RESUMO
Charcot-Marie-Tooth disease(CMT) is a hereditary peripheral neuropathy, characterized by progressive distal hypoesthesia and amyotrophia. CMT is characterized by an X- linked recessive inheritance pattern. The apoptosis-inducing factor mitochondria associated-1 (AIFM1) is the main pathogenic gene of the X-linked recessive Charcot-Marie-Tooth disease-4 with or without cerebellar ataxia (CMTX4), also known as Cowchock syndrome. In this study, we enrolled a family with CMTX from the southeast region of China and identified a novel AIFM1 variant (NM_004208.3: c.931C>G; p.L311V) using whole exon sequencing technology. The results of our study may also be useful for genetic counseling, embryo screening of in vitro fertilization embryos, and prenatal genetic diagnosis.
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Doença de Charcot-Marie-Tooth , Humanos , Doença de Charcot-Marie-Tooth/genética , Fator de Indução de Apoptose/genética , Sequenciamento do Exoma , População do Leste Asiático , Linhagem , MutaçãoRESUMO
BACKGROUND: Pruritus is one of the most common and challenging side effects of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and has impaired patients' quality of life and treatment compliance. Our study evaluated the efficacy and safety of aprepitant in managing EGFR-TKIs-related pruritus. METHODS: This randomized, double-blind, placebo-controlled study was conducted between December 2016 and August 2020 in China. Patients were eligible if they were 18 years or older and had histologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) with first onset of moderate to severe pruritus during EGFR-TKI treatment. RESULTS: A total of 130 eligible patients were randomly assigned to aprepitant (n = 65) or desloratadine (n = 65) groups. The median (interquartile range [Q1, Q3]) age was 63 (54, 70) years, and 79 (60.8%) were women. Mean visual analog scale scores at baseline were 6.35 (95% confidence interval [CI], 5.89-6.82) in the aprepitant group and 5.94 (95% CI, 5.56-6.32) in the desloratadine group. After 1 week of treatment, 33 (53.2%) patients responded to aprepitant, which was significantly higher than that of 14 (23.7%) patients responded to desloratadine (p = .001). Moreover, patients in the aprepitant group had a significantly shorter response time than patients in the desloratadine group (mean [days], 13.39 [95% CI, 11.08-15.70] vs. 16.67 [95% CI, 14.19-19.13], p = .04). The most frequent drug-related adverse events in aprepitant group and desloratadine were constipation and dry mouth, and all adverse events were grade 1-2. CONCLUSIONS: To the authors' knowledge, this is the first study to prospectively present that aprepitant elicited a better and faster response and mild toxicity for managing EGFR-TKI induced pruritus than desloratadine. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02646020.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Humanos , Masculino , Aprepitanto/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Prurido/induzido quimicamente , Qualidade de Vida , Pessoa de Meia-Idade , IdosoRESUMO
The knowledge of accurate geometrical parameters from X-ray diffraction studies in the solid state of metal nucleotide is very important for understanding the relationship between structures and properties, including biochemical processes and even enzyme-metal-substrate interactions. The research is also very necessary to precisely and controllably design the functional materials. Here, seven types of coordination polymers of inosine 5'-diphosphate nucleotide (IDP) with transition metals, {[Zn(HIDP)(azpy)(H2O)2]·4H2O}n (1), {[Cd2(IDP)2(bpda)2]·[Cd(H2O)6]·11H2O}n (2), {[Cd3(IDP)2(4,4'-bipy)2(H2O)3]·6H2O}n (3), {[Cd2(IDP)2(bpe)2(H2O)2]·(H2bpe)·26H2O}n (4), {[Cu3(IDP)2(azpy)2(H2O)5]·5H2O}n (5), {[Cu3(IDP)2(bpe)2(H2O)5]·9H2O}n (6), and {[Co(HIDP)(azpy)(H2O)2]·7H2O}n (7) [4,4'-bipy = 4,4'-bipyridine, azpy = 4,4'-azopyridine, bpe = 1,2-bis(4-pyridyl)ethene, and bpda = 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene], were designed, synthesized, and firmly characterized using single-crystal X-ray diffraction. The coordination patterns of the diphosphate group of IDP in these complexes were studied by crystallographic analysis, namely, open, close, and open-close hybrid types. We have investigated the diverse coordination patterns of the diphosphate group and its spatial relationship relative to the pentose ring on the basis of two conformational parameters, the pseudorotation phase angle and the degree of puckering. Crystallographic studies clearly reveal the correlation between the backbone torsion angle (ω' and φ) of the sugar-diphosphate and the conformational preference of the pentose ring, i.e., the signs of the backbone torsion angles ω' and φ are both plus (+) or minus (-), the conformation of the pentose ring is envelope form (E), while when one of the two signs is plus (+) and the other is minus (-), the pentose ring is in the twist form (T). This is the first time elucidation of the coordination pattern of diphosphate relative to the conformation of the pentose ring in nucleotide metal complexes, which are different from the other inorganic or organic diphosphate compounds. The chirality of these coordination polymers was examined by combining solid-state circular dichroism spectroscopy measurements with the explanation of their crystal structures. The results presented in this paper are very important for understanding their nucleotide coordination chemistry, their supramolecular chemistry, and even their biochemistry.
Assuntos
Complexos de Coordenação , Inosina Difosfato , Difosfatos , Cádmio , Nucleotídeos , PolímerosRESUMO
Traditional wound dressings often cannot treat wounds caused by bacterial infections or other wound types that are insensitive to these wound treatments. Therefore, a biodegradable, bioactive hydrogel wound dressing could be an effective alternative option. The purpose of this study was to develop a hydrogel membrane comprised of sodium alginate, polyvinyl alcohol, acrylic acid, and gallic acid for treating skin wounds. The newly developed membranes were analyzed using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), sol-gel fraction, porosity, mechanical strength, swelling, drug release and data modelling, polymeric network parameters, biodegradation, and antioxidation (DPPH and ABTS) and antimicrobial activity against Gram-positive and negative bacteria. The results revealed that hydrogel membranes were crosslinked successfully and had excellent thermal stability, high drug loading, greater mechanical strength, and exhibited excellent biodegradation. Additionally, the swelling ability and the porosity of the surface facilitated a controlled release of the encapsulated drug (gallic acid), with 70.34% release observed at pH 1.2, 70.10% at pH 5.5 (normal skin pH), and 86.24% at pH 7.4 (wounds pH) in 48 h. The gallic acid-loaded hydrogel membranes showed a greater area of inhibition against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli bacteria as well as demonstrated excellent antioxidant properties. Based on Franz cell analyses, the permeation flux of the drug from optimized formulations through mice skin was 92 (pH 5.5) and 110 (pH 7.4) µg/cm2·h-1. Moreover, hydrogel membranes retained significant amounts of drug in the skin for 24 h, such as 2371 (pH 5.5) and 3300 µg/cm2 (pH 7.4). Acute dermal irritation tests in rats showed that hydrogel membranes were nonirritating. Hydrogel membranes containing gallic acid could be an effective option for improving wound healing and could result in faster wound healing.
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Hidrogéis , Álcool de Polivinil , Camundongos , Ratos , Animais , Álcool de Polivinil/química , Hidrogéis/química , Alginatos/farmacologia , Ácido Gálico/farmacologia , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Herein, spindle-shaped block copolymer (BCP) nanoparticles are used in seeded polymerization of methyl methacrylate as a novel approach to generating cylindrical nanostructures. The chain-extension of BCP seeds by an amorphous coil-type polymer within the seed core composed of semifluorinated liquid-crystalline blocks triggers the deforming, stretching, and directional growth of the seeds along the long axis, eventually leads to nanorods.
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Nanopartículas , Nanoestruturas , Micelas , Polimerização , PolímerosRESUMO
BACKGROUND AND OBJECTIVE: Mesenchymal stem cells (MSCs) have been widely used in tissue engineering, such as for regenerating the supporting structures of teeth destroyed by periodontal diseases. In recent decades, dental tissue-derived MSCs have drawn much attention owing to their accessibility, plasticity and applicability. Dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs) and gingival MSCs (GMSCs) are the most readily available MSCs among all types of dental MSCs. The purpose of this study was to comprehensively compare the characteristics of MSCs from dental pulp (DP), periodontal ligament (PDL) and gingiva (G) in vitro and thus provide insight into optimizing the performance of cells and seed cell selection strategies for tissue regeneration. MATERIALS AND METHODS: In this study, patient-matched (n = 5) cells derived from DP, PDL and G which, respectively, contained DPSCs, PDLSCs and GMSCs were evaluated using multiple methods in terms of their proliferation, senescence, apoptosis, multilineage differentiation and stemness maintenance after long-term passage. RESULTS: Mesenchymal stem cells-containing cells from G (MSCs/GCs) showed superior proliferation capability, whereas patient-matched MSCs-containing cells from PDL (MSCs/PDLCs) exhibited excellent osteogenic and adipogenic differentiation ability; MSCs-containing cells from DP (MSCs/DPCs) achieved mediocre results in both aspects. In addition, MSCs/GCs were the least susceptible to senescence, while MSCs/PDLCs were the most prone to ageing. Furthermore, the biological properties of these three types of cells were all affected after long-term in vitro culture. CONCLUSION: These three types of dental MSCs showed different biological characteristics. MSCs/PDLCs are the best candidate cells for bone regeneration, but the application of MSCs/PDLCs might be limited to certain number of passages. Improving the differentiation of MSCs/GCs remains the key issue regarding their application in tissue engineering.
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Proliferação de Células , Polpa Dentária/citologia , Gengiva/citologia , Células-Tronco Mesenquimais/fisiologia , Ligamento Periodontal/citologia , Engenharia Tecidual , Apoptose , Diferenciação Celular , Células Cultivadas , Senescência Celular , Humanos , Células-Tronco Mesenquimais/classificaçãoRESUMO
OBJECTIVE: To assemble infectious bronchitis virus (IBV)-like particles bearing the recombinant spike protein and investigate the humoral immune responses in chickens. RESULTS: IBV virus-like particles (VLPs) were generated through the co-infection with three recombinant baculoviruses separately encoding M, E or the recombinant S genes. The recombinant S protein was sufficiently flexible to retain the ability to self-assemble into VLPs. The size and morphology of the VLPs were similar to authentic IBV particles. In addition, the immunogenicity of IBV VLPs had been investigated. The results demonstrated that the efficiency of the newly generated VLPs was comparable to that of the inactivated M41 viruses in eliciting IBV-specific antibodies and neutralizing antibodies in chickens via subcutaneous inoculation. CONCLUSIONS: This work provides basic information for the mechanism of IBV VLP formation and develops a platform for further designing IBV VLP-based vaccines against IBV or other viruses.
Assuntos
Vírus da Bronquite Infecciosa/metabolismo , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/metabolismo , Virossomos/metabolismo , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Baculoviridae , Galinhas , Vetores Genéticos , Vírus da Bronquite Infecciosa/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/ultraestrutura , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/metabolismo , Virossomos/genéticaRESUMO
OBJECTIVES: To observe the effect of type 2 diabetes mellitus (T2DM) on mandibular bone regeneration and the expression of factors related to T helper cell 17 (Th17 cell) and regulatory T cell (Treg cell) in mice. METHODS: Thirty-six 6-week-old C57BL/6J male mice were randomly divided into normal control (NC) and T2DM groups. Fasting blood glucose levels were detected 0 d, 7 d, 14 d, and 28 d after surgery for mandibular defects. Hematoxylin-eosin (HE) staining was used in observing the bone after 7 d, 14 d, and 28 d of the healing process. Immunohistochemical staining was used in observing the expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), forkhead box protein P3 (Foxp3), retinoic acid related orphan receptor gamma T (RORγt), and protein tyrosine phosphatase non-receptor type 2 (PTPN2) after 7 d, 14 d, and 28 d of healing. RESULTS: HE staining showed that the area with new bones in the T2DM group was significantly smaller than that in the NC group. Immunohistochemical staining showed that the expression of osteogenesis related proteins ALP and RUNX2 were significantly reduced in the T2DM group. In addition, the number of RORγt positive cells increased, whereas the number of Foxp3 positive cells and the expression PTPN2 decreased significantly in the mandibular bone defect in mice with T2DM. CONCLUSIONS: T2DM significantly inhibit mandibular bone regeneration in mice. Decline in PTPN2 expression and the transition of Treg and Th17 may be the underlying molecular mechanisms.
Assuntos
Diabetes Mellitus Tipo 2 , Animais , Regeneração Óssea , Fatores de Transcrição Forkhead , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição TCF , Células Th17RESUMO
OBJECTIVE: To observe the influence of three types of dental ceramic alloys on magnetic resonance imaging (MRI). METHODS: Ni-Cr alloy, Co-Cr alloy, and Ti alloy were elaborated into three crowns with the same shape and size by computer aided design, computer aided manufacturing device. Afterwards we fixed the crown in the mouth of a volunteer at the same location separately. Then we scanned them with MRI. The extents of artifacts were compared. RESULTS: All these alloys caused MR artifacts. The extent of the artifact of Co-Cr alloy was larger than those of Ni-Cr alloy and Ti alloy under MRI. CONCLUSION: Ti alloy has the smallest influence on MRI than Ni-Cr alloy and Co-Cr alloy.
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Artefatos , Imageamento por Ressonância Magnética , Ligas Metalo-Cerâmicas , Adulto , Ligas de Cromo , Prótese Parcial Fixa , Humanos , MasculinoRESUMO
Curdlan, a bacteria-derived polysaccharide resource, possesses substantial potential for periodontal antimicrobial delivery. Here, the facile engineering of a functionalized curdlan/polydopamine (PDA) composite hydrogels was reported. The physiochemical evaluations of composite hydrogels proved their tunable properties associated with concentration of PDA including pore size, rheological property and swelling behavior. We have systematically assessed biocompatibility in vitro and found these hydrogels toxicity-free. Moreover, photothermal performance upon near infrared light (NIR) exposure was conducted and eventually indicated the best matches for antibacterial application. The acetate chlorhexidine (CHX) was chosen as a model antimicrobial and the release profiles demonstrated the entrapped CHX could be triggered and nicely controlled by NIR. The optimized bacteriostatic rate reached 99.9 %. Overall, we aimed to provide new curdlan-based hydrogels for periodontal antibacterial treatment by combining photothermal effect and antimicrobial simultaneously.
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Antibacterianos/química , Hidrogéis/química , Indóis/química , Polímeros/química , Polissacarídeos Bacterianos/química , beta-Glucanas/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Clorexidina/farmacologia , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Humanos , Raios Infravermelhos , Viabilidade Microbiana/efeitos dos fármacos , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Processos Fotoquímicos , Polissacarídeos Bacterianos/farmacologia , Porosidade , Reologia/métodos , Staphylococcus aureus/efeitos dos fármacos , beta-Glucanas/farmacologiaRESUMO
OBJECTIVE: To ascertain the fittest technical parameters by studying the application of macroporous resins used to purify active components of baicalin. METHODS: To evaluate the ability of adsorption and re-adsorption of macroporous resins selected, the statical and dynamic adsorption-readsorption durations were also investigated to select the optimum macroporous resins, with the content of flavonoids as the standard. RESULTS: The optimum macroporous resins was HPD-100. In the adsorption cours, the ratio between the amount of medicinal materials and the volume of macroporous resins was 3.0 and there was no more absorbed when the ratio was 12.5; the optimum ethanol concentration was 50% in readsorption duration. CONCLUSION: HPD-100 is the optimum macroporous resin to purify bailcalin and enhance its refined rate.
Assuntos
Flavonoides/isolamento & purificação , Plantas Medicinais/química , Resinas Sintéticas/química , Scutellaria baicalensis/química , Tecnologia Farmacêutica/métodos , Adsorção , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Etanol/química , Flavonoides/química , Concentração de Íons de Hidrogênio , Espectrofotometria UltravioletaRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) and hyperlipidemia are negatively related to bone regeneration. The aim of this study was to evaluate the effect of high-fat and high-glucose microenvironment on bone regeneration and to detect the expression of runt-related transcription factor 2 (Runx2) and transcriptional co-activator with PDZ-binding domain (TAZ) during this process. METHODS: After establishing a high-fat and high-glucose mouse model, a 1 mm × 1.5 mm bone defect was developed in the mandible. On days 7, 14, and 28 after operation, bone regeneration was evaluated by hematoxylin-eosin staining, Masson staining, TRAP staining, and immunohistochemistry, while Runx2 and TAZ expression were detected by immunohistochemistry, RT-PCR, and Western blot analysis. RESULTS: Our results showed that the inhibition of bone regeneration in high-fat and high-glucose group was the highest among the four groups. In addition, the expression of Runx2 in high-fat, high-glucose, and high-fat and high-glucose groups was weaker than that in the control group, but the expression of TAZ only showed a decreasing trend in the high-fat and high-glucose group during bone regeneration. CONCLUSIONS: In conclusion, these results suggest that high-fat and high-glucose microenvironment inhibits bone regeneration, which may be related to the inhibition of Runx2 and TAZ expression.
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Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Regeneração Óssea/fisiologia , Microambiente Celular/fisiologia , Subunidade alfa 1 de Fator de Ligação ao Core/biossíntese , Dieta Hiperlipídica/efeitos adversos , Glucose/toxicidade , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Regeneração Óssea/efeitos dos fármacos , Microambiente Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/antagonistas & inibidores , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Expressão Gênica , Glucose/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , TransativadoresRESUMO
Increasing attention has been paid to anaerobic ammonium oxidation (anammox) in river ecosystems due to their special role in the global nitrogen cycle from land to the ocean. This study have revealed the spatial patterns of anammox bacterial response to geographic characteristics and dam operation along the Yangtze River, using 15N tracers and molecular analyses of microbial communities in sediment samples over a 4300â¯km continuum. Here we found a significant temperature-related increase in anammox bacterial abundance and alpha diversity from mountainous area in the upper, fluvial plain area in the middle and lower reach, to the river mouth. In contrast, an opposite trend in anammox contribution to N2 production (ra) was observed down the Yangtze River due to enhanced denitrification induced by spatial heterogeneity of total organic carbon. Interestingly, the Three Gorges Dam resulted in an intensive erosion and thus a change from muddy to sandy sediments within 400â¯km downstream the dam, which readjusted the anammox community characterized with a decreased bacterial diversity and enhanced anammox contribution to nitrogen loss. Our study highlights the importance of natural and anthropogenic impacts on anammox bacterial community and function in a complex large river ecosystem.
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Compostos de Amônio/toxicidade , Monitoramento Ambiental , Poluentes Químicos da Água/toxicidade , Bactérias , China , Desnitrificação , Ecossistema , Sedimentos Geológicos , Nitrogênio , Oxirredução , RNA Ribossômico 16S , Rios/química , Microbiologia da ÁguaRESUMO
Salecan polysaccharide produced by Agrobacterium sp. ZX09 is an attractive biopolymer to construct hydrogel scaffolds for cell culture. However, some limitations such as poor mechanical performance, complicated fabrication process and slow gelation times still exist in the biomedical applications of microbial-based salecan polysaccharide hydrogels. Here, a series of polysaccharide hydrogels composed of salecan and agarose with adjustable structural properties are designed. The resultant hybrid salecan/agarose hydrogels exhibit controllable physical and chemical properties including thermal stability, water uptake, mechanical strength and microarchitecture, which can be readily realized with minimum change of the polysaccharide content. Furthermore, cytotoxicity assays reveal that the designed composite hydrogels are non-toxic. More importantly, these hydrogels support cell survival, proliferation, and migration. Together, this work opens up a new avenue to build polysaccharide hydrogel platforms for tissue engineering.
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Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Hidrogéis/química , Sefarose/química , beta-Glucanas/química , Agrobacterium/química , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Camundongos , Reologia , Engenharia TecidualRESUMO
Background: An equal number of women and men are now graduating from dental school, but women dentists have lower income and are less likely to achieve positions of leadership, including within dental academia. Materials and Methods: Demographic information and academic rank were obtained for all faculty at the eight dental schools who received the most funding from the National Institute of Dental and Craniofacial Research in 2017. Years since dental school graduation, total number of PubMed-indexed citations, first- and last-author publications, and H-index were determined for each faculty member. Gender differences in productivity and advancement were evaluated. Results: Of 702 faculty members, 36.5% were female; only 24.4% of full professors were women. Men had significantly higher numbers of publications (30.2 [95% confidence interval [CI, 28.6-39.5] vs. 20.4 [95% CI 16.3-24.6], p = 0.02) and higher H-index (8.2 [95% CI 7.1-9.1] vs. 4.7 [95% CI 3.9-5.5], p < 0.0001). Women had graduated more recently than their male colleagues at all levels of academic advancement (overall 22.83 years [95% CI 21.29-24.39] vs. 30.19 years [95% CI 28.84-31.55], p < 0.0001). When corrected for academic productivity and years since graduation, the association between gender and academic rank was not significant. Conclusions: Women are underrepresented at each academic rank except instructor; however, women may advance more quickly than their male counterparts. Increasing scholarship and mentorship opportunities for female faculty members may help improve gender equity in dental academia.
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Mobilidade Ocupacional , Odontólogas/estatística & dados numéricos , Docentes de Odontologia/estatística & dados numéricos , Faculdades de Odontologia/organização & administração , Eficiência , Feminino , Humanos , Liderança , Masculino , Projetos Piloto , Fatores Sexuais , Sexismo , Estados UnidosRESUMO
Orthodontic tooth movement (OTM) is a periodontal tissue remodeling and regeneration process that is caused by bio-mechanical stimulation. This mechanical-chemical transduction process involves a variety of biological factors and signaling pathways. It has been shown that the Hippo-YAP/TAZ signaling pathway plays a pivotal role in the mechanical-chemical signal transduction process. Moreover, YAP and TAZ proteins interact with RUNX family proteins via different mechanisms. To explore the regulation of the Hippo signaling pathway during periodontal tissue remodeling, we examined the upper first molar OTM model in rats. We examined YAP, TAZ and RUNX2 expression at 12 hours, 24 hours, 2 days (2d), 4 days, 7 days (7d) and 14 days (14d) after force application. Haemotoxylin and eosin staining, immunohistochemical staining and western blot analysis were used to examine the expression level and localization of these proteins. We found that YAP, TAZ and RUNX2 expression started increasing at 2d, YAP and TAZ expression was proportional to the orthodontic force applied until peaking at 7d, and at 14d the expression started to decrease. YAP and TAZ were observed in osteocytes, bone matrix and periodontal ligament cells during OTM. Furthermore, using double labeling immunofluorescence staining, we found that the increase in TAZ expression was associated with RUNX2 expression, however, YAP and RUNX2 showed different expression patterns. These results suggest that the Hippo-YAP/TAZ signaling pathway participates in periodontal tissue remodeling through various mechanisms; TAZ may adjust bone tissue remodeling through RUNX2 during OTM, while YAP may regulate periodontal cell proliferation and differentiation.
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Proteínas Reguladoras de Apoptose/análise , Subunidade alfa 1 de Fator de Ligação ao Core/análise , Técnicas de Movimentação Dentária , Fatores de Transcrição/análise , Aciltransferases , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Transdução de Sinais , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAPRESUMO
Cationic solid lipid nanoparticles (cSLNs) are promising nanoparticles for controlled drug delivery. Increasing surface charge and/or reducing PEG density enhance cellular uptake of cSLNs in vitro, but for unknown reasons fail to improve drug delivery in vivo. Herein, we show that cSLNs present a risk for systemic platelet activation and aggregation in vivo, and this toxic effect can be significantly augmented by increasing the surface charge and reducing the PEG density. Furthermore, thrombotic toxicity significantly reduces blood circulation time and in vivo cellular uptake of cSLNs. Mechanistic studies revealed that the intrinsic coagulation pathway is responsible for cSLN-induced platelet activation. Importantly, pretreatment of the recipient mice with heparin, a clinically-approved intrinsic coagulation inhibitor, was highly effective in preventing toxicity, prolonging the circulation time of cSLNs, and improving cSLN-based antitumor drug delivery and therapeutic efficacy in tumor-bearing mice. This study offers a useful strategy for improving both the safety and efficacy of cSLN-based anticancer therapies.
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Coagulação Sanguínea/fisiologia , Sistemas de Liberação de Medicamentos , Lipídeos/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Circulação Sanguínea , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/metabolismo , Cátions , Linhagem Celular Tumoral , Feminino , Heparina/farmacologia , Lipídeos/toxicidade , Camundongos Endogâmicos BALB C , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Neoplasias/patologia , Ativação Plaquetária , Polietilenoglicóis/química , Trombose/patologiaRESUMO
Gold nanoparticles (AuNPs) have been extensively explored as a drug carrier and have been widely used to provide advanced biomedical research tools in diagnostic imaging and therapy for cancer. Although the mononuclear phagocyte system and immune system are known to play the main roles in the clearance of AuNPs during the circulation, the particle distribution within the immune cells under the condition of immune dysfunction caused by tumor growth has not been thoroughly studied. Here, the cellular distribution of Cy5 labeled AuNPs with diameters of 5, 30 and 50 nm is characterized within the immune populations of the blood, spleen and bone marrow from tumor free and tumor bearing mice using flow cytometry. Tumor-associated immune dysfunction was observed in all immune organs and cell lineages, and it changed with tumor growth. Furthermore, the particle cellular distribution significantly changed in the tumor bearing mice compared with the tumor free mice. Finally, the particle distribution in the immune cells was also different at different stages of the tumor. Overall, these results can help inform and influence future AuNP design criteria including the future applications for nanoparticle-mediated cancer therapy.
Assuntos
Ouro/química , Ouro/farmacocinética , Nanopartículas Metálicas , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Tamanho da Partícula , Polietilenoglicóis/química , Distribuição Tecidual , Carga TumoralRESUMO
BACKGROUND: Tooth is vital not only for a good smile, but also good health. Yet, we lose tooth regularly due to accidents or diseases. An ideal solution to this problem is to regenerate tooth with patients' own cells. Here we describe the generation of tooth-like structures from integration-free human urine induced pluripotent stem cells (ifhU-iPSCs). RESULTS: We first differentiated ifhU-iPSCs to epithelial sheets, which were then recombined with E14.5 mouse dental mesenchymes. Tooth-like structures were recovered from these recombinants in 3 weeks with success rate up to 30% for 8 different iPSC lines, comparable to H1 hESC. We further detected that ifhU-iPSC derived epithelial sheets differentiated into enamel-secreting ameloblasts in the tooth-like structures, possessing physical properties such as elastic modulus and hardness found in the regular human tooth. CONCLUSION: Our results demonstrate that ifhU-iPSCs can be used to regenerate patient specific dental tissues or even tooth for further drug screening or regenerative therapies.
RESUMO
OBJECTIVE: To explore the expression of glucose transporter (GLUT)-1 and insulin receptor (IR) alpha1 in osteoblast obtained from diabetic rats' mandibles. METHODS: The expression of GLUT-1 and IR alpha1 of diabetic and control groups were measured by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry stain. RESULTS: The mRNA expressions of GLUT-1 and IR alpha1 of diabetic group were significantly higher than control group (P<0.05). The protein expressions of GLUT-1 and IR alpha1 were similar to the mRNA expressions. CONCLUSION: Osteoblasts obtained from diabetic rats' mandibles keep the adaptation changes to hyperglycemia and hypoinsulinemia, which may contribute to their dysfunction.