 months (P<0.05). BMPR1a+ proportion was associated with BMD increases at 6 months in the R1 region. BMPR2+ was not significantly associated with BMD (P>0.05). CONCLUSIONS: Elevated Stro-1+ bone marrow cell profile may be a useful prognostic indicator for uncemented THA patients.
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Antígenos de Superfície/metabolismo , Artroplastia de Quadril , Cimentos Ósseos/uso terapêutico , Densidade Óssea , Células da Medula Óssea/metabolismo , Cuidados Pós-Operatórios , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Células da Medula Óssea/patologia , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Feminino , Fêmur/diagnóstico por imagem , Fêmur/patologia , Prótese de Quadril , Humanos , Masculino , Pessoa de Meia-Idade , Células Estromais/metabolismo , Células Estromais/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Aseptic loosening (AL) is a major complication of total joint replacement. Recent approaches to limiting AL have focused on inhibiting periprosthetic inflammation and osteoclastogenesis. QUESTIONS/PURPOSES: The purpose of this study was to determine the effects of erythromycin (EM) on polymethylmethacrylate (PMMA) particle-challenged MC3T3 osteoblast precursor cells. MetHODS: MC3T3 cells were pretreated with EM (0-10 µg/mL) and then stimulated with PMMA (1 mg/mL). Cell viability was evaluated by both a lactate dehydrogenase (LDH) release assay and cell counts. Cell differentiation was determined by activity of alkaline phosphatase (ALP). Gene expression was measured via real-time quantitative RT-PCR. RESULTS: We found that exposure to PMMA particles reduced cellular viability and osteogenetic potential in MC3T3 cell line. EM treatment mitigated the effects of PMMA particles on the proliferation, viability and differentiation of MC3T3 cells. PMMA decreased the gene expression of Runx2, osterix and osteocalcin, which can be partially restored by EM treatment. Furthermore, EM suppressed PMMA- induced increase of NF-κB gene expression. CONCLUSIONS: These data demonstrate that EM mitigates the effects of PMMA on MC3T3 cell viability and differentiation, in part through downregulation of NF-κB pathway. EM appeared to represent an anabolic agent on MC3T3 cells challenged with PMMA particles.
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Movimento Celular/efeitos dos fármacos , Eritromicina/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Polimetil Metacrilato/farmacologia , Células 3T3 , Fosfatase Alcalina/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Lactato Desidrogenases/metabolismo , Camundongos , Osteoblastos/citologia , Osteogênese/efeitos dos fármacos , Osteogênese/genéticaRESUMO
OBJECTIVE: To study Chinese medicine (CM) syndrome types of chronic aplastic anemia (CAA) patients and the distribution laws of typical CM symptoms in different genders. METHODS: From June 2002 to June 2012, 220 CAA outpatients/inpatients at Department of Hematology, Zhejiang Chinese Medical Hospital were recruited. Patients' symptoms and signs, as well as four diagnostic information at the first onset were collected. CM syndrome differentiation was performed. The syndrome types and typical symptoms were analyzed. RESULTS: (1) In the 220 CAA patients, there were 121 cases of Shen yang deficiency syndrome (55.0%), 18 of Shen yin deficiency syndrome type (8.18%), 81 cases of Shen yin-yang deficiency syndrome (36.82%). (2) The distribution of typical symptoms: fatigue and shortness of breath (77.12% males and 73.53% females), pale complexion (64.41% males and 57.84% females), low temperature of four limbs (12.71% males and 26.47% females), spontaneous perspiration and night sweating (32.20% males and 26.47% females), dry mouth and throat (6.78% males and 6.86% females), feverish feelings in palms and soles (14.41% males and 20.59% females), loose stool (6.78% males and 2.94% females), petechiae and ecchymosis (42.37% males and 43.14% females). CONCLUSIONS: Shen yang deficiency syndrome was most often seen in CAA patients at the initial diagnosis, followed by Shen yin-yang deficiency syndrome. Shen yin deficiency syndrome was the least seen. In CM symptoms, fatigue and shortness of breath were most common seen, followed by pale complexion, skin petechia and ecchymosis.
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Anemia Aplástica/diagnóstico , Medicina Tradicional Chinesa/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Deficiência da Energia Yang/diagnóstico , Deficiência da Energia Yin/diagnóstico , Adulto JovemRESUMO
PURPOSE: To explore the cytotoxic effect of a menthol-favored E-liquid on human periodontal ligament stem cells (hPDLSCs), as well as the underlying mechanism of electronic cigarette (E-cig)-induced cell apoptosis. METHODS: PDLSCs were isolated and cultured from periodontal ligament tissues of healthy premolars extracted for orthodontic reasons. Cells in passage 3 were used to detect the surface markers of stem cells by flow cytometry. Then the cells were exposed to different doses of menthol-favored E-liquid (at 59 mg/L nicotine concentration) in the culture median (the final nicotine concentrations were 0.1 µg/mL, 1.0 µg/mL, 10 µg/mL, 50 µg/mL, 0.1 mg/mL, 0.2 mg/mL and 0.5 mg/mL, respectively) for different period of times (24, 48 and 72 h). The cell viability was analyzed by CCK-8 assay. Cell apoptosis was evaluated by flow cytometry (7-AAD and Annexin V staining) and TUNEL assay. Reactive oxygen species (ROS) production was detected with fluorescence probe DCFH-DA by confocal microscopy and flow cytometry. The protein expression levels associated with ROS/JNK/caspase 3 axis(p-JNK, JNK, c-Jun, p-c-Jun, Bcl-2, Bax and cleaved-caspase 3) were analyzed by Western blot. Immunocytofluorescense staining was applied to evaluate the expression level of p-JNK. After addition of NAC, a ROS scavenger, and MAPK/JNK specific blocker SP600125, their effects on E-cig-induced cell apoptosis were evaluated. Statistical analysis was performed with Graph Pad 5.0 software package. RESULTS: Human PDLSCs were successfully isolated and cultured and flow cytometry assay showed the mesenchymal stem cell surface biomarkers (CD73, CD90 and CD105) were positively expressed. CCK8 assay indicated cell viability was significantly(Pï¼0.001) different among all concentration groups at various time points (24, 48 or 72 h), and the difference in apoptosis rate among all concentration groups was also statistically significant (Pï¼0.001). After exposure to E-liquid with nicotine concentration ≥50 µg/mL, cell viability was significantly reduced, and the proportion of apoptotic cells and the cellular ROS level was significantly increased in a dose-dependent manner as compared with the control group(0.0 mg/mL). Western blot assay showed E-cig exposure could promote MAPK/JNK phosphorylation in a dose-dependent and time-dependent manner. Either NAC or SP600125 could partially rescue the E-cig-induced cell apoptosis via reversing up-regulation of p-JNK and cleaved caspase 3. CONCLUSIONS: ROS/JNK/caspase 3 axis is involved in menthol-favored E-liquid-induced apoptosis of hPDLSCs.
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Antracenos , Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Caspase 3/metabolismo , Caspase 3/farmacologia , Mentol/farmacologia , Ligamento Periodontal/metabolismo , Nicotina/efeitos adversos , Apoptose , Células-Tronco/metabolismoRESUMO
Tympanic membrane perforation (TMP) is prevalent in clinical settings. Patients with TMPs often suffer from infections caused by Staphylococcus aureus and Pseudomonas aeruginosa, leading to middle ear and external ear canal infections, which hinder eardrum healing. The objective of this study is to fabricate an enzyme-responsive antibacterial electrospun scaffold using poly(lactic-co-glycolic acid) and hyaluronic acid for the treatment of infected TMPs. The properties of the scaffold were characterized, including morphology, wettability, mechanical properties, degradation properties, antimicrobial properties, and biocompatibility. The results indicated that the fabricated scaffold had a core-shell structure and exhibited excellent mechanical properties, hydrophobicity, degradability, and cytocompatibility. Furthermore, in vitro bacterial tests and ex vivo investigations on eardrum infections suggested that this scaffold possesses hyaluronidase-responsive antibacterial properties. It may rapidly release antibiotics when exposed to the enzyme released by S. aureus and P. aeruginosa. These findings suggest that the scaffold has great potential for repairing TMPs with infections.
Assuntos
Antibacterianos , Ácido Hialurônico , Hialuronoglucosaminidase , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Pseudomonas aeruginosa , Staphylococcus aureus , Alicerces Teciduais , Membrana Timpânica , Antibacterianos/farmacologia , Antibacterianos/química , Hialuronoglucosaminidase/metabolismo , Hialuronoglucosaminidase/química , Staphylococcus aureus/efeitos dos fármacos , Alicerces Teciduais/química , Pseudomonas aeruginosa/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Animais , Humanos , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacologia , Ácido Láctico/química , Ácido Láctico/farmacologia , Perfuração da Membrana Timpânica/tratamento farmacológico , Perfuração da Membrana Timpânica/terapia , Testes de Sensibilidade MicrobianaRESUMO
Fabrication of sustainable bio-based malleable thermosets (BMTs) with excellent mechanical properties and reprocessing ability for applications in electronic devices has attracted more and more attention but remains significant challenges. Herein, the BMTs with excellent mechanical robustness and reprocessing ability were fabricated via integrating with radical polymerization and Schiff-base chemistry, and employed as the flexible substrate to prepare the capacitive sensor. To prepare the BMTs, an elastic bio-copolymer derived from plant oil and 5-hydroxymethylfurfural was first synthesized, and then used to fabricate the dynamic crosslinked BMTs through Schiff-base chemistry with the amino-modified cellulose and polyether amine. The synergistic effect of rigid cellulose backbone and the construction of dynamic covalent crosslinking network not only achieved high tensile strength (8.61 MPa) and toughness (3.77 MJ/m3) but also endowed the BMTs with excellent reprocessing ability with high mechanical toughness recovery efficiency of 104.8 %. More importantly, the BMTs were used as substrates to fabricate the capacitive sensor through the CO2-laser irradiation technique. The resultant capacitive sensor displayed excellent and sensitive humidity sensing performance, which allowed it to be successfully applied in human health monitoring. This work paved a promising way for the preparation of mechanical robustness malleable bio-thermosets for electronic devices.