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1.
Clin Oral Implants Res ; 35(4): 407-418, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38287504

RESUMO

OBJECTIVES: To study bone healing of two-wall bone defects after alveolar ridge preservation using mineralized dentin matrix. MATERIALS AND METHODS: After distal roots extraction of second and fourth premolars (P2, P4) on one lateral mandible in 12 beagles, two-wall bone defects (5 × 5 × 5 mm) were surgically created distally to the remaining mesial roots of P2 and P4. A total of 24 sites were randomly allocated to three groups (implant material- time of execution): mineralized dentin matrix (MDM)-3 m (MDM + collagen membrane; 3 months), MDM-6 m (MDM particles + collagen membrane; 6 months), and C-6 m (collagen membrane only; 6 months). Clinical, radiographic, digital, and histological examinations were performed 3 and 6 months after surgery. RESULTS: The bone healing in MDM groups were better compared to Control group (volume of bone regenerated in total: 25.12 mm3 vs. 13.30 mm3, p = .046; trabecular volume/total volume: 58.84% vs. 39.18%, p = .001; new bone formation rate: 44.13% vs. 31.88%, p = .047). Vertically, the radiological bone level of bone defect in MDM-6 m group was higher than that in C-6 m group (vertical height of bone defect: 1.55 mm vs. 2.74 mm, p = .018). Horizontally, no significant differences in buccolingual bone width were found between MDM and C groups at any time or at any level below the alveolar ridge. The percentages of remaining MDM were <1% in both MDM-3 m and MDM-6 m groups. CONCLUSIONS: MDM improved bone healing of two-wall bone defects and might be considered as a socket fill material used following tooth extraction.


Assuntos
Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Cães , Animais , Alvéolo Dental/cirurgia , Alvéolo Dental/patologia , Processo Alveolar/cirurgia , Processo Alveolar/patologia , Colágeno , Extração Dentária , Dentina , Perda do Osso Alveolar/prevenção & controle , Perda do Osso Alveolar/cirurgia , Perda do Osso Alveolar/patologia
2.
Nature ; 542(7640): 228-231, 2017 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-28135722

RESUMO

Deuterostomes include the group we belong to (vertebrates) as well as an array of disparate forms that include echinoderms, hemichordates and more problematic groups such as vetulicolians and vetulocystids. The Cambrian fossil record is well-populated with representative examples, but possible intermediates are controversial and the nature of the original deuterostome remains idealized. Here we report millimetric fossils, Saccorhytus coronarius nov. gen., nov. sp., from an Orsten-like Lagerstätte from the earliest Cambrian period of South China, which stratigraphically are amongst the earliest of deuterostomes. The bag-like body bears a prominent mouth and associated folds, and behind them up to four conical openings on either side of the body as well as possible sensory structures. An anus may have been absent, and correspondingly the lateral openings probably served to expel water and waste material. This new form has similarities to both the vetulicolians and vetulocystids and collectively these findings suggest that a key step in deuterostome evolution was the development of lateral openings that subsequently were co-opted as pharyngeal gills. Depending on its exact phylogenetic position, the meiofaunal habit of Saccorhytus may help to explain the major gap between divergence times seen in the fossil record and estimates based on molecular clocks.


Assuntos
Evolução Biológica , Fósseis , Tronco/anatomia & histologia , Canal Anal , Animais , China , Brânquias/anatomia & histologia , Boca/anatomia & histologia , Filogenia
3.
Environ Res ; 229: 115925, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37086884

RESUMO

Ruminant animals house a dense and diverse community of microorganisms in their rumen, an enlarged compartment in their stomach, which provides a supportive environment for the storage and microbial fermentation of ingested feeds dominated by plant materials. The rumen microbiota has acquired diverse and functionally overlapped enzymes for the degradation of plant cell wall polysaccharides. In rumen Bacteroidetes, enzymes involved in degradation are clustered into polysaccharide utilization loci to facilitate coordinated expression when target polysaccharides are available. Firmicutes use free enzymes and cellulosomes to degrade the polysaccharides. Fibrobacters either aggregate lignocellulose-degrading enzymes on their cell surface or release them into the extracellular medium in membrane vesicles, a mechanism that has proven extremely effective in the breakdown of recalcitrant cellulose. Based on current metagenomic analyses, rumen Bacteroidetes and Firmicutes are categorized as generalist microbes that can degrade a wide range of polysaccharides, while other members adapted toward specific polysaccharides. Particularly, there is ample evidence that Verrucomicrobia and Spirochaetes have evolved enzyme systems for the breakdown of complex polysaccharides such as xyloglucans, peptidoglycans, and pectin. It is concluded that diversity in degradation mechanisms is required to ensure that every component in feeds is efficiently degraded, which is key to harvesting maximum energy by host animals.


Assuntos
Metagenoma , Rúmen , Animais , Rúmen/metabolismo , Rúmen/microbiologia , Lignina , Bactérias/genética , Bactérias/metabolismo , Polissacarídeos/metabolismo , Bacteroidetes/genética , Bacteroidetes/metabolismo
4.
Appl Microbiol Biotechnol ; 107(13): 4395-4408, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37266585

RESUMO

In vitro intestinal epithelium models have drawn great attention to investigating intestinal biology in recent years. However, the difficulty to maintain the normal physiological status of primary intestinal epithelium in vitro limits the applications. Here, we designed patterned electrospun polylactic acid (PLA) nanofibrous membranes with crypt-like topography and mimic ECM fibrous network to support crypt culture and construct in vitro intestinal epithelium models. The patterned electrospun PLA nanofibrous membranes modified with Matrigels at 0 °C showed high biocompatibility and promoted cell growth and proliferation. The constructed duodenum epithelium models and colon epithelium models on the patterned electrospun PLA nanofibrous membranes expressed the typical differentiation markers of intestinal epithelia and the gene expression levels were close to the original tissues, especially with the help of probiotics. The constructed intestinal epithelium models could be used to assess probiotic adhesion and colonization, which were verified to show significant differences with the Caco-2 cell models due to the different cell types. These findings provide new insights and a better understanding of the roles of biophysical, biochemical, and biological signals in the construction of in vitro intestinal epithelium models as well as the potential applications of these models in the study of host-gut microbes interactions. KEY POINTS: • Patterned electrospun scaffold has crypt-like topography and ECM nanofibrous network. • Matrigels at 0°C modify scaffolds more effectively than at 37°C. • Synergy of biomimic scaffold and probiotics makes in vitro model close to tissue.


Assuntos
Nanofibras , Alicerces Teciduais , Humanos , Engenharia Tecidual , Células CACO-2 , Diferenciação Celular , Mucosa Intestinal/metabolismo , Poliésteres/metabolismo
5.
Cancer Immunol Immunother ; 71(12): 2969-2983, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35546204

RESUMO

Heparanase has been identified as a universal tumor-associated antigen, but heparanase epitope peptides are difficult to recognize. Therefore, it is necessary to explore novel strategies to ensure efficient delivery to antigen-presenting cells. Here, we established a novel immunotherapy model targeting antigens to dendritic cell (DC) receptors using a combination of heparanase CD4+ and CD8+ T-cell epitope peptides to achieve an efficient cytotoxic T-cell response, which was associated with strong activation of DCs. First, pegylated poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) were used to encapsulate a combined heparanase CD4+ and CD8+ T-cell epitope alone or in combination with Toll-like receptor 3 and 7 ligands as a model antigen to enhance immunogenicity. The ligands were then targeted to DC cell-surface molecules using a DEC-205 antibody. The binding and internalization of these PLGA NPs and the activation of DCs, the T-cell response and the tumor-killing effect were assessed. The results showed that PLGA NPs encapsulating epitope peptides (mHpa399 + mHpa519) could be targeted to and internalized by DCs more efficiently, stimulating higher levels of IL-12 production, T-cell proliferation and IFN-γ production by T cells in vitro. Moreover, vaccination with DEC-205-targeted PLGA NPs encapsulating combined epitope peptides exhibited higher tumor-killing efficacy both in vitro and in vivo. In conclusion, delivery of PLGA NP vaccines targeting DEC-205 based on heparanase CD4+ and CD8+ T-cell epitopes are suitable immunogens for antitumor immunotherapy and have promising potential for clinical applications.


Assuntos
Nanopartículas , Neoplasias , Humanos , Epitopos de Linfócito T/metabolismo , Ácido Poliglicólico/química , Ácido Poliglicólico/metabolismo , Receptor 3 Toll-Like , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/metabolismo , Ácido Láctico/química , Ácido Láctico/metabolismo , Ligantes , Células Dendríticas , Imunoterapia/métodos , Linfócitos T CD8-Positivos , Interleucina-12/metabolismo , Peptídeos/metabolismo , Linfócitos T CD4-Positivos , Polietilenoglicóis
6.
J Anat ; 240(4): 669-677, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34761390

RESUMO

In 2016, two adult male sperm whales beached off of Yangkou Port in Nantong City, Jiangsu Province, China. The local government planned to preserve them as specimens, one was entrusted to Dalian Hoffen Biological Co., Ltd., and thus became the first sperm whale to be preserved by plastination. The other sperm whale was preserved in Nantong by the traditional stripping method (The skin was preserved, and then the prosthesis was filled into the skin to preserve the specimens. The material of the prosthesis was polyurethane. The outline of the animal was sculpted by suturing the skin like a bag and filling it with polyurethane). Plastination of such a large marine mammal allowed us to view the mutual adaptations of its internal structure to its specific living environment and daily habits. This sperm whale is the largest specimen in the world and this is the first time a sperm whale has been preserved using the plastination method. The plastination process also provides a method for studying the anatomy of large marine mammals for humans to understand deep-sea organisms at close contact and visual level. The plastination of this sperm whale promises to be a world class resource holding tremendous scientific, educational, and artistic value.


Assuntos
Plastinação , Cachalote , Animais , China , Masculino , Poliuretanos
7.
Lasers Med Sci ; 36(3): 619-629, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33590365

RESUMO

The aim of this study was comparing different lasers with conventional non-surgical treatment (CNT) for the management of peri-implantitis, regarding probing depth (PD), plaque index (PLI), clinical attachment level (CAL), and sulcus bleeding index (SBI). Randomized controlled trials (RCTs) on different lasers and CNT for peri-implantitis were searched. Pairwise and network meta-analyses were performed to analyze the PD, PLI, CAL, and SBI outcomes. The risk of bias, evidence quality, statistical heterogeneity, and ranking probability were also evaluated. Eleven studies were included in this study, involving three types of lasers. Diode + CNT had significantly superior efficacy to CNT alone, regarding PD reduction, while Er:YAG + CNT had significantly superior efficacy than CNT in terms of the PLI, CAL, and SBI. The highest probability of being most effective for PD was diode + CNT (49%), while Er:YAG + CNT had the highest probability of improving the PLI, CAL, and SBI (66%, 53%, and 79%, respectively). Diode + CNT was significantly superior for PD management in peri-implantitis compared with CNT alone, while Er:YAG + CNT significantly improved the PLI, CAL, and SBI. Therefore, Er:YAG + CNT might be recommended methods considered for management of peri-implantitis.


Assuntos
Lasers , Peri-Implantite/cirurgia , Adulto , Índice de Placa Dentária , Hemorragia/etiologia , Humanos , Metanálise em Rede , Probabilidade , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Resultado do Tratamento
8.
Proc Natl Acad Sci U S A ; 114(33): 8835-8840, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28760981

RESUMO

The early Cambrian problematica Xianguangia sinica, Chengjiangopenna wangii, and Galeaplumosus abilus from the Chengjiang biota (Yunnan, China) have caused much controversy in the past and their phylogenetic placements remain unresolved. Here we show, based on exceptionally preserved material (85 new specimens plus type material), that specimens previously assigned to these three species are in fact parts of the same organism and propose that C. wangii and G. abilus are junior synonyms of X. sinica Our reconstruction of the complete animal reveals an extinct body plan that combines the characteristics of the three described species and is distinct from all known fossil and living taxa. This animal resembled a cnidarian polyp in overall morphology and having a gastric cavity partitioned by septum-like structures. However, it possessed an additional body cavity within its holdfast, an anchoring pit on the basal disk, and feather-like tentacles with densely ciliated pinnules arranged in an alternating pattern, indicating that it was a suspension feeder rather than a predatory actiniarian. Phylogenetic analyses using Bayesian inference and maximum parsimony suggest that X. sinica is a stem-group cnidarian. This relationship implies that the last common ancestor of X. sinica and crown cnidarians was probably a benthic, polypoid animal with a partitioned gastric cavity and a single mouth/anus opening. This extinct body plan suggests that feeding strategies of stem cnidarians may have been drastically different from that of their crown relatives, which are almost exclusively predators, and reveals that the morphological disparity of total-group Cnidaria is greater than previously assumed.


Assuntos
Cnidários/anatomia & histologia , Cnidários/classificação , Fósseis , Animais
9.
J Oral Rehabil ; 47(12): 1566-1573, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32969078

RESUMO

BACKGROUND: Research on resolving implant fracture is still gaining attention as it can be a serious treatment failure outcome. The implant fracture is likely to occur due to increased stress in implant body associated with peri-implant bone resorption. OBJECTIVE: This study aimed to investigate the relationship between degree of peri-implant bone resorption and stress distribution in implant body by using finite element analysis (FEA). METHODS: The magnitude and direction of loads on implants at the mandibular molar region were measured with 3D piezoelectric force transducers in a patient during maximal voluntary clenching, grinding and tapping to obtain input for the FEA as the loading condition. Simplified finite element bone models were generated to simulate the six patterns of peri-implant bone resorption progression which the bone levels from implant platform were set at 0, 1, 2, 3, 4 and 5 mm. Three types of implants with different diameters (3.5, 4.0 and 5.0 mm), corresponding abutments and screws were created. FEA using the in vivo measured load was conducted to investigate how peri-implant bone loss affects stress distribution in the implant body. RESULTS: Loading condition affected stress distribution in the implant body. As bone resorption increased, von Mises stress in the implant body became larger, which was marked in smaller diameter implants, and this change was amply demonstrated when the bone resorption increased from 0 to 2 mm. CONCLUSION: The FEA demonstrated that as peri-implant bone loss increased, the magnitude of stress in the implant increased, especially in small diameter implants.


Assuntos
Reabsorção Óssea , Implantes Dentários , Fenômenos Biomecânicos , Reabsorção Óssea/etiologia , Simulação por Computador , Implantes Dentários/efeitos adversos , Análise do Estresse Dentário , Análise de Elementos Finitos , Humanos , Estresse Mecânico
10.
J Prosthet Dent ; 124(1): 26-35.e2, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31753461

RESUMO

STATEMENT OF PROBLEM: Differences between ceramic and metal-ceramic implant-supported fixed dental prostheses are unclear. PURPOSE: The purpose of this systematic review and meta-analysis was to compare the technical, biological, and esthetic complication rates of implant-supported ceramic and metal-ceramic restorations. MATERIAL AND METHODS: Six databases were searched to identify randomized controlled clinical trials (RCTs) and prospective and retrospective cohort studies of implant-supported fixed dental prostheses. The survival rate, marginal adaptation, marginal bone loss, pocket probing depth, crown color match, and mucosal discoloration of ceramic and metal-ceramic single crowns were assessed. For implant-supported fixed partial dental prostheses (FPDPs), only the survival rate was assessed. The risk of bias was assessed for individual studies and across studies by using the Cochrane guidelines, Newcastle-Ottawa scale, and funnel plots. RESULTS: Twenty studies were included in this meta-analysis. Ceramic and metal-ceramic implant-supported single crowns were compared in terms of the survival rate (OR=0.84 [0.32, 2.23], P=.730), marginal adaptation (mean difference [MD]=0.33 [0.19, 0.47], P<.001), marginal bone loss (MD=-0.03 [-0.07, 0.02], P=.260), pocket probing depth (MD=-0.07 [-0.14, 0.00], P=.060), crown color match (MD=-0.15 [-0.29, 0.00], P=.040), and mucosal discoloration (standardized mean difference [SMD]=-0.14 [-0.86, 0.58], P=.710). The survival rate of ceramic and metal-ceramic implant-supported FPDPs was also compared (odds ratio [OR]=1.92 [1.26, 2.94], P=.003). CONCLUSIONS: No significant difference was observed between ceramic and metal-ceramic implant-supported single crowns in terms of the survival rate, marginal bone loss, pocket probing depth, or mucosal discoloration. However, metal-ceramic single crowns had better marginal adaptation and poorer crown color match than did ceramic single crowns. In addition, current evidence indicates that metal-ceramic implant-supported FPDPs might have a higher survival rate than ceramic FPDPs.


Assuntos
Implantes Dentários , Falha de Restauração Dentária , Cerâmica , Coroas , Planejamento de Prótese Dentária , Prótese Dentária Fixada por Implante , Estética Dentária , Metais
11.
J Environ Manage ; 245: 105-113, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31150901

RESUMO

Thin-walled multi-cavities ß-cyclodextrin polymers (Hß-CDs) were prepared by the suspension polymerization method using SiO2 nanoparticles as a template. The components and morphology structure of Hß-CDs were characterized by FTIR, BET, SEM, and TEM. The adsorption performances of the prepared nano-adsorbent Hß-CDs on crystal violet (CV), heavy metal ions, some cationic, neutral, and anionic dyes were investigated. The influences of the pH and ionic strength on CV adsorption by the Hß-CDs were explored. The correlation coefficient (R2) of pseudo-second-order kinetic model reached 0.9984 and the adsorption isotherm was closer to the Langmuir model. As the temperature increased, the R2 of the Freundlich isotherm model rose. Compared to anionic ones and heavy metal ions, Hß-CDs had a better adsorption efficiency for cationic dyes. Dynamic adsorption also indicated the thin-walled multi-cavities structure was beneficial for improving absorptivity and application of ß-cyclodextrin polymers. In addition, the Hß-CDs exhibited potentially applicable for the regeneration and reuse with the removal efficiency of CV was as high as 89% in the fourth cycle.


Assuntos
Poluentes Químicos da Água , Purificação da Água , beta-Ciclodextrinas , Adsorção , Celulose , Corantes , Ciclodextrinas , Polímeros , Dióxido de Silício
12.
J Evid Based Dent Pract ; 19(2): 115-130, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31326044

RESUMO

OBJECTIVES: The aim of the study was to evaluate the immediate and long-term desensitizing effect of lasers in reducing dentine hypersensitivity (DH) compared with negative controls. MATERIAL AND METHODS: Six databases were searched to identify relevant articles published up to June 8, 2018. Randomized controlled trials comparing lasers with placebo or no treatment control in adult patients who suffer from DH were included. The risk of bias was assessed according to the Cochrane guidelines, and the quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation tool. Inverse-variance random effects meta-analyses of standardized mean differences and 95% confidence intervals were performed using the RevMan 5.3 software. RESULTS: Twenty-two randomized controlled trials were finally included in the meta-analysis, and 21 studies of these were conducted to analyze the immediate and long-term effects. All types of lasers had better immediate and long-term desensitizing effects on DH than negative controls. The quality of evidence of the included studies showed that lasers compared with negative controls had moderate-quality immediate and long-term effects on DH. The statistical heterogeneity of these comparisons was high, for which the result of I2 ranged from 90% to 98%. CONCLUSIONS: Our results indicate that all types of lasers had a better desensitizing effect on DH than negative controls, both in immediate and long term. Furthermore, more high-quality studies with a large sample size are needed to confirm our results (PROSPERO CRD42018102260).


Assuntos
Sensibilidade da Dentina , Terapia a Laser , Adulto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
AAPS PharmSciTech ; 18(3): 749-758, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27287244

RESUMO

A novel multifunctional drug delivery system was fabricated by conjugating galactose-based polymer, methoxy-poly(ethylene glycol)-block-poly(6-O-methacryloyl-D-galactopyranose) (mPEG-b-PMAGP) with doxorubicin (DOX) via an acid-labile carbamate linkage. The mPEG-b-PMAGP-co-DOX nanoparticles were spherical in shape, and the diameter determined by dynamic light scattering (DLS) was 54.84 ± 0.58 nm, larger than that characterized by transmission electron microscopy (TEM). The in vitro drug release profiles were studied, and the release of DOX from the nanoparticles was pH-responsive. The cellular uptake behavior of free-DOX and mPEG-b-PMAGP-co-DOX nanoparticles by asialoglycoprotein (ASGP) receptor-positive cancer cell line (HepG2) and ASGP receptor-negative cancer cell lines (MCF-7 and A549 cells) was evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM), respectively. The mPEG-b-PMAGP-co-DOX nanoparticles which contain galactose functional groups exhibited higher cellular uptake behavior via ASGP receptor-mediated endocytosis in HepG2 cells than in other two cancer cells. The in vitro cytotoxicity assay manifested that the mPEG-b-PMAGP-co-DOX nanoparticles exhibited higher anticancer efficacy against HepG2 cells than MCF-7 cells. These results indicated that the multifunctional mPEG-b-PMAGP-co-DOX nanoparticles possessing pH-responsible and hepatoma-targeting function have great potential to be used as a targeting drug delivery system for hepatoma therapy.


Assuntos
Doxorrubicina/química , Doxorrubicina/farmacologia , Galactose/química , Polímeros/química , Células A549 , Antineoplásicos/química , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Células MCF-7 , Nanopartículas/química , Polietilenoglicóis/química
14.
J Biol Chem ; 290(6): 3198-208, 2015 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-25492868

RESUMO

Hand-foot-and-mouth disease (HFMD) remains a major health concern in the Asia-Pacific regions, and its major causative agents include human enterovirus 71 (EV71) and coxsackievirus A16. A desirable vaccine against HFMD would be multivalent and able to elicit protective responses against multiple HFMD causative agents. Previously, we have demonstrated that a thermostable recombinant EV71 vaccine candidate can be produced by the insertion of a foreign peptide into the BC loop of VP1 without affecting viral replication. Here we present crystal structures of two different naturally occurring empty particles, one from a clinical C4 strain EV71 and the other from its recombinant virus containing an insertion in the VP1 BC loop. Crystal structure analysis demonstrated that the inserted foreign peptide is well exposed on the particle surface without significant structural changes in the capsid. Importantly, such insertions do not seem to affect the virus uncoating process as illustrated by the conformational similarity between an uncoating intermediate of another recombinant virus and that of EV71. Especially, at least 18 residues from the N terminus of VP1 are transiently externalized. Altogether, our study provides insights into vaccine development against HFMD.


Assuntos
Capsídeo/química , Enterovirus Humano A/química , Vacinas de Partículas Semelhantes a Vírus/química , Sequência de Aminoácidos , Capsídeo/ultraestrutura , Cristalografia por Raios X , Enterovirus Humano A/genética , Enterovirus Humano A/imunologia , Dados de Sequência Molecular
15.
J Virol ; 88(6): 3114-26, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24352461

RESUMO

UNLABELLED: Human enterovirus 71 (EV71) is the major causative agent of severe hand-foot-and-mouth diseases (HFMD) in young children, and structural characterization of EV71 during its life cycle can aid in the development of therapeutics against HFMD. Here, we present the atomic structures of the full virion and an uncoating intermediate of a clinical EV71 C4 strain to illustrate the structural changes in the full virion that lead to the formation of the uncoating intermediate prepared for RNA release. Although the VP1 N-terminal regions observed to penetrate through the junction channel at the quasi-3-fold axis in the uncoating intermediate of coxsackievirus A16 were not observed in the EV71 uncoating intermediate, drastic conformational changes occur in this region, as has been observed in all capsid proteins. Additionally, the RNA genome interacts with the N-terminal extensions of VP1 and residues 32 to 36 of VP3, both of which are situated at the bottom of the junction. These observations highlight the importance of the junction for genome release. Furthermore, EV71 uncoating is associated with apparent rearrangements and expansion around the 2- and 5-fold axes without obvious changes around the 3-fold axes. Therefore, these structures enabled the identification of hot spots for capsid rearrangements, which led to the hypothesis that the protomer interface near the junction and the 2-fold axis permits the opening of large channels for the exit of polypeptides and viral RNA, which is an uncoating mechanism that is likely conserved in enteroviruses. IMPORTANCE: Human enterovirus 71 (EV71) is the major causative agent of severe hand-foot-and-mouth diseases (HFMD) in young children. EV71 contains an RNA genome protected by an icosahedral capsid shell. Uncoating is essential in EV71 life cycle, which is characterized by conformational changes in the capsid to facilitate RNA release into host cell. Here we present the atomic structures of the full virion and an uncoating intermediate of a clinical C4 strain of EV71. Structural analysis revealed drastic conformational changes associated with uncoating in all the capsid proteins near the junction at the quasi-3-fold axis and protein-RNA interactions at the bottom of the junction in the uncoating intermediate. Significant capsid rearrangements also occur at the icosahedral 2- and 5-fold axes but not at the 3-fold axis. Taking the results together, we hypothesize that the junction and nearby areas are hot spots for capsid breaches for the exit of polypeptides and viral RNA during uncoating.


Assuntos
Capsídeo/química , Enterovirus Humano A/química , Doença de Mão, Pé e Boca/virologia , Capsídeo/metabolismo , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Cristalização , Enterovirus Humano A/genética , Enterovirus Humano A/metabolismo , Humanos , Modelos Moleculares
16.
Gastroenterol Nurs ; 38(6): 417-28, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26626031

RESUMO

During the dual-therapy era, many patients with chronic hepatitis C discontinued therapy for reasons other than lack of efficacy (non-LOE). We determined whether selected patient characteristics predicted non-LOE discontinuation using national databases of U.S. veterans with Genotypes 1-4. We identified U.S. veterans in the Veterans Health Administration system in 2004-2009 who had hepatitis C-confirming RNA laboratory results and initiated therapy with pegylated interferon and ribavirin. We used a rule to classify patients who discontinued pegylated interferon early, based on pharmacy refill and viral response data. Multivariate Cox regression was used to identify predictors of non-LOE discontinuation. Of 321,238 patients with a hepatitis C International Classification of Diseases, Ninth Revision, code, 15,297 (4.8%) met all inclusion criteria. Non-LOE discontinuers comprised 30.3% of patients. For Genotypes 1-4, the predictors (adjusted hazard ratio) of greatest magnitude were comorbidities of myocardial infarction/congestive heart failure (1.36), renal disease (1.34), and platelets 100/mm or more (1.38). For Genotypes 2 and 3, predictors of greatest magnitude were Black race (1.30), myocardial infarction/congestive heart failure (1.84), albumin 3.5 mg/dl or more (1.65), sleep aid use (1.32), and poor persistence with antidepressants (1.31) and antihypertensive agents (1.37). Our study suggests that many host factors may have contributed to non-LOE dual-therapy discontinuation in veterans and may possibly predict non-LOE discontinuation in triple therapy.


Assuntos
Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Feminino , Previsões , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Ribavirina/administração & dosagem , Estados Unidos , Veteranos
17.
Acta Odontol Scand ; 72(8): 839-45, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24791610

RESUMO

OBJECTIVE: To examine the initial viscosity and adhesive strength of modern denture adhesives in vitro. MATERIALS AND METHODS: Three cream-type denture adhesives (Poligrip S, Corect Cream, Liodent Cream; PGS, CRC, LDC) and three powder-type denture adhesives (Poligrip Powder, New Faston, Zanfton; PGP, FSN, ZFN) were used in this study. The initial viscosity was measured using a controlled-stress rheometer. The adhesive strength was measured according to ISO-10873 recommended procedures. All data were analyzed independently by one-way analysis of variance combined with a Student-Newman-Keuls multiple comparison test at a 5% level of significance. RESULTS: The initial viscosity of all the cream-type denture adhesives was lower than the powder-type adhesives. Before immersion in water, all the powder-type adhesives exhibited higher adhesive strength than the cream-type adhesives. However, the adhesive strength of cream-type denture adhesives increased significantly and exceeded the powder-type denture adhesives after immersion in water. For powder-type adhesives, the adhesive strength significantly decreased after immersion in water for 60 min, while the adhesive strength of the cream-type adhesives significantly decreased after immersion in water for 180 min. CONCLUSION: Cream-type denture adhesives have lower initial viscosity and higher adhesive strength than powder type adhesives, which may offer better manipulation properties and greater efficacy during application.


Assuntos
Adesivos/química , Retenção de Dentadura , Adesividade , Humanos , Imersão , Teste de Materiais , Pomadas/química , Pós/química , Reologia/instrumentação , Estresse Mecânico , Propriedades de Superfície , Temperatura , Viscosidade , Água/química
18.
Int J Biol Macromol ; 270(Pt 1): 132260, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38734338

RESUMO

The utilization of bioderived flame retardants in biodegradable poly (lactic acid) (PLA) has profound practical implications for extending the widespread application of PLA composites and protecting the environment. Nevertheless, there are still certain challenges that require prompt attention, especially the ineffectiveness of bio-based flame retardants and their deterioration of the mechanical properties of PLA. This work introduced triglycidyl isocyanurate (TGIC), which has multiple epoxy functions, into the self-assembly process of phytic acid (PA) and chitosan (CS). The epoxy-modified bioderived flame retardant PA@CS-TGIC (PCT) was well dispersed in the PLA matrix and had a strong interfacial adhesion, while also TGIC had a synergistic char-forming effect. By compounding epoxy-modified ammonium polyphosphate (MAPP), 3%PCT/MAPP-PLA composites may reach a LOI value of 28.8 % and UL-94 V-0 rating. Simultaneously, the melting droplets had been considerably reduced. Tensile strength of the 3%PCT/MAPP-PLA composites was 67.0 MPa, 10.8 % higher than that of pure PLA. This work paves a new avenue for the development of PLA composites with robust mechanical and flame retardant properties.


Assuntos
Retardadores de Chama , Poliésteres , Poliésteres/química , Resistência à Tração , Quitosana/química , Ácido Fítico/química , Triazinas/química
19.
Int J Biol Macromol ; 262(Pt 1): 129976, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331074

RESUMO

In high molecular weight poly(L-lactic acid)/poly(D-lactic acid) (HMW PLLA/PDLA) blends, the construction of exclusive stereocomplex crystals (SC) with high crystallinity and strong melt memory remains a great challenge. In the present study, various norbornene dicarboxylate complexes (TMXNa, Mg, Al, or Ca) were employed as the stereo-selective nucleating agents (NAs), and their effect on the crystallization characteristics, rheological behavior, and heat resistance of PLLA/PDLA blends were thoroughly studied. Strikingly, TMX-Al facilitated the construction of exclusive SC with over 50 % crystallinity and excellent melt memory. The dense SC crystals network structure boosted the heat resistance of L/D-xAl blends with a VST as high as 145 °C. The strengthened intermolecular interaction fostered the generation of pre-ordered structure in the melt and enhanced chain interdiffusion, which contributed to intermolecular nucleation and SC crystallization in L/D-xAl blend. This study opens up a new avenue for melt processing and application development of SC-PLA materials.


Assuntos
Temperatura Alta , Ácido Láctico , Cristalização , Ácido Láctico/química , Peso Molecular , Estereoisomerismo , Poliésteres/química
20.
Int J Biol Macromol ; 277(Pt 2): 134338, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39089539

RESUMO

Sodium alginate (SA) has gained widespread acclaim as a carrier medium for three-dimensional (3D) bioprinting of cells and a diverse array of bioactive substances, attributed to its remarkable biocompatibility and affordability. The conventional approach for fabricating alginate-based tissue engineering constructs entails a post-treatment phase employing a calcium ion solution. However, this method proves ineffectual in addressing the predicament of low precision during the 3D printing procedure and is unable to prevent issues such as non-uniform alginate gelation and substantial distortions. In this study, we introduced borate bioactive glass (BBG) into the SA matrix, capitalizing on the calcium ions released from the degradation of BBG to incite the cross-linking reaction within SA, resulting in the formation of BBG-SA hydrogels. Building upon this fundamental concept, it unveiled that BBG-SA hydrogels greatly enhance the precision of SA in extrusion-based 3D printing and significantly reduce volumetric contraction shrinkage post-printing, while also displaying certain adhesive properties and electrical conductivity. Furthermore, in vitro cellular experiments have unequivocally established the excellent biocompatibility of BBG-SA hydrogel and its capacity to actively stimulate osteogenic differentiation. Consequently, BBG-SA hydrogel emerges as a promising platform for 3D bioprinting, laying the foundation for the development of flexible, biocompatible electronic devices.


Assuntos
Alginatos , Materiais Biocompatíveis , Bioimpressão , Boratos , Cálcio , Vidro , Hidrogéis , Impressão Tridimensional , Alginatos/química , Alginatos/farmacologia , Bioimpressão/métodos , Boratos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Cálcio/química , Hidrogéis/química , Vidro/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Humanos , Diferenciação Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos
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