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1.
Dev Biol ; 510: 8-16, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38403101

RESUMEN

Physiological root resorption is a common occurrence during the development of deciduous teeth in children. Previous research has shown that the regulation of the inflammatory microenvironment through autophagy in DDPSCs is a significant factor in this process. However, it remains unclear why there are variations in the autophagic status of DDPSCs at different stages of physiological root resorption. To address this gap in knowledge, this study examines the relationship between the circadian clock of DDPSCs, the autophagic status, and the periodicity of masticatory behavior. Samples were collected from deciduous teeth at various stages of physiological root resorption, and DDPSCs were isolated and cultured for analysis. The results indicate that the circadian rhythm of important autophagy genes, such as Beclin-1 and LC3, and the clock gene REV-ERBα in DDPSCs, disappears under mechanical stress. Additionally, the study found that REV-ERBα can regulate Beclin-1 and LC3. Evidence suggests that mechanical stress is a trigger for the regulation of autophagy via REV-ERBα. Overall, this study highlights the importance of mechanical stress in regulating autophagy of DDPSCs via REV-ERBα, which affects the formation of the inflammatory microenvironment and plays a critical role in physiological root resorption in deciduous teeth.


Asunto(s)
Relojes Circadianos , Resorción Radicular , Niño , Humanos , Resorción Radicular/genética , Beclina-1/genética , Ritmo Circadiano/genética , Células Madre , Diente Primario
2.
Stem Cells ; 42(10): 914-927, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39167061

RESUMEN

BACKGROUND: This study aims to address challenges in dental pulp regeneration therapy. The heterogeneity of DPSCs poses challenges, especially in stem cell transplantation for clinical use, particularly when sourced from donors of different ages and conditions. METHODS: Pseudotime analysis was employed to analyze single-cell sequencing data, and immunohistochemical studies were conducted to investigate the expression of fibronectin 1 (FN1). We performed in vitro sorting of PDGFRß+ DPSCs using flow cytometry. A series of functional assays, including cell proliferation, scratch, and tube formation assays, were performed to experimentally validate the vasculogenic capabilities of the identified PDGFRß+ DPSC subset. Furthermore, gene-edited mouse models were utilized to demonstrate the importance of PDGFRß+ DPSCs. Transcriptomic sequencing was conducted to compare the differences between PDGFRß+ DPSCs and P1-DPSCs. RESULTS: Single-cell sequencing analysis unveiled a distinct subset, PDGFRß+ DPSCs, characterized by significantly elevated FN1 expression during dental pulp development. Subsequent cell experiments demonstrated that this subset possesses remarkable abilities to promote HUVEC proliferation, migration, and tube formation. Gene-edited mouse models confirmed the vital role of PDGFRß+ DPSCs in dental pulp development. Transcriptomic sequencing and in vitro experiments demonstrated that the PDGFR/PI3K/AKT signaling pathway is a crucial factor mediating the proliferation rate and pro-angiogenic properties of PDGFRß+ DPSCs. CONCLUSION: We defined a new subset, PDGFRß+ DPSCs, characterized by strong proliferative activity and pro-angiogenic capabilities, demonstrating significant clinical translational potential.


Asunto(s)
Pulpa Dental , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Pulpa Dental/metabolismo , Pulpa Dental/citología , Humanos , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Análisis de la Célula Individual/métodos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Animales , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Análisis de Secuencia de ARN/métodos , Transducción de Señal , Proliferación Celular/genética , Neovascularización Fisiológica/genética , Fibronectinas/metabolismo , Fibronectinas/genética
3.
Chem Soc Rev ; 53(3): 1592-1623, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38167687

RESUMEN

Supramolecular chemistry combines the strength of molecular assembly via various molecular interactions. Hydrogen bonding facilitated self-assembly with the advantages of directionality, specificity, reversibility, and strength is a promising approach for constructing advanced supramolecules. There are still some challenges in hydrogen bonding based supramolecular polymers, such as complexity originating from tautomerism of the molecular building modules, the assembly process, and structure versatility of building blocks. In this review, examples are selected to give insights into multiple hydrogen bonding driven emerging supramolecular architectures. We focus on chiral supramolecular assemblies, multiple hydrogen bonding modules as stimuli responsive sources, interpenetrating polymer networks, multiple hydrogen bonding assisted organic frameworks, supramolecular adhesives, energy dissipators, and quantitative analysis of nano-adhesion. The applications in biomedical materials are focused with detailed examples including drug design evolution for myotonic dystrophy, molecular assembly for advanced drug delivery, an indicator displacement strategy for DNA detection, tissue engineering, and self-assembly complexes as gene delivery vectors for gene transfection. In addition, insights into the current challenges and future perspectives of this field to propel the development of multiple hydrogen bonding facilitated supramolecular materials are proposed.


Asunto(s)
Materiales Biocompatibles , Polímeros , Enlace de Hidrógeno , Polímeros/química
4.
Small ; 20(25): e2309279, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38214439

RESUMEN

Radiation resistance in breast cancer resulting in residual lesions or recurrence is a significant cause to radiotherapy failure. Cancer-associated fibroblasts (CAFs) and radiotherapy-induced senescent CAFs can further lead to radiation resistance and tumor immunosuppressive microenvironment. Here, an engineering cancer-cell-biomimetic nanoplatform is constructed for dual-targeted clearance of CAFs as well as senescent CAFs. The nanoplatform is prepared by 4T1 cell membrane vesicles chimerized with FAP single-chain fragment variable as the biomimetic shell for targeting of CAFs and senescent CAFs, and PLGA nanoparticles (NPs) co-encapsulated with nintedanib and ABT-263 as the core for clearance of CAFs and senescent CAFs, which are noted as FAP-CAR-CM@PLGA-AB NPs. It is evidenced that FAP-CAR-CM@PLGA-AB NPs directly suppressed the tumor-promoting effect of senescent CAFs. It also exhibits prolonged blood circulation and enhanced tumor accumulation, dual-cleared CAFs and senescent CAFs, improved radiation resistance in both acquired and patient-derived radioresistant tumor cells, and effective antitumor effect with the tumor suppression rate of 86.7%. In addition, FAP-CAR-CM@PLGA-AB NPs reverse the tumor immunosuppressive microenvironment and enhance systemic antitumor immunity. The biomimetic system for dual-targeted clearance of CAFs and senescent CAFs provides a potential strategy for enhancing the radio-sensitization of breast cancer.


Asunto(s)
Neoplasias de la Mama , Fibroblastos Asociados al Cáncer , Senescencia Celular , Nanopartículas , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Nanopartículas/química , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/efectos de los fármacos , Animales , Línea Celular Tumoral , Senescencia Celular/efectos de los fármacos , Tolerancia a Radiación/efectos de los fármacos , Ratones , Biomimética/métodos , Microambiente Tumoral/efectos de los fármacos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química
5.
J Oral Pathol Med ; 53(3): 201-207, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38402639

RESUMEN

BACKGROUND: The objective of this study was to evaluate and compare the expression levels of TNF-α, omentin-1, and IL-6 in periodontitis patients before and after treatment with biological antimicrobial peptide (AMP) periodontal gel. METHODS: There involved 86 periodontitis patients admitted to our hospital from January 2020 to March 2021. They were equally and randomly distributed into the study group and the control group. The efficacy and adverse reactions were compared between the two groups after treatment, Additionally, the sulcus bleeding index (SBI), plaque index (PLI), gingival index (GI), periodontal probing depth (PD), and levels of TNF-α, omentin-1, and IL-6 were measured before and after treatment. RESULTS: After treatment, the total effective rate of the study group was significantly higher than that of the control group (p < 0.05), while the scores of four indicators (SBI, PLI, GI, and PD) and the levels of TNF-α, omentin-1, and IL-6 in the study group were evidently lower than the control group (p < 0.05). The study group had 1 case of mild irritant reaction, with an adverse reaction rate of 2.33% (1/43). And the control group had 1 case of nausea and 1 case of allergy, with an adverse reaction rate of 4.65% (2/43). The adverse reactions demonstrated no statistical difference between the two groups (χ2 = 0.345, p = 0.557). CONCLUSIONS: The levels of TNF-α and IL-6 were highly expressed before the auxiliary therapy of biological AMP periodontal gel for periodontitis, alongside low expression of omentin-1. Subsequently, the biological antibacterial polypeptide periodontal gel demonstrated efficacy in the treatment of periodontitis.


Asunto(s)
Periodontitis Crónica , Periodontitis , Humanos , Factor de Necrosis Tumoral alfa , Interleucina-6 , Antibacterianos , Periodontitis/tratamiento farmacológico , Péptidos Antimicrobianos , Líquido del Surco Gingival , Periodontitis Crónica/tratamiento farmacológico
6.
Int J Med Sci ; 21(6): 1155-1164, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38774749

RESUMEN

Introduction: Clinical studies have shown that endodontically-treated nonvital teeth exhibit less root resorption during orthodontic tooth movement. The purpose of this study was to explore whether hypoxic dental pulp stem cells (DPSCs) can promote osteoclastogenesis in orthodontically induced inflammatory root resorption (OIIRR). Methods: Succinate in the supernatant of DPSCs under normal and hypoxic conditions was measured by a succinic acid assay kit. The culture supernatant of hypoxia-treated DPSCs was used as conditioned medium (Hypo-CM). Bone marrow-derived macrophages (BMDMs) from succinate receptor 1 (SUCNR1)-knockout or wild-type mice were cultured with conditioned medium (CM), exogenous succinate or a specific inhibitor of SUCNR1 (4c). Tartrate-resistant acid phosphatase (TRAP) staining, Transwell assays, qPCR, Western blotting, and resorption assays were used to evaluate osteoclastogenesis-related changes. Results: The concentration of succinate reached a maximal concentration at 6 h in the supernatant of hypoxia-treated DPSCs. Hypo-CM-treated macrophages were polarized to M1 proinflammatory macrophages. Hypo-CM treatment significantly increased the formation and differentiation of osteoclasts and increased the expression of osteoclastogenesis-related genes, and this effect was inhibited by the specific succinate inhibitor 4c. Succinate promoted chemotaxis and polarization of M1-type macrophages with increased expression of osteoclast generation-related genes. SUCNR1 knockout decreased macrophage migration, M1 macrophage polarization, differentiation and maturation of osteoclasts, as shown by TRAP and NFATc1 expression and cementum resorption. Conclusions: Hypoxic DPSC-derived succinate may promote osteoclast differentiation and root resorption. The regulation of the succinate-SUCNR1 axis may contribute to the reduction in the OIIRR.


Asunto(s)
Pulpa Dental , Ratones Noqueados , Osteoclastos , Osteogénesis , Resorción Radicular , Células Madre , Ácido Succínico , Animales , Ratones , Pulpa Dental/citología , Pulpa Dental/efectos de los fármacos , Pulpa Dental/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Resorción Radicular/patología , Resorción Radicular/metabolismo , Humanos , Ácido Succínico/metabolismo , Osteogénesis/efectos de los fármacos , Células Madre/metabolismo , Células Madre/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Hipoxia de la Célula/efectos de los fármacos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Medios de Cultivo Condicionados/farmacología , Células Cultivadas
7.
J Periodontal Res ; 58(1): 70-82, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36346119

RESUMEN

BACKGROUND AND OBJECTIVES: Periodontitis is the top reason for tooth loss, and smoking significantly increases severe periodontitis risk. Defective autophagy has been reported to play a vital role in periodontitis. This study aimed to elucidate the relationship between autophagy and inflammation factors production in nicotine-treated periodontal ligament stem cells (PDLSCs) and the underlying mechanism. METHODS: In this study, transmission electron microscopy, immunofluorescence, and the mCherry-GFP-LC3 plasmid were used to study autophagy flux. The gene levels of inflammation factors and long noncoding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) were detected by quantitative real-time PCR (qRT-PCR). Western blot was performed to assess the protein levels of autophagic markers and α7 nicotinic acetylcholine receptor (α7nAChR). RESULTS: We found that nicotine impaired autophagosome-lysosome fusion and lysosome functions to block autophagy flux, contributing to inflammatory factors production in nicotine-treated PDLSCs. Moreover, nicotine upregulated NEAT1 by activating α7nAChR. NEAT1 decreased autophagy flux by downregulating syntaxin 17 (STX17). CONCLUSION: Our data indicate that NEAT1-decreased autophagy flux is pivotal for inflammation factors production in nicotine-treated PDLSCs.


Asunto(s)
Periodontitis , ARN Largo no Codificante , Humanos , Receptor Nicotínico de Acetilcolina alfa 7/genética , Autofagia/genética , Células Cultivadas , Inflamación/metabolismo , Nicotina/farmacología , Nicotina/metabolismo , Ligamento Periodontal/metabolismo , Periodontitis/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Células Madre/metabolismo
8.
Surg Endosc ; 37(10): 7649-7657, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37491656

RESUMEN

INTRODUCTION: Although transoral endoscopic thyroidectomy (TOETVA) is widely utilized in clinical practice, some problems and restrictions still remain. Our study compared the perioperative features and early surgical efficacy of TOETVA and a modified transoral and submental endoscopic thyroidectomy (TOaST) in early stage papillary thyroid carcinoma (PTC). METHODS: The clinical data of PTC patients who underwent endoscopic thyroidectomy, including 42 modified TOaST patients and 114 traditional TOETVA patients, were retrospectively collected. Propensity score matching was employed to reduce patient selection bias. The perioperative features and early surgical efficacy data of two groups were compared. RESULTS: The operation time of the TOaST group was significantly shorter than that of the TOETVA group (150.00 ± 35.47 min vs. 168.75 ± 44.49 min; P = 0.030). Furthermore, the TOaST group required shorter days for a normal diet (3.38 ± 0.93 days vs. 4.04 ± 1.03 days; P = 0.000) and a shorter hospital stay than the TOETVA group (5.85 ± 2.17 days vs. 6.12 ± 2.01 days; P = 0.003). There was no statistical difference in complications between the two groups, but the probability of numbness of the lower lip and chin in the TOaST group was lower than that in the TOETVA group(5.12% vs. 13.04%, P = 0.321). The symptoms of mandibular numbness and hoarseness of most patients were relieved in both groups 6 months after surgery, and no abnormalities and recurrence were found in the thyroid ultrasound. All the patients were satisfied with the appearance of their surgical incision. CONCLUSION: In early stage PTC patients, TOaST had the same surgical effectiveness as traditional TOETVA but can minimize the probability of mandibular numbness and improve the perioperative quality of life.


Asunto(s)
Cirugía Endoscópica por Orificios Naturales , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Tiroidectomía , Estudios Retrospectivos , Hipoestesia/cirugía , Calidad de Vida , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología
9.
Clin Oral Investig ; 26(6): 4419-4426, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35157134

RESUMEN

OBJECTIVE: To compare the different restoration types of primary teeth to determine which type is appropriate for extensive caries of primary molars and incisors based on mechanical properties. MATERIALS AND METHODS: A total of 160 primary teeth were evaluated in this study, including 80 incisors and 80 molars. Each category was divided into four groups: the control group, composite resin group, pre-veneered stainless steel crown (stainless steel crown) group, and zirconia crown group. Compressive strength test and fatigue strength test were performed. RESULTS: The compressive strength and fatigue strength of the composite resin group were significantly decreased compared with the control group (P < 0.05). The prefabricated crown groups showed increased fatigue and compressive strength compared with the control group, and the zirconia crown group was higher than that of the pre-veneered stainless steel crown group (P < 0.05). The zirconia crown group was less than the stainless steel crown group (P < 0.05) in the compressive strength but more than the stainless steel crown group (P < 0.05) in the fatigue strength. CONCLUSIONS: The compressive strength and fatigue strength of crown restoration were superior to that of the composite resin filling. The fatigue strength of the zirconia crown also performed better than the pre-veneered stainless steel crown and the stainless steel crown. The compressive strength of the zirconia crown was less than that of the stainless steel crown. CLINICAL RELEVANCE: The zirconia crown is a new restoration method for primary teeth that may be commonly applied in clinical practice.


Asunto(s)
Coronas , Restauración Dental Permanente , Diente Primario , Resinas Compuestas , Fuerza Compresiva , Humanos , Pruebas Mecánicas , Acero Inoxidable , Circonio
10.
Biochem Biophys Res Commun ; 554: 123-130, 2021 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-33784507

RESUMEN

Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy has been implicated in the ferroptosis in cancer cells and hematopoiesis in the bone marrow. However, the role of iron metabolism, especially NCOA4-mediated degradation of ferritin, has not been explored in the proliferation of mesenchymal stem cells. The present study was designed to explore the role of NCOA4-mediated ferritinophagy in hypoxia-treated dental pulp stem cells (DPSCs). Hypoxia treatment increased ROS generation, boosted cytosolic labile iron pool, increased expression of transferrin receptor 1 and NCOA4. Moreover, colocalization of LC3B with NCOA4 and ferritin was observed in hypoxia-treated DPSCs, indicating the development of ferritinophagy. Hypoxia promoted the proliferation of DPSCs, but not ferroptosis, under normal serum supplement and serum deprivation. NCOA4 knock-down reduced ferritin degradation and inhibited proliferation of DPSCs under hypoxia. Furthermore, the activation of hypoxia inducible factor 1α and p38 mitogen-activated protein kinase signaling pathway was involved in the upregulation of NCOA4 in hypoxia. Therefore, our present study suggested that NCOA4-mediated ferritinophagy promoted the level of labile iron pool, leading to enhanced iron availability and elevated cell proliferation of DPSCs. Our present study uncovered a physiological role of ferritinophagy in the proliferation and growth of mesenchymal stem cells under hypoxia.


Asunto(s)
Hipoxia de la Célula/fisiología , Pulpa Dental/patología , Ferritinas/metabolismo , Hierro/metabolismo , Coactivadores de Receptor Nuclear/metabolismo , Células Madre/patología , Autofagia , Proliferación Celular/fisiología , Pulpa Dental/metabolismo , Humanos , Células Madre/metabolismo
11.
Small ; 17(14): e2006612, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33711201

RESUMEN

The adoption of neural interfacing into neurological diagnosis is severely hampered by the complex, costly, and error-prone manufacturing methods, requiring new fabrication processes and materials for flexible neural interfacing. Here a strategy for fabricating highly stretchable neural electrode arrays based on screen printing of liquid metal conductors onto polydimethylsiloxane substrates is presented. The screen-printed electrode arrays show a resolution of 50 µm, which is ideally applicable to neural interfaces. The integration of liquid metal-polymer conductor enables the neural electrode arrays to retain stable electrical properties and compliant mechanical performance under a significant (≈108%) strain. Taking advantage of its high biocompatibility, liquid metal electrode arrays exhibit excellent performance for neurite growth and long-term implantation. The stretchable electrode arrays can spontaneously conformally come in touch with the brain surface, and high-throughput electrocorticogram signals are recorded. Based on stretchable electrode arrays, real-time monitoring of epileptiform activities can be provided at different states of seizure. The method reported here offers a new fabrication strategy to manufacture stretchable neural electrodes, with additional potential utility in diagnostic brain-machine interfaces.


Asunto(s)
Metales , Polímeros , Encéfalo , Electrodos
12.
BMC Oral Health ; 21(1): 560, 2021 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-34732192

RESUMEN

BACKGROUND: Nicotine is an important risk factor and the main toxic component associated with periodontitis. However, the mechanism of nicotine induced periodontitis is not clear. To investigated the mechanism through which nicotine regulates autophagy of human periodontal ligament cells (hPDLCs) through the alpha7 nicotinic acetylcholine receptor (α7 nAChR) and how autophagy further regulates the release of IL-1ß and IL-8 secretion in hPDLCs. METHODS: HPDLCs were obtained from root of extracted teeth and pre-incubated in alpha-bungarotoxin (α-BTX) or 3-Methyladenine (3-MA), followed by culturing in nicotine. We used a variety of experimental detection techniques including western blotting, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM) and RT-qPCR to assess the expression of the LC3 protein, autolysosome, and release of IL-1ß and IL-8 from hPDLCs. RESULTS: Western blots, immunofluorescence and TEM results found that the nicotine significantly increased the autophagy expression in hPDLCs that was time and concentration dependent and reversed by α-BTX treatment (p < 0.05). RT-qPCR and ELISA results revealed a noticeable rise in the release of inflammatory factors IL-1ß and IL-8 from hPDLCs in response to nicotine. RT-qPCR and ELISA results showed that nicotine can significantly up-regulate the release of inflammatory factors IL-1ß and IL-8 in hPDLCs, and this effect can be inhibited by 3-MA (p < 0.05). CONCLUSIONS: Nicotine regulated autophagy of hPDLCs through α7 nAChR and in turn the regulation of the release of inflammatory factors 1L-1ß and 1L-8 by hPDLCs.


Asunto(s)
Interleucina-8 , Nicotina , Autofagia , Células Cultivadas , Humanos , Interleucina-8/genética , Nicotina/toxicidad , Ligamento Periodontal
13.
J Cell Mol Med ; 24(4): 2663-2676, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31930698

RESUMEN

Periodontitis is the leading cause of adult tooth loss, and those who smoke are at an increased risk of developing periodontitis. α7 nicotinic acetylcholine receptor (α7 nAChR) is proposed to mediate the potential synergistic effect of nicotine and inflammation in smoking-related periodontitis. However, this has not been experimentally demonstrated. We isolated and cultured human periodontal ligament stem cells (PDLSCs) from healthy and inflamed tissues. PDLSCs were treated with either inflammatory factors or nicotine. We measured expression of genes that are associated with osteogenic differentiation and osteoclast formation using RT-qPCR and Western blot analyses. Besides, immunohistochemical staining, micro-CT analysis and tartaric acid phosphatase staining were used to measure α7 nAChR expression and function. Inflammation up-regulated α7 nAChR expression in both periodontal ligament tissues and PDLSCs. The up-regulated α7 nAChR contributed to the synergistic effect of nicotine and inflammation, leading to a decreased capability of osteogenic differentiation and increased capability of osteoclast formation-induction of PDLSCs. Moreover, the inflammation-induced up-regulation of α7 nAChR was partially dependent on the level of phosphorylated GSK-3ß. This study provides experimental evidence for the pathological development of smoking-related periodontitis and sheds new light on developing inflammation and α7 nAChR-targeted therapeutics to treat and prevent the disease.


Asunto(s)
Glucógeno Sintasa Quinasa 3 beta/metabolismo , Inflamación/patología , Nicotina/efectos adversos , Periodontitis/inducido químicamente , Periodontitis/patología , Regulación hacia Arriba/efectos de los fármacos , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Adolescente , Adulto , Animales , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Niño , Humanos , Inflamación/metabolismo , Masculino , Ratones , Ratones Desnudos , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoclastos/patología , Osteogénesis/efectos de los fármacos , Ligamento Periodontal/efectos de los fármacos , Ligamento Periodontal/metabolismo , Periodontitis/metabolismo , Fosforilación , Transducción de Señal/efectos de los fármacos , Fumar , Células Madre , Adulto Joven
14.
J Mol Recognit ; 31(3)2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28326626

RESUMEN

Molecularly imprinted polymers (MIPs) were designed and prepared via bulk thermal polymerization with gossypol as the template molecule and dimethylaminoethyl methacrylate as the functional monomer. The morphology and microstructures of MIPs were characterized by scanning electron microscope and Brunauer-Emmett-Teller surface areas. Static adsorption tests were performed to evaluate adsorption behavior of gossypol by the MIPs. It was found that adsorption kinetics and adsorption isotherms data of MIPs for gossypol were fit well with the pseudo-second-order model and Freundlich model, respectively. Scatchard analysis showed that heterogeneous binding sites were formed in the MIPs, including lower-affinity binding sites with the maximum adsorption of 252 mg/g and higher-affinity binding sites with the maximum adsorption of 632 mg/g. Binding studies also revealed that MIPs had favorable selectivity towards gossypol compared with non-imprinted polymers. Furthermore, adsorption capacity of MIPs maintained above 90% after 5 regeneration cycles, indicating MIPs were recyclable and could be used multiple times. These results demonstrated that prepared MIPs could be a promising functional material for selective adsorption of gossypol.


Asunto(s)
Gosipol/aislamiento & purificación , Metacrilatos/química , Impresión Molecular , Polímeros/química , Adsorción , Sitios de Unión , Gosipol/química , Polimerizacion , Polímeros/síntesis química , Extracción en Fase Sólida , Espectroscopía Infrarroja por Transformada de Fourier
15.
Drug Dev Ind Pharm ; 44(4): 563-569, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29148846

RESUMEN

OBJECTIVE: Curcumin being used to treat various chronic diseases while its poor bioavailability issue limited its wide clinical application as a therapeutic agent. The aim of this work was to prepare curcumin-loaded self-assembled micelles using soluplus and solutol®HS15 (SSCMs) to enhance curcumin's solubility and thus oral bioavailability. METHODS: Optimum formulation was investigated and the optimized ratio of drugs and excipients was obtained and the SSCMs were prepared via ethanol solvent evaporation method. The optimal SSCMs were characterized by transmission electron microscopy, drug content analysis including loading efficiency (LE%) and entrapment efficiency (EE%), and the cumulative amount of curcumin released from the micelles were all calculated using HPLC method. The in vitro cytotoxicity and the permeability of SSCMs were measured by Caco-2 cell monolayers and the oral bioavailability was evaluated by SD rats. KEY FINDINGS: The solubility of curcumin in self-assembled micelles was dramatically increased by 4200 times as compared to free curcumin. Caco-2 cells transport experiment exhibited that while soluplus and solutol®HS15 were self-assembled into micelles, it could not only promote the permeability of curcumin across membrane for better absorption, but also could restrain the curcumin pumped outside due to the role of P-gp efflux mechanism of soluplus and solutol®HS15. Furthermore, the prepared SSCMs formulation was almost nontoxic and had safety performance on Caco-2 cells model. Moreover, curcumin's oral bioavailability of SSCMs formulation in SD rats had doubled than that of free curcumin. CONCLUSIONS: The prepared SSCMs were characterized by PS, PDI, LE%, EE% data analysis. After the soluplus and solutol®HS15 were self assembled into micelles, both the solubility and membrane permeability of curcumin were evaluated to have been enhanced, as well as the effect of efflux pump of curcumin was inhibited, hence to promote oral absorption and generate an increased bioavailability.


Asunto(s)
Curcumina/administración & dosificación , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Disponibilidad Biológica , Células CACO-2 , Supervivencia Celular , Curcumina/química , Curcumina/farmacocinética , Composición de Medicamentos , Excipientes , Humanos , Micelas , Polietilenglicoles , Polivinilos , Ratas , Ratas Sprague-Dawley , Solubilidad , Solventes
16.
J Microencapsul ; 35(3): 241-248, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29624090

RESUMEN

Freeze-drying is an effective way to improve long-term physical stability of nanosuspension in drug delivery applications. Nanosuspension also known as suspension of nanoparticles. In this study, the effect of freeze-drying with different cryoprotectants on the physicochemical characteristics of resveratrol (RSV) nanosuspension and quercetin (QUE) nanosuspension was evaluated. D-α-tocopheryl polyethylene glycol succinate (TPGS) and folate-modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA) were selected as functional stabilisers formulated nanosuspension which were prepared by anti-solvent precipitation method. RSV nanoparticle size and QUE nanoparticle size were about 210 and 110 nm, respectively. The AFM and TEM results of nanosuspension showed uniform and irregular shape particles. After freeze-drying, the optimal concentration of four cryoprotectants was determined by the particle size of re-dispersed nanoparticles. The dissolution profile of drug nanoparticle significantly showed approximately at a 6-8-fold increase dissolution rate. Moreover, TPGS and DSPE-PEG-FA stabilised RSV nanosuspension and QUE nanosuspension samples showed better effect on long-term physical stability.


Asunto(s)
Antioxidantes/química , Excipientes/química , Liofilización/métodos , Nanopartículas/química , Quercetina/química , Estilbenos/química , Crioprotectores/química , Estabilidad de Medicamentos , Ácido Fólico/análogos & derivados , Nanopartículas/ultraestructura , Tamaño de la Partícula , Fosfatidiletanolaminas/química , Polietilenglicoles/química , Resveratrol , Solubilidad , Suspensiones , Vitamina E/química
17.
Biochem Biophys Res Commun ; 493(1): 152-157, 2017 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-28917834

RESUMEN

Membrane fusion proteins (MFPs) play an essential role in the action of the drug efflux pumps and protein secretion systems in bacteria. The sporulation delaying protein (SDP) efflux pump YknWXYZ has been identified in diverse Bacillus species. The MFP YknX requires the ATP-binding cassette (ABC) transporter YknYZ and the Yip1 family protein YknW to form a functional complex. To date, the crystal structure, molecular function and mechanism of action of YknX remain unknown. In this study, to characterize the structural and biochemical roles of YknX in the functional assembly of YknWXYZ from B. amyloliquefaciens, we successfully obtained crystals of the YknX protein that diffracted X-rays to a resolution of 4.4 Å. We calculated an experimentally phased map using single-wavelength anomalous diffraction (SAD), revealing that YknX forms a hexameric assembly similar to that of MacA from Gram-negative bacteria. The hexameric assembly of YknX exhibited a funnel-like structure with a central channel and a conical mouth. Functional studies in vitro suggest that YknX can bind directly to peptidoglycan. Our study provides an improved understanding of the assembly of the YknWXYZ efflux pump and the role of YknX in the complex.


Asunto(s)
Bacillus amyloliquefaciens/química , Proteínas Bacterianas/química , Proteínas Bacterianas/ultraestructura , Proteínas de la Fusión de la Membrana/química , Proteínas de la Fusión de la Membrana/ultraestructura , Peptidoglicano/química , Sitios de Unión , Dimerización , Proteínas de Transporte de Membrana , Modelos Químicos , Modelos Moleculares , Unión Proteica , Conformación Proteica , Esporas Bacterianas/química , Esporas Bacterianas/ultraestructura , Relación Estructura-Actividad
18.
J Ind Microbiol Biotechnol ; 44(3): 453-464, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28101807

RESUMEN

To achieve a cost-effective bioconversion of lignocellulosic materials, a novel xylose/glucose co-fermentation process by co-culture of cellulose-utilizing recombinant Saccharomyces cerevisiae (S. cerevisiae) and xylan-utilizing recombinant Pichia pastoris (P. pastoris) was developed, in which ethanol was produced directly from wheat straw without additional hydrolytic enzymes. Recombinant S. cerevisiae coexpressing three types of cellulase and recombinant P. pastoris coexpressing two types of xylanase were constructed, respectively. All cellulases and xylanases were successfully expressed and similar extracellular activity was demonstrated. The maximum ethanol concentration of 32.6 g L-1 with the yield 0.42 g g-1 was achieved from wheat straw corresponding to 100 g L-1 of total sugar after 80 h co-fermentation, which corresponds to 82.6% of the theoretical yield. These results demonstrate that the direct and efficient ethanol production from lignocellulosic materials is accomplished by simultaneous saccharification (cellulose and hemicellulose) and co-fermentation (glucose and xylose) with the co-culture of the two recombinant yeasts.


Asunto(s)
Etanol/metabolismo , Pichia/metabolismo , Saccharomyces cerevisiae/metabolismo , Triticum , Celulosa/química , Técnicas de Cocultivo , Análisis Costo-Beneficio , Fermentación , Glucosa/metabolismo , Lignina/química , Microorganismos Modificados Genéticamente , Polisacáridos/química , Ingeniería de Proteínas , Xilosa/metabolismo
19.
Int J Biometeorol ; 61(3): 453-461, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27557791

RESUMEN

Hand, foot, and mouth disease (HFMD) is one of the most common communicable diseases in China, and current climate change had been recognized as a significant contributor. Nevertheless, no reliable models have been put forward to predict the dynamics of HFMD cases based on short-term weather variations. The present study aimed to examine the association between weather factors and HFMD, and to explore the accuracy of seasonal auto-regressive integrated moving average (SARIMA) model with local weather conditions in forecasting HFMD. Weather and HFMD data from 2009 to 2014 in Huainan, China, were used. Poisson regression model combined with a distributed lag non-linear model (DLNM) was applied to examine the relationship between weather factors and HFMD. The forecasting model for HFMD was performed by using the SARIMA model. The results showed that temperature rise was significantly associated with an elevated risk of HFMD. Yet, no correlations between relative humidity, barometric pressure and rainfall, and HFMD were observed. SARIMA models with temperature variable fitted HFMD data better than the model without it (sR 2 increased, while the BIC decreased), and the SARIMA (0, 1, 1)(0, 1, 0)52 offered the best fit for HFMD data. In addition, compared with females and nursery children, males and scattered children may be more suitable for using SARIMA model to predict the number of HFMD cases and it has high precision. In conclusion, high temperature could increase the risk of contracting HFMD. SARIMA model with temperature variable can effectively improve its forecast accuracy, which can provide valuable information for the policy makers and public health to construct a best-fitting model and optimize HFMD prevention.


Asunto(s)
Enfermedad de Boca, Mano y Pie/epidemiología , Modelos Teóricos , Tiempo (Meteorología) , China/epidemiología , Ciudades/epidemiología , Femenino , Predicción , Humanos , Incidencia , Masculino
20.
Macromol Rapid Commun ; 35(16): 1387-96, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24789700

RESUMEN

Nanotubes have attracted considerable attention due to their unique 1D hollow structure; however, the fabrication of pure nanotubes via block copolymer self-assembly remains a challenge. In this work, the successful preparation of core-shell-corona (CSC) nanotubular micelles with uniform diameter and high aspect ratio is reported, which is achieved via self-assembly of a poly (styrene-b-4-vinyl pyridine-b-ethylene oxide) triblock terpolymer in binary organic solvents with assistance of solution thermal annealing. Via direct visualization of trapped intermediates, the nanotube is believed to be formed via large sphere-large solid cylinderical aggregates-nanotube transformations, wherein the unique solid to hollow transition accompanied with the unidirectional growth is distinct from conventional pathway. In addition, by virtue of the CSC structure, gold nanoparticles are able to be selectively incorporated into different micellar domains of the nanotubes, which may have potential applications in nanoscience and nanotechnology.


Asunto(s)
Nanotubos/química , Polietilenglicoles/química , Polímeros/química , Poliestirenos/química , Polivinilos/química , Oro/química , Nanopartículas del Metal/química , Micelas , Microscopía de Fuerza Atómica , Nanotubos/ultraestructura , Temperatura
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