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Converting industrial wastes into value-added building products in an environmental management strategy is a challenging yet vital component of the industrial process. Steel slag (SS), an industrial waste by-product from the steel-making process, is typically disposed of in landfill which consumes land resources and pollutes the environment. This paper explores the possibility of a closed-loop system to convert steel slag into a cement material through carbonation activation, thereby significantly reducing the amount of steel slag waste sent to landfills across Canada. The production of this cementing material can occur next to the steel mill, utilizing steel slag and carbon dioxide collected on-site to fabricate carbon-negative products. To save energy and allow production to be feasible on an industrial scale, ambient pressure (AP) carbonation is developed to reduce carbon emissions while improving their performance. High pressure (HP) carbonation curing and normal hydration (NH) references were also implemented at the same time to justify the application of AP carbonation in reducing CO2 emission. The results of this study found AP carbonation-activated SS compacts have comparable CO2 uptake (about 7.5 tons CO2/100 tons slag) and mechanically compressive strength values as those subjected to HP carbonation, suggesting that AP could be used to replace HP in carbonation curing to ensure a lower energy input. Additionally, AP seemed to possess as effective carbonation as HP. The studies investigated by multiple techniques including X-ray diffractometer (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopic analysis, and scanning electron microscopy (SEM) aim to identify the microstructure development of carbonated SS paste to assess carbonation results. Developed with life cycle assessment (LCA), environmental impact evaluation shows that AP presents a smaller global warming potential (GWP) value than HP. The comparable CO2 sequestration, satisfactory engineering properties, enhanced microstructure and lesser environmental impact in AP carbonation confirm the feasibility of replacing high pressure with extremely low pressure to cure concrete products. The use of AP carbonation for cement material created using steel slag reduces carbon emissions, energy usage, and natural resource consumption.
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Dióxido de Carbono , Resíduos Industriais , Resíduos Industriais/análise , Dióxido de Carbono/química , Aço/química , Carbonatos/química , Instalações de Eliminação de ResíduosRESUMO
BACKGROUND: Optimum Glide Path (OGP) is a new reciprocating motion aiming to perform efficient glide path preparation in constricted canals. The aim of this study was to investigate and compare manual and OGP movement in terms of canal transportation and centering ability in glide path preparation of constricted canals. METHODS: Thirty constricted mesial root canals of mandibular molars, with initial apical size no larger than ISO#8, were selected and negotiated with #6-#8 K-files under the microscope. Canals were randomly divided into two experimental groups: Group 1 (MAN, n = 15): Glide path was established by using #10-#15 stainless steel K-files manually; Group 2 (OGP, n = 15): #10-#15 Mechanical Glide Path super-files were used with OGP motion (OGP 90°, 300 rpm). Each instrument was used to prepare only 2 canals (as in one mesial root). Canals were scanned before and after glide path preparation with micro-computed tomography (micro-CT) to evaluate root canal transportation and centering ratio at 1, 3 and 5 mm levels from the root apex. File distortions and separations were recorded. Paired t-test was used to statistically evaluate the data (P < .05). RESULTS: Group 2 showed a significantly lower transportation value than group 1 at 1-mm and 3-mm levels (P < .05), however the difference at 5-mm level was not significant. There was no significant difference regarding the centering ratio between the groups. Six #10 K-files were severely distorted in group 1, while no file separation or distortion was found in group 2. CONCLUSIONS: OGP motion performed significantly less canal transportation (apical 3 mm) and file distortion during glide path establishment in constricted canals comparing to manual motion, while the centering ability between the two was similar. CLINICAL RELEVANCE: OGP reciprocating motion provides a safer and efficient clinical approach compared to traditional manual motion in glide path establishment with small files in constricted canals.
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Cavidade Pulpar , Preparo de Canal Radicular , Cavidade Pulpar/diagnóstico por imagem , Desenho de Equipamento , Humanos , Dente Molar/diagnóstico por imagem , Dente Molar/cirurgia , Raiz Dentária , Microtomografia por Raio-XRESUMO
The periodontal ligament (PDL) is a distinctive yet critical connective tissue vital for maintaining the integrity and functionality of tooth-supporting structures. However, PDL repair poses significant challenges due to the complexity of its mechanical microenvironment encompassing hard-soft-hard tissues, with the viscoelastic properties of the PDL being of particular interest. This review delves into the significant role of viscoelastic hydrogels in PDL regeneration, underscoring their utility in simulating biomimetic three-dimensional microenvironments. We review the intricate relationship between PDL and viscoelastic mechanical properties, emphasizing the role of tissue viscoelasticity in maintaining mechanical functionality. Moreover, we summarize the techniques for characterizing PDL's viscoelastic behavior. From a chemical bonding perspective, we explore various crosslinking methods and characteristics of viscoelastic hydrogels, along with engineering strategies to construct viscoelastic cell microenvironments. We present a detailed analysis of the influence of the viscoelastic microenvironment on cellular mechanobiological behavior and fate. Furthermore, we review the applications of diverse viscoelastic hydrogels in PDL repair and address current challenges in the field of viscoelastic tissue repair. Lastly, we propose future directions for the development of innovative hydrogels that will facilitate not only PDL but also systemic ligament tissue repair. STATEMENT OF SIGNIFICANCE.
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Hidrogéis , Ligamento Periodontal , Ligamentos , ViscosidadeRESUMO
Healthy alveolar bone is the cornerstone of oral function and oral treatment. Alveolar bone is highly dynamic during the entire lifespan and is affected by both systemic and local factors. Importantly, alveolar bone is subjected to unique occlusal force in daily life, and mechanical force is a powerful trigger of bone remodeling, but the effect of occlusal force in maintaining alveolar bone mass remains ambiguous. In this study, the Piezo1 channel is identified as an occlusal force sensor. Activation of Piezo1 rescues alveolar bone loss caused by a loss of occlusal force. Moreover, we identify Piezo1 as the mediator of occlusal force in osteoblasts, maintaining alveolar bone homeostasis by directly promoting osteogenesis and by sequentially regulating catabolic metabolism through Fas ligand (FasL)-induced osteoclastic apoptosis. Interestingly, Piezo1 activation also exhibits remarkable efficacy in the treatment of alveolar bone osteoporosis caused by estrogen deficiency, which is highly prevalent among middle-aged and elderly women. Promisingly, Piezo1 may serve not only as a treatment target for occlusal force loss-induced alveolar bone loss but also as a potential target for metabolic bone loss, especially in older patients.
Daily occlusal force and estrogen synergistically maintain alveolar bone homeostasis. PIEZO1 in osteoblasts plays a critical role in sensing occlusal force and maintaining bone mass. PIEZO1 may promote osteoclastic apoptosis through osteoblast-secreted FasL through a PIEZO1-STAT3/ESR1-FasL pathway. Restoration of occlusal force with dental therapies as early as possible to prevent alveolar bone loss is the major priority in oral health care. PIEZO1 may serve as a potential target for bone metabolism disorders.
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Homeostase , Canais Iônicos , Animais , Feminino , Canais Iônicos/metabolismo , Camundongos , Força de Mordida , Osteogênese , Humanos , Osteoblastos/metabolismo , Perda do Osso Alveolar/metabolismo , Perda do Osso Alveolar/patologia , Apoptose , Osteoclastos/metabolismoRESUMO
Mechanical force is essential to shape the internal architecture and external form of the skeleton by regulating the bone remodeling process. However, the underlying mechanism of how the bone responds to mechanical force remains elusive. Here, we generated both orthodontic tooth movement (OTM) model in vivo and a cyclic stretch-loading model in vitro to investigate biomechanical regulation of the alveolar bone. In this study, signal transducer and activator of transcription 3 (STAT3) was screened as one of the mechanosensitive proteins by protein array analysis of cyclic stretch-loaded bone mesenchymal stem cells (BMSCs) and was also proven to be activated in osteoblasts in response to the mechanical force during OTM. With an inducible osteoblast linage-specific Stat3 knockout model, we found that Stat3 deletion decelerated the OTM rate and reduced orthodontic force-induced bone remodeling, as indicated by both decreased bone resorption and formation. Both genetic deletion and pharmacological inhibition of STAT3 in BMSCs directly inhibited mechanical force-induced osteoblast differentiation and impaired osteoclast formation via osteoblast-osteoclast cross-talk under mechanical force loading. According to RNA-seq analysis of Stat3-deleted BMSCs under mechanical force, matrix metalloproteinase 3 (Mmp3) was screened and predicted to be a downstream target of STAT3. The luciferase and ChIP assays identified that Stat3 could bind to the Mmp3 promotor and upregulate its transcription activity. Furthermore, STAT3-inhibitor decelerated tooth movement through inhibition of the bone resorption activity, as well as MMP3 expression. In summary, our study identified the mechanosensitive characteristics of STAT3 in osteoblasts and highlighted its critical role in force-induced bone remodeling during orthodontic tooth movement via osteoblast-osteoclast cross-talk. © 2022 American Society for Bone and Mineral Research (ASBMR).
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Reabsorção Óssea , Metaloproteinase 3 da Matriz , Humanos , Metaloproteinase 3 da Matriz/metabolismo , Técnicas de Movimentação Dentária , Fator de Transcrição STAT3/metabolismo , Ligamento Periodontal/metabolismo , Remodelação Óssea/fisiologia , Reabsorção Óssea/metabolismo , Osteoclastos/metabolismoRESUMO
The alveolar bone, with a high turnover rate, is the most actively-remodeling bone in the body. Orthodontic tooth movement (OTM) is a common artificial process of alveolar bone remodeling in response to mechanical force, but the underlying mechanism remains elusive. Previous studies have been unable to reveal the precise mechanism of bone remodeling in any time and space due to animal model-related restrictions. The signal transducer and activator of transcription 3 (STAT3) is important in bone metabolism, but its role in osteoblasts during OTM is unclear. To provide in vivo evidence that STAT3 participates in OTM at specific time points and in particular cells during OTM, we generated a tamoxifen-inducible osteoblast lineage-specific Stat3 knockout mouse model, applied orthodontic force, and analyzed the alveolar bone phenotype. Micro-computed tomography (Micro-CT) and stereo microscopy were used to access OTM distance. Histological analysis selected the area located within three roots of the first molar (M1) in the cross-section of the maxillary bone as the region of interest (ROI) to evaluate the metabolic activity of osteoblasts and osteoclasts, indicating the effect of orthodontic force on alveolar bone. In short, we provide a protocol for using inducible osteoblast lineage-specific Stat3 knockout mice to study bone remodeling under orthodontic force and describe methods for analyzing alveolar bone remodeling during OTM, thus shedding new light on skeletal mechanical biology.
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Fator de Transcrição STAT3 , Técnicas de Movimentação Dentária , Camundongos , Animais , Camundongos Knockout , Fator de Transcrição STAT3/genética , Microtomografia por Raio-X , Remodelação Óssea , Modelos Animais de DoençasRESUMO
Dental mesenchymal stem cells (DMSCs) are multipotent progenitor cells that can differentiate into multiple lineages including odontoblasts, osteoblasts, chondrocytes, neural cells, myocytes, cardiomyocytes, adipocytes, endothelial cells, melanocytes, and hepatocytes. Odontoblastic differentiation of DMSCs is pivotal in dentinogenesis, a delicate and dynamic process regulated at the molecular level by signaling pathways, transcription factors, and posttranscriptional and epigenetic regulation. Mutations or dysregulation of related genes may contribute to genetic diseases with dentin defects caused by impaired odontoblastic differentiation, including tricho-dento-osseous (TDO) syndrome, X-linked hypophosphatemic rickets (XLH), Raine syndrome (RS), hypophosphatasia (HPP), Schimke immuno-osseous dysplasia (SIOD), and Elsahy-Waters syndrome (EWS). Herein, recent progress in the molecular regulation of the odontoblastic differentiation of DMSCs is summarized. In addition, genetic syndromes associated with disorders of odontoblastic differentiation of DMSCs are discussed. An improved understanding of the molecular regulation and related genetic syndromes may help clinicians better understand the etiology and pathogenesis of dentin lesions in systematic diseases and identify novel treatment targets.
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In order to obtain drug delivery carriers with good stability in blood and high cellular uptake efficiency, carboxyl groups and tertiary amine groups were respectively introduced into polyurethane to synthesize two kinds of amphiphilic polyurethanes with opposite charges (PUC and PUN). Their structures were characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (1H NMR) spectroscopy and gel permeation chromatography (GPC). PUC-PUN co-assembled nanomicelles were prepared by electrostatic interaction between PUC and PUN micelles, which showed acid-sensitive property. When the pH of the solution was decreased from 7.4 to 6.5, PUC-PUN-1 micelles showed negative-to-positive charge-reversal property among these micelles. The results of stability and cell experiments demonstrated that PUC-PUN-1 micelles not only had excellent stability in simulated normal physiological environment but also could obviously enhance the cellular uptake efficiency. PUC-PUN-1 micelles had low cytotoxicity against SGC-7901 and MGC-803 cells, whereas PUC-PUN-1/DOX micelles had higher cytotoxicity compared to pure DOX and PUN-1/DOX micelles. Moreover, the results of in vivo antitumor activity experiments showed that PUC-PUN-1/DOX micelles had better tumor inhibition ability and safety than pure DOX. In addition, the results of in vitro drug release experiments indicated that PUC-PUN-1/DOX micelles had almost no burst release or leakage of drugs in pH 7.4 environment. However, the drug release was accelerated in pH 5.0, which followed Fickian diffusion mechanism.
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Portadores de Fármacos , Poliuretanos , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , MicelasRESUMO
BACKGROUND: Recurring outbreaks of infectious diseases highlight the importance of population vaccination strategies. We aimed to assess the impact of national vaccination strategies on vaccine-preventable infectious diseases (VPDs) in Shanghai, China and to identify vulnerable groups that may benefit from future vaccination policies. METHODS: Infectious disease data from 1953 to 2018 was obtained from Xuhui District Center for Disease Control and Prevention, Shanghai China. We used joinpoint regression to show incidence, mortality and fatality trends and to determine annual percent change in incidence of 12 VPDs among three eras of national immunization strategies: (1)1953-1977, (2)1978-2007, and(3)2008-2018. FINDINGS: Incidence, mortality, and fatality from VPDs have decreased drastically over the three eras, despite the inclusion of more diseases over time. Strikingly, the overall yearly incidence of VPDs shows an increasing trend from 2000 to 2018 in Shanghai (annual percentage changes, APC:7.7, p = 0.025). In the third era (2008-2018), the three VPDs with the highest incidence were varicella (80.2 cases/100,000), hand, foot, and mouth disease (HFMD) (73.6 cases/100,000), and hepatitis (43.5 cases/100,000). A significant upward trend was also observed in hepatitis (APC:24.9, p<0.001), varicella (APC:5.9, p = 0.006), and HFMD (APC:11.8, p = 0.003) from 2008-2018. Hepatitis and tuberculosis are the only VPDs with fatality cases in this period. INTERPRETATION: Focus is needed in controlling adult hepatitis and tuberculosis, either by introducing adult booster vaccines or by research into more effective vaccines. Varicella and HFMD are on the rise, but vaccines for these are not included in national programs. Strategies funded by government agencies or encouraged by research incentives are needed for varicella and HFMD, such as two-dose and novel multi-valent vaccines, respectively. FUNDING: Chinese Ministry of Education, Shanghai Municipal Government.
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Objective: To investigate the effects of Er:YAG laser on the attachment of human periodontal ligament fibroblasts (hPDLFs) to denuded root surfaces simulating delayed replantation cases. Background data: Dental avulsion is one of the most severe dental traumas, which is often treated with replantation. In delayed replantation scenarios, poor prognosis, including root resorption, usually occurs due to poor root surface conditioning and nonviable hPDLF attachment. Methods: Thirty-six root fragments (5 × 5 × 2 mm) were obtained from periodontium tissue-free premolar root surfaces. Specimens were randomly and equally assigned to the following: Group A, untreated control; Group B, 25 J/cm2 and 10 Hz of Er:YAG laser irradiation; and Group C, 50 J/cm2 and 10 Hz of Er:YAG laser irradiation. Some specimens in each group were then prepared for surface topography visualization under SEM, others were subjected to coculture with hPDLF suspension, and cell adhesion was further evaluated by SEM. Results: Group A presented homogenous smooth root surface, with fewer and round-shaped cells attached; Group B and C exhibited rather rough and irregular morphologies, and spindle-shaped fibroblasts were firmly attached by numerous lamellipodia and extensions. After a 3-day coculture, the number of fibroblasts attached in Group A was significantly lower compared with the other two laser-treated groups (p = 0.008 < 0.05). No significant alterations were observed between the two laser groups (p = 0.135 > 0.05). Conclusions: Er:YAG laser-treated root surfaces are compatible for the attachment of PDLFs, which suggests that Er:YAG laser irradiation may be used as a promising strategy for root surface conditioning in delayed replantation cases.
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Fibroblastos/efeitos da radiação , Lasers de Estado Sólido , Ligamento Periodontal/efeitos da radiação , Reimplante Dentário , Raiz Dentária/efeitos da radiação , Dente Pré-Molar , Adesão Celular/efeitos da radiação , Técnicas de Cocultura , Humanos , Técnicas In Vitro , Microscopia Eletrônica de Varredura , Distribuição Aleatória , Propriedades de SuperfícieRESUMO
Glucosamine (GlcN) has been widely used to reduce joint pain and osteoarthritis progression, but the efficacy of GlcN remains controversial because of the low GlcN concentration reaching the articular cavity. The aim of this study is to provide an effective approach of GlcN delivery to a target site using photocrosslinkable methacrylated gelatin (GelMA)-based hydrogels, where GlcN could be gradually released during the degradation of the GelMA hydrogel. Herein, GlcN was acrylated as the acryloyl glucosamine (AGA) and covalently grafted to GelMA, and more than 87.7% of 15% (w/v) GelMA hydrogel was grafted with AGA. Moreover, in vitro outgrowth and apoptosis assay of bone marrow stem cells (BMSCs) demonstrated that the GelMA-AGA hydrogels had better biocompatibility, larger cell attachment, and higher cell viability than pure GlcN and AGA materials. Also, 15% (w/v) GelMA-AGA hydrogel was injected into the defect site for in vivo rabbit cartilage repair. Compared with oral administration of pure GlcN and injection of pure GelMA, the repaired cartilages using GelMA-AGA hydrogels had the smoothest surface of the defect site, filling more than 95% defect bulk. The similar content of glycosaminoglycans to the native tissue and the maximum amount of type II collagen was found in the repaired cartilage using GelMA-AGA hydrogels, indicating the outgrowth of hyaline cartilage.
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Materiais Biocompatíveis/química , Cartilagem/efeitos dos fármacos , Gelatina/química , Glucosamina/química , Hidrogéis/química , Animais , Apoptose , Células da Medula Óssea/citologia , Osso e Ossos , Cartilagem/metabolismo , Proliferação de Células , Força Compressiva , Reagentes de Ligações Cruzadas/química , Matriz Extracelular/metabolismo , Cartilagem Hialina/química , Técnicas In Vitro , Masculino , Teste de Materiais , Metacrilatos/química , Fotoquímica , Coelhos , Reologia , Células-Tronco/citologia , Estresse Mecânico , Engenharia Tecidual , Alicerces TeciduaisRESUMO
A series of ligand-targeted nanosystems have been rapidly exploited to selectively deliver drug molecules to desired cell populations. The conjugation of protein ligands to the nanoparticle (NP) surface endows nanovehicles with active targeting properties. However, the nonspecific covalent coupling of protein ligands to nanocarriers may compromise the protein targeting due to the uncontrolled ligand orientation as well as the decline in ligand activity during linkage process. With this regard, biomimetic synthetic strategies are employed for the preparation of genetically engineered nanovesicles (GNV) from cellular plasma membrane with targeting moieties on the surface in a ligand-oriented manner. Herein, we introduce the biomimetic synthetic strategy and procedures for GNV preparation. This chapter may guide readers to design analogous NPs for cell-specific targeting by displaying particular protein probes (e.g., antibody, nanobody, and single-chain antibody) on the surface of GNVs.
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Antineoplásicos/administração & dosagem , Engenharia Genética/métodos , Nanopartículas/química , Neoplasias/terapia , Nanomedicina Teranóstica/métodos , Animais , Antineoplásicos/farmacocinética , Materiais Biomiméticos/síntese química , Linhagem Celular Tumoral , Membrana Celular/genética , Terapia Combinada/métodos , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Composição de Medicamentos/métodos , Exossomos/genética , Humanos , Hipertermia Induzida/métodos , Lipossomos , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Técnicas Fotoacústicas , Fotoquimioterapia/métodos , Anticorpos de Cadeia Única/administração & dosagem , Distribuição Tecidual , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Neurodegenerative diseases (NDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), threaten the health of an ever-growing number of older people worldwide; so far, there are no effective cures. Significant efforts have been devoted to developing new drugs for NDs in recent years, and some small molecules have been shown to be promising in preclinical studies. However, the major challenge for brain-targeting drugs is how to efficiently deliver the drugs across the blood-brain barrier (BBB) to desired targets. To address this issue, liposomal delivery systems have proved to be ideal carriers for neuroprotective small molecules. Here, we summarize recent advances in the brain-targeting liposomal delivery of small hydrophobic molecules (SHMs) and propose strategies for developing liposomal SHMs as disease-modifying neurotherapeutics for NDs.
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Encéfalo/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Animais , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lipossomos , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores/químicaRESUMO
BACKGROUND: Sellar infections represent less than 1% of all sellar lesions and can be life-threatening. These infections occur de novo in up to 70% of patients or can less commonly develop after surgical treatment of another primary lesion, such as a pituitary adenoma. CASE DESCRIPTION: We report a unique case of a 27-year-old woman with a recurrent pituitary adenoma treated with 2 previous transsphenoidal resections. She ultimately presented with hypopituitarism, followed by headaches, malaise, chills, and visual-field and acuity deficits 9 years after her second transsphenoidal resection. During the second operation, the sellar floor was reconstructed with hydroxyapatite bone cement. On the most recent presentation, magnetic resonance imaging of the brain and pituitary demonstrated a residual sellar mass accompanied by significant enhancement and T2 hyperintensity of the infundibulum, hypothalamus, optic chiasm, and optic tracts. The patient was started on empiric antibiotics and steroids before frank purulence in the sella was discovered and removed by transsphenoidal endoscopy. Cultures were positive for methicillin-sensitive Staphylococcus aureus and Propionibacterium acnes. At her 3-month follow-up evaluation, the patient had complete resolution of her symptoms and radiographic findings. CONCLUSIONS: This case demonstrates the fact that patients with pituitary lesions who have foreign material used for surgical closure can present with infections many years after the initial intervention. Furthermore, with appropriate clinical diagnosis and treatment, the reactive inflammation caused by sellar infection is reversible. We review the literature regarding the risk factors and management strategies for delayed postoperative sellar infections.
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Adenoma/cirurgia , Neoplasias Hipofisárias/cirurgia , Base do Crânio/cirurgia , Infecção da Ferida Cirúrgica/diagnóstico , Adulto , Cimentos Ósseos/efeitos adversos , Abscesso Encefálico/diagnóstico , Abscesso Encefálico/terapia , Feminino , Humanos , Base do Crânio/diagnóstico por imagem , Infecção da Ferida Cirúrgica/terapia , Fatores de TempoRESUMO
RNA interference (RNAi) represents a promising strategy for the treatment of HCV infection. However, the development of an effective system for in vivo delivery of small interfering RNA (siRNA) to target organ remains a formidable challenge. Here, we develop a unique nanoparticle platform (VE-DC) composed of α-tocopherol (vitamin E) and cholesterol-based cationic liposomes (DOTAP-Chol) for systemic delivery of siRNAs to the liver. A HCV-replicable cell line, Huh7.5.1-HCV, and a transient HCV core expressing cell line, Huh7.5.1-Core, were constructed and used to assess the in vitro anti-HCV activity of VE-DC/siRNAs. A transient in vivo HCV model was also constructed by hydrodynamic injection of pCDNA3.1(+)-3FLAG-Core (pCore-3FLAG) plasmid expressing core protein or pGL3-5'UTR-luciferase (pGL3-5'UTR-luc) plasmid expressing luciferase driven by HCV 5'UTR. Nanoscale VE-DC/siRNA was intravenously injected to assess the liver-targeting property as well as antiviral activity. The nanoscale VE-DC effectively exerted an anti-HCV activity in the in vitro cell models. Post-administration of VE-DC/siRNAs also effectively delivered siRNAs to the liver, suppressing core protein production and firefly luciferase activity, without inducing an innate immunity response or off-target and toxicity effects. The VE-DC platform has high potential as a vehicle for delivery of siRNAs to the liver for gene therapy for targeting hepatitis C.
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Antivirais/administração & dosagem , Portadores de Fármacos/administração & dosagem , Hepatite C/tratamento farmacológico , Nanopartículas/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Vitamina E/administração & dosagem , Animais , Antivirais/efeitos adversos , Linhagem Celular , Modelos Animais de Doenças , Hepatócitos/metabolismo , Humanos , Lipossomos/administração & dosagem , Camundongos Endogâmicos BALB C , RNA Interferente Pequeno/farmacocinéticaRESUMO
OBJECTIVE: To investigate the expression of stromal cell-derived factor-1 (SDF-1) in human stem cells from apical papilla (SCAP), and to evaluate the effect of lipopolysaccharide (LPS) on SDF-1 expression by SCAP. METHODS: SCAP were isolated from dental papilla of human immature third molars. The expression of SDF-1 was evaluated by reverse transcription-PCR (RT-PCR). After SCAP being exposed to different concentrations (0.1, 1.0, 10 mg/L) of LPS for 24 and 48 h, the effect of LPS on cell proliferation and gene expression of SDF-1 was investigated by cell counting kit-8 and real-time PCR respectively, while cells without LPS stimulation were considered as negative control. RESULTS: LPS had no significant effect on SCAP proliferation until day 7. RT-PCR assays demonstrated that SCAP expressed SDF-1 mRNA. Different concentrations of LPS significantly promoted the SDF-1 expression in SCAP after 24 h (F = 12.102, P = 0.002) and 48 h (F = 39.054, P < 0.001) exposure, with relative gene expression ratio (experimental/control) increased to 1.4 ± 0.1, 2.2 ± 0.4, 2.3 ± 0.5 in 24 h group and 2.1 ± 0.4, 3.4 ± 0.3, 3.8 ± 0.5 in 48 h group. CONCLUSIONS: Isolated SCAP in cultures have the expression of SDF-1 mRNA. LPS can significantly promote the expression of SDF-1 in SCAP.
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Proliferação de Células/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Papila Dentária/citologia , Lipopolissacarídeos/farmacologia , Células-Tronco/efeitos dos fármacos , Diferenciação Celular , Quimiocina CXCL12/genética , Expressão Gênica , Humanos , Células-Tronco/metabolismoRESUMO
INTRODUCTION: Stem cells from the apical papilla (SCAPs) at the apex may be attracted into the root canal space as a cell source for pulp-dentin regeneration. To test this possibility, we used in vitro transmigration models to investigate whether SCAPs can be chemoattracted by the delivery of the chemotactic cytokine stromal cell-derived factor-1α (SDF-1α). METHODS: We first examined the expression of CXC chemokine receptor 4 (CXCR4) for SDF-1α in the apical papilla and in cultured SCAPs using immunofluorescence, reverse-transcription polymerase chain reaction (RT-PCR), and flow cytometric analyses. A standard Transwell migration assay and a 3-dimensional cell migration assay were used to analyze transmigration of SCAPs via the SDF-1α/CXCR4 axis. RESULTS: CXCR4 was expressed in the paravascular region of the apical papilla and detected in SCAP cultures. Most cultured SCAPs harbored intracellular CXCR4 (58%-99%, n = 4), whereas only a few cells had detectable CXCR4 on the cell surface (0.3%-2.34%, n = 4). Although SDF-1α had no significant effect on SCAP proliferation, it significantly promoted a higher number of migrated cells; this effect was abolished by anti-CXCR4 antibodies. Interestingly, cell surface CXCR4 on SCAPs was not detectable until after transmigration. The 3-dimensional migration assay revealed that SDF-1α significantly enhanced SCAP migration in the collagen gel. CONCLUSIONS: SCAPs can be chemoattracted via the SDF-1α/CXCR4 axis, suggesting that SDF-1α may be used clinically to induce CXCR4-expressing SCAPs in the apical papilla to transmigrate into the root canal space as an endogenous cell source for pulp regeneration.
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Quimiocina CXCL12/metabolismo , Quimiotaxia , Receptores CXCR4/metabolismo , Células-Tronco/citologia , Ápice Dentário/citologia , Ápice Dentário/metabolismo , Adolescente , Células Cultivadas , Polpa Dentária/fisiologia , Dentina/fisiologia , Humanos , Regeneração , Adulto JovemRESUMO
OBJECTIVE: To understand the status of HBV infection among family members with HBV infected persons in Shanghai and to probe the determinants of HBV infection so as to provide evidence for improving the related strategies on hepatitis B prevention and control. METHODS: Three hundred and four hepatitis B patients together with 288 HBsAg carriers from 6 districts in Shanghai were randomly sampled in 2010. All the said persons and their families members were asked to fill in questionnaires and to be drawn 5 ml venous blood for HBV serologic indicators detection. The subjects were divided into case group and control group according to their status of HBV infection. Univariate analysis and multivariate logistic regression analysis were carried out to identify the determinants of HBV infection among family members. RESULTS: Among 1485 subjects from 592 households, a total of 1137 persons were infected by HBV, with the overall infection rate as 76.57%. Fifteen infection modes were noticed, in which double positive of anti-HBs and anti-HBc, triple positive of HBsAg, anti-HBe and anti-HBc, together with triple positive of anti-HBs, anti-HBe and anti-HBc accounted for the top three, with the proportions as 30.69%, 26.65% and 10.03% respectively. The differences between the years of carrying HBV and the proportions of numbers that carrying HBV in families, were not statistically significant. The infection rate among children (42.86%) was significantly lower than that of their parents (87.54%) (P < 0.001). Results from both univariate and multivariate analysis showed that gender, age, utensil sharing, histories of receiving hepatitis B vaccines and dental outpatient service were determinants of HBV infection among families members (P < 0.05), with OR values being 9.009 for persons without immunization history of hepatitis B vaccines, 3.817 for persons above 40 years old and 2.283 for persons of 21 - 40 years old, 2.222 for families members who sharing utensil, 2.124 for persons with history of dental outpatient service and 1.339 for male members, respectively. CONCLUSION: Family clustering of HBV infection in was seen in Shanghai. In order to reduce the number of HBV infection in families, hepatitis B vaccination program need to be carried out. Healthy lifestyle should be emphasized to prevent HBV infection due to close contact. The risk of iatrogenic HBV transmission should also be prevented.
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Família , Hepatite B/epidemiologia , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Within the past 10 years, the use of saliva as a diagnostic tool has gained considerable attention and become a well-accepted method. As a diagnostic fluid, saliva offers superiority over serum due to both a noninvasive collection method by specially trained persons and a cost-effective approach for screening of large populations. Collection of saliva offers a reduced risk of infection compared to the collection of serum. Moreover, obtaining saliva samples from infant, disabled or anxious patients, is much easier than obtaining other samples. There is a lot of useful components-changing information in saliva when a person is in sick. Therefore, we define these changing components as "biomarkers". The utilization of biomarkers as early predictors for clinical disease not only contributes to the effective prevention and treatment of diseases, but also enhances the assessment of potential health risks. In this article, we have reviewed the properties of saliva, the salivary analysis method for biomarker discovery, and the diagnostic potentials of salivary biomarkers in monitoring and detecting periodontal disease, Oral and Breast cancers, and Sjögren's syndrome. We also discussed some barriers of applications of saliva as a diagnostic media as well as recent improvements. We also prospected the future processing directions of using biomarkers in disease diagnosis and draw a conclusion that saliva is indeed an effective media in various disease monitoring and diagnosis.